Screening Assessment Aromatic Azo and Benzidine-based Substance Grouping

Screening Assessment Aromatic Azo and Benzidine-based Substance Grouping
Screening Assessment
Aromatic Azo and Benzidine-based Substance
Grouping
Certain Diarylide Yellow Pigments
Environment Canada
Health Canada
October 2014
Cat. No.: En14-201/2014E-PDF
ISBN 978-1-100-25183-7
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i
Synopsis
Pursuant to sections 68 or 74 of the Canadian Environmental Protection Act, 1999
(CEPA 1999), the Ministers of the Environment and of Health have conducted a
screening assessment onfive structurally related diarylide yellow pigments. These
substances constitute a subgroup of the Aromatic Azo and Benzidine-based Substance
Grouping being assessed as part of the Substance Groupings Initiative of the
Government of Canada’s Chemicals Management Plan (CMP) based on structural
similarity and applications. Substances in this Grouping were identified as priorities for
assessment as they met the categorization criteria under subsection 73(1) of CEPA
1999 and/or were considered as a priority based on other human health concerns.
The Chemical Abstracts Service Registry Number (CAS RN) 1, Domestic Substances
List (DSL) name, Colour Index (C.I) generic name, and chemical acronym of the five
substances are presented in the following table.
Identity of five diarylide yellow pigments in the Aromatic Azo and
based Substance Grouping
CAS RN
DSL name
C.I. generic
name
5102-83-0
Butanamide, 2,2′-[(3,3′-dichloro[1,1′-biphenyl]- Pigment
4,4′-diyl)bis(azo)]bis[N-(2,4-dimethylphenyl)-3- Yellow 13
oxo5567-15-7a Butanamide, 2,2′-[(3,3′-dichloro[1,1′-biphenyl]- Pigment
4,4′-diyl)bis(azo)]bis[N-(4-chloro-2,5Yellow 83
dimethoxyphenyl)-3-oxo6358-85-6
Butanamide, 2,2′-[(3,3′-dichloro[1,1′-biphenyl]- Pigment
4,4′-diyl)bis(azo)]bis[3-oxo-N-phenylYellow 12
78952-70-2 Butanamide,
2-[[3,3′-dichloro-4′-[[1-[[(2- N/A
chlorophenyl)amino]carbonyl]-2oxopropyl]azo][1,1′-biphenyl]-4-yl]azo]-N-(2,4dimethylphenyl)-3-oxoa
90268-24-9 Pigment Yellow 176
Pigment
Yellow 176
BenzidineChemical
acronym
PY13
PY83
PY12
CPAOBP
PY176
Abbreviations: N/A, not available.
1
The Chemical Abstracts Service Registry Number (CAS RN) is the property of the American Chemical Society and
any use or redistribution, except as required in supporting regulatory requirements and/or for reports to the
government when the information and the reports are required by law or administrative policy, is not permitted without
the prior written permission of the American Chemical Society.
ii
a
These substances were not identified under subsection 73(1) of CEPA 1999 but were included in this assessment
as they were considered as priorities based on other human health concerns.
These five diarylide yellow pigments do not occur naturally in the environment. Four of
the five substances have been reported to be manufactured in Canada and/or imported
for use in industrial activities. Some of the substances are also present in consumer
products and cosmetics. No data on measured concentrations in the Canadian
environment (or in other countries) have been identified for any of these substances.
Environment
Diarylide yellow pigments exist principally as particles in the nanometer or low micrometer size range, and the pigment powder is typically composed of primary particles
(i.e., the crystal lattice of a pigment), aggregates and agglomerates. These pigments
have very low solubility in both water (generally, in the low micrograms per litre range)
and in octanol (below 1 mg/L); because of this, it was proposed that a quotient of the
molar solute concentrations in octanol and in water (Soct/Sw) would reasonably
represent the octanol–water partition coefficients (Kow) for these pigments. The physical
and chemical properties and the particulate nature of these substances suggest that soil
and sediments would be the two major environmental media to which diarylide yellow
pigments partition.
Experimental data indicate that under aerobic conditions, diarylide yellow pigments are
expected to degrade slowly in water, soil and sediments.
Diarylide yellow pigments are not expected to bioaccumulate given their physical and
chemical properties (i.e., based on the particulate character of these substances, their
very low solubility in both water and octanol, and the high weight and large size of
molecules of these substances).
Due to the limited bioavailability of diarylide yellow pigments, no effects were found at
the concentration of 1 000 mg/kg soil or sediment (dry weight) in chronic soil and
sediment toxicity studies. These pigments also showed no effect at saturation in acute
and chronic aquatic ecotoxicity studies in which solvents were not used. Based on these
studies, diarylide yellow pigments are not expected to be harmful to aquatic, soildwelling or sediment-dwelling organisms at low concentrations.
To evaluate potential exposures to diarylide yellow pigments in the environment,
predicted environmental concentrations (PEC) were estimated; an industrial release
scenario was chosen to evaluate the potential exposure to these substances. Predicted
no-effect concentration (PNEC) values for each relevant environmental compartment
(soil, sediment and water) were calculated based on the experimental critical toxicity
values (CTVs). Calculated risk quotient (PEC/PNEC) values were much lower than 1 for
each environmental compartment (soil, sediment and water), indicating that harm to
organisms in these media is not expected.
iii
Considering all available lines of evidence presented in this Screening Assessment,
there is low risk of harm to organisms and the broader integrity of the environment from
the diarylide yellow pigmentsevaluated in this assessment. It is concluded that these
diarylide yellow pigments do not meet the criteria under paragraphs 64(a) or 64(b) of
CEPA 1999, as they are not entering the environment in a quantity or concentration or
under conditions that have or may have an immediate or long-term harmful effect on the
environment or its biological diversity or that constitute or may constitute a danger to the
environment on which life depends.
Human Health
For the human health assessment, exposure of the general population of Canada to
these diarylide yellow pigments is not expected to be significant from environmental
media while potential exposure by dermal, oral, and inhalation routes may occur from
the use of these substances in consumer products and cosmetics. These substances
are expected to exhibit low to negligible absorption and low toxicity. The margins
between the estimates of exposure from the use of consumer products and cosmetics,
and conservative effect levels are considered adequate to address uncertainties in the
exposure and health effects databases.
Based on the information presented in this Screening Assessment, it is concluded that
the diarylide yellow pigments evaluated in this assessment do not meet the criteria
under paragraph 64(c) of CEPA 1999 as they are not entering the environment in a
quantity or concentration or under conditions that constitute or may constitute a danger
in Canada to human life or health.
Overall Conclusion
It is concluded that the five diarylide yellow pigments evaluated in this assessment do
not meet any of the criteria set out in section 64 of CEPA 1999.
iv
Table of Contents
Synopsis ........................................................................................................................ ii
1. Introduction ............................................................................................................... 1
2. Identity of Substances .............................................................................................. 4
2.1 Selection of Analogues and Use of (Q)SAR Models .......................................... 6
2.2 Impurities ............................................................................................................. 9
3. Physical and Chemical Properties......................................................................... 11
3.1 Particle Size Distribution and Density ................................................................ 12
3.2 Melting and Decomposition Temperatures ........................................................ 13
3.3 Solubility in Water and Octanol ......................................................................... 13
3.4 Octanol–Water Partition Coefficient .................................................................. 14
3.5 Cross-sectional Diameter .................................................................................. 14
3.6 Data Outliers ..................................................................................................... 14
4. Sources and Uses ................................................................................................... 16
4.1 Sources ............................................................................................................. 16
4.2 Uses .................................................................................................................. 17
4.2.1 Uses in Canada ...................................................................................... 17
4.2.2 Other Jurisdictions .................................................................................. 20
5. Environmental Fate ................................................................................................. 21
5.1 Environmental Persistence ................................................................................ 22
5.1.1 Biodegradation in the Aquatic Environment............................................ 22
5.1.2 Biodegradation in Soil and Sediments .................................................... 26
5.1.3 Abiotic Degradation ................................................................................ 27
5.1.4 Summary of Persistence in the Environment.......................................... 27
5.2 Potential for Bioaccumulation ............................................................................ 27
5.2.1 Octanol–Water Partition Coefficient........................................................ 27
5.2.2 Bioconcentration Factor (BCF) ............................................................... 28
5.2.3 Summary of Bioaccumulation Potential .................................................. 31
6. Potential to Cause Ecological Harm ...................................................................... 32
6.1 Ecological effects assessment .......................................................................... 32
6.1.1 Aquatic Environment .............................................................................. 32
6.1.2 Other Environmental Compartments ...................................................... 37
6.1.3 Derivation of the Predicted No Effects Concentration (PNEC) for Water 38
6.1.4 Derivation of the PNECs for Soil and Sediment ..................................... 39
6.1.5 Ecological Effects Summary ................................................................... 39
6.2 Ecological exposure assessment ...................................................................... 40
6.2.1 Releases to the Environment ................................................................. 40
6.2.2 Aquatic Exposure from Recycled Paper Deinking Operations................ 41
6.2.3 Sediment Exposure from Recycled Paper Deinking Operations ............ 42
6.2.4 Soil Exposure from Recycled Paper Deinking Operations...................... 43
6.3 Characterization of Ecological Risk ................................................................... 43
6.3.1 Risk Quotient Analysis............................................................................ 43
6.3.2 Consideration of Lines of Evidence and Conclusion .............................. 44
v
6.3.3 Uncertainties in the Evaluation of Ecological Risk .................................. 45
7. Potential to Cause Harm to Human Health ........................................................... 47
7.1 Exposure Assessment ....................................................................................... 47
7.2 Health Effects Assessment................................................................................ 50
7.3 Human Health Risk Characterization................................................................. 61
8. Conclusion .............................................................................................................. 64
References ................................................................................................................... 65
Appendices .................................................................................................................. 85
Appendix A. Experimental Physical and Chemical Properties .................................. 85
Appendix B. Experimental Data on Biodegradation .................................................. 88
Appendix C. Empirical Data for Aquatic Ecotoxicity .................................................. 89
Appendix D. Exposures from Deinking Operations ................................................... 92
Appendix E. Upper-Bounding Estimates of Oral Exposure ..................................... 101
Appendix F. Upper-Bounding Estimates of Inhalation Exposure ............................ 103
Appendix G. Upper-Bounding Estimate of Short-Term Exposure from Tattoo Ink .. 107
vi
List of Tables
Table 2-1. Identity of the five diarylide yellow pigments .................................................. 4
Table 2-2. Chemical structures, molecular formula and molecular masses for the five
diarylide yellow pigments ............................................................................... 5
Table 2-3. Identity of the five analogues.......................................................................... 7
Table 2-4. Chemical structures, molecular formulas and molecular masses for the five
analogues ...................................................................................................... 7
Table 3-1. Experimental physical and chemical properties (at standard temperature of
approximately 25°C where applicable) of PY12, PY13, PY83 and PY176 and
their analogues ............................................................................................ 11
Table 4-1. Production volumes of diarylide yellow pigments identified in ESIS, TSCA
IUR and SPIN databases ............................................................................ 17
Table 4-2. Summary of the major uses of diarylide yellow pigments in Canada submitted
in response to section 71 surveys (Environment Canada 2012) ................. 18
Table 5-1. Biodegradation of diarylide yellow pigments: pure pigments tested ............. 23
Table 5-2. Biodegradation of diarylide yellow pigments: pigment formulations tested .. 24
Table 5-3. Experimental BCF data for diarylide yellow pigments in common carp
(Cyprinus carpio) ......................................................................................... 28
Table 6-1. Summary of empirical data for aquatic toxicity of diarylide yellow pigments 32
Table 6-2. Empirical data for ecotoxicity of diarylide yellow pigments in sediment and
soil ............................................................................................................... 38
Table 7-1. Upper-bounding estimates of oral exposure and acute inhalation exposure to
PY12, PY13, PY83 and PY176.................................................................... 48
Table 7-2. Oral metabolism/absorption of diarylide yellow pigments............................. 51
Table 7-3. Inhalation metabolism/absorption of diarylide yellow pigments (Hofman and
Schmidt 1993) ............................................................................................. 53
Table 7-4. Dermal metabolism/absorption of diarylide yellow pigments (Decad et al.
1983) ........................................................................................................... 53
Table 7-5. Intra-tracheal metabolism/absorption of diarylide yellow pigments .............. 53
Table 7-6. Margins of exposure for inhalation exposure scenarios ............................... 62
vii
1. Introduction
Pursuant to sections 68 or 74 of the Canadian Environmental Protection Act, 1999
(CEPA 1999) (Canada 1999), the Minister of the Environment and the Minister of Health
conduct screening assessments of substances to determine whether these substances
present or may present a risk to the environment or to human health.
The Substance Groupings Initiative is a key element of the Government of Canada’s
Chemicals Management Plan (CMP). The Aromatic Azo and Benzidine-based
Substance Grouping consists of 358 substances that were identified as priorities for
assessment, as they met the categorization criteria under section 73 of CEPA 1999
and/or were considered as a priority based on human health concerns (Environment
Canada and Health Canada 2007). Some substances within this Substance Grouping
have been identified by other jurisdictions as a concern due to the potential cleavage of
the azo bonds, which can lead to the release of aromatic amines that are known or
likely to be genotoxic and/or carcinogenic.
While many of these substances have common structural features and similar functional
uses as dyes or pigments in multiple sectors, diversity within the substance group has
been taken into account through the establishment of subgroups. Subgrouping based
on structural similarities, physical and chemical properties, and common functional uses
and applications accounts for variability within this substance grouping and allows for
subgroup-specific approaches in the conduct of screening assessments. This Screening
Assessment considers substances that belong to the Diarylide Yellow Pigments
subgroup. Consideration of azo bond cleavage products (aromatic amines) is a key
element of human health assessment in each subgroup. Some aromatic amines,
commonly referred to as EU22 aromatic amines, 2 as well as associated azo dyes are
restricted in other countries (EU 2006). Information on the subgrouping approach for the
Aromatic Azo and Benzidine-based Substance Grouping under Canada’s CMP, as well
as additional background information and regulatory context, is provided in a separate
document prepared by the government of Canada (Environment Canada and Health
Canada 2013.
Seven diarylide yellow pigments (Chemical Abstracts Service Registry Numbers [CAS
RNs] 5102-83-0, 5567-15-7, 6358-85-6, 78952-70-2, 90268-24-9, 7147-42-4 and
29398-96-7) originally constituted a subgroup of the Aromatic Azo and Benzidine-based
Substance Grouping. Two substances in this subgroup, BPAOPB (CAS RN 7147-42-4)
2
Twenty-two aromatic amines listed in Appendix 8 of Regulation (EC) No. 1907/2006.
1
and Pigment Brown 22 (PB22; CAS RN 29398-96-7), have been previously assessed
by the Government of Canada under the Challenge Initiative of the CMP (Environment
Canada and Health Canada 2010, 2011). PB22 is not included in this Screening
Assessment as no significant new information was identified since its assessment in
2010, and because this non-azo pigment does not inform the other azo-based diarylide
yellow pigments in this subgroup. Similarly, no significant new information was identified
for BPAOPB since its Challenge assessment and therefore this substance is not
included in the current Screening Assessment. However, BPAOPB is used in this report
for read-across purposes due to its structural similarity to the other diarylide yellow
pigments in this subgroup. Therefore, only the remaining five substances (CAS RN
5102-83-0, 5567-15-7, 6358-85-6, 78952-70-2 and 90268-24-9) are considered in this
Screening Assessment.
Screening assessments focus on information critical to determining whether substances
meet the criteria as set out in section 64 of CEPA 1999, by examining scientific
information to develop conclusions by incorporating a weight of evidence approach and
precaution. 3
This Screening Assessment includes consideration of information on chemical
properties, environmental fate, hazards, uses and exposure, including additional
information submitted by stakeholders. Relevant data were identified up to December
2013. Empirical data from key studies as well as some results from models were used
to reach conclusions. When available and relevant, information presented in
assessments from other jurisdictions was considered.
The Screening Assessment does not represent an exhaustive or critical review of all
available data. Rather, it presents the most critical studies and lines of evidence
pertinent to the conclusion.
3
A determination of whether one or more of the criteria of section 64 are met is based upon an assessment of
potential risks to the environment and/or to human health associated with exposures in the general environment. For
humans, this includes, but is not limited to, exposures from ambient and indoor air, drinking water, foodstuffs, and the
use of consumer products. A conclusion under CEPA 1999 on the substances in the Chemicals Management Plan
(CMP) is not relevant to, nor does it preclude, an assessment against the hazard criteria for WHMIS (Workplace
Hazardous Materials Information Systems) that are specified in the Controlled Products Regulations, which are part
of the regulatory framework for the Workplace Hazardous Materials Information System for products intended for
workplace use. Similarly, a conclusion based on the criteria contained in section 64 of CEPA 1999 does not preclude
actions being taken under other sections of CEPA or other Acts.
2
The Screening Assessment was prepared by staff in the Existing Substances Programs
at Health Canada and Environment Canada and incorporates input from other programs
within these departments. The ecological and human health portions of this assessment
have undergone external written peer review and consultation. Comments on the
technical portions relevant to the environment were received from Dr. Harold Freeman
(North Carolina State University, USA) and Dr. Gisela Umbuzeiro (University of
Campinas, Brazil). Comments on the technical portions relevant to human health were
received from Dr. Harold Freeman (North Carolina State University, USA), Dr. David
Josephy (University of Guelph, Canada), Dr. Michael Bird (University of Ottawa,
Canada) and Dr. Kannan Krishnan (University of Montreal, Canada). Additionally, the
draft of this Screening Assessment was subject to a 60-day public comment period.
While external comments were taken into consideration, the final content and outcome
of the Screening Assessment remain the responsibility of Health Canada and
Environment Canada.
The critical information and considerations upon which the Screening Assessment is
based are given below.
3
2. Identity of Substances
This Screening Assessment focuses on five substances that belong to the subgroup of
Diarylide Yellow Pigments that is part of the Aromatic Azo and Benzidine-based
Substance Grouping. The identities of the individual substances in this Screening
Assessment are presented in Table 2-1. The CAS RNs, Domestic Substances List
(DSL) names, Colour Index (C.I.) generic names, C.I. constitution numbers and
chemical acronyms of these substances are presented in Table 2-1. Chemical
acronyms are derived from the C.I. generic names when available; otherwise, they are
based on the DSL names. A list of additional chemical names (e.g., trade names) is
available from the National Chemical Inventories (NCI 2007).
Table 2-1. Identity of the five diarylide yellow pigments
CAS RN
DSL name
C.I. generic name
(C.I. constitution
number)
6358-85-6
Butanamide, 2,2'-[(3,3'-dichloro[1,1'- Pigment Yellow 12
biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxoN-phenyl(C.I. 21090)
5102-83-0
Butanamide, 2,2′-[(3,3′-dichloro[1,1′- Pigment Yellow 13
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(2,4dimethylphenyl)-3-oxo(C.I. 21100)
5567-15-7
Butanamide, 2,2′-[(3,3'-dichloro[1,1′- Pigment Yellow 83
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(4chloro-2,5-dimethoxyphenyl)-3-oxo(C.I. 21108)
90268-24-9 C.I. Pigment Yellow 176
Pigment Yellow 176
78952-70-2
(C.I. 21103)
Butanamide, 2-[[3,3’-dichloro-4’-[[1- C.I.
name
[[(2-chlorophenyl)amino]carbonyl]-2- number
oxopropyl]azo][1,1’-biphenyl]-4available
yl]azo]-N-(2,4-dimethylphenyl)-3-oxo-
Chemical
acronym
PY12
PY13
PY83
PY176
and CPAOBP
not
The chemical structures, molecular formulas and molecular weights of all five diarylide
yellow pigments are presented in Table 2-2. As presented in Table 2-2, all substances
in this subgroup are disazo diarylide pigments containing a 3,3′-dichlorobenzidine (3,3′DCB) fragment in their structures.
4
Table 2-2. Chemical structures, molecular formula and molecular masses for the
five diarylide yellow pigments
Substance
Chemical structure and molecular formula1
Molecular
weight
(g/mol)
O
H
N
N
N
O
Cl
Cl
O
N
N
PY12
630
N
H
O
C32H26Cl2N6O4
O
H
N
N
N
O
Cl
Cl
O
N
N
686
N
H
PY13
O
C36H34Cl2N6O4
O
H
N
O
N
N
O
Cl
Cl
O
Cl
O
Cl
N
H
O
O
N
N
PY83
PY176
819
O
C36H32Cl4N6O8
Three structures suggested in the REACH registration
dossier for this UVCB substance are presented below to
more comprehensively characterize the substance.
O
PY176
686
H
N
N
N
O
Cl
Cl
O
N
N
N
H
O
C36H34Cl2N6O4 (representative structure, PY13)
O
PY176
O
H
N
752
N
N
Cl
O
Cl
O
Cl
O
N
N
N
H
O
C36H33Cl3N6O6 (representative structure, CAS RN 12423634-6)
5
Chemical structure and molecular formula1
Substance
O
PY176
O
H
N
Molecular
weight
(g/mol)
819
N
N
Cl
O
Cl
O
Cl
O
Cl
N
H
O
O
N
N
O
C36H32Cl4N6O8 (representative structure, PY83)
O
CPAOBP
H
N
692
N
N
O
Cl
Cl
Cl
O
N
N
N
H
O
C34H29Cl3N6O4
Abbreviations: REACH, Registration, Evaluation, Authorisation and Restriction of Chemicals; UVCB, unknown or
variable composition, complex reactions products, or biological materials
The diarylide yellow pigment PY176 is a UVCB (unknown or variable composition,
complex reaction products, or biological materials) substance—i.e. it is not a discrete
chemical, and thus it may be characterized by a mixture of structures. Structural
information for PY176 has been reported in the European Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH) registration dossier for this
substance and is available in a database maintained by the European Chemicals
Agency (ECHA 2012). Therefore, three structures reported for PY176 (two of which are
PY13 and PY83) are presented in Table 2-2 to more comprehensively characterize the
substance. Although Schmidt et al. (2007) indicated that PY176 is a mixture of only the
two different pigments (PY13 and PY83), for the purposes of this assessment, all three
structures that were reported in the REACH registration dossier are considered for this
substance.
2.1 Selection of Analogues and Use of (Q)SAR Models
Guidance on the use of read-across approaches has been prepared by various
organizations such as the Organisation for Economic Co-operation and Development
(OECD). It has been applied in various regulatory programs including the European
Union’s (EU) Existing Substances Programme. The general method for analogue
selection and the use of (quantitative) structure–activity relationship ((Q)SAR) models is
provided in Environment Canada and Health Canada (2013). For characterization of
human health effects, the basis for the use of analogues and/or (Q)SAR modelling data
is documented in the Health Effects Assessment section of this report.
Analogues used to inform the ecological assessment were selected based on structural
similarity and the availability of relevant empirical data pertaining to physical-chemical
6
properties, persistence, bioaccumulation and ecotoxicity. Such data were used as readacross data for those Diarylide Yellow Pigments that lacked empirical data, where
appropriate, or to support the weight of evidence of existing empirical information.
Although analogue data are used preferentially to fill data gaps for the substances in
this assessment, the applicability of (Q)SAR models to the Diarylide Yellow Pigments is
determined on a case-by-case basis.
The five identified analogues are presented in Table 2-3.
Table 2-3. Identity of the five analogues
CAS RN
DSL name (English)
4531-49-1
5468-75-7
6358-37-8
7147-42-4
31775-20-9
C.I. generic name Chemical
(C.I.
constitution acronym
number)
Butanamide,
2,2′-[(3,3′-dichloro[1,1′- Pigment Yellow 17
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(2PY17
methoxyphenyl)-3-oxo(C.I. 21105)
Butanamide,
2,2′-[(3,3′-dichloro[1,1′- Pigment Yellow 14
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(2PY14
methylphenyl)-3-oxo(C.I. 21095)
Butanamide,
2,2′-[(3,3′-dichloro[1,1′- Pigment Yellow 55
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(4PY55
methylphenyl)-3-oxo(C.I. 21096)
Butanamide, 2,2′-[(3,3′-dimethoxy[1,1′C.I.
name
and
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(2BPAOPB
number not available
methylphenyl)-3-oxoButanamide,
2,2′-[(3,3′-dichloro[1,1′- Pigment Yellow 152
biphenyl]-4,4′-diyl)bis(azo)]bis[N-(4PY152
ethoxyphenyl)-3-oxo- (NDSL name)
(C.I. 21111)
The structural identities (chemical structures, chemical formulas and molecular masses)
of the five analogues of the diarylide yellow pigments are presented in Table 2-4.
Table 2-4. Chemical structures, molecular formulas and molecular masses for the
five analogues
Molecular
Substance
Chemical structure and chemical formula1
mass
(g/mol)
BPAOPB
649
O
H
N
N
N
O
O
O
O
N
N
N
H
O
C36H36N6O6
7
Substance
Chemical structure and chemical formula
1
Molecular
mass
(g/mol)
658
O
H
N
N
N
O
Cl
Cl
O
N
N
N
H
O
PY14
C34H30Cl2N6O4
690
O
PY17
H
N
N
N
O
Cl
O
O
Cl
O
N
N
H
N
O
C34H30Cl2N6O6
PY55
658
O
H
N
N
N
O
Cl
Cl
O
N
N
N
H
O
C34H30Cl2N6O4
PY152
718
8
Substance
Chemical structure and chemical formula
1
Molecular
mass
(g/mol)
O
H
N
N
N
O
O
Cl
O
Cl
O
N
N
N
H
O
C36H34Cl2N6O6
2.2 Impurities
The purities of PY12, PY13 and PY83 were reported in a draft assessment of diarylide
pigments by the Organisation for Economic Co-operation and Development (OECD)
(OECD 2003a) to be >96%, with expected impurities consisting primarily of the
respective acetoacetanilide derivative coupling components at levels ranging from 0.5 to
2% (i.e., CAS RNs 102-01-2, 97-36-9 and 4433-79-8, respectively). The levels of
residual 3,3′-DCB for these three diarylide yellow pigments were also reported to be <
25 parts per million (ppm) (OECD 2003a) while a recent source also indicated 3,3’-DCB
impurity of 10 ppm from a tattoo ink containing PY13 (Hauri 2013). It is expected that
the other diarylide yellow pigments included in this Screening Assessment will also
contain residues of their respective unreacted acetoacetanilide derivative coupling
component along with the 3,3′-DCB/3,3′-dimethoxybenzidine (3,3′-DMOB) residual. In
the European marketplace, PY13 and PY83 are allowed for use in rinse-off cosmetic
products under the condition that the concentration of 3,3′-dimethylbenzidine (3’3-DMB)
in the colouring agent is no more than 5 ppm according to the European Union 2010
Cosmetics Directive Annex IV, a list of colouring agents that are allowed for use in
cosmetic products under certain conditions (EU 2010). While 3,3’-DMB is cited in Annex
IV as the restricted impurity for PY13 and PY83, the residual benzidine derivative for
these substances would be 3,3’-DCB and therefore the citation in Annex IV is presumed
to be an administrative error.
In addition, the presence of a soluble 3,3′-DCB-based monoazo compound at a
concentration of 220 ppm (i.e., 0.022%) has been reported in purified PY13 (Sagelsdorff
et al. 1996), while a similar impurity was suggested in an OECD assessment (OECD,
2003a) to have been present in a study on PY17 (Zwirner-Baier and Neumann 1994),
although the concentration of the suspected 3,3′-DCB-containing impurity was not
indicated. No further details on the nature or identity of the soluble 3,3′-DCB-based
impurities were provided in the references available.
Some substances, such as resins, rosins and aliphatic amines, and some other
compounds, including surfactants, dispersing agents and coupling agents, are common
9
additives used in pigment preparation, depending on the application of the pigments. It
is impossible to remove such impurities by pigment filtration and intensive washing, and
even the effect of hot extraction procedures tends to be slow and unsatisfactory (Herbst
and Hunger, 2004). It is possible that certain amounts of these substances were present
in some pigments that were tested. If so, this could cause data variability and
inconsistency between studies (e.g., biodegradability and water solubility studies).
Polychlorinated biphenyls (PCBs) are known to be found as inadvertent impurities in
various classes of pigments including azo pigments (ETAD 2011; Grossman 2013). In
Canada, the levels of incidentally-produced PCBs in colouring pigments are regulated
under Sections 11 and 35 of the PCB Regulations. The regulations limit the annual
maximum concentration of PCBs, produced incidentally in colouring pigments, to less
than 50 mg/kg (ppm), and an annual average PCB concentration in pigments of not
more than 25 mg/kg (ppm). Reported PCB levels in some diarylide yellow pigments
used in Canada are well below the maximum limits set out in these regulations. For
example, reported PCB levels in PY12 range from 0.04 - 1.5 ppm for reporting years
2009-2011, and for PY83 the reported PCB levels range from 0.02 - 9 ppm for reporting
years 2008-2012 (personal communication, email from Waste Reduction and
Management Division [Environment Canada] to Existing Substances Risk Assessment
Bureau [Health Canada], dated 2014; unreferenced).
There is some uncertainty regarding whether the data above fully represents the range
of purity for different grades of diarylide yellow pigments available in consumer products
in Canada. It is therefore possible that use of lower-quality grades of diarylide yellow
pigments could result in exposure to these and other potential impurities at levels higher
than reported here.
10
3. Physical and Chemical Properties
A summary of experimental physical and chemical properties that play a critical role in
determining the environmental fate and biological effects of diarylide yellow pigments is
presented in Table 3-1. Detailed substance-specific information on these pigments and
their analogues can be found in Appendix A of this report. The general assumption was
that the properties of pigments depend strongly on the manner in which they have been
prepared by manufacturers.
Experimental data on vapour pressure and Henry’s Law constants are not available for
most of the pigments. However, since the diarylide yellow pigments are similar in
molecular size and complexity to some disperse dyes, they can be expected to have
vapour pressures in the same range as values reported for disperse dyes (i.e., 10−11 to
10−19 Pa; Baughman and Perenich 1988). Similarly, all diarylide yellow pigments are
also expected to have very low Henry’s Law constant values. Therefore, exposure
vapour phase is expected to be of low environmental relevance for this subgroup.
However, airborne exposure to diarylide yellow pigments as dusts or particulates may
be possible, especially for some consumer products.
Due to a lack of ionizable groups, dissociation of diarylide yellow pigments is expected
to be negligible. Ionization or acid dissociation constants (Ka, pKa) are therefore not
considered relevant to the environmental fate and ecotoxicity of these pigments. Also,
these diarylide yellow pigments decompose before boiling, so a boiling point is not
applicable for these substances.
Table 3-1. Experimental physical and chemical properties (at standard
temperature of approximately 25°C where applicable) of PY12, PY13, PY83 and
PY176 and their analogues
Property
Mean
Property
acronym used Range
(number
of
in the text
data points)
Melting point (°C)
MP
306–323
314 (n = 6)
Decomposition temperature
DT
300–339
317 (n = 8)
(°C)
Particle
size
distribution
D50
2–8.5
4.0 (n = 8)
(mass median diameter, µm)
Density (g/cm3)
1.26–1.50
1.38 (n = 4)
Water solubility (µg/L)
WS; Sw
0.35–10.6
3.4 (n = 9)
Solubility in n-octanol (µg/L)
Soct
2.6–140
41 (n = 11)
Quotient logarithm of the
molar solute concentrations
log (Soct/Sw)
0.4–2.1
1.5 (n = 8)
in
octanol
and
water
(dimensionless)
Effective molecular diameter Deff
1.14–1.29
1.23 (n = 6)
11
Property
Property
acronym used Range
in the text
(calculated average; nm)
Maximum
molecular
diameter
(calculated Dmax
average; nm)
2.19–2.53
Mean
(number
of
data points)
2.42 (n = 6)
3.1 Particle Size Distribution and Density
The majority of organic pigments generally do not exist as individual molecules but are
principally particles in the sub- or low micrometre size range. The pigment powder is
typically composed of primary particles (i.e., the crystal lattice of a pigment), aggregates
and agglomerates. Manufacturers usually provide the physical specifications of their
pigments, which include the average particle size of the pigment powder. Users can
then determine which pigment is the most appropriate to colour their products, since
performance is chiefly controlled by the particle size distribution (Herbst and Hunger
2004). In terms of the particle size distribution, reported data on mass median diameter
(D50) were taken from information reported in the REACH registration dossiers for these
substances, available from the European Chemicals Agency (ECHA 2012). The particle
size data presented in Table 3-1 indicate that for this group of pigments, the D50 values
vary within a relatively narrow range of 2–8.5 µm (i.e., 50% of the total mass of particles
are smaller than 2–8.5 µm).
In terms other than mass-dependent particle size distribution, some authors have
reported particle sizes for diarylide yellow pigments to be very small, often below 1 µm.
For example, while an inhalation toxicity study using PY13 showed the majority of
particle diameters to be between 1 and 7 µm, roughly 10–20% of particles were less
than 1 µm (Ciba Geigy Corp. 1979). Bäumler et al. (2000) reported sub-micrometre
particle sizes of azo pigments (including several diarylide yellow pigments 4) in tattoo
inks ranging from 20 to 900 nm. While not specifically measuring diarylide yellow
pigments, the work of Bäumler et al. (2000) is supported by a study by Høgsberg et al.
(2011), which demonstrated tattoo inks containing red and yellow azo pigments of
monoazo class and disazo dichlorobenzidine-based pyrazolone class exhibiting particle
size ranges from < 100 to 1000 nm.As well, a technical paper illustrated that two
different preparation methods for PY12 (micro-mixer vs. batch process) resulted in
4
Diarylide yellow pigments cited in Bäumler et al. (2000) included PY14, PY55, PY83 and Pigment Yellow 87 (PY87;
CAS RN 15110-84-6).
12
different particle size distributions, ranging from well below 1 µm to > 100 µm
(Pennemann et al. 2005). Therefore, it should be considered that the particle size range
of diarylide yellow pigments could be broad, including very small particles in the submicrometre (< 1 µm) and even nanoscale particle size range (1–100 nm; Canada 2007;
Health Canada 2011a), and may be a factor in potential uptake and absorption as the
insoluble particulate form (discussed further in the respective sections on ecological and
human health assessment).
The density of diarylide yellow pigments varies within a relatively narrow range (from
~1.3 to 1.5 g/cm3), which is higher than the density of water. Therefore, when released
to water, the pigments, being relatively heavy particles, are expected to deposit and
further reside in sediments, with eventual burial to deeper sediments.
3.2 Melting and Decomposition Temperatures
Results indicate that melting points are just slightly below the decomposition
temperatures (314ºC and 317ºC, respectively). In some tests with the diarylide yellow
pigments, decomposition of the substances started without discernible melting (see
Appendix A for more details).
3.3 Solubility in Water and Octanol
Most of the data show that the diarylide yellow pigments in this Screening Assessment
are characterized by very low water solubility—from less than 1 µg/L to 10.6 µg/L (Table
A-1; Appendix A); the reported solubilities in octanol are relatively higher than that in
water (2.6–140 µg/L). Both water and octanol solubilities for the diarylide yellow
pigments are considered very low in absolute terms and also relatively low compared
with the solubilities reported for some other azo pigments of different structural classes
(Anliker and Moser 1987).
The low solubility of organic pigments is a result of the inherent design of colorants,
which have strong interactive forces between molecules, achieved by the introduction of
substituents such as –CONH– in the molecule (Lincke 2003; Herbst and Hunger 2004).
The resulting intermolecular bonding in turn generates a crystal structure that lends
stability to organic pigments (Lincke 2003). Panina (2009) emphasized that due to the
molecular structure features, organic pigments tend to form highly crystalline solids;
very typical structural motifs are π-π stacking of conjugated rings and intermolecular
hydrogen bonds C=O…H–N. Such strong intermolecular interactions inside the crystal
structure lead to a high lattice energy and, often as a consequence, a very low solubility.
(It should, however, also be mentioned that all azo pigments exist in crystal form as
solid particulate with hydrogen bonding, yet there might be substantial differences in
solubility in water and octanol between diarylide and some monoazo pigments;
therefore, some major differences in apparent stability of the crystal also have to be
taken into account.) Such differences in water and octanol solubilities have been
observed for azo pigments of different structural classes (Anliker and Moser 1987;).
13
3.4 Octanol–Water Partition Coefficient
No experimental data on octanol–water partition coefficients (Kow) are available for the
diarylide yellow pigments. The Kow values derived from fragment-based models such as
KOWWIN (2010) often overestimate the actual Kow of sparingly soluble substances such
as pigments. For example, for PY12 and PY13, Koch (2008) reported KOWWINestimated log Kow values of 7 and 8.1, respectively, and indicated that for organic
pigments, KOWWIN far overestimates the “true” Kow values in most cases. At the
Environment Canada–sponsored QSAR Workshop in 1999, invited modelling experts
identified many structural classes of pigments and dyes as “difficult to model” using
most QSARs (Environment Canada 2000). The physical and chemical properties of
many of the structural classes of pigments and dyes are often not amenable to model
prediction because they are typically considered out of the model domain of applicability
(e.g., structural and/or property parameter domains).
According to the European Chemicals Agency’s Guidance on Information Requirements
and Chemical Safety Assessment (ECHA 2008), in order to overcome the difficulties in
measuring the Kow, the solubilities in octanol and water may be determined in separate
tests. With these solubilities, the quotient of solubilities in octanol and in water (Soct/Sw)
can be calculated. Although the European Chemicals Agency notes that this quotient is
not exactly identical to log Kow, as the latter is related to the partitioning of the substance
in water-saturated octanol and octanol-saturated water, it recommends that this method
be considered for sparingly soluble substances.
Therefore, it is considered that a Soct/Sw parameter would reasonably represent the
octanol–water partition coefficient for organic pigments. This approach has been used in
previous screening assessments on pigments (e.g., see Environment Canada and
Health Canada 2009a, b) and is also used in this report. For diarylide yellow pigments,
the log (Soct/Sw) values, based on experimental solubility values in water and in octanol,
vary within a reasonably narrow range of 0.4–2.1, with the mean value being 1.5 (Table
3-1); therefore, low bioaccumulation of these substances in organisms is expected.
3.5 Cross-sectional Diameter
Average effective cross-sectional diameters of molecules of diarylide yellow pigments
are greater than 1.1 nm, while average maximum diameters can reach 2.5 nm. Since
this parameter is important in terms of the permeation of substances through biological
membranes, detailed discussion on cross-sectional diameters of these pigments is
presented in the Potential for Bioaccumulation section.
3.6 Data Outliers
Table 3-1 does not contain the data that are considered to be obvious outliers. For
example, an unusually high solubility value of 8 900 µg/L (PY83), a very high solubility
14
in octanol value of 500 mg/L (PY12), an abnormally low decomposition temperature
(200°C) and unusually high melting points (360–400°C) are not presented in Table 3-1;
however, all these atypical data can be found in Appendix A of this report.
Some of the abnormal physical and chemical property values may be typographical
errors, but most likely these atypical values reported in the studies were from testing of
relatively low-purity pigments; the unexpectedly high solubility values or unusual melting
and/or decomposition temperatures can likely be attributed to the impurities and/or
additives (formulants) contained in the pigments’ final products. For example, large
amounts of additives such as rosin are frequently used in manufacturing highly
transparent types of azo pigments for application in process colour printing inks (Herbst
and Hunger 2004). These substances are largely adsorbed on the surface of the
pigment particles. The extent to which measurement results can be distorted by
additives is particularly severe in the case of disazo yellow pigments, whose preparation
involves fatty amines (Herbst and Hunger 2004).
15
4. Sources and Uses
4.1 Sources
All five diarylide yellow pigments are anthropogenically produced; they are not expected
to occur naturally in the environment.
In recent years, the five diarylide yellow pigments and the analogue BPAOPB have
been included in industry surveys issued pursuant to section 71 of CEPA 1999. Four
substances (PY83, PY176, CPAOBP and the analogue BPAOPB) were included in a
survey conducted pursuant to section 71 of CEPA 1999 for the 2005 calendar year
(Canada 2006), one substance (the analogue BPAOPB) was included in a survey
conducted pursuant to section 71 for the 2006 calendar year under the Government of
Canada’s Challenge Initiative (Canada 2008), and four substances (PY12, PY13, PY83
and PY176) were included in a survey conducted pursuant to section 71 of CEPA 1999
for the 2010 calendar year (Canada 2011a).
Based on the most recent information submitted via the section 71 survey (Canada
2011a), four of the five diarylide yellow pigments assessed in this report (PY12, PY13,
PY83 and PY176) as well as BPAOPB are imported or manufactured in quantities
greater than 100 kg/year. The total manufacture and import quantity for these
substances is in the range of 100 to 1 000 tonnes. In addition, stakeholder interest in
these substances was declared by several companies, although the activities of these
substances did not meet the mandatory reporting requirements at the time of the
survey.
Elsewhere, four of the five diarylide yellow pigments are found in the European
Chemical Substances Information System (ESIS). PY12, PY13 and PY83 are reported
as high production volume (HPV) substances, while PY176 is reported as a low
production volume (LPV) chemical (see Table 4-1).
PY12, PY13 and PY83 have also been reported in the Inventory Update Reporting
(IUR) (US EPA 2006) Modifications Rule under the Toxic Substances Control Act
(TSCA) in the United States. The aggregated national production volumes of these
substances in the year 2006 are presented in Table 4-1.
During the last several years, PY12, PY13, PY83 and PY176 were also used in
Denmark, Norway and/or Sweden. The quantities of these substances used, for
example, in the year 2010 (see Table 4-1) can be found in the Substances in
Preparations in Nordic Countries (SPIN) database, which is based on data from the
product registries of Norway, Sweden, Denmark and Finland and supported by the
Nordic Council of Ministers.
16
Table 4-1. Production volumes of diarylide yellow pigments identified in ESIS,
TSCA IUR and SPIN databases
Substance ESIS (©1995–2012)
IUR (2006)
SPIN (2010)
PY12
HPV substance
10 to < 50 million pounds 600
tonnes
(Sweden
and
(i.e., 4 500 to < 22 700 Denmark)
tonnes)
PY13
HPV substance
1 to < 10 million pounds
192
tonnes
(Sweden, Denmark
(i.e., 454 to < 4 500 and Norway)
tonnes)
PY83
HPV substance
1 to < 10 million pounds
131
tonnes
(Sweden, Denmark
(i.e., 454 to < 4 500 and Norway)
tonnes)
PY176
LPV substance
No data
14
tonnes
(Sweden)
CPAOBP
Not found in ESIS
No data
No data
Abbreviations: HPV, high production volume; LPV, low production volume; ESIS, European Chemical Substances
Information System; IUR, Inventory Update Reporting ;SPIN, Substances in Preparations in Nordic Countries.
4.2 Uses
The five diarylide yellow pigments evaluated in this assessment (PY12, PY13, PY83,
PY176 and CPAOBP) are used in various sectors, such as “Ink, toner and colorants,”
“Paints and coatings,” “Fabric, textile and leather articles” and “Plastic and rubber
materials.” Linak et al. (2011) indicated that diarylide yellow pigments are popular with
ink makers because of their bright shades and their outstanding tinting strength. They
have good printing qualities and are economical on the basis of cost per unit of tinting
strength. Although semi-opaque, they can be resinated to produce transparent grades
for three- and four-colour printing processes. With the largest volume of all organic
pigments, PY12 is used in lithographic, letterpress and publication gravure inks. Some
diarylide yellow pigments (e.g., PY13 and PY83) can also be used for textile printing,
and PY83 is also used in the paints and coatings sector, replacing lead chromate yellow
pigments (Linak et al. 2011).
4.2.1 Uses in Canada
Table 4-2 presents a summary of the major uses of the four diarylide yellow pigments
used in Canada (Environment Canada 2012) based on the section 71 survey conducted
under CEPA 1999 (Canada 2011a) and/or Phase 1 of the DSL Inventory Update
(Canada 2009). No uses were reported from section 71 surveys for CPAOBP.
17
Table 4-2. Summary of the major uses of diarylide yellow pigments in Canada
submitted in response to section 71 surveys (Environment Canada 2012)
Substance
Ink,
toner, Paints
and colorants coatings
PY12
PY13
PY83
PY176
X
X
X
X
X
X
-
and Plastic
rubber
and Textile
leather
X
X
-
X
X
-
and
Section 71 data indicate that the “Ink, toner, and colorants” sector is the major sector for
the diarylide yellow pigment group of substances. Information available for four
pigments from this group of substances shows that all five pigments are used in the
“Ink, toner, and colorants” sector—i.e., as “substances in ink, toners and colorants used
for writing, printing, creating an image on paper; or as substances contained in other
substrates or applied to substrates to change their colour or hide images”—with 86% of
the total declared quantities (Canada 2011a; Environment Canada 2012). The second
major use is “Paints and coatings” (8% of the total declared quantities), followed by the
“Plastic and rubber” sector (3%).
PY12 is also known to be used in cosmetics, metal and paper (HSDB 1983–; Lewis
2001; INCI 2004). Based on notifications submitted under the Cosmetic Regulations to
Health Canada, it is used in certain cosmetic products in Canada such as, bath salts for
infants, face makeup, hair dye, mascara, nail polish and bath showering products
(personal communication, email from the Consumer Products Safety Directorate [Health
Canada] to the Existing Substances Risk Assessment Bureau [Health Canada], dated
2011; unreferenced).
PY13 is used in the textile and leather, plastic and rubber, and paints and coatings
packaging sectors(Environment Canada 2012) , as well as in cosmetics and paper
(HSDB 1983–; INCI 2004; SPIN 2010; SRD 2010).
More than five uses have been reported for PY83 (Environment Canada 2012);
therefore, only the top uses (reflecting the top use-based quantities in the reporting
year) for this substance, are presented in Table 4-2. PY83 has additional uses in
building materials (the volume of this use is almost identical to the “textile and leather”
use pattern). It is also known to be used in cosmetics and paper (HSDB 1983–; INCI
2004) and based on notifications submitted under the Cosmetic Regulations to Health
Canada, it is used in certain cosmetic products in Canada such as foundation, hair dye,
hair grooming products, lipstick, mascara and nail polish (personal communication,
email from the Consumer Products Safety Directorate [Health Canada] to the Existing
Substances Risk Assessment Bureau [Health Canada], dated 2011; unreferenced).
Based on notifications submitted under the Cosmetic Regulations to Health Canada,
PY12 and PY83 are used in permanent tattoo inks (personal communication, email from
18
the Consumer Products Safety Directorate [Health Canada] to the Existing Substances
Risk Assessment Bureau [Health Canada], dated 2011; unreferenced). The diarylide
pigment PY83 is also listed as an ingredient in the MSDS sheets of two brands of tattoo
inks available internationally including Canada (SkinCandy 2013; Starbrite 2013). The
Color Pigment Manufacturers Association (CPMA), representing importers and
manufacturers of diarylide pigments in Canada, have indicated that in Canada, their
members do not supply these substances for use in tattoo inks (CPMA 2013).
No uses for CPAOBP were reported in the section 71 survey (Environment Canada
2005), although other sources have identified its use in textiles (OTA 2003).
In Canada, food colouring agents to be added directly to food are regulated as food
additives under the Food and Drug Regulations (Canada [1978]). Colours that are
permitted for use in food are included in the List of Permitted Colouring Agents,
incorporated by reference in the Marketing Authorization for Food Additives that May be
Used As Colouring Agents, issued under the authority of the Food and Drugs Act
(Canada 1985). None of the five diarylide yellow pigments in this Screening
Assessment are included on the List of Permitted Colouring Agents as a permitted food
colourant.
PY12, PY13 and PY83 are identified for use in food packaging materials, as
components of inks not intended to have direct contact with food. In addition, PY13 and
PY83 were identified as components of colour concentrates also for use in food
packaging with few applications in direct contact with food (July and September 2011
emails from the Food Directorate, Health Canada to the Risk Management Bureau,
Health Canada; unreferenced).
Colourants that are permitted to be used in drugs in Canada are regulated under Part C,
Division 1, of the Food and Drug Regulations (Canada [1978]). None of the five diarylide
yellow pigments are listed as a permitted drug colourant, nor have any been identified to
be present in pharmaceuticals, veterinary drugs or biologics in Canada (personal
communication, email from the Therapeutic Products Directorate [Health Canada] to the
Risk Management Bureau [Health Canada], dated 2011; unreferenced; personal
communication, email from the Veterinary Drugs Directorate [Health Canada] to the
Risk Management Bureau [Health Canada], dated 2011; unreferenced; personal
communication, email from the Biologics and Genetic Therapies Directorate [Health
Canada] to the Risk Management Bureau [Health Canada], dated 2011; unreferenced).
PY13 is listed in the Natural Health Products Ingredients Database (NHPID 2011) with a
non-medicinal ingredient role (colour additive) for topical use only. However, PY13 is
not present in any currently licensed natural health products (Licensed Natural Health
Products Database (LNHPD 2011). None of the remaining four diarylide yellow
pigments are listed in the NHPID, or are listed in the LNHPD to be present in currently
licensed natural health products (NHPID 2011; LNHPD 2011).
19
None of the five diarylide yellow pigments are included on the List of Prohibited and
Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient
Hotlist or simply the “Hotlist”), an administrative tool that Health Canada uses to
communicate to manufacturers and others that certain substances, when present in a
cosmetic, may contravene the general prohibition found in section 16 of the Food and
Drugs Act or a provision of the Cosmetic Regulations (Health Canada 2011b).
None of the five diarylide yellow pigments were identified as a formulant in pest control
products registered in Canada (personal communication, email from the Pest
Management Regulatory Agency [Health Canada] to the Risk Management Bureau
[Health Canada], dated 2011; unreferenced).
4.2.2 Other Jurisdictions
PY12, PY13 and PY83 have been reported in the IUR (US EPA 2006) Modifications
Rule under the TSCA in the United States. In 2006, the industrial sectors (based on the
North American Industry Classification System) involved included “Printing,” “Printing
ink manufacturing,” “Synthetic dye and pigment manufacturing,” “Paint and coating
manufacturing” and “Plastics product manufacturing.” “Coloring agents, pigments” was
the only industrial function of these substances.
During the last several years, PY12, PY13, PY83 and PY176 were also used in
Denmark, Norway and/or Sweden. The industrial use and use category quantities of
these substances can be found in the SPIN database, which is based on data from the
product registries of Norway, Sweden, Denmark and Finland and supported by the
Nordic Council of Ministers. For example, in the year 2010, some industrial uses of
these substances included “Publishing, printing and reproduction of recorded media,”
“Manufacture of paper and paper products,” “Manufacture of fabricated metal products,”
“Manufacture of rubber and plastic products” and “Manufacture of textiles.” “Colouring
agents,” “Paints, lacquers, and varnishes” and “Reprographic agents” were the major
use categories of PY12, PY13 and PY83, while “Reprographic agents” was the only use
category of PY176.The use in tattoo inks of several diarylide yellow pigments, including
PY13, PY14, PY55, PY83 and PY87, and Pigment Orange 16 (PO16), has been
reported in studies from Europe (Bäumler et al. 2000; De Cuyper and D’hollander 2010;
KEMI 2010; Hauri 2011, 2013; Danish EPA 2012) and Australia (Poon et al. 2008). The
diarylide pigment PO16 is also listed as an ingredient in the MSDS sheets of two brands
of tattoo inks available internationally (SkinCandy 2013; Starbrite 2013). Collectively,
this information indicates that there is a potential for exposure to diarylide yellow
pigments through use in tattoos.
20
5. Environmental Fate
The environmental fate of chemicals describes the processes by which chemicals move
and are transformed in the environment. Environmental fate processes that are usually
addressed include, for example, persistence of the substances in environmental
compartments, their degradation, distribution among media, migration in groundwater,
removal from effluents by standard wastewater treatment methods and bioaccumulation
in organisms.
However, the combination of variability among chemicals and variability among
environments creates complexity that it is challenging to readily survey a set of
properties and forecast how a specific chemical is likely to behave (Mackay et al. 2001).
While certain attributes of chemicals in the environment (e.g., concentrations) can be
measured directly, other attributes (e.g., evaporation rates or distance travelled) cannot
be measured directly and can only be estimated using models. However, present
models do not always satisfactorily address some chemicals, including pigments
(Mackay et al. 2009).
It must also be emphasized that the majority of organic pigments generally do not exist
as individual molecules but are principally particles in the sub- or low micrometre size
range. The pigment powder is typically composed of primary particles (i.e., the crystal
lattice of a pigment), aggregates and agglomerates.
Taking these considerations into account, fugacity modelling for describing the
distribution of these substances among environmental compartments would not be
applicable for the model-difficult pigments. It was also considered that reasonably
reliable conclusions on the environmental fate of diarylide yellow pigments could be
made on the basis of available experimental information on the physical and chemical
properties of these pigments.
As has been already mentioned, diarylide yellow pigments have very low water solubility
– in the sub- or low micrograms per litre range (see Table 3-1). Taking this into account,
as well as the fact that these pigments are principally particles in the sub- or low
micrometre size range, it may be supposed that when released into water, these
substances would be mostly present as particles or adsorbed to other suspended solids
and, therefore, would be expected to eventually sink to bed sediments.
Direct releases of diarylide yellow pigments to air are not expected to be significant, but
even if they occur, these substances are not expected to reside in this environmental
compartment. Indeed, even in a worst-case theoretical scenario, if pigments are
released as molecules, not as particles, they, being large, complex molecules, can be
expected to have very low vapour pressures. While experimental data on vapour
pressure are not available for most of the pigments, these substances can be expected
to have vapour pressures similar to those of similarly large and complex azo disperse
dyes (i.e., from 10−11 to 10−19 Pa, as indicated by Baughman and Perenich 1988).
21
Another reason for volatilization to be unlikely for the uncharged pigments is that the
escaping tendency or fugacity that drives volatilization is also the driving force for both
sorption and bioconcentration (Baughman and Perenich 1988).
The particulate character of diarylide yellow pigments should have a key influence on
their fate in the environment. This, together with their density (higher than the density of
water), high chemical stability and extremely low aqueous solubility, suggests that
diarylide yellow pigments will partition by gravity to sediments if released to surface
waters and will tend to remain in soils if released to terrestrial environments.
Therefore, for this group of diarylide yellow pigments, soil and sediments are expected
to be the two major environmental media of concern.
It should also be noted that, based on the information on the physical and chemical
properties and uses of diarylide yellow pigments, air emissions of these substances are
not expected to occur. Therefore, the potentials for long-range atmospheric transport of
these substances from their emission sources were not calculated.
5.1 Environmental Persistence
In order to evaluate the environmental persistence of the substances in the diarylide
yellow pigments group, empirical data, modelled data and available information for
structural analogues were considered.
It was expected that the characteristics imparted to pigments would result in the
diarylide yellow pigments being persistent in the environment. For example, the Color
Pigments Manufacturers Association has indicated that pigments are designed to be
durable or persistent in the environment in order to provide colour to finished products
(e.g., coatings, inks, paints and others) (CPMA 2003).
5.1.1 Biodegradation in the Aquatic Environment
The results of multiple biodegradation studies are available for some of the substances
in this group of diarylide yellow pigments (see Appendix B for detailed, substancespecific information). The range of biodegradation values for these substances in water
is very large – from 0% to 83% (Appendix B). Three major factors probably explain such
significant data variations given the similar structures of substances in this group, as
described below.
5.1.1.1 Pigments’ purity
Substance-specific information on the biodegradation of diarylide yellow pigments (see
Appendix B) indicates that in some tests, pigment formulations have been used instead
of high-purity pigments. For example, in two tests with PY83, 40% and 52%
22
formulations were tested, with the biodegradation values being 65% and 83%,
respectively.
Therefore, two different summary tables with the results of studies of the biodegradation
of diarylide yellow pigments are presented in this report. The first table, Table 5-1,
shows the results of the studies where “pure” pigments (i.e., not pigment formulations or
final products) have been tested.
Table 5-1. Biodegradation of diarylide yellow pigments: pure pigments tested
Test
Degradation
Biodegradation
Substance
duration type (ready or Reference
(%)
(days)
inherent)
J-CHECK
PY12
0
14
Ready
2012
Not
readily
PY13
28
Ready
US EPA 2010
biodegradable
J-CHECK
PY83
6
28
Ready
2012
J-CHECK
PY14 (analogue)
2; 4
28
Ready
2012
Group submission
for diarylide yellow
pigments:
PY12,
1
28
Ready
ECHA 2012
PY13,
PY83,
PY176;
PY14
(analogue)
The results of ready biodegradability studies clearly indicate that under aerobic
conditions, diarylide yellow pigments are not readily biodegradable (0–6%
biodegradation). Therefore, based on the experimental data presented in Table 5-1, it
may be concluded that this group of substances is expected to be persistent in water
under aerobic conditions.
The second table, Table 5-2, shows the results of the biodegradation studies in which
pigment formulations have been tested. The results of three studies show very high
biodegradation potential of the tested substances (65–83%). One study, however, has a
relatively low biodegradation value of 16%. At the same time, the study contains the
statement that “only 70% of the total carbon in the tested product is contained in the
pigment. Assuming that the pigment component was stable, the observed BOD
(biological oxygen demand) of 16% indicates that, besides carbon assimilation by the
microorganisms, 53% of the additives were mineralized during the test” (see also
Appendix B). Therefore, the results of the study may suggest that the higher than
expected (for the pigment) biodegradation value of 16% can be attributed to
biodegradation of additives or formulants rather than to the pigment itself. It may be
supposed that if the amounts of additives in this pigment formulation were lower, the
23
biodegradation value in this study would also be lower (or much lower) than 16%.
However, there is some uncertainty here, since this is a ready—not inherent—
biodegradability study. (Inherent vs. ready biodegradation issues are discussed in the
next part of this section.)
Table 5-2. Biodegradation of diarylide yellow pigments: pigment formulations
tested
Substance
Biodegradation Test
Degradation
Reference
(%)
duration
type (ready or
(days)
inherent)
European
PY12
81
15
Inherent
Commission
©2000b
European
PY83
65; 83
15
Inherent
Commission
©2000a
Group submission 16
28
Ready
ECHA 2012
for diarylide yellow
pigments:
PY12,
PY13,
PY83,
PY176;
PY14
(analogue)
It should be noted that even in the tests with the pure pigments (see Table 5-1), the
biodegradation values of 4–6% could probably be attributed to the additives rather than
to the pigment component itself. Indeed, azo pigments are very difficult to purify; in
particular, it is impossible to remove some impurities by pigment filtration and intensive
washing, and even the effect of hot extraction procedures tends to be slow and
unsatisfactory. Considerable amounts of such soluble species may remain within the
pigment even after hours of refluxing and repeated filtration with freshly distilled water
(Herbst and Hunger 2004). Another example would be highly transparent pigments
(e.g., PY83), which are almost exclusively resinated. However, considerable amounts of
resin remain on the pigment surface, even after repeated washing with petrol ether
(Herbst and Hunger 2004).
Resins, rosins, aliphatic amines and other compounds, such as surfactants, dispersing
agents and coupling agents, are common additives used in pigment preparation,
depending on the application of the pigments (Herbst and Hunger 2004), and their
biodegradation in the biodegradability studies may result in higher than expected
biodegradation values.
However, the purity of the pigments may not be the only reason for the unexpected high
biodegradation values in some studies.
24
5.1.1.2 Inherent biodegradability vs. ready biodegradability
Some of the studies represent the results of ready biodegradability tests, while others
are inherent biodegradation studies (see Table 5-1and Table 5-2 and Appendix B). Data
indicate that in the ready biodegradation tests, the biodegradation values do not exceed
16%, while in the inherent biodegradation studies, some biodegradation values were
greater than 80%. These differences can be explained by the differences in the test
procedures of these two types of biodegradability tests.
Indeed, the ready biodegradability tests are stringent screening tests, conducted under
aerobic conditions, in which the inoculum should not have been pre-adapted to
degradation of the test substance by previous exposure to the test substance or
structurally related chemicals. On the contrary, inherent biodegradability tests allow
prolonged exposure of the test substance to microorganisms and a low ratio of test
substance to biomass, which offers a better chance to obtain a positive result compared
with tests for ready biodegradability. Some of these tests may be conducted using
microorganisms that have previously been exposed to the test substance, which
frequently results in adaptation, leading to a significant increase in the degradation rate
(OECD 2005). As a result, biodegradation values from inherent biodegradability studies
are usually higher (and sometimes much higher) than those from ready biodegradation
tests.
Therefore, it may be supposed that in the inherent biodegradation studies—i.e., under
the most favourable conditions—with the pigment formulations, the additives/formulants
may quickly degrade, and high biodegradation values in these studies do not reflect
actual degradability of the pigment component.
5.1.1.3 Adsorption of pigments on the inoculum matrix (sludge)
Adsorption of pigments on the sludge (used as inoculum, i.e., the source of
microorganisms in the test) could be another explanation for the unusually high
biodegradation values. Indeed, two studies with PY83 contained the important
statement that 20% (one study) and 50% (another study) of the elimination of dissolved
organic carbon “occurred due to adsorption on activated sludge, not due to
biodegradation” (see Appendix B for more details).
Therefore, pigment purity (i.e., pure pigment vs. pigment formulation), the type of
biodegradation test (i.e., inherent vs. ready biodegradability) and adsorption of pigments
on the inoculum (sludge) are the major factors explaining the unusually high
biodegradation values in some biodegradation tests with the diarylide yellow pigments
in the water compartment. Therefore, the results of these tests with unexpectedly high
biodegradation values cannot be considered applicable for the risk assessment of
diarylide yellow pigments.
25
It may also be concluded that the multiple ready biodegradation studies with the pure
diarylide yellow pigments indicate their very low biodegradation potential in water. Thus,
considering all this information, it is expected that under aerobic conditions, diarylide
yellow pigments will have long residence times in water.
The environmental persistence of disazo diarylide yellow pigments in anoxic
environments is an important area of uncertainty, because of a lack of biodegradation
data for the pigments. While some azo dyes are reported to be biodegradable in anoxic
waters via anaerobic reduction of the azo bond (–N=N–), which results in releasing
potentially harmful aromatic amines (Øllgaard et al. 1998), almost no documentation
has been found regarding the potential for anaerobic degradation of azo pigments in
aqueous environments. In principle, the pigment crystals would have to dissolve first,
which would release the constituent molecules to the aqueous medium and make the
azo bonds available for biotic reduction (Øllgaard et al. 1998). However, it may be
expected that only a very small (if any) proportion of the disazo diarylide yellow
pigments may be reduced in this manner, given their unique physical state (pigments
are typically composed of primary particles —i.e., the crystal lattice of a pigment, as well
as aggregates and agglomerates), along with their very low water solubility, which
would limit the availability of the molecules for biotic reduction.
5.1.2 Biodegradation in Soil and Sediments
No studies on the biodegradation of diarylide yellow pigments in soils or sediments have
been identified. However, the approach to estimating the required soil and sediment
half-lives is to use the recommended values for water and extrapolate to the other
media using scaling factors. Scaling factors are numbers that, when multiplied by a
degradation rate constant or half-life for one set of environmental or test conditions, they
yield a rate for a second, different set of conditions (US EPA 2000).
Boethling et al. (1995) collected measured half-life data for a wide variety of chemicals
that had been tested in both soil and water samples collected from the environment and
then calculated mean ratios of half-life in water to half-life in aerobic surface soil for 20
chemicals. It was suggested that for screening purposes, it is valid to assume that
biodegradation in aerobic surface water is about as fast as degradation in aerobic
surface soil and that sediment half-lives may be assumed to be 3–4 times longer (US
EPA 2000).
Therefore, in terms of biodegradation half-life, using a water to soil to sediment
extrapolation ratio of 1:1:4 (Boethling et al. 1995) and the ultimate biodegradation halflife in water of ≥ 182 days based on experimental biodegradation data of 0–6% (for pure
pigments), it may be concluded that the ultimate biodegradation half-life of diarylide
yellow pigments in aerobic soils is also expected to be ≥ 182 days, and the half-life in
aerobic sediments is expected to be ≥ 365 days.
26
In anaerobic sediment conditions, there is the possibility that solubility-limited azo
reduction may occur. However, given the unique physical and chemical characteristics
of diarylide yellow pigments (particulate nature, extremely low solubility), it is expected
that only a very small proportion of these pigments may be available to microorganisms
for biotic reduction.
Therefore, taking into account that diarylide yellow pigments generally do not exist as
individual molecules but are principally particles in the sub- or low micrometre size
range, and that the water solubility of diarylide yellow pigments is very low (sub- to low
micrograms per litre), it may be supposed that the bioavailability of these substances to
microorganisms for biotransformation (biotic reduction) is very limited, which is
confirmed by the results of multiple ready biodegradability studies (0–6%
biodegradation in water) with the pure pigments (not pigment formulations). In soil and
sediments, these substances are also expected to be not readily biodegradable.
5.1.3 Abiotic Degradation
No experimental data have been found for photodegradation of diarylide yellow
pigments in air. The predictions using the AOPWIN model from EPISuite version 4.10
(AOPWIN 2010) indicate that calculated half-lives (indirect reaction with hydroxyl
radicals based on a 12-hour day) were relatively short—only 1.7–4.9 hours. These
results are consistent with the fact that these pigments are generally not used in artists’
colours, since diarylide yellow pigments have significantly reduced light-fastness
(Herbst and Hunger 2004; MacEvoy 2008).
Diarylide yellow pigments are expected to be hydrolytically stable, as indicated in a
study on PY83 that did not detect hydrolysis in a 56-day experiment (European
Commission ©2000a).
5.1.4 Summary of Persistence in the Environment
Based on empirical data (Table 5-1 and Appendix B) and the above-mentioned
considerations, it is expected that under aerobic conditions, diarylide yellow pigments
will have long residence times in water, soil, and sediment.
5.2 Potential for Bioaccumulation
In order to evaluate the bioaccumulation potential of substances in this group of
diarylide yellow pigments, only empirical data were considered, given the high level of
uncertainty associated with modelling the bioaccumulation of this substance group.
5.2.1 Octanol–Water Partition Coefficient
As indicated in the Physical and Chemical Properties section of this report, a Soct/Sw
parameter can represent octanol–water partition coefficient for organic pigments. For
27
diarylide yellow pigments, the log (Soct/Sw) values, based on experimental solubility
values in water and in octanol, vary within a reasonably narrow range of 0.4–2.1, with a
mean value of 1.5 (see Table 3-1), which is significantly lower than the criterion of Kow
for bioaccumulation (log Kow ≥ 5) when neither a bioaccumulation factor (BAF) nor a
bioconcentration factor (BCF) of the substance can be determined in accordance with a
method referred to in section 5 of the Persistence and Bioaccumulation Regulations
(Canada 2000). Therefore, based on the experimental log (Soct/Sw) values, diarylide
yellow pigments have a low potential to bioaccumulate in organisms.
Other physiological parameters and processes, such as metabolism, are important to
consider along with information on octanol–water partition coefficients (indeed, the
substance may be characterized by a high Kow and, at the same time, quickly
metabolized or biotransformed in the organism). Therefore, octanol–water partition
coefficient data have to ideally be considered along with other information related to the
bioaccumulation of these substances.
5.2.2 Bioconcentration Factor (BCF)
For the group of diarylide yellow pigments, several experimental BCF studies have been
identified. The results of these studies are presented in Table 5-3.
Table 5-3. Experimental BCF data for diarylide yellow pigments in common carp
(Cyprinus carpio)
Substance
BCF (L/kg)
Test conditions
Reference
MITI 1992;
Test duration 6
PY12
2.4–5.4 (at 0.01 mg/L) weeks; lipid level
J-CHECK
in fish 2.8%
2012
MITI 1992;
Test duration 6
PY12
0.38–3.2 (at 0.1 mg/L) weeks; lipid level
J-CHECK
in fish 2.8%
2012
Test duration 6
J-CHECK
PY14 (analogue)
< 4.9 (at 0.1 mg/L)
weeks; lipid level
2012
in fish 3.8%
Test duration 6
J-CHECK
PY14 (analogue)
≤ 0.5–0.6 (at 1 mg/L)
weeks; lipid level
2012
in fish 3.8%
Group submission for
diarylide
yellow
Test duration 28
pigments: PY12, PY13, ≤ 6.2 (at 0.09 mg/L)
days; lipid level in ECHA 2012
PY83, PY176; PY14
fish 1.69%
(analogue)
28
Data show that for the diarylide yellow pigments, all available BCF values do not exceed
6.2 L/kg in common carp (the highest definitive experimental BCF value was 5.4 L/kg),
indicating that these diarylide yellow pigments have a low potential to bioconcentrate
from water in fish.
In the scientific literature and recommendations from international jurisdictions, there
are some data regarding bioaccumulation of pigments. In particular, ECHA (2008)
presented a weight of evidence approach for PY12. Based on low solubility in octanol
and low log (Soct/Sw), as well as on pharmacokinetic data (14C pharmacokinetic rat
study showing no uptake from food and complete excretion of PY12 through feces),
ECHA (2008) concluded that PY12 is not a bioaccumulative substance.
Anliker and Moser (1987) studied the limits of bioconcentration of azo pigments in fish
and their relation to the partition coefficient and solubilities in water and octanol. Despite
a high calculated log Kow for two pigments, the experimentally determined log BCFs
were low. The explanation for this apparent inconsistency is the very limited fat (lipid)
storage potential of these pigments, as indicated by their low solubility in n-octanol (< 1
and < 0.1 mg/L) and their large molecular size (cross-sectional diameters of 0.97 and
1.68 nm).
In another study, Anliker et al. (1988) assessed different dyes and pigments, including
two organic pigments, for which the experimental BCFs in fish were known (16
halogenated aromatic hydrocarbons were included for comparison). None of the
disperse dyestuffs, even the highly lipophilic colorants with log Kow > 3, accumulated
significantly in fish. The authors suggested that the large molecular size of the colorants
prevented their effective permeation through biological membranes and thus limited
their uptake during the time of exposure. Anliker et al. (1988) proposed that a crosssectional diameter of more than 1.05 nm with a molecular weight of greater than 450
g/mol would suggest a lack of bioconcentration for organic colorants.
Molecular size and cross-sectional diameter are commonly used by international
jurisdictions in weight of evidence for conclusions on bioaccumulation potential. For
example, ECHA (2008), describing “Indicators for limited bioaccumulation,” showed that
some additional indicators for low bioaccumulation potential might be applicable for
substances with low solubility in octanol and water. In particular, an average Dmax of
> 1.7 nm may be considered as one of these additional indicators.
Investigations relating fish BCF data and molecular size parameters (Dimitrov et al.
2002, 2005) suggest that the probability of a molecule crossing cell membranes as a
result of passive diffusion declines significantly with increasing maximum diameter
(Dmax). The probability of passive diffusion decreases appreciably when the maximum
diameter is greater than approximately 1.5 nm, and much more so for molecules having
a maximum diameter of greater than 1.7 nm. Sakuratani et al. (2008) also investigated
the effect of cross-sectional diameter on passive diffusion in a BCF test set of about
1200 new and existing chemicals. They observed that substances that do not have a
29
very high bioconcentration potential (i.e., BCF < 5000) often have a Dmax of greater than
2.0 nm and an effective diameter (Deff) of greater than 1.1 nm.
Table 3-1 in the Physical and Chemical Properties section presents estimates of the
ranges and averages of maximum diameters (Dmax) and effective diameters (Deff) of
diarylide yellow pigments performed by the BCFmax model with mitigating factors
(Dimitrov et al. 2005). The statistics for calculations of cross-sectional diameters of
diarylide yellow pigments include the consideration of conformational analysis for up to
30 conformers.
Average effective cross-sectional diameters of molecules of diarylide yellow pigments
are greater than 1.1 nm, while average maximum diameters can reach 2.5 nm. Since all
these values exceed the threshold values recommended by Dimitrov et al. (2002, 2005)
and Sakuratani et al. (2008), it can be supposed that diarylide yellow pigments will likely
experience restricted uptake from steric effects at the gill surface of fish, which helps
explain the low observed empirical BCF values (≤ 6.2 L/kg) for these substances.
It should, however, be noted that according to Arnot et al. (2010), there are some
uncertainties associated with the thresholds proposed by Dimitrov et al. (2002, 2005)
and Sakuratani et al. (2008), since the bioaccumulation studies used to derive them
were not always critically evaluated. Arnot et al. (2010) pointed out that molecular size
influences solubility and diffusivity in water and organic phases (membranes), and
larger molecules may have slower uptake rates. However, these same kinetic
constraints apply to diffusive routes of chemical elimination (i.e., slow uptake = slow
elimination). Thus, significant bioaccumulation potential may remain for substances that
are subject to slow absorption processes, if they are slowly biotransformed or slowly
eliminated by other processes. However, if the rate of gill uptake is sufficiently mitigated
by steric hindrance to the point that the rate of elimination exceeds uptake,
bioconcentration will be lowered.
Steric effects, however, cannot be considered directly applicable to dietary exposure
studies (e.g., studies on biomagnification factor). The “transepithelial electrical
resistance” of fish intestines compared with gills is 2 orders of magnitude lower (Arnot et
al. 2010), which suggests that the permeability of chemicals from the gastrointestinal
tract is likely much greater than that from the gill; thus, dietary uptake cannot be
explained by the studies relating molecular size to BCF.
Another aspect of bioavailability and bioaccumulation of pigments in non-human
organisms may also be considered. Many pigments have a particle size in the low submicrometre range and therefore potentially fall partially within the “nanoscale” size
range (i.e., 1–100 nm; Canada 2007; Health Canada 2011a). Lynch et al. (2006),
Rothen-Rutishauser et al. (2006), Smart et al. (2006) and others indicate that
nanoparticles can be taken up by different types of mammalian cells and are able to
cross the cell membrane and become internalized. Importantly, the interaction of
nanoparticles with the cells and their uptake are size dependent (Limbach et al. 2005;
30
Chithrani et al. 2006) and shape dependent (Pal et al. 2007), and uptake occurs via
endocytosis or phagocytosis in specialized cells.
Passive diffusion is considered the predominant mechanism for the transport of
substances across epithelia for most pharmaceuticals and environmental organic
contaminants, although facilitated, active, paracellular and phagocytosis (pinocytosis
and endocytosis) transport mechanisms can be important for certain substances
(DeVito 2000). Passive diffusion rather than a facilitated process controls the absorption
of hydrophobic persistent organic pollutants (Kelly et al. 2004).
At the same time, bioaccumulation studies in which the endocytosis or phagocytosis
mechanism could be reliably confirmed could not be identified for the diarylide yellow
pigments. If this mechanism was typical (or significant) for diarylide yellow pigments, the
results of bioaccumulation studies—namely, high (or relatively high) BCF values—would
reflect the existence of this phenomenon in terms of the pigments’ uptake. However, all
available experimental BCF values show that diarylide yellow pigments have a very low
potential to bioconcentrate from water in fish.
The results of ecotoxicity studies, which are discussed in the next section of this report,
indicate that aqueous dispersions of diarylide yellow pigments do not cause noticeable
biological effects. This indicates that the bioavailability of these substances is limited,
and phagocytosis most likely does not play a significant role in the uptake of diarylide
yellow pigments.
5.2.3 Summary of Bioaccumulation Potential
Based on the consistency of various lines of evidence, including low experimental log
(Soct/Sw) values of approximately 1.5 (mean), low experimental solubility in octanol
(mean ~40 µg/L), large molecular cross-sectional diameter (average Deff of 1.1–1.3 nm
and Dmax of 2.2–2.5 nm) and very low experimental BCF values (≤ 6.2 L/kg), it is
expected that the substances in the diarylide yellow pigments group will have low
bioaccumulation potential in aquatic organisms.
31
6. Potential to Cause Ecological Harm
6.1 Ecological effects assessment
In order to provide the best possible weight of evidence for assessing the ecological
effects of substances in the diarylide yellow pigments group, only empirical data were
considered, given the high level of uncertainty associated with modelling the ecotoxicity
of this substance group.
6.1.1 Aquatic Environment
Both acute and chronic aquatic toxicity studies are available for this group of diarylide
yellow pigments. Table 6-1 presents a summary of available empirical ecotoxicity data
for the diarylide yellow pigments and one of their structural analogues, while Appendix
C contains more detailed, substance-specific information on the specific studies.
Table 6-1. Summary of empirical data for aquatic toxicity of diarylide yellow
pigments
Substance Test
Organism
Endpoint,
Details
Reference
type
value
PY12
Chronic
(72 h)
PY12
PY12
PY12
PY12
Alga
(Selenastrum
capricornutum)
NOEC
>
NA100 mg/L
Effects:
EC50 > 100 immobilization;
mg/L
high-purity
test
(72 h)
substance (98%)
55% and 63%
LC50 = 5–
formulations;
Acute
22 mg/L;
Zebrafish
TWEEN
80
(Brachydanio
(polyethylene
rerio)
(48 h)
LC100 = 10–
sorbitol
ester)
22 mg/L
added
LC50 > 500
Acute
mg/L;
Ide (Leuciscus
35% solution in
(48 h, idus)
water
LC50 > 1
96 h)
000 mg/L
Acute
Ide (Leuciscus LC50 = 10– 81%
solution;
idus)
100 mg/L
acetone added
Acute
Water
(Daphnia
magna)
flea
32
CPMA
2009
US
EPA
2006
European
Commissio
n ©2000a
European
Commissio
n ©2000a
European
Commissio
Substance Test
type
(96 h)
PY12
Acute
PY13
(48 h)
Chronic
(21
days)
PY83
Chronic
(72 h)
PY83
Acute
PY83
(96 h)
Acute
(48 h)
Group
Chronic
submission
for
diaryl (72 h)
pigments2
Organism
Endpoint,
value
Details
Reference
n ©2000a
Medaka
(Oryzias
latipes)
Water
(Daphnia
magna)
LC50 > 420
NA
mg/L
MITI 1992
flea NOEC = 1 Effects:
US
EPA
mg/L
immobilization,
2006
reproduction; highpurity
test
substance (99.7%)
Alga
(Selenastrum
capricornutum)
Zebrafish
(Brachydanio
rerio)
Fish (Phoxinus
phoxinus;
Oncorhynchus
mykiss;
Leuciscus idus)
Alga
(Desmodesmus
subspicatus;
Selenastrum
capricornutum)
Group
submission
for
diaryl Acute
pigments2
(48 h)
Water
(Daphnia
magna)
Group
Chronic
submission
for
diaryl (21
pigments2
days)
Water
(Daphnia
magna)
EC50 = 190 High-purity
test US
EPA
mg/L
substance (94.5%) 2006
LC50 > 100 High-purity
test US
EPA
mg/L
substance (94.5%) 2006
LC50 = 18–
80 mg/L1;
LC100
=
100–200
mg/L
NOEC
=
100 mg/L
Aqueous ethylene
glycol preparation
(concentration of
ethylene glycol not
reported)
Effects:
growth
inhibition, growth
rate
reduction;
filtered
solution
was prepared at
100
mg/L
of
pigment
flea NOEC
= Effects:
100 mg/L;
immobilization;
Hamburger
et al. 1977
ECHA
2012
ECHA
2012
EC50 > 1 filtered solution (at
000 mg/L
a loading of 100
mg/L
of
the
substance)
or
aqueous
dispersion of the
substance (loading
rate of 1000 mg/L)
flea NOEC = 10 Effects:
ECHA
mg/L
reproduction,
2012
mortality,
body
weight,
length,
33
Substance Test
type
Group
Acute
submission
for
diaryl (96 h)
pigments2
Organism
Endpoint,
value
Details
Reference
etc.;
centrifuged
solution (loading of
10
mg/L
of
pigment)
Rainbow trout LC50 = 124 Aqueous
ECHA
(Oncorhynchus mg/L
suspension;
the 2012
mykiss)
LC50 of 124 mg/L
equals 49 mg/L of
test substance (far
above
solubility
limit)
Abbreviations: CTV, critical toxicity value; EC50, effective concentration for 50% of test organisms; LCx, lethal
concentration for x% of test organisms; NOEC, no-observed-effect concentration ; NA, not available
1 LC50 of 18 mg/L from this study was selected as the CTV.
2 Submission for a group of diaryl yellow pigments from ECHA 2012 includes experimental data on pigments PY12,
PY13, PY83, PY176, and PY14.
It should first be noted that the results of all these studies are based on loading rates,
and no studies with measured or nominal concentrations have been identified. For
aquatic tests, the nominal concentration is the concentration that would exist if all test
material added to the test solution was completely dissolved and did not dissipate (US
EPA 1996). Although many of these studies refer to “nominal concentrations,” they
appear to be using this terminology as a synonym for “loading rate” or “non-measured
concentration,” which, strictly speaking, is not necessarily the same. Particularly in
studies in which solvents or dispersants were not applied, the reported values (e.g.,
NOEC = 10 mg/L, LC50 > 1 000 mg/L) were 4–6 orders of magnitude above the water
solubility limits of the tested pigments, suggesting that the test solution was not
completely dissolved and that these were, in fact, loading rates. Consequently, in
studies in which the loading rates exponentially exceeded the water solubility limits of
the pigments (when solvents or dispersants were not applied), the endpoints probably
should have been more accurately reported as EL50 (loading rate causing adverse effect
in 50% of exposed organisms) instead of EC50, or as LL50 (loading rate causing
mortality of 50% of exposed organisms) instead of LC50, and NOELR (no-observedeffect loading rate) instead of NOEC (no-observed-effect concentration). However, there
appear to be differing opinions in the literature. The OECD’s Guidance Document on
Aquatic Toxicity Testing of Difficult Substances and Mixtures (OECD 2000), in which the
water accommodated fractions (WAF) protocol is discussed, indicates that “WAFs may
be thus considered analogous to the term ‘nominal concentration’ used for typical test
substances, with all the limitations inherent to that term.” It is further stated that “LL50 or
EL50 values are comparable to LC50 or EC50 values determined for pure substances
tested within their solubility range.”
Nonetheless, the results presented in Table 6-1 are considered somewhat questionable
in those cases where the concentrations are exponentially higher than the water
34
solubility limits for the pigments. It may therefore be concluded that in all aquatic tests
with the diarylide yellow pigments where solvents or dispersants were not applied (see
Table 6-1 and Appendix C) and where the toxicity values were far above the water
solubility values of the substances, the results can only be, strictly speaking, interpreted
as “not toxic at saturation” or “no effect at saturation” (i.e., at water solubility limits).
It must also be mentioned that in aquatic tests where solvents or dispersants were
used, very significant biological effects (such as mortality of 50% and even 100% of test
organisms) have been reported, and some toxicity values are at relatively low
concentrations (e.g., LC50 of 18–80 mg/L for PY83 or LC100 of 10–22 mg/L for PY12;
see Table 6-1 and Appendix C), which, according to ecotoxicity classification schemes,
indicate that the tested pigments can be considered as moderately toxic (i.e., EC50 or
LC50 from 1 to 100 mg/L). Unfortunately, similar to the above-mentioned studies without
solvents, no measured concentrations were reported in these studies.
There are different reasons for such pronounced biological effects in the studies with
solvents or dispersants. The first reason is that diarylide yellow pigments might
theoretically be potentially moderately toxic substances—that is, when their solubility
limits are substantially increased to certain levels (by using the solvents or dispersants),
these substances can cause adverse effects.
Herbst and Hunger (2004) indicated that although, according to definition, the ideal
pigment is practically insoluble in its medium of application, organic pigments may, in
reality, deviate more or less from this postulate of insolubility. Since a pigment that is to
a certain extent soluble in its carrier is expected to perform poorly and may even
recrystallize, bleed or bloom, it is important to prevent pigment dissolution. There are
even certain accepted tests used to determine the extent to which a given organic
pigment tolerates solvents. The results of these tests, for example, indicate that,
compared with other diarylide yellow pigments, PY12 is only moderately fast to organic
solvents (Herbst and Hunger 2004).
Therefore, it may be supposed that in the aquatic toxicity tests with dispersants and
solvents (see Table 6-1 and Appendix C), the solubility of pigments is very likely to have
been increased from the low microgram per litre range to the low milligram per litre
range.
There is also an opinion (Rufli et al. 1998) that dispersants, even if non-toxic, may have
a pronounced effect on the physical form of the hydrophobic test substances in the test
medium and may thereby influence their bioavailability. Thus, results from a test
involving a dispersant may be specific for a defined substance–dispersant system, and
it may be difficult to extrapolate to other exposure conditions. Rufli et al. (1998) believed
that controls containing dispersant only can identify dispersant-related effects, but not
dispersant–substance interactions.
35
In addition, test concentrations far above the water solubility of the test substance can
contain more soluble impurities whose effects might also confuse the interpretation of
true substance toxicity (Weyman et al. 2012). Weyman et al. (2012) indicated that when
a solvent is used, but the test substance is not completely dissolved, undissolved
material present in the test media has the potential to exert adverse (physical) effects
on test organisms, such as blocking of fish gill membranes, encapsulation/entrapment
of daphnids or the reduction of light intensity in algal tests.
If studies with the pure pigments only—not pigment formulations—are considered, the
important question would probably be whether the no effect at saturation situations
occurred due to the low bioavailability of the pigments or their low inherent toxicity, or
both. To answer this question, a critical body burden (CBB), or internal critical
concentration (ICC), approach can be applied where the acute external effect
concentrations of pigments causing the mortality of organisms can be calculated and
compared with the results of ecotoxicity studies with pronounced biological effects (i.e.,
tests with solvents or dispersants), and are also compared with the cut-off values of
ecotoxicity classification schemes (i.e., LC50/EC50 values reflecting low, moderate or
high aquatic toxicity levels).
Calculated data indicate that to reach the CBB threshold levels for the acute endpoints
(mortality), the external LC50 values of diarylide yellow pigments should be in the range
of 565–803 mg/L, which suggests that these pigments are of low toxicity. This is also in
line with the low bioaccumulation potential of these substances in fish. Indeed, very low
BCFs (i.e., little uptake) of these substances of a particulate nature with low solubility in
water and octanol mean low risk of toxic effects, which is confirmed by the abovementioned CBB-based external effect concentrations and by the lack of significant
adverse effects observed in any of the bioconcentration tests.
It should, however, be noted that the calculated external effect concentrations are
higher than the LC50 values of 5–22 mg/L (PY12) and 18–80 mg/L (PY83) that were
reported in the studies in which solvents or dispersants were used (see Table 6-1). The
apparent discrepancy between the observed toxicity as indicated by the LC50 in water
and the calculated CBB-based toxicity values may be due to toxic effects caused by
impurities (contained in the tested pigments) and different additives (contained in the
pigment formulations), the dispersant–pigment (or solvent–pigment) interactions, as well
as a mode of toxic action not predictable by the CBB approach.
Regarding the experimental LC50 values of 5–22 mg/L (PY12) and 18–80 mg/L (PY83)
in aquatic tests in which solvents or dispersants were used to enhance the apparent
water solubility above the maximum thermodynamic equilibrium solubility in water, it
should be emphasized that reaching such high concentrations (in molecular form) of
diarylide yellow pigments is not likely realistic in the Canadian environment. It is
acknowledged that in the realistic aquatic environment and in laboratory studies, water
solubility values will rarely be identical. Indeed, laboratory tests are conducted under
conditions that do not take into account the various co-solvents that exist in the
36
environment, which may ultimately affect the solubility and bioavailability of a
substance. Temperature, pressure and surfactants (which may be present in the aquatic
environments) are other important factors that may affect the solubility of chemicals in
the environment. At the same time, water solubility enhancement in the environment
would not, probably, be as high as 4–5 orders of magnitude over solubility under
laboratory conditions.
Accordingly, studies without strong solvents and dispersants have greater inference, as
they are more environmentally relevant. In these studies, the no effect at saturation
situations occurred due to the very low bioavailability of the diarylide yellow pigments.
Therefore, it is expected that diarylide yellow pigments will not be harmful to aquatic
organisms, due to the very limited bioavailability of these substances under realistic
environmental conditions.
Finally, it should be noted that the absence of effects in short-term studies does not
necessarily mean that the substance would not be toxic during longer-term exposure.
For diarylide yellow pigments, two chronic studies (21-day tests with Daphnia magna)
are available (see Table 6-1 and Appendix C). In these studies, multiple endpoints have
been studied, including (but not limited to) reproduction, mortality and immobilization of
organisms, as well as their body weight and body length. No adverse effects were
observed at loading rates of 1 and 10 mg/L (i.e., no effect at saturation).
The above information allows one to conclude that no effect at saturation situations in
both acute and chronic studies occurred due to the low bioavailability of the pigments
and their low inherent toxicity. All the results therefore support the conclusion that
diarylide yellow pigments are of low inherent toxicity to aquatic organisms.
6.1.2 Other Environmental Compartments
In order to provide the best possible weight of evidence for assessing the ecological
effects of substances in the diarylide yellow pigments group, empirical data for soil and
sediments were also considered. It should be emphasized that, in terms of
environmental fate, these two environmental compartments are critical, because the
substances from this group are expected to almost solely reside in soils or sediments
(depending on the exposure scenario). Therefore, soil and sediment toxicity data are
highly relevant to the diarylide yellow pigments group.
One study on soil toxicity and one study on sediment toxicity are available for diarylide
yellow pigments (group submission for PY12, PY13, PY83, PY176, and PY14, see
Table 6-2). Data show that at a loading rate of 1 000 mg/kg of soil or sediment, no
effects (e.g., mortality, behaviour, reproduction and biomass of organisms) were
observed in chronic toxicity studies.
37
Table 6-2. Empirical data for ecotoxicity of diarylide yellow pigments
and soil
Test type
Organism
Endpoint,
Details
value
Freshwater
Effects:
biomass,
Sediment
NOEC = 1 000
oligochaete
mortality, behaviour,
toxicity, longmg/kg
reproduction; spiking
term
(28
sediment (dry
(Lumbriculus
the test item (1 000
days)
weight)
variegatus)
mg/kg) into sediment
Effects: reproduction,
Soil toxicity,
NOEC = 1 000 mortality,
body
Earthworm
long-term (56
mg/kg soil (dry weight; test item (1
(Eisenia fetida)
days)
weight)
000
mg/kg)
was
mixed with soil
in sediment
Reference
ECHA
2012
ECHA
2012
Therefore, it may be concluded that diarylide yellow pigments are of low inherent toxicity
to soil- or sediment-dwelling organisms, which can most likely be explained by the very
low bioavailability of these substances.
6.1.3 Derivation of the Predicted No Effects Concentration (PNEC) for
Water
As has already been mentioned, multiple experimental toxicity data from acute and
chronic aquatic ecotoxicity studies are available for this group of substances (see Table
6-1 and Appendix C). The range of empirical acute toxicity values from these studies is
quite significant—from 5 mg/L to more than 1 000 mg/L. It has already been noted that
in most studies, loading rates were reported, and very often the toxicity data were
expressed as ranges, not as definitive values (e.g., LC50 > 100 mg/L).
For deriving a PNEC value, it was decided to use the study with obvious biological
effect (e.g., mortality) and a conservative exposure scenario (i.e., the use of dispersant
or solubilizer to significantly increase the bioavailability of the pigment) instead of
studies with “no effect at saturation” results. One study (Hamburger et al. 1977; see
Table 6-1 and Appendix C), containing one of the lowest definitive acute toxicity values
available for this group of substances (namely, LC50 of 18 mg/L), has been critically
reviewed and is considered to be a high-quality study; therefore, the toxicity value of 18
mg/L was selected as the critical toxicity value (CTV), which is also consistent with other
risk assessments on azo-colorants. For example, this toxicity value of 18 mg/L was also
chosen for calculation of the aquatic PNEC in the Danish Environmental Protection
Agency’s Survey of Azo-colorants in Denmark (Øllgaard et al. 1998) and in the
screening assessment for the Challenge on the diarylide yellow pigment analogue
BPAOPB (Environment Canada and Health Canada 2011).
38
Therefore, the aquatic PNEC of 180 µg/L was derived based on the CTV of 18 mg/L
and an assessment (safety) factor of 100 to account for interspecies and intraspecies
variability in sensitivity and to estimate a long-term no-effect concentration.
6.1.4 Derivation of the PNECs for Soil and Sediment
One study on sediment toxicity and one study on soil toxicity are available for a group of
diarylide yellow pigments (see Table 6-2). These two studies have been considered as
key, high-quality studies, and the toxicity values (NOEC) of 1 000 mg/kg sediment (dry
weight) and 1 000 mg/kg soil (dry weight) were selected as the CTVs. Importantly, the
European Chemicals Agency has also considered these tests as key studies for a group
of diarylide yellow pigments (ECHA 2012).
Taking into account that the CTVs were based on NOEC values in long-term studies,
where no lethal or sublethal adverse effects (including sensitive endpoints, such as
reproduction) were found at the loading concentration of 1 000 mg/kg sediment or soil,
an application factor of 10 was used to account for inter- and intra-species variability in
sensitivity only. A PNEC for sediment or soil of 100 mg/kg soil (dry weight) was
calculated.
It should also be mentioned that the soil toxicity study was conducted with earthworms,
which are excellent model organisms in ecotoxicity studies due to their exposure to soil
contaminants via both ingestion and passive absorption through their skin. Since no
adverse biological effects were observed in this study, it was considered that a safety
factor of 100 would be overly conservative for calculation of a PNEC value.
Therefore, for characterization of ecological risk in different environmental
compartments, the following PNEC values will be used: aquatic PNEC, 180 µg/L; soil
PNEC, 100 mg/kg; and sediment PNEC, 100 mg/kg.
6.1.5 Ecological Effects Summary
Based on various lines of evidence involving empirical ecotoxicity data in various
environmental compartments, it may be concluded that diarylide yellow pigments are
not expected to cause harm to aquatic or soil- and sediment-dwelling organisms at low
concentrations. It should be emphasized that this conclusion does not contradict the
relatively low aquatic CTV of 18 mg/L, because this CTV is very conservative, assuming
very high bioavailability (provided by the use of a solvent in the aquatic ecotoxicity
study), which is not expected in the realistic environment.
Empirical data allowed derivation of the PNEC values for water, soil and sediments for
further characterization of the ecological risk of diarylide yellow pigments in different
environmental compartments.
39
6.2 Ecological exposure assessment
6.2.1 Releases to the Environment
No data on measured environmental concentrations (in water, soils or sediments) of the
five diarylide yellow pigments in Canada have been identified. Environmental
concentrations have therefore been estimated from available information.
Anthropogenic releases of a substance to the environment depend upon various losses
that occur during the manufacture, industrial use, consumer/commercial use and
disposal of the substance. In order to estimate releases to the environment occurring at
different stages of the life cycle of the diarylide yellow pigments, Environment Canada
compiled information on the relevant sectors and product lines as well as emission
factors 5 to wastewater, land and air at different life cycle stages in order to identify the
life cycle stages that are the largest contributors to environmental concentrations.
Recycling activities and transfer to waste disposal sites (landfill, incineration) were also
considered. However, releases to the environment from disposal were not quantitatively
accounted for unless reliable specific information on the rate of (or potential for) release
from landfills and incinerators was available.
Factors relevant to the life cycle of these substances have been considered,
uncertainties have been recognized, and assumptions may be made during each stage,
depending on information available. Exposure scenarios for the uses and media of
concern have been developed, including the determination of applicable predicted
environmental concentrations (PECs).
In order to evaluate potential exposures to the diarylide yellow pigments in the
environment, environmental concentrations are estimated from available information on
substance quantities, industrial use patterns, estimated release rates, characteristics of
wastewater treatment systems and characteristics of the receiving environment.
5
An emission factor is generally expressed as the fraction of a substance released to a given medium, such as
wastewater, land or air, during a life cycle stage, such as manufacture, processing, industrial application or
commercial/consumer use. Sources of emission factors include emission scenario documents developed under the
auspices of the OECD, data reported to Environment Canada’s National Pollutant Release Inventory, industrygenerated data and monitoring data.
40
In order to characterize the ecological exposure to diarylide yellow pigments, the sector
or use likely to be responsible for the highest potential releases in Canada was
identified, and a conservative exposure scenario was developed. When a sector or use
with the highest potential releases is determined to present low ecological concern, then
all other sectors or uses are also considered to be of low concern due to the lower
potential releases, i.e., no further analysis is necessary. However, additional sectors or
activities may be examined if there is cause for concern to determine the extent of the
ecological risk.
In the case of diarylide yellow pigments, the recycled paper deinking sector has been
determined to incur the highest potential environmental releases among all sectors or
uses identified from the survey data for the diarylide yellow pigments. This is supported
by data compiled from the 2006 and 2010 section 71 surveys, which show that the use
as ink, toner and colorants represented the majority (in the range of 100 000 – 500 000
kg/yr) of the diarylide yellow pigments reported. The other uses reported (paints and
coatings; food and beverage packaging applications; plastics and rubber; textile and
leather; building materials; automotive industry; adhesive sealants) accounted for lower
total quantities (10 000 – 100 000 kg). An approach focusing on the recycled paper
deinking sector was taken based on this information, which represents the scenario with
highest expected exposure.
PY12 is the dominant substance with respect to volume used under the code “Ink, toner
and colorants” and is known, along with other diarylide yellow pigments, to be used for
printing on both paper and plastic film according to the information provided by major
pigment producers and ink/toner formulators. It was therefore induced that the entire
quantity of diarylide yellow pigments, formulated into inks and toners, ended up on
printed paper and plastic film. Although the proportions of these pigments between the
two substrates were unknown, a substantial quantity was expected to be used on the
paper substrate. Considering this and a large recycled portion of the printed paper, it
was expected that a significant quantity of the ink/toner-destined diarylide yellow
pigments was subject to deinking.
For pigments in general, the emission factor to wastewater was estimated to be 20%
from deinking operations (see Appendix D), while the emission factor from any other
sector or use is much lower, ranging from 2.5% for plastics manufacture (OECD 2009c)
and 3% from the formulation of paints and coatings (OECD 2009b) to 5% from printing
(Baumann et al. 2001). The combination of a high emission factor of 20% and more
than 50% of the total quantity potentially reaching deinking facilities resulted in the
recycled paper deinking sector being chosen as the highest potential release source.
6.2.2 Aquatic Exposure from Recycled Paper Deinking Operations
Fifteen facilities were identified as sites that perform recycled paper deinking operations
from three reference sources: MacDonald (2013), Lockwood-Post Directory (Dyer 2001
and Jones et al 2011) and FisherSolve (2012). Of these 15 facilities, sufficient
41
information was available for 6 facilities to permit aquatic exposure analyses, while
there were insufficient data related to the remaining 9 facilities. Nevertheless, these six
facilities were judged to be a good representation of the Canadian deinking operations
sector.
The six recycled paper deinking facilities generate and treat their respective wastewater
on site and subsequently discharge directly to receiving water. An aquatic PEC was
estimated for each facility based on the quantity of the diarylide yellow pigments
entering the facility, the emission factor to wastewater, the wastewater volume, the
removal efficiency of the on-site wastewater treatment and the dilution of the receiving
water. These PECs are considered conservative, since the total quantity of the diarylide
yellow pigments used for paper printing is assumed to be 500 000 kg/year, and this
quantity is higher than the quantity reported to the 2006 and 2010 section 71 surveys.
At one of the sites, the highest PEC value of 28.5 µg/L was derived for the deinking
sector. This highest PEC represents the greatest potential for exposure for the deinking
sector, since the facility is estimated to receive the highest quantity of the diarylide
yellow pigments while generating the lowest wastewater volume, both on a per tonne of
pulp basis. This combination of having the highest quantity of the pigments and the
lowest wastewater volume results in the highest concentration in receiving water, when
all other parameters (emission factor to wastewater, removal efficiency of on-site
wastewater treatment and receiving water dilution) used in PEC calculations, are
assumed to be the same between facilities. For the other five facilities, lower PEC
values (0.2–3.8 µg/L) were derived because they receive lower quantities of the
diarylide yellow pigments and have higher wastewater dilution volumes.
More detailed calculations are provided and explained in Appendix D.
6.2.3 Sediment Exposure from Recycled Paper Deinking Operations
The European Chemicals Agency (ECHA 2010) suggests using the concentration of a
substance in freshly deposited sediment to evaluate its risk to sediment-dwelling
organisms. This approach implies that the concentration in suspended sediment instead
of bottom sediment should be used in PEC and risk quotient calculations. This approach
is used in estimating the concentration of the diarylide yellow pigments in sediment.
The concentration of the diarylide yellow pigments in suspended sediment or the
sediment PEC is estimated based on equilibrium partitioning between the aqueous
phase and suspended sediment. The method used for this estimate is discussed in
detail by Gobas (2007, 2010). The resulting sediment PEC is estimated as 0.15
mg/kg—at the same site where the highest aquatic PEC of 28.5 µg/L was derived. This
estimate is conservative, because not only the highest aquatic PEC is used, but also a
conservative log (Soct/Sw) value (representing octanol–water partition coefficient for
pigments as described in the Physical and Chemical Properties section) is selected for
the diarylide yellow pigments.
42
Detailed calculations are provided and explained in Appendix D of this report.
6.2.4 Soil Exposure from Recycled Paper Deinking Operations
The soil exposure to the diarylide yellow pigments is estimated under a conservative
scenario. In this scenario, it is assumed that pigment-containing biosolids generated
from the deinking sector are applied on agricultural lands at the maximum allowable rate
of 4.4 t/ha (Crechem 2005) over a substantial number of years (i.e., 10 years). It is also
assumed that the pigments are accumulated in soil and do not incur any degradation,
volatilization, soil runoff or leaching losses. This conservative scenario yields a soil PEC
of 6.8 mg/kg.
Detailed calculations are provided and explained in Appendix D of this report.
6.3 Characterization of Ecological Risk
The approach taken in this ecological screening assessment was to examine various
supporting information and develop conclusions based on a weight of evidence
approach, and using precaution as required under CEPA 1999. Lines of evidence
considered include results from a conservative risk quotient analysis, as well as
information on physical and chemical properties, environmental fate, ecotoxicity and
sources of the diarylide yellow pigments.
6.3.1 Risk Quotient Analysis
As a line of evidence to support the ecological risk characterization of diarylide yellow
pigments, risk quotients (RQ) were calculated for relevant exposure scenarios by
dividing the PEC values with the corresponding PNEC values.
The following PNEC values (see Ecological Effects Assessment section of this report)
were used for the calculation of risk quotients:
•
•
•
aquatic PNEC = 180 µg/L;
soil PNEC = 100 mg/kg soil (dry weight);
sediment PNEC = 100 mg/kg sediment (dry weight).
The aquatic risk quotients from deinking vary from only 0.001 to 0.158. The highest risk
quotient estimate was 0.158 (at the site where the highest aquatic PEC was derived),
representing the worst-case aquatic exposure scenario. All seven facilities are
estimated to have RQ values below (or well below) 0.1.
The sediment risk quotient is calculated by dividing the sediment PEC by the sediment
PNEC of 100 mg/kg. A sediment RQ of 0.0015 was calculated.
43
The soil risk quotient is determined by dividing the soil PEC by the soil PNEC. A soil RQ
of 0.07 was calculated.
Therefore, for the deinking operations scenario, all RQ values for diarylide yellow
pigments in water, sediment and soil are well below one which suggests a very low risk.
Due to their lower releases, all other sectors or uses are not expected to cause
ecological concern and were, therefore, not a subject to further analysis.
6.3.2 Consideration of Lines of Evidence and Conclusion
Diarylide yellow pigments are anthropogenically produced; they are not expected to
occur naturally in the environment. According to recent surveys, four of the five
pigments in this grouping have been found to be in Canadian commerce. No data
concerning concentrations of these substances in the Canadian environment have been
identified.
Diarylide yellow pigments do not exist as individual molecules; they are principally
particles in the sub- or low micrometre size range, and the pigment powder is typically
composed of primary particles (i.e., the crystal lattice of a pigment), aggregates and
agglomerates. In terms of the distribution among environmental compartments, the
physical and chemical properties and the particulate nature of these substances
suggest that soil and sediments are expected to be the two major media where diarylide
yellow pigments may be found in the environment.
Diarylide yellow pigments are expected to be persistent in the environment based on
the available multiple experimental biodegradation data for the pigments from this group
of substances as well as their analogues, using a category approach for pigments. High
persistence of these substances is also supported by experimental physical and
chemical properties of pigments (e.g., particulate nature of pigments, their high density,
high chemical and hydraulic stability, and very low aqueous solubility). Indeed, pigments
are expected to be durable, given their intended use as colorants in finished products.
Physical-chemical properties, experimental degradation data and medium-to-medium
half-life extrapolations indicate that under aerobic conditions, diarylide yellow pigments
are expected to be persistent not only in water, but also in soil and sediments.
The bioavailability of diarylide yellow pigments is expected to be very low based on the
particulate character of these substances, their very low solubility in both water and
octanol, and the high molecular weight and large cross-sectional diameter of molecules
of these substances. As a result, the potential to bioaccumulate in aquatic organisms is
expected to be low, which is confirmed by the results of bioconcentration studies.
Due to the limited bioavailability of diarylide yellow pigments, no effects were found in
chronic soil and sediment toxicity studies at the concentration of 1 000 mg/kg soil or
sediment (dry weight). In terms of biological effects on aquatic organisms, these
44
pigments showed no effect at saturation (i.e., at water solubility limits) in acute and
chronic aquatic ecotoxicity studies where solvents were not used. The results of these
studies allowed the conclusion that diarylide yellow pigments are not expected to be
inherently toxic to aquatic, soil-dwelling or sediment-dwelling organisms at low
concentrations.
To evaluate potential exposures to diarylide yellow pigments in the environment,
environmental concentrations were estimated (PECs) from available information on
substance quantities, industrial use patterns, estimated release rates, characteristics of
on-site or municipal treatment plants and characteristics of the receiving environment.
The industrial release scenario chosen to evaluate the potential exposure to these
substances relates to the major use of these pigments as “Ink, toner and colorants.”
Risk quotient analyses compare PEC with the appropriate predicted no-effect
concentration (PNEC) values in order to evaluate potential risks. The PEC in water, soil
and sediments for the group of diarylide yellow pigments were well below the respective
PNEC for sensitive aquatic, soil-dwelling and sediment-dwelling organisms, resulting in
risk quotients of much lower than 1.
Overall, the results of this assessment lead to the conclusion that the five diarylide
yellow pigments have a low potential to cause ecological harm in Canada.
6.3.3 Uncertainties in the Evaluation of Ecological Risk
There were some uncertainties associated with the assessment of diarylide yellow
pigments. For example, pigment concentrations associated with toxicity for aquatic
organisms may have a source of uncertainty in the studies where these concentrations
exceeded the water solubility limits of pigments, or when dispersants or solvents were
used in aquatic toxicity tests. For instance, calculations based on a CBB approach
indicated that diarylide yellow pigments are not expected to be acutely toxic to aquatic
organisms; however, some experimental acute toxicity studies in which dispersants or
solvents were used (to increase the solubility of diarylide yellow pigments) suggested
otherwise, showing pronounced biological effects at moderate concentrations (e.g., ~20
mg/L). The apparent data discrepancy may be attributed to toxic effects caused by
impurities (contained in the tested pigments) and different additives (contained in the
pigment formulations), dispersant–pigment (or solvent–pigment) interactions or a mode
of toxic action that is not predictable by the CBB approach. There might also be
uncertainty in the aquatic toxicity studies even without solvents, because in all these
studies with diarylide yellow pigments, only loading rates were reported, and no
information on measured concentrations was provided.
In this risk assessment, there are two areas of uncertainty associated with the purity of
diarylide yellow pigments. The first relates to the purity itself, because many substances
(e.g., resins, rosins, different surfactants, dispersing agents, coupling agents) are used
in pigment preparation, and it is impossible to remove such impurities by even intensive
45
washing and hot extraction procedures. As a result, certain amounts of these
substances can most likely be found even in pigments of relatively high-quality grade.
Another area of uncertainty is that instead of pure pigments, pigment formulations (i.e.,
final products) were tested. In both cases, impurities and additives may affect physical
and chemical properties, persistence and biological effects of pigments.
Another area of uncertainty relates to the degradation of diarylide yellow pigments.
Because of a lack of experimental data, there is uncertainty as to the rate and extent to
which degradation of diarylide yellow pigments occurs in anaerobic environments and
whether those degradation products (e.g., aromatic amines) could ever become
biologically available. (It may be expected, however, that the unique physical state of
diarylide yellow pigments [particles] along with their very low water solubility would limit
the availability of the molecules for biotic reduction, so that the formation of degradation
products will also be very limited.)
In terms of the bioavailability and bioaccumulation of pigments, there is also some
uncertainty. Since many azo pigments have particle sizes in the low sub-micrometre
range, a portion of the size distribution may fall partially in the “nanoparticle” domain.
Some nanoparticles can be taken up by different types of cells and are able to cross the
cell membrane and become internalized. Importantly, the interaction of nanoparticles
with the cells and their uptake can occur via, for example, endocytosis or phagocytosis
in specialized cells. (It should be noted, however, that no bioaccumulation studies with
diarylide yellow pigments where these mechanisms could be reliably confirmed have
been identified.)
Uncertainties are also associated with the lack of information on environmental
concentrations of the diarylide yellow pigments in Canada. It is also recognized that
releases from waste disposal sites are possible, although difficult to quantify due to the
lack of data, and would contribute to overall environmental concentrations.
It is anticipated that the proportions of diarylide yellow pigments released to the various
environmental media would not be significantly different from those estimated here,
given the conservative assumptions used in the exposure analysis.
46
7. Potential to Cause Harm to Human Health
7.1 Exposure Assessment
Environmental Media
Empirical data on concentrations of the five diarylide yellow pigments in environmental
media in Canada or elsewhere were not identified. Due to the very low volatility and
water solubility of diarylide yellow pigments, these substances are expected to be
adsorbed onto soil and sediments when released to the environment and not partition
into water. Therefore exposure for the general population to diarylide yellow pigments
through drinking water is not expected. Due to the very low expected vapour pressures
of these substances, inhalation of the volatile fraction via air is not expected to be a
significant route of exposure (refer to Environmental Fate section). Thus, environmental
media are not expected to be a significant source of exposure for these substances for
the general population of Canada.
As summarized in the Uses section, three of the five diarylide yellow pigments were
identified to be used in food packaging applications. Minimal potential for direct food
contact is expected; therefore, food is not considered as a significant source of
exposure to the diarylide yellow pigments evaluated in this assessment.
Consumer Products
Four of the diarylide yellow pigments (PY12, PY13, PY83 and PY176) are known to be
used as colourants in a variety of consumer products in Canada (Canada 2011b;
Environment Canada 2012) which may lead to exposure for the general population
during use of these products through the oral, inhalation, and dermal routes. A summary
of estimates of oral and inhalation exposure to consumer products containing PY12,
PY13, PY83 and PY176 is provided in Table 7-1. However, these estimates no not
reflect the limited systemic exposure to diarylide yellow pigments expected due to very
low absorption of these substances from the oral and inhalation routes (see Health
Effects Assessment section for study details). Also, while topical exposures to the
diarylide yellow pigments can occur from uses of these substances in consumer
products and cosmetics, systemic exposure is not expected from the dermal route since
dermal absorption of the predominantly insoluble diarylide yellow pigment particles is
considered to be negligible. Therefore, dermal estimates of exposure were not derived.
Based on the use information obtained specific to the Canadian market, exposure
estimates for oral ingestion of lipstick and finger paint, as well as mouthing of a painted
toy car were derived (Table 7-1). PY83 was identified at a maximum concentration of
0.1% by weight in a lipstick (personal communication, email from the Consumer
Products Safety Directorate [Health Canada] to the Existing Substances Risk
Assessment Bureau [Health Canada], dated 2011; unreferenced), resulting in a daily
oral exposure estimate of 3.4x10-4 mg/kg-bw per day for an adult (20–59 years of age).
47
As a conservative approach, oral exposure to these substances for younger age groups
(0.5-4 years old) for finger painting was estimated. Available information indicates that it
is foreseeable for PY12, PY13 and PY83 to be used in finger paints (Clariant 2010; BS
2002). Another source indicates pigments are generally found at concentration ranges
of 1 – 3% by weight in finger paints (Delta Creative 2008). This range is consistent with
the levels of monoazo pigments in finger paints (personal communication, email from
Duke University Toxicology Program to the Existing Substances Risk Assessment
Bureau [Health Canada], dated 2013; unreferenced). A generic approach was taken to
apply the information to the four diarylide yellow pigments (PY12, PY13, PY83 and
PY176) and the range of oral exposures were estimated to be 0.87 - 2.6 mg/kg-bw per
event for incidental ingestion during finger painting (refer to Appendix E for details).
Table 7-1. Upper-bounding estimates of oral exposure and acute inhalation
exposure to PY12, PY13, PY83 and PY176
Consumer
product
Age
range
(years)
Pigment
Concentration
range
(% w/w)
Hair dyes
(spray)
Hair dyes
(spray)
Spray paint
5–11
PY83
0.1–3
5–11
PY12
0.1–0.3
20–59
3–60
Lipstick
Finger
paint
Hair spray
20–59
0.5–4
PY12, Y13,
PY83, PY176
PY83
PY12, PY13,
PY83, PY176
PY83
20–59
a
a
b
a
Oral (daily)
(mg/kg-bw
per day)
N/A
Oral
(per
event)
(mg/kg-bw
per event)
N/A
N/A
N/A
N/A
N/A
4.1 × 10 –
−4
1.2 × 10
−6
4.1 × 10 –
−5
1.2 × 10
c
0.008–0.15
N/A
0.87 - 2.6
N/A
N/A
N/A
6.1 × 10
-4
0.1
b
1–3
3.4 x 10
0.1
4.2 × 10
−4
Inhalation
3
(mg/m )
−6
−6
Abbreviation: N/A, not applicable
a
Personal communication, email from the Consumer Products Safety Directorate [Health Canada] to the
Existing
Substances Risk Assessment Bureau [Health Canada], dated 2011; unreferenced
b
Delta Creative (2008); 2013 personal communication from Duke University Toxicology Program to Health Canada
regarding concentrations of monoazo pigments in finger paints (unreferenced).
c
An airless wall sprayer was considered relevant due to the generation of respirable paint aerosols. An airless wall
sprayer is a typical product available for spray painting walls. However, the use of an airless wall sprayer by
homeowners/consumers is not expected to be common.
Inhalation exposure to diarylide yellow pigments is expected via aerosol particles only,
due to the very low vapour pressures of these substances (i.e., < 10−11 to 10−9 Pa)
(Baughman and Perenich 1988). PY83 and PY12 were identified in hair dyes at
concentration ranges of 0.1–3% by weight and 0.1–0.3% by weight, respectively
(personal communication, email from the Consumer Products Safety Directorate [Health
Canada] to the Existing Substances Risk Assessment Bureau [Health Canada], dated
2011; unreferenced). Exposure to PY83 and PY12 from the use of a temporary hair dye
spray was considered due to the potential for application in aerosol form and the
potential for use by younger age groups. Inhalation exposure estimates, expressed as
mean concentration ranges on the day of exposure to these substances, were 4.1×10−6
– 1.2×10−4 mg/m3 and 4.1×10−6 – 1.2×10−5 mg/m3 for a child (5–11 years of age), for
PY83 and PY12, respectively. PY83 was identified at a maximum concentration of 0.1%
48
by weight in a hair spray product (personal communication, email from the Consumer
Products Safety Directorate [Health Canada] to the Existing Substances Risk
Assessment Bureau [Health Canada], dated 2011; unreferenced), which results in an
inhalation exposure estimate expressed as a mean concentration on the day of
exposure of 6.1×10−6 mg/m3 for an adult (20–59 years of age). In addition, an oral daily
exposure to the non-respirable fraction for PY83 of 4.2×10−4 mg/kg-bw per day was
determined for adults (20–59 years of age). PY12, PY13, PY83 and PY176 are known
to be used in paints at concentrations of 3–60% by weight (IARC 2010a). For this
product category for inhalation exposure, an airless wall sprayer was considered
relevant due to the generation of respirable paint aerosols. The inhalation mean event
concentration range for PY12, PY13, PY83 and PY176 was estimated to be 0.008–0.15
mg/m3 for an adult (20–59 years of age). The details of the inhalation exposure
scenarios are summarized in Appendix E.
PY12 and PY83 were identified as being present in permanent tattoo inks in Canada
(personal communication, email from the Consumer Products Safety Directorate [Health
Canada] to the Existing Substances Risk Assessment Bureau [Health Canada], dated
2011; unreferenced). Therefore, the exposure potential of diarylide yellow pigments
from use in tattoos is considered.
Permanent tattoos are a potential source of exposure, as they are injected into the
dermis, below the epidermal–dermal junction at a depth of 1–2 mm (Lea and Pawlowski
1987; Sperry 1992). Therefore, in contrast to dermal exposures to diarylide yellow
pigments, where dermal absorption is expected to be negligible, intradermal injection of
tattoo ink is considered to be a route of systemic exposure to these substances.
After injection of tattoo ink into the dermis, the fate of the pigment particles is expected
to follow one of three paths (Danish EPA 2012). First, injected pigment may migrate
upward through the individual needle tracts into the epidermis where it is sloughed off
(epidermal removal)(Lea and Pawlowski 1987). Second, removal of the injected
pigment can occur over the short-term (first few weeks after injection) by macrophages
into the lymphatic system due to the dermal inflammatory response (Sperry 1992).
Finally, the injected tattoo pigment which is retained in the dermis forms the stable
tattoo by which the pigment is sequestered into secondary lysosomes after being
engulfed by dermal fibroblasts and macrophages (Bäumler et al. 2000). The fractions of
injected pigment making up the short-term removal and the stable tattoo are together
considered potential sources of systemic exposure from a single tattoo.
For the fraction of the tattoo subject to lymphatic removal over the short-term, a shortterm exposure estimate for the diarylide yellow pigments in tattoo inks was based
mainly on the results of Engel et al. (2009), an in vivo study of mice that were injected
with monoazo Pigment Red 22 into their dermis. The short-term daily systemic
exposure was estimated to range from 0.12 mg/kg-bw per day - 1.1 mg/kg-bw per day
for an adult (refer to Appendix G for details).
49
For the fraction of injected tattoo pigment forming the stable tattoo, the long-term in vivo
fate of this injected material is largely unknown. While fading of tattoos over time is
known to occur (Lehner et al. 2011), several mechanisms may be responsible including:
ongoing phagocytosis and translocation via lymphatic system (Gopee et al. 2005,
Jemec 2010), photodegradation of the pigment at the tattoo site (Doll et al. 2008,
Kuramoto et al. 1996, Engel et al. 2007, 2009; Cui et al. 2004; Vasold et al. 2004;
Bäumler et al. 2000, 2004; Hauri 2013), in vivo metabolism, and removal via venous
drainage (Danish EPA 2012). The Danish EPA (2012) stated that regarding tattoo
exposure, “the current knowledge is considered as being insufficient for a valid
quantitative exposure assessment”. Accordingly, an estimate of long-term systemic
exposure from certain azo pigments in permanent tattoo inks has not been derived.
7.2 Health Effects Assessment
Reviews of the health effects data for diarylide yellow pigments have previously been
published, including a draft OECD assessment(OECD 2003a, b), and a more recent
Screening-Level Hazard Characterization by the US Environmental Protection Agency
(US EPA 2010) and a Screening Assessment for the Challenge under Canada’s CMP
(Environment Canada and Health Canada 2011). The available studies on the critical
health effects for the five substances, as well as analogues, are presented below. The
interpretation of these studies by other organizations (e.g. OECD, US EPA) has also
been taken into consideration. Overviews of other endpoints are briefly summarized
based on descriptions from secondary sources (BIBRA 1991, 1996a, b; OECD 2003a,
b; US EPA 2010).
A key consideration in the potential health effects of aromatic azo and benzidine-based
substances in general is the potential generation of aromatic amine metabolites
following reduction of the azo bond (Environment Canada and Health Canada 2013).
While biological azo bond cleavage is generally considered an important metabolic
reaction for more soluble aromatic azo and benzidine-based substances, it is not
considered to apply to the same magnitude for poorly soluble azo pigments (Golka et al.
2004). However, given the high hazard potential of the benzidine derivative structural
moiety found in diarylide yellow pigments (i.e. 3,3′-DCB), the potential for absorption,
azo bond cleavage and metabolism of these substances was evaluated.
The information available in support of the negligible absorption, azo bond cleavage
potential and low hazard for the diarylide yellow pigments are summarized in
subsequent sections based on the following lines of evidence:
•
•
•
negligible absorption of the parent diarylide yellow pigment and/or azo cleavage
products as generated by the intestinal bacteria or by tissues in vivo;
lack of evidence for adverse effects, including no evidence for carcinogenicity
from repeated-dose studies primarily from the oral route;
negative results in Prival-modified Ames assays and other standard in vivo and in
vitro genotoxicity tests;
50
•
•
low hazard potential from acute toxicity studies; and
other information, including mechanistic data and low solubility in both water and
octanol.
Absorption Potential
In vivo absorption and metabolism studies provide direct evidence to evaluate azo bond
cleavage in the gastro-intestinal tract (GIT) or by mammalian tissues following
absorption of aromatic azo and benzidine-based substances. There are several in vivo
absorption and/or metabolism studies available for the diarylide yellow pigments,
primarily for the oral route (Table 7-2), while single studies following each of inhalation
(Table 7-3) and dermal exposure (Table 7-4) were also identified. Other studies by intratracheal instillation provide supporting data (Table 7-5). These data are summarized in
the sections below.
The evidence of potential azo bond cleavage or absorption of diarylide yellow pigments
was first reported by Akiyama (1970), where free 3,3′-DCB was detected in the urine
samples of rabbits orally exposed to a single gavage dose of PY13 as “purified
benzidine yellow” (recovered 3,3′-DCB approximately 0.05% of the 50 mg dose,
equivalent to 0.025 mg) (Table 7-2). The small portion of free 3,3′-DCB recovered in the
urine may have been due to azo bond cleavage and absorption of free 3,3′-DCB in the
GIT. It could also be due to residual 3,3′-DCB in the dosage formulation, since the
detection limit of free 3,3′-DCB in the “purified benzidine yellow” was not indicated. The
observation in this study, however, was not supported by several subsequent follow-up
oral studies by other authors on various species and diarylide yellow pigments, with
higher tested doses, repeated exposures and more sensitive detection methods (Table
7-2). Thus, in light of these subsequent studies, the findings reported by Akiyama
(1970) are uncertain and therefore considered equivocal. An inhalation study on PY17
looking at 3,3′-DCB and conjugates in urine and serum (Table 7-3) as well as a dermal
study with [14C]DCB-labelled PY12 (Table 7-4) also did not demonstrate evidence of
azo bond cleavage or absorption of these substances, further supporting the overall
evidence of limited bioavailability for the diarylide yellow pigments.
Table 7-2. Oral metabolism/absorption of diarylide yellow pigments
Dose Evidencea for
Substance
(mg/kg- absorption/
Species
Tissue
Analyte
Exposure
tested
bw per
azo bond
day)
cleavage
single
rabbitb
PY13
urine
DCB
dose
20
+/gavage
6 & 23
ratc
PY12, PY83
urine
DCB
630
month diet
single
rabbitc
PY13
urine
DCB
50
dose
51
Species
Substance
tested
Tissue
rabbitd,
rat,
monkey
PY13
urine
hamstere
PY12
urine
ratf
PY12
blood,
liver,
urine
ratg
PY13,
PY174
liver
ratg
PY13,
PY174
urine
rath
PY17
blood
rath
PY17
blood
rati
PY13, PY17
blood
rati
PY13, PY17
liver
Dose Evidencea for
(mg/kg- absorption/
Analyte
Exposure
bw per
azo bond
day)
cleavage
gavage
single
DCB or
dose
20-400
conjugates
gavage
single
DCB or
dose
100
conjugates
gavage
single
[14C]DCB
dose
1.1
gavage
single
DCB-DNA
dose
400
adducts
gavage
single
DCB or
dose
400
conjugates
gavage
DCB- &
single
mNAcDCBdose
138
Hb adducts
gavage
DCB- &
mNAcDCB- 4wk diet
100
+/Hb adducts
DCB- &
+/- (PY13)
mNAcDCB- 4wk diet 165-170
- (PY17)
Hb adducts
DCB-DNA
+/- (PY13)
4wk diet 165-170
adducts
- (PY17)
Abbreviations: DCB, 3,3′-dichlorobenzidine; DNA, deoxyribonucleic acid; dNAcDCB, di-N,N-acetyl-3,3′dichlorobenzidine; Hb, hemoglobin; mNAcDCB, mono-N-acetyl-3,3′-dichlorobenzidine
a
Evidence for absorption/azo cleavage: + (positive), +/− (equivocal), − (negative at limit of detection).
b
Akiyama 1970
Leuschner 1978
d
Mondino et al. 1978
e
Nony et al.1979; 1980
f
Decad, et al. 1983
g
Sagelsdorff et al. 1990
h
Zwirner-Baier & Neuman 1994
I
Sagelsdorff et al 1996
c
52
Table 7-3. Inhalation metabolism/absorption of diarylide yellow pigments (Hofman
and Schmidt 1993)
Dose Evidencea for
Substance
(mg/kg- absorption/
Species
Tissue
Analyte
Exposure
tested
bw per
azo bond
day)
cleavage
urine,
DCB or
230
rat
PY17
4hr
serum
conjugates
(mg/m3)
Abbreviations: DCB, 3,3′-dichlorobenzidine
a
Evidence for absorption/azo cleavage: − (negative at limit of detection).
Table 7-4. Dermal metabolism/absorption of diarylide yellow pigments (Decad et
al. 1983)
Dose Evidencea for
Substance
(mg/kg- absorption/
Species
Tissue
Analyte
Exposure
tested
bw per
azo bond
day)
cleavage
blood
dose
rat
PY12
liver
[14C]DCB
24hr
not
urine
provided
Abbreviations: DCB, 3,3′-dichlorobenzidine
a
Evidence for absorption/azo cleavage: − (negative at limit of detection).
Table 7-5. Intra-tracheal metabolism/absorption of diarylide yellow pigments
Dose Evidencea for
Substance
(mg/kg- absorption/
Species
Tissue
Analyte
Exposure
tested
bw per
azo bond
day)
cleavage
5
DCB-Hb
+/- (PY83)
ratb
PY17, PY83 blood
exposures 10-20
adducts
- (PY17)
over 4wk
5
+/- (PY83)
ratb
PY17, PY83
urine
DCB
exposures 10-20
- (PY17)
over 4wk
DCB-Hb,
single
c
rat
PY17
blood
mNAcDCB13.8-69
+/exposure
Hb adducts
Abbreviations: DCB, 3,3′-dichlorobenzidine; Hb, hemoglobin; mNAcDCB, mono-N-acetyl-3,3′-dichlorobenzidine
a
Evidence for absorption/azo cleavage: +/− (equivocal), − (negative at limit of detection).
b
Bartsch et al. 2001
c
Zwirner-Baier & Neuman 1994
However, two studies by Zwirner-Baier and Neumann (1994) and Sagelsdorff et al.
(1996) did report detectable 3,3′-DCB adducts in hemoglobin and liver deoxyribonucleic
acid (DNA) of rats exposed for 4 weeks in the diet to PY17 and PY13 respectively
(Table 7-2). In both studies, levels of 3,3′-DCB adducts of hemoglobin (Hb) and liver
53
DNA were relatively low and slightly above the analytical method of detection. The
tested pigments were both reported to have relatively low levels of free 3,3′-DCB (< 5
ppm for PY17, < 0.1 ppm for PY13), which suggests that 3,3′-DCB impurity was not the
source of the adducts. While a low level of azo bond cleavage of the tested diarylide
yellow pigments may have occurred, the presence of soluble 3,3′-DCB-containing
impurities has been suggested as the potential source of the 3,3′-DCB adducts
observed (OECD 2003a). A “readily soluble” “monoazo compound” was reported to be
present at relatively high levels in PY13 (220 ppm) compared with a lower level in PY17
(21 ppm) in the study by Sagelsdorff et al. (1996) and was considered to be the
explanation for the 3,3′-DCB adducts in Hb and liver produced by PY13 but not PY17 in
this study (OECD 2003a). Similarly, the draft OECD assessment (OECD 2003a)
reported a follow-up communication with the study authors of Zwirner-Baier and
Neumann (1994), which indicated the presence of a “soluble extractable impurity” that
was also present in the sample of PY17 tested and may possibly explain the Hbadducts detected in that study. No more information was available on the nature and
identity of these putative 3,3′-DCB-based impurities. Similar low levels of 3,3′-DCB in
urine and Hb-adducts were reported in rats during repeated intratracheal instillations of
PY83 but not PY17 over a 4-week period (Bartsch et al. 2001). However, since no 3,3′DCB or Hb-adducts were detected in the 4-week recovery period, the study authors
stated that “no unequivocal proof of the bioavailability” of PY83 could be concluded from
this study.
Some evidence of limited uptake for the diarylide yellow pigments was reported, based
on an inhalation study of PY13 and an intratracheal dosing study of PY17 and PY83, as
well as two repeated-dose oral studies on PY12. Accumulation of pigment particles in
lung-associated lymphatic tissue of rats was observed in an inhalation study of PY13
(Table 7-3) and following intratracheal instillation of PY17 and PY83 (Table 7-5). From
the oral studies on PY12 (Table 7-2), observations of faint yellow discoloration of organs
and internal mucosal surfaces were reported in all exposure groups of rats and mice in
a chronic dietary study (NCI 1978), and some discoloration was observed in parents
and pups in a reproductive/developmental toxicity screening study (Frieling 2001). It
was suggested that impurities (e.g., monoazo substances) or contamination during
necropsy may have been the reason for the observations in the oral studies (OEDC
2003a, b; US EPA 2010); however, another explanation may be low-level absorption of
insoluble diarylide yellow pigment particles from the intestine. Low levels of uptake and
systemic distribution to local lymph nodes and other distal tissues have been described
for other insoluble microparticles and nanoparticles administered to the lungs and GIT
(Oberdörster et al. 2005; Carr et al. 2012). Given the likelihood of some of the diarylide
yellow pigments in these studies to have been in the sub-micrometre size range (see
section on Particle Size Distribution and Density), it is reasonably expected that similar
uptake of insoluble diarylide yellow pigment particles would occur for the oral and
inhalation routes. Therefore, it is possible that small amounts of parent diarylide yellow
pigments are absorbed systemically in the particle form following oral and inhalation
exposure; however, the fraction of the total administered dose that could be absorbed in
this way is expected to be low.
54
The potential for dermal absorption of diarlyide yellow pigments was investigated in rats
using [14C]-DCB-labelled PY12 (Decad et al. 1983). Briefly, three to six male F344 rats
were exposed to the [14C]-PY12 on the shaved dorsal area which was occluded with
aluminum foil for up to one day. The [14C]-PY12 was applied in a 1:1 solution of
Emulphor EL 620/ethanol and distilled water to a 4x4 cm2 area at a dose of radio-label
of 2.57-2.95 µCi/rat (application volume and concentration of [14C]-PY12 was not
provided in the study). Blood collected at intervals from 10 minutes to 8 hours and liver
homogenate and collected urine did not show radioactivity above background levels
after 1 day of exposure. The applied dose of radioactivity was fully accounted from the
skin application site, aluminum patch, and pipet tip. This data provide evidence of
negligible systemic absorption of PY12 or its metabolites from the dermal route of
application. Although the dermal study by Decad et al. (1983) has limitations (only 3–6
replicates, only PY12 tested), the evidence for negligible oral absorption outlined in
Table 7-2 supports a similar expectation for the dermal route. In addition, the low water
and octanol solubility of diarylide yellow pigments suggests that these substances would
exist almost entirely as insoluble particles in dermal applications further limiting their
potential dermal absorption, thus dermal absorption is expected to be negligible.
Overall, the in vivo metabolism and absorption studies on diarylide yellow pigments
generally demonstrated negligible absorption and/or azo bond cleavage of the parent
diarylide yellow pigments investigated. The presence of impurities (residual 3,3′-DCB
and/or undefined soluble “monoazo impurity”) may also have been responsible for some
of the results observed in these studies, while limited uptake of diarylide yellow
pigments in particle form cannot be excluded.
Repeated-dose Studies
The available repeated-dose data are primarily oral studies on PY12 and PY83, with
one short-term inhalation study on PY13. These studies are summarized in this section,
with all dose conversions from dietary concentration to milligrams per kilogram of body
weight per day (mg/kg-bw/day) using values by Health Canada (1994) unless otherwise
noted.
In chronic dietary studies conducted by the US National Cancer Institute (NCI), there
was no significant positive correlation between dosage and tumour incidence observed
in Fischer 344 rats or B6C3F1 mice (n = 50/sex) administered concentrations of 0, 2.5
or 5% PY12 in the diet for 78 weeks (dose equivalents of 0, 1250 and 2500 mg/kg-bw
per day in rats and 0, 3 250 and 6 500 mg/kg-bw per day in mice) followed by a 28week observation period (NCI 1978). The precise purity of the test material was not
indicated in the study report; however, the melting point range between 311°C and
320ºC “suggested the presence of impurities” (NCI 1978). The body weight changes for
the control and exposed groups of rats of both sexes were generally equivalent
throughout the dosing period. No statistically significant positive association between
dose and mortality in rats was observed. Faint yellow discoloration of internal organ
mucosa was observed at all dose levels in both rats and mice, indicating some possible
55
systemic absorption of either the parent PY12 or an impurity (refer to Absorption
Potential section). No differences in non-cancer effects were generally observed
between control and exposure groups in this study. However, exposure-related
basophilic cytoplasm changes in hepatocytes of low and high dose groups of both
sexes of rats were observed in this study and were noted by the NCI study authors as
the “the only clinical sign or pathologic lesion observed” in the study (NCI 1978). While
hepatocytes with basophilic cytoplasm are common in older F344 rats (Ward 1981),
these changes were generally limited to the exposure groups in this study, and
displayed dose-dependent increase in both sexes (females: control 2/48, low dose
42/49, high dose 40/48; males: control 0/50, low dose 5/49, high dose 11/47) and are
therefore considered to be exposure related. While hepatocellular basophilic cell foci
are generally regarded as a proliferative lesion in the liver (Goodman et al. 1994,
Thoolen et al. 2010), the toxicological significance and adversity of these findings in the
NCI study are uncertain based on the absence of other reported effects. Therefore, this
effect from the NCI study is being treated as a lowest-observed-effect level (LOEL) (1
250 mg/kg-bw per day, lowest dose tested) rather than a lowest-observed-adverseeffect level (LOAEL). While the highest doses tested were considered by the US EPA
(2010) and OECD (2003a) to be the no-observed-adverse-effect levels (NOAELs) for
mice and rats in these studies, a discussion of the significance (or lack) of the basophilic
hepatocellular changes in rats in the NCI study was absent from these assessments. An
8-week subchronic dose-finding study by NCI also showed no apparent changes in
body weights, mortality, feed consumption or gross abnormalities in mice or rats (n =
5/sex/dose) at dietary concentrations up to 3% (dose conversion equivalents are 2 500
mg/kg-bw per day in rats and 3 900 mg/kg-bw per day in mice).
In a chronic oral study in which groups of 50 Sprague-Dawley rats or NMRI mice of
each sex were administered PY83 (< 0.5 ppm 3.3′-DCB and < 20 ppm acetoacetanilide
derivatives) or PY12 (< 20 ppm 3,3′-DCB, < 20 ppm acetoacetanilide derivatives and <
0.005% 2,5-dimethoxy-4-chloroaniline) in the diet at doses of 0, 68, 205 or 630 mg/kgbw per day in rats and 0, 215, 650 or 1 960 mg/kg-bw per day in mice for 104 weeks.
No evidence of a significant correlation between exposure and tumour incidence was
found. Feed consumption and water consumption were within the normal range for the
strains used, and data analyses showed no exposure-related statistically significant
increase in mortality rate for either male or female rats and mice. The study authors
reported that gross examinations of the surviving animals at week 104 showed no
pathological conditions that were unusual or that could be related to the exposure.
Subsequent histological examinations did not provide evidence for any cellular changes
caused by the pigment exposures (Leuschner 1978). However it should be noted that
unlike the full study report by the NCI (1978), limited pathology results were shown in
the Leuchner study adding uncertainty when interpreting the study author’s conclusions.
Freiling (2001) reported no observed changes in reproductive parameters in rats
exposed to PY12 at 0, 50, 200 or 1 000 mg/kg-bw/day via gavage for 4 weeks (males)
or 6 to 7 weeks (females). The NOAEL for parental and reproductive toxicity was
greater than 1 000 mg/kg-bw per day, based on no exposure-related effects on
56
mortality, body weight or feed consumption in female rats in the study. All females,
including controls, showed diarrhea, feces discoloration was observed in all treated
females, while no exposure-related organ weight changes or histopathological effects
were observed in male and female parents (Frieling 2001). Some “staining” of parents
and pups was reported for this study, but the significance of this finding is unknown
(refer to Absorption Potential section).
In a 21-day inhalation study, groups of 10 male and 10 female RAI fSPF rats were
exposed to dusts of PY13 (Ciba Geigy Corp. 1979). This study was designed to
generate a high proportion of respirable particles (80% < 7 µm) at concentrations of 0,
54, 157 and 410 mg/m3 for 6 hours per day, 5 days per week. In the treated rats from all
concentration level groups, yellowish or yellow discoloration of the lungs was seen at
autopsy. Slight increases in both absolute and relative weights of the lungs of both
sexes were reported, which showed a statistically significant difference from the control
group (trend from control to high dose P = 0.01, control versus high dose P = 0.05).
Accumulation of brown and yellow particles in the macrophages in the interstitium,
alveoli, bronchi and lymphatic tissues was reported for rats in all exposure groups and
appeared to be dose dependent. At the high dose, these observations were also
associated with pneumoconiosis, focal accumulation of foamy pneumocytes in the
alveoli and focal lymphohistiocytic infiltration. These effects were still noted in the highdose group following a recovery period. No systemic effects were reported at the
highest concentration tested. The study authors concluded that the no-observed-effect
concentration (NOEC) for this study was below the lowest tested concentration of 54
mg/m3. The lowest concentration of 54 mg/m3 was considered to be a lowest-observedeffect concentration (LOEC) for local effects in the lung in this study (OECD 2003a) and
is expected to be primarily due to the inhaled pigment particle rather than a sign of
chemical-specific toxicity of PY13 or its metabolites.
Several other oral studies also indicated no evidence of carcinogenicity and other noncancer effects from repeated-dose studies; however, these results were reported only
very briefly from secondary sources (ICI 1973; Colipa 1984; Anliker 1990) and are
therefore not considered as critical studies for informing the hazard profile of diarylide
yellow pigments in this assessment. However, a short-term 28 day gavage study in rats
using the analogue diarylide pigment PO16 also demonstrated low oral toxicity (JECDB
2013). With repeated doses of up to 1 000mg/kg per day in rats (5-10/sex/dose,
Crj:CD(SD)IGS strain), there were no exposure-related changes observed in survival,
organ weights, urine, hematologic parameters, or histopathology findings. This study
further supports the overall low oral toxicity of diarylide yellow pigments.
Modified Ames Assay and Other Genotoxicity Data
Positive results of an Ames assay under reductive conditions (i.e. incubation with
intestinal contents or Prival modification) are also considered as a line of evidence for
cleavage of azo bonding of the parent substance into one or more mutagenic
metabolites (i.e. 3,3’-DCB). Previous Ames tests conducted on PY12 and PY83 under
57
reductive conditions were negative for both substances (Prival et al. 1984; Reid et al.
1984; Kauffmann 2002). Recent Ames tests using reductive S9 with and without the
reducing agent flavin mononucleotide (FMN) on PY83 and PY176 at concentrations up
to 6 000 µg/plate were all negative (ILS 2011a, b). In addition, analogue 3,3′-DMOBbased diarylide pigments BPAOPB (previously evaluated in the Challenge) and PO16
were also not mutagenic in modified Ames assays (BF Goodrich Co. 1992; ILS 2011a).
Overall, the results from the mutagenicity testing under reductive conditions for diarylide
yellow pigments were negative. Given that the potential azo bond cleavage product 3,3′DCB,is genotoxic (NTP 1990; IARC 2010b), azo bond cleavage would be expected to
lead to a positive result in these modified Ames assays. Therefore, negative results
from modified Ames assays for the diarylide yellow pigments provide evidence that a
negligible azo bond cleavage did not allow for generation of 3,3′-DCB in amounts
sufficient to elicit a positive response in this assay.
The available data on other genotoxicity endpoints (other than Prival-modified Ames
assay) for the diarylide yellow pigments were negative overall. In an in vivo study with
PY13, groups of 3–6 female rats were administered PY13 (containing 0.02% soluble
monoazo substance) in the diet for four weeks; liver DNA adducts or Hb adducts were
either not detected or detected at levels only slightly above the detection limits. The low
level of adducts was considered to result from a small amount of the azo bond cleavage
metabolite, 3,3′-DCB, released from the contaminated soluble monoazo substance
(Sagelsdorff et al. 1996). While some individual genotoxicity assays showed some
positive or mixed results (Møller et al. 1998; NTP 2006a, b), the overall weight of
evidence of in vitro genotoxicity studies, including Ames tests under standard
conditions, chromosomal aberrations and sister chromatid exchange, was negative for
these diarylide yellow pigments (refer to references in OECD 2003a). Ambiguous
results were observed in a mouse lymphoma assay, in which a positive response was
seen in one of three replicates with induced S9, but the positive result was not
confirmed in the following two replicates; overall, the US National Toxicology Program
considered this study to be negative (NTP 2006a, 2012 email from the US NTP to the
Existing Substances Risk Assessment Bureau, Health Canada, unreferenced). The
analogue 3,3’DMOB-based diarylide pigment PO16 was also shown to be negative in a
standard Ames assay and test for chromosome aberrations in vitro (JECDB 2013).
Other Health Effects
Diarylide yellow pigments are of very low acute toxicity to mammals, with the acute oral
median lethal dose (LD50) greater than 1 750 mg/kg-bw and acute dermal LD50 greater
than 3 000 mg/kg-bw, while the acute inhalation LC50 was reported to be 4 448 mg/m3
(OECD 2003a; US EPA 2010). The substances may be slightly irritating to the skin and
eyes (BIBRA 1996a, b; European Commission 2000a, b, c; OECD 2003a; US EPA
2010). There was no indication of sensitizing potential for PY12, PY13 and PY83 in
guinea pigs and humans reported in several studies (Thierbach et al. 1992; BIBRA
1996a, b; OECD 2003a; US EPA 2010); however, sensitizing effects of PY12 were
58
observed in humans and guinea pig patch tests and have also been reported in a case
study (Sugai et al. 1977; Lovell and Peachey 1981; European Commission 2000b).
Other Supporting Data
The limited azo bond cleavage of diarylide yellow pigments has been suggested by
several authors to be primarily explained by the low solubility of these substances,
which makes them generally unavailable for biological azo bond cleavage (reviewed in
Golka et al. 2004). To investigate this hypothesis, Decad et al. (1983) showed that
“somewhat solubilized” PY12 (by addition of a sulfonate group on the benzene ring of
each of the acetoacetanilide coupling components) was not appreciably absorbed in
rats exposed orally, with only 0.02% of the applied radiolabelled dose detected in the
urine and the rest of the dose excreted in the feces, presumably as unchanged PY12. In
the same study, another 3,3′-DCB-based disazo non-diarylide type pigment, chlorodiane
blue 6 (CAS RN 41709-76-6), had also been similarly “solubilized” with a sulfonate group
added to the naphthol AS coupling component. Whereas both sulfonated 3,3′-DCBbased colourants were soluble in distilled water, neither was soluble in physiological
saline, and both precipitated in the stomach of dosed rats. However, sulfonated
chlorodiane blue showed approximately 200 times greater absorption with radiolabelled
3,3′-DCB or metabolites detected 1 day after dosing in blood (0.2%), liver (1.4%) and
urine (2.6%); approximately half the radiolabel detected in urine was 3,3′-DCB acetate
and glucuronide conjugates, suggesting azo bond cleavage in the GIT to release
[14C]3,3′-DCB, which was subsequently absorbed and metabolized (Decad et al. 1983).
The explanation for the significantly lower relative amount of azo bond cleavage
observed for sulfonated PY12 than for sulfonated chlorodiane blue is unclear, although
it is possible that sulfonated PY12 was still relatively less soluble (no additional
information was provided in this study).
Further support for the inluence of solubility on azo bond cleavage comes from studies
using chemical reduction with sodium dithionite conducted by ETAD (2008), which
demonstrated that all tested diarylide yellow pigments (including PY12, PY13, PY17,
PY83, PY176 and PO16) did not release any benzidine derivatives or other aromatic
amines examined at levels greater than 30 ppm. However, in this report, there were two
monoazo pigments and one disazo 3,3′-DCB-based pyrazolone pigment, which did
release aromatic amines at levels above 30 ppm. The study authors acknowledged that
“some azo pigments are sufficiently soluble under the analytical test conditions to yield
Chlorodiane blue is based on 3,3′-DCB fragment disazo coupled to naphthol AS derivatives rather than
acetoacetanilide and is therefore not a diarylide yellow pigment.
6
59
detectable amounts of a listed amine” (ETAD 2008). In a recent survey of tattoo inks in
Denmark (Danish EPA 2012) containing diarylide yellow pigments as a product label
ingredient, the levels of measured 3,3′-DCB, while measurable in some cases, were not
dramatically different before or following chemical azo reduction, suggesting that a
limited amount is released from these substances under the test conditions. However, a
recent study reported some instances of 3,3’-DCB released at levels of 34 to 36 ppm
following azo cleavage of a tattoo ink containing PY13 (Hauri 2013). This information
demonstrates that even low-solubility azo pigments can potentially release aromatic
amines by reduction of the azo bond, although the release may be quite limited (Platzek
2010). Based on this premise, and given the large range of solubility observed for
different structural classes of aromatic azo and benzidine-based substances, including
within the azo pigment subgroup, a broad range of azo bond cleavage potentials would
be expected, with diarylide yellow pigments placed near the very low end of the range
as per their relative lower solubility compared with other azo substances.
Other authors suggest a structural basis for the negligible azo bond cleavage of
diarylide yellow pigments and aromatic azo and benzidine-based substances, with βdiketone coupling, due to azo-hydrazone tautomerism, playing a role (US EPA 1979; De
France et al. 1986; Brown and DeVito 1993). De France et al. (1986) demonstrated that
benzidine and several benzidine derivatives (3,3′-DCB, 3,3′-DMOB), which were disazo
coupled to diethyl malonate (a β-diketone), were not azo reduced following in vitro
incubation with hamster liver S9 and FMN, nor were they mutagenic in the Privalmodified Ames assay, indicating no release of the mutagenic benzidine derivatives.
These synthesized hydrazone substances were not water soluble. However, unlike
diarylide yellow pigments, they were readily soluble in organic solvents, including the
dimethyl sulfoxide vehicle used in these studies, thereby excluding the possibility of the
substances not being available in solution. Nuclear magnetic resonance spectroscopy
of these synthesized diethyl malonate benzidine-based substances verified that only the
hydrazone tautomer was observed, while the azo tautomer was not detected (De
France et al. 1986). The diarylide yellow pigments are also predominantly in the
hydrazone tautomeric form, due to similar hydrogen bonding with the acetoacetanilide
coupling components (Barrow et al. 2000, 2002, 2003). De France and colleagues
(1986) speculated that hydrazone tautomers stabilized by the acetoacetanilide coupling
components may contribute to the resistance of diarylide yellow pigments to undergo
azo bond cleavage. While structural features are known to impact the rate and degree
of azo bond cleavage in aromatic azo and benzidine-based substances in general
(Environment Canada and Health Canada 2013), their significance for the diarylide
yellow pigments is currently unclear.
Other information on azo bond cleavage and metabolism of diarylide yellow pigments
comes from the empirical data on bacterial degradation in the environment and overall
suggests that the diarylide yellow pigments are not likely to be biodegraded or are
biodegraded at a very slow rate (refer to Ecological Effects Assessment section).
60
7.3 Human Health Risk Characterization
The available information indicates that azo bond cleavage following exposure to
diarylide yellow pigments is unlikely and does not identify a genotoxicity or carcinogenity
concern for these substances. Overall, it is expected that the five diarylide yellow
pigments in this assessment, PY12, PY13, PY83, PY176 and CPAOBP, will pose a low
hazard potential from the dermal, inhalation and oral routes of exposure. The lowest
effect level from oral studies is based on observations of basophilic cytoplasm observed
in hepatocytes of male and female rats in a chronic dietary study using PY12 (LOEL of
1 250 mg/kg-bw/day, the lowest dose tested; NCI 1978). The toxicological significance
of the hepatocellular basophilic cytoplasm is uncertain in the context of the absence of
other effects observed in repeated-dose studies for these substances, and therefore this
effect is not considered to be adverse. In terms of the potential hazard from inhalation
exposure, increased lung weights and diarylide yellow pigment particle deposition in the
lungs were observed in an inhalation study in rats exposed to PY13 dusts (LOEC of 54
mg/m3, lowest concentration tested; Ciba Giegy Corp. 1979) for 21 days. It is uncertain
whether the increased lung weights were simply due to pigment deposition or
associated with the inflammatory immune responses observed at the highest
concentration tested in this study (410 mg/m3). Therefore, while the 54 mg/m3
concentration is considered a LOEC rather than a lowest-observed-adverse-effect
concentration (LOAEC) for this study, clear adverse inflammatory responses at higher
doses do indicate a potential inhalation hazard for these substances at elevated levels
of inhalation exposure. No repeated-dose dermal toxicity data were identified for these
substances, however dermal absorption of insoluble diarylide yellow pigment particles is
considered to be negligible, and therefore systemic exposure is not expected following
dermal applications.
In terms of risk characterization for the oral route of exposure, as a conservative
approach, the LOEL of 1 250 mg/kg-bw per day (lowest dose tested) for changes in
hepatocytes (basophilic cytoplasm, NCI 1978) was compared to daily oral exposure
estimates to lipstick (3.4×10−4 mg/kg-bw per day), resulting in margins of exposure of
more than 3 million which is considered adequate to address uncertainties in the health
effects and exposure databases. For other scenarios that could result in repeated, but
intermittent exposure in early childhood (finger painting and mouthing a painted object),
the levels of exposure combined with the low hazard nature of these substances
indicates a low concern for human health.
For the risk from inhalation exposure scenarios, a LOEC of 54 mg/m3 (lowest
concentration tested) has been selected as the critical effect level based on increased
lung weights and deposition of particles in pulmonary tissues reported in a short-term
(21 day) inhalation study in rats (Ciba Geigy Corp. 1979). This is considered a
conservative approach for risk characterization, as it is likely that the effect is due to the
pigment particle rather than a chemical-specific toxicity of the diarylide yellow pigment
and/or metabolites. Margins of exposure resulting from a comparison of this effect level
with mean event exposure estimates for inhalation for three consumer product
61
scenarios are presented in Table 7-3. Due to the conservative nature of both the hazard
and exposure estimates, as well as they fact that two of the exposure scenarios are
more acute in nature rather than repeated (hair dye and wall sprayer), the margins of
exposure, ranging from 360 to greater than 13 million, are considered adequate to
address uncertainties in the health effects and exposure databases.
As systemic exposure is not expected from the dermal route due to negligible dermal
absorption, the risk from dermal exposure to these substances would be low.
While an upper-bounding daily systemic exposure to tattoo pigments has been
presented in this assessment based on the available information (0.12 to 1.1 mg/kg-bw
per day, Appendix G), no specific health effects data were identified for the intradermal
exposure route with which to derive the associated MOEs. As the general lack of
observed effects for the diarylide pigments from oral studies are considered primarily
due to the limited absorption from this route, a comparison of the short-term tattoo
exposure estimate with the oral chronic effect level (i.e., LOEL of 1250 mg/kg-bw per
day) is considered not appropriate for tattoo exposure since systemic exposure is
expected to occur from the intradermal injection route.
Table 7-6. Margins of exposure for inhalation exposure scenarios
Short-term inhalation
Inhalation exposure estimates
MOE
effect level
LOEC of 54 mg/m3
4.1 × 10−. – 1.2 × 10−– mg/m3
0.5 × 106 to > 13 × 106
(temporary hair dye spray)
3
LOEC of 54 mg/m
6.1 × 10−. mg/m3
> 8 × 106
(hair spray)
3
LOEC of 54 mg/m
0.008–0.15 mg/m3
360 – 6 800
(airless wall sprayer)
Uncertainties with Human Health Risk Characterization
Uncertainty is recognized as to whether the limited observed absorption and health
effects in some studies were the result of impurities, such as residual 3,3′-DCB or
unidentified “soluble monoazo” substances, or the intact parent diarylide yellow pigment
in a discrete molecular form or as an insoluble pigment particle.
Exposure estimates presented in this Screening Assessment are based on conservative
assumptions. There is uncertainty pertaining to the specific types of paint products that
contain some of the diarylide yellow pigments presented in this report. As a result,
conservative inputs were selected in deriving exposure estimates. The exposure
estimate derived for finger paint is based on the range of reported weight fractions of
pigments in paint (IARC 2010) not specific to diarylide yellow pigments in finger paint.
Therefore uncertainty is recognized with the assumption that finger paints contain the
same range of diarylide yellow pigments evaluated in this Screening Assessment.
Although the exposure factors used in this assessment are comparable to those used
62
by US EPA (2008) and RIVM (2002), using a lower ingestion quantity was
recommended in more recent publication elsewhere (RIVM 2008). Considering these
factors, confidence is high that oral exposure estimated for younger population during
use of finger paints is a conservative estimate.
With respect to various routes of exposure to the diarylide yellow pigments, the limited
effects from oral studies observed are considered primarily due to the negligible
absorption from this route. While there were no dermal metabolism data, an available
dermal absorption study did not show any evidence of absorption of radio-labelled
PY12. Uncertainty is recognized around the dermal route of exposure in the absence of
dermal toxicity studies identified for these substances; however, low oral hazard
potential provides confidence that the potential dermal hazard would also be very low
given that absorption is considered negligible from both oral and dermal routes. In
addition, while low solubility may largely explain the low biological activity of these
substances in the studies identified, the contribution from other potential factors is not
well understood.
Information on tattoo exposure is limited, and high uncertainty is recognized in the
potential exposure from the particular diarylide yellow pigments used in tattoo inks. The
Danish EPA (2012) stated that regarding tattoo exposure, “the current knowledge is
considered as being insufficient for a valid quantitative exposure assessment”.
Accordingly, an estimate of long-term systemic exposure from certain azo pigments in
injected tattoo inks has not been derived.
63
8. Conclusion
Considering all available lines of evidence presented in this Screening Assessment,
there is low risk of harm to organisms and the broader integrity of the environment from
the five diarylide yellow pigments evaluated in this assessment. It is concluded that the
five diarylide pigments do not meet the criteria under paragraphs 64(a) or 64(b) of
CEPA 1999 as they are not entering the environment in a quantity or concentration or
under conditions that have or may have an immediate or long-term harmful effect on the
environment or its biological diversity or that constitute or may constitute a danger to the
environment on which life depends.
Based on the information presented in this Screening Assessment, it is concluded that
the diarylide yellow pigments evaluated in this assessment do not meet the criteria
under paragraph 64(c) of CEPA 1999, as they are not entering the environment in a
quantity or concentration or under conditions that constitute or may constitute a danger
in Canada to human life or health.
It is concluded that the five diarylide yellow pigments evaluated in this assessment do
not meet any of the criteria set out in section 64 of CEPA 1999.
64
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Appendices
Appendix A: Experimental Physical and Chemical Properties
Table A-1: Experimental Physical and
Temperature) of Diarylide Yellow Pigments
Chemical
Properties
(at
Normal
Chemical
name
PY12
PY12
PY12
Property
Value
Reference
Melting point (ºC)
Melting point (ºC)
Melting point (ºC)
Lide 2003
US EPA 2006
US EPA 2010
PY12
PY12
PY12
PY12
Melting point (ºC)
Particle size distribution: D50
(mass median diameter, µm)
3
Density (g/cm )
Water solubility (µg/L)
317
320
320°C. Decomposition starts at ~200°C
(i.e., measured melting point may not be
true melting point, but rather the final
decomposition temperature).
306°C. Decomposition starts at 310°C.
4.8
1.39
0.4
PY12
PY12
Water solubility (µg/L)
Solubility in n-octanol (µg/L)
ECHA 2012
ECHA
2012;
CPMA
2009,
2011
OECD 2003b
Anliker
and
Moser 1987
PY12
Solubility in n-octanol (µg/L)
PY12
Log (Soct/Sw) (dimensionless)
2.1
(calculated
from
equilibrium
concentrations in water and in octanol)
PY13
PY13
PY13
Melting point (ºC)
Melting point (ºC)
Melting point (ºC)
PY13
PY13
PY13
PY13
PY13
Particle size distribution: D50
(mass median diameter, µm)
3
Density (g/cm )
Water solubility (µg/L)
Water solubility (µg/L)
Water solubility (µg/L)
350
Decomposition starts at ~200°C
Decomposition starts at 330°C without
discernible melting
3
PY13
Solubility in n-octanol (µg/L)
< 20
PY13
Solubility in n-octanol (µg/L)
22
PY13
Log (Soct/Sw) (dimensionless)
PY13
Log (Soct/Sw) (dimensionless)
PY83
PY83
Melting point (ºC)
Melting point (ºC)
1.44 (calculated from equilibrium
concentrations in water and in octanol)
1.8
(calculated
from
equilibrium
concentrations in water and in octanol)
400
400°C. Decomposition starts at ~200°C
< 20
500. This value is significantly higher
than the values from other studies (e.g.,
ECHA 2012).
49
1.36
< 20
0.35
0.8
85
ECHA 2012
ECHA 2012
CPMA
2009,
2011
ECHA
2012;
CPMA
2009,
2011
US EPA 2006
US EPA 2010
ECHA 2012
ECHA 2012
ECHA 2012
Clariant 2003
ECHA 2012
CPMA
2009,
2011
Clariant 2003;
OECD 2003b
CPMA
2009,
2011
CPMA
2009,
2011
ECHA 2012
US EPA 2006
US EPA 2010
Chemical
name
Property
PY83
Melting point (ºC)
PY83
PY83
PY83
Particle size distribution: D50
(mass median diameter, µm)
3
Density (g/cm )
Water solubility (µg/L)
PY83
PY83
Water solubility (µg/L)
Water solubility (µg/L)
PY83
PY83
PY83
Solubility in n-octanol (µg/L)
Solubility in n-octanol (µg/L)
Solubility in n-octanol (µg/L)
PY83
Log (Soct/Sw) (dimensionless)
PY176
Melting point (ºC)
PY176
Particle size distribution: D50
(mass median diameter, µm)
Water solubility (µg/L)
3
Density (g/cm )
Solubility in n-octanol (µg/L)
Log (Soct/Sw) (dimensionless)
PY176
PY176
PY176
PY176
Value
Reference
(i.e., measured melting point may not be
true melting point, but rather the final
decomposition temperature).
Decomposition starts at 300°C without
discernible melting
2
1.50
< 20
8.1
8900 µg/L. Note: In the US EPA Test
Plan (US EPA 2006), this value is
reported as 8.9 mg/L. However, in the
screening-level hazard characterization
(US EPA 2010), this value is not
presented. Probably, it was a typo and
was meant to be 8.9 µg/L instead of 8.9
mg/L.
20
9.0
< 500
0.02 (calculated from equilibrium
concentrations in water and in octanol)
Decomposition starts at 305°C without
discernible melting
4
ECHA 2012
ECHA 2012
ECHA 2012
Clariant 2003;
OECD 2003b
ECHA 2012
US EPA 2006
Clariant 2003
CPMA 2011
Anliker
and
Moser 1987
ECHA 2012
ECHA 2012
ECHA 2012
2
1.26
41
1.3
(calculated
from
equilibrium
concentrations in water and in octanol)
360°C. Decomposition begins at ~200°C
(i.e., measured melting point may not be
true melting point, but rather the final
decomposition temperature).
Decomposition starts at 308°C without
discernible melting
3.5
ECHA 2012
ECHA 2012
ECHA 2012
ECHA 2012
0.8
ECHA 2012
Solubility in n-octanol (µg/L)
85
Clariant 2003
Solubility in n-octanol (µg/L)
3.0
CPMA 2011
Solubility in n-octanol (µg/L)
2.6
ECHA 2012
Log (Soct/Sw) (dimensionless)
0.5
PY14
(analogue)
Melting point (ºC)
PY14
(analogue)
PY14
(analogue)
PY14
(analogue)
PY14
(analogue)
PY14
(analogue)
PY14
(analogue)
PY14
Melting point (ºC)
Particle size distribution: D50
(mass median diameter, µm)
Water solubility (µg/L)
(calculated
86
from
equilibrium
US EPA 2006
ECHA 2012
ECHA 2012
ECHA 2012
Chemical
name
(analogue)
PY17
(analogue)
Property
PY17
(analogue)
PY17
(analogue)
PY17
(analogue)
PY17
(analogue)
PY55
(analogue)
PY55
(analogue)
PY55
(analogue)
PY55
(analogue)
PY55
(analogue)
PY152
(analogue)
PY152
(analogue)
PY152
(analogue)
PY152
(analogue)
PY152
(analogue)
Particle size distribution: D50
(mass median diameter, µm)
Water solubility (µg/L)
Melting point (ºC)
Value
concentrations in water and in octanol)
323ºC. Decomposition starts from the
melting substance; the (exothermal)
decomposition reaction shows an onset
at 325°C (taken as decomposition
temperature).
4.2
Reference
ECHA 2012
ECHA 2012
2.6
ECHA 2012
Solubility in n-octanol (µg/L)
6.8
ECHA 2012
Log (Soct/Sw) (dimensionless)
0.4
(calculated
from
equilibrium
concentrations in water and in octanol)
Decomposition starts at 339°C without
discernible melting
8.5
ECHA 2012
5.2
ECHA 2012
Solubility in n-octanol (µg/L)
72
ECHA 2012
Log (Soct/Sw) (dimensionless)
1.1
(calculated
from
equilibrium
concentrations in water and in octanol)
310°C
with
a
decomposition
temperature of 315°C
2.1
ECHA 2012
10.6
ECHA 2012
Solubility in n-octanol (µg/L)
140
ECHA 2012
Log (Soct/Sw) (dimensionless)
1.1
(calculated
from
equilibrium
concentrations in water and in octanol)
ECHA 2012
Melting point (ºC)
Particle size distribution: D50
(mass median diameter, µm)
Water solubility (µg/L)
Melting point (ºC)
Particle size distribution: D50
(mass median diameter, µm)
Water solubility (µg/L)
87
ECHA 2012
ECHA 2012
ECHA 2012
ECHA 2012
Appendix B: Experimental Data on Biodegradation
Table B-1: Experimental Data on Biodegradation of Diarylide Yellow Pigments
Chemical
name
Biodegradation
(%)
PY12
0
Test
duration
(days)
14
PY12
81
15
PY13
28
PY83
Not readily
biodegradable
6
PY83
65
15
PY83
83
15
PY14
(analogue)
Group
submission for
diarylide
yellow
1
pigments
Group
submission for
diarylide
yellow
1
pigments
2; 4
28
1
28
16
28
28
Reference
Details
Ready biodegradation.
Inherent
biodegradation.
Multicomponent final product (not pure
pigment) was tested.
Ready biodegradation. No quantitative
results are available
Ready biodegradation.
Inherent
biodegradation.
40%
formulation (not a pure pigment) was
tested. 20% of elimination of dissolved
organic carbon occurred due to
adsorption on activated sludge, not due
to biodegradation.
Inherent
biodegradation.
52%
formulation (i.e., not a pure pigment)
was tested. 50% of elimination of
dissolved organic carbon occurred due
to adsorption on activated sludge, not
due to biodegradation.
Ready
biodegradation.
2%
biodegradation by BOD, 4% by weight.
Key study on ready biodegradability. It
is impossible to reliably identify which
diarylide pigments were tested.
Key study on ready biodegradability.
Only 70% of the total carbon in the
tested product is contained in the
pigment. Assuming that the pigment
component was stable, the observed
BOD of 16% indicates that, besides
carbon
assimilation
by
the
microorganisms, 53% of the additives
were mineralized during the test. The
HPLC analysis of the pigment and
three possible degradation products
indicated stability of the pigment during
the test.
J-CHECK
2012
European
Commission
©2000b
US EPA 2010
J-CHECK
2012
European
Commission
©2000a
European
Commission
©2000a
J-CHECK
2012
ECHA 2012
ECHA 2012
Abbreviations: BOD, biological oxygen demand; HPLC, high-performance liquid chromatography
1
Submission for a group of diaryl yellow pigments from ECHA 2012 includes experimental data on pigments PY12,
PY13, PY83, PY176, and PY14.
88
Appendix C: Empirical Data for Aquatic Ecotoxicity
Table C-1: Empirical Data for the Aquatic Ecotoxicity of Diarylide Yellow Pigments
Chemical
name
PY12
Test
type
Acute
Organism
Endpoint, value
Zebrafish
(Brachydanio rerio)
LC50 = 14.8 mg/L;
(48 h)
PY12
Acute
LC100 = 22 mg/L
Zebrafish
(Brachydanio rerio)
Reference
~55% and ~63%
formulations; TWEEN
80
(polyethylene
sorbitol ester) added
European
Commission
©2000b
European
Commission
©2000b
PY12
Acute
Ide (Leuciscus idus)
LC50 > 500 mg/L
~55% and ~63%
formulations; TWEEN
80
(polyethylene
sorbitol ester) added
~55% and ~63%
formulations; TWEEN
80
(polyethylene
sorbitol ester) added
~55% and ~63%
formulations; TWEEN
80
(polyethylene
sorbitol ester) added
35% solution in water
PY12
(48 h)
Acute
Ide (Leuciscus idus)
LC50 > 1000 mg/L
35% solution in water
Ide (Leuciscus idus)
LC50
mg/L
81%
formulation;
acetone added
Ide (Leuciscus idus)
LC50 > 500 mg/L
35% solution in water
European
Commission
©2000b
Water flea (Daphnia
magna)
EC50 > 100 mg/L
Effects:
immobilization;
substance
purity:
98%
US
2006
Alga (Selenastrum
capricornutum)
NOEC > 100 mg/L
CPMA 2009
Medaka
latipes)
LC50 > 420 mg/L
MITI 1992
(48 h)
PY12
Acute
LC100 = 22 mg/L
Zebrafish
(Brachydanio rerio)
(48 h)
PY12
Acute
LC50 = 5–10 mg/L;
Details
LC50 = 7.1 mg/L;
LC100 = 10 mg/L
Zebrafish
(Brachydanio rerio)
(48 h)
LC50 = 10–22 mg/L;
LC100 = 22 mg/L
(48 h)
PY12
=
10–100
Acute
European
Commission
©2000b
European
Commission
©2000b
European
Commission
©2000b
European
Commission
©2000b
European
Commission
©2000b
(96 h)
PY12
Acute
(96 h)
PY12
Acute
(72 h)
PY12
Acute
PY12
(72 h)
Acute
(Oryzias
89
EPA
Chemical
name
PY13
Test
type
(48 h)
Chronic
Organism
Endpoint, value
Water flea (Daphnia
magna)
NOEC = 1 mg/L
Zebrafish
(Brachydanio rerio)
LC50 > 100 mg/L
Alga
(Selenastrum
capricornutum)
Rainbow
trout
(Salmo
gairdneri;
new
name
Oncorhynchus
mykiss)
Effects:
immobilization,
reproduction;
substance
purity:
99.7%
Substance
purity:
94.5%
US
2006
EPA
US
2006
EPA
EC50 = 190 mg/L
Substance
94.5%
US
2006
EPA
LC50 = 18 mg/L;
LC50 = 45 mg/L;
LC50 = 80 mg/L;
Aqueous
ethylene
glycol
preparation
(conc. of ethylene
glycol not reported)
Hamburger
et al. 1977
Aqueous
ethylene
glycol
preparation
(conc. of ethylene
glycol not reported)
Hamburger
et al. 1977
Aqueous
ethylene
glycol
preparation
(conc. of ethylene
glycol not reported)
Effects: growth curve
(biomass) and growth
rate; filtered solution
(visually
clear)
prepared at a loading
of 100 mg/L of the
substance
Effects:
growth
inhibition, growth rate
reduction;
filtered
solution
(visually
clear and colourless)
was prepared at a
loading of 100 mg/L
of the substance
Effects:
immobilization;
a
filtered solution was
prepared at a loading
of 100 mg/L of the
substance
Hamburger
et al. 1977
(21
days)
PY83
Acute
PY83
(96 h)
Acute
(72 h)
PY83
Acute
(48 h)
PY83
PY83
Acute
Golden orfe
(48 h)
(Leuciscus idus)
Acute
Common
(Phoxinus
phoxinus)
(48 h)
Group
submission
for diarylide
yellow
1
pigments
Acute
Group
submission
for diarylide
yellow
1
pigments
Acute
Group
submission
for diarylide
yellow
1
pigments
Acute
(72 h)
(72 h)
minnow
Reference
Details
purity:
LC100 = 100 g/L;
LC100 = 200 mg/L
LC50 = 45 mg/L;
LC50 = 70 mg/L;
LC50 = 75 mg/L;
LC100 = 100 mg/L
LC50 = 45 mg/L;
LC100 = 100 mg/L
Alga
(Desmodesmus
subspicatus)
NOEC = 100 mg/L
Alga (Selenastrum
capricornutum; new
name
Pseudokirchneriella
subcapitata)
NOEC = 100 mg/L
Water flea (Daphnia
magna)
NOEC = 100 mg/L
(48 h)
90
ECHA 2012
ECHA 2012
ECHA 2012
Chemical
name
Group
submission
for diarylide
yellow
1
pigments
Test
type
Acute
Group
submission
for diarylide
yellow
1
pigments
Chronic
Group
submission
for diarylide
yellow
1
pigments
Acute
Organism
Endpoint, value
Water flea (Daphnia
magna)
EC50 > 1000 mg/L
Water flea (Daphnia
magna)
NOEC = 10 mg/L
Rainbow
trout
(Oncorhynchus
mykiss)
LC50 = 124 mg/L
(24
h;
48 h)
(21
days)
(96 h)
Details
Effects:
immobilization;
the
test item is 39.6%
aqueous dispersion
of the substance, so
the results based on
the content of the
substance would be
EC50 > 396 mg/L
Effects: reproduction,
mortality,
body
weight, length, etc.; a
solution (10 mg/L test
item) was prepared
with dilution water by
shaking at 20 rpm for
48 h; undissolved
particles
were
removed (10 min
centrifugation
at
10000 rpm)
The
test
item
contained
39.6%
substance, so the
effect concentration
of 124 mg/L with
regard
to
the
substance is 49 mg/L;
suspension
of
a
nominal
concentration
far
above the solubility
limit
had
been
prepared, and the
study
summary
contains
the
statement that the
results of the study
are not reliable
Reference
ECHA 2012
ECHA 2012
ECHA 2012
Abbreviations: EC50, effective concentration for 50% of test organisms; LCx, lethal concentration for x% of test
organisms; NOEC, no-observed-effect concentration; rpm, revolutions per minute
1
Submission for a group of diaryl yellow pigments from ECHA 2012 includes experimental data on pigments PY12,
PY13, PY83, PY176, and PY14.
91
Appendix D: Exposures from Deinking Operations
Aquatic Exposure Calculations for Deinking Operations
In total, 15 facilities were identified as performing recycled paper deinking operations
from the Pulp and Paper Canada Directory (Macdonald 2013), the Lockwood-Post
Directory (Dyer 2001; Jones2011) and FisherSolve (2012). Out of this total, six facilities
are found to have sufficient information for aquatic exposure calculations. The six
facilities are judged to be a good representation of the Canadian deinking sector.
The aquatic PEC is estimated for each of the six facilities. These facilities generate and
treat their respective wastewater on site and subsequently discharge directly to
receiving water. The aquatic PEC for each facility is estimated based on the quantity of
the diarylide yellow pigments entering the facility, the emission factor to wastewater, the
wastewater volume, the removal efficiency of the on-site wastewater treatment and the
dilution of the receiving water.
The aquatic PEC values for the six facilities vary within 0.2-28.5 μg/L. These PECs are
considered conservative, since the total quantity of the diarylide yellow pigments used
for paper printing is assumed to be 500 000 kg/year, and this quantity is higher than the
quantity reported to the 2006 and 2010 section 71 surveys.
A detailed explanation of the aquatic PEC calculations for the diarylide yellow pigments
using the site in Alma, Quebec, as an example follows.
1. Total quantity of diarylide yellow pigments
The total quantity of the diarylide yellow pigments imported to and manufactured in
Canada is less than 500 000 kg/year for use as ink, toner and colorants based on
the 2006 and 2010 section 71 surveys. This quantity is assumed to end up in paper
products.
2. Quantity of disposed paper
In Canada, in 2010, the paper recycling rate reached 69%, or 0.69 (Christine Burow
Consulting 2011), which is 4 170 000 tonnes (2012 email from Christine Burow
Consulting, unreferenced). These figures translate into 6 043 000 tonnes of waste
paper products generated in 2010 in Canada:
Quantity of waste paper generated: 4,170,000 tonnes/69% ≈ 6,043,000 tonnes
3. Average pigment content
92
The average content of the diarylide yellow pigments in printed paper products can
therefore be estimated by dividing the total quantity of the pigments (500 000
kg/year) by the quantity of waste paper products (6 043 000 tonnes/year).
Average content of diarylide yellow pigments in paper:
0.0827 kg/t
500,000/6,043,000 t/yr =
4. Annual pigment input
This average content can be used to estimate the amount of the pigments entering a
given deinking facility based on its deinking capacity. For example, the deinking
capacity at Alma, Quebec, was 35 700 tonnes/year [see Lockwood-Post’s Directory
of Pulp & Paper Mills (Dyer 2001 and Jones et al 2011)]. The annual input of the
pigments into the facility is then estimated as:
Annual input of diarylide yellow pigments: 0.0827 kg/tonne × 35 700 tonnes/year =
2952 kg/year
5. Daily pigment input
In general, deinking facilities operate 350 days/year on a continuous basis. On the
basis of this operation, the daily input of the pigments into the facility in Alma,
Quebec, can be estimated as:
Daily input of diarylide yellow pigments: 2,952 kg/yr/350 day/yr = 8.44 kg/day
6. Emission factor to wastewater
An experimental study by Körkkö et al. (2008) showed that the ink removal using a
flotation process was in the range of 65–94%. Air flotation is commonly used for
deinking in recycled paper mills. The waste paper tested in the study consisted of
50% newspapers and 50% magazines. The composition of this waste paper is
assumed to be representative of the recycled paper processed by the Canadian
deinking sector. The ink removal determined in the study refers to the fraction of the
ink in feed that was collected in the flotation froth (reject). The reject is typically
disposed of as a solid waste. Based on the range of 65–94% given in the study, an
average ink removal rate is estimated as 80%. The reason for using an average is
because varying deinking operations are used for different paper types across the
deinking sector, and an average is judged to be statistically representative of these
variations and differences. Since the remaining 20% remains in water and pulp, the
maximum fraction entering wastewater would be 20%. This maximum is used as a
conservative estimate for the emission factor to wastewater.
93
Therefore, the emission factor to wastewater: 20%
7. Daily pigment release to raw wastewater
The daily quantity of the diarylide yellow pigments emitted to raw wastewater at the
facility in Alma, Quebec, is estimated based on the emission factor to wastewater
(20%, or 0.2) and the daily input quantity into the facility (8.44 kg/day).
Daily emission of pigments to raw wastewater: 8.44 kg/day × 0.2 = 1.69 kg/day =
1.69 × 109 µg/day
8. Water use rate
To estimate the concentrations of the diarylide yellow pigments in raw and treated
wastewater, the daily wastewater generation volume is required and can be
estimated based on the per tonne water use rate, the per tonne water evaporation
rate and the total pulp production.
The per tonne water use rate is derived from the water use volume and the total pulp
production found in the Lockwood-Post Directory of the Pulp, Paper and Allied
Trades (2002) book. For the same facility, which was then owned by AbitibiConsolidated Inc. instead of the more recent company AbiBow Canada Inc., the
daily water use volume was 7 570 000 L/day, and the total daily pulp capacity was
800 tonnes/day. The per tonne water use rate is then determined as:
Water use rate: 7,570,000 L/d/800 t/d = 9,643 L/t
This water use rate is in line with the range of 8000–16 000 L/tonne provided in the
OECD emission scenario document on pulp and paper (OECD 2009a, p. 48) for
deinking facilities.
9. Water evaporation rate
Water is lost to air via evaporation when pulp is dried via paper machines to produce
paper. The per tonne water evaporation rate is relatively constant at 1500 L/tonne
regardless of the type (deinked or virgin) of pulp (European Commission 2001).
Therefore,
Water evaporation rate: 1500 L/tonne
10. Wastewater generation rate
The wastewater generation rate can then be determined as the difference between
the per tonne water use rate and the per tonne water evaporation rate. For the
facility in Alma, Quebec, this parameter is given as
94
Wastewater generation rate: 9463 L/tonne − 1500 L/tonne = 7963 L/tonne
11. Total pulp production
The total pulp production at a given facility includes all pulp types and can therefore
be more than the production of deinked pulp only. These total production data can
be found in Lockwood-Post Directory of Pulp & Paper Mills (Dyer 2001 and Jones et
al 2011). For example, the total daily pulp production of the facility in Alma, Quebec,
was 993 tonnes/day (total annual pulp capacity at 347 500 tonnes/year divided by a
typical number of annual operation days at 350 days/year). This total capacity was
much higher than the deinked pulp capacity at 102 tonnes/day.
Total pulp production: 993 tonnes/day
12. Daily wastewater generation volume
The daily wastewater generation volume is determined by multiplying the
wastewater generation rate by the total pulp production. For the facility in Alma,
Quebec, this parameter is, therefore, calculated as:
Daily wastewater generation volume: 7963 L/tonne × 993 tonnes/day = 7 907 259
L/day
13. Pigment concentration in raw wastewater
The concentration of the diarylide yellow pigments in raw wastewater is estimated by
dividing the daily emission of pigments to wastewater by the daily wastewater
generation volume. For the facility in Alma, Quebec, this concentration can be
calculated as:
Concentration of pigments in raw wastewater: 1.69 kg/d x109 µg/kg/7,907,259 L/d =
214 µg/L
(where 109 μg/kg is a conversion factor).
14. Pigment concentration in treated wastewater
Pigments with water solubility under 1 mg/L are expected to be removed by 90% (or
0.9) via primary sludge (OECD 2009, p. 58). Since all the diarylide yellow pigments
have water solubility well below 1 mg/L and the wastewater generated from deinking
facilities in Canada is subject to at least primary treatment, the reduction in the
concentration of the diarylide yellow pigments would be even more than 90%
through the wastewater treatment.
95
For the facility in Alma, Quebec, the maximum concentration of the diarylide yellow
pigments in treated wastewater is estimated as:
Concentration of pigments in treated wastewater: 214 µg/L × (1−0.9) = 21.4 µg/L
15. Pigment concentration in receiving water
The receiving water for the facility in Alma, Quebec, is Petite-Decharge River, and its
10th percentile flow rate is 950 400 000 L/day. The full dilution capacity of the
receiving water is estimated as the ratio of the 10th percentile flow to the daily
wastewater volume, i.e.:
Receiving water full dilution capacity: 950,400,000 L/d/7,907,625 L/d = 120
In estimating the concentration of a chemical in receiving water, an appropriate
dilution factor should be used to properly characterize the concentration near the
discharge point. For the purpose of this risk assessment, 10-fold dilution is chosen to
account for limited dilution near the discharge point when the full dilution capacity is
over 10. For the facility in Alma, Quebec, the concentration of the diarylide yellow
pigments in receiving water near the discharge point, or PEC, is therefore estimated
as:
PEC of benzidine-based pigments: 21.4 µg/L/10 ≈ 2.1 µg/L
16. Risk quotient (RQ)
The aquatic risk quotient of the diarylide yellow pigments is then determined by
dividing the PEC by the PNEC:
Aquatic RQ = PEC/PNEC = 2.1 µg/L/180 µg/L = 0.012
Sediment Exposure Calculations for Deinking Operations
The European Chemicals Agency (ECHA 2010, p. 64) suggests using the concentration
of a substance in freshly deposited sediment to evaluate its risk to sediment-dwelling
organisms. This suggested approach implies that the concentration in suspended
sediment instead of bottom sediment should be used in exposure and risk quotient
calculations. This approach is used below in estimating the concentration of the
diarylide yellow pigments in sediment.
The concentration of the diarylide yellow pigments in suspended sediment or the
sediment PEC is estimated based on equilibrium partitioning between the aqueous
96
phase and suspended sediment. At equilibrium partitioning, the sediment PEC can
linearly correlate with the concentration in the aqueous phase as follows (Gobas 2007):
Sediment PEC = Ksw × Cw
where Ksw (L/kg) is the sediment–water partition coefficient and Cw (mg/L) is the
chemical concentration in the aqueous phase.
The aquatic PEC is normally higher than the chemical concentration in the aqueous
phase (Cw) and can therefore be used as a conservative estimate for Cw. A conservative
sediment PEC can then be estimated from the equation
Sediment PEC = Ksw × PECaquatic
According to Gobas (2010), the sediment–water partition coefficient (Ksw, L/kg) can be
estimated from the organic carbon (OC) fraction of suspended sediment (Foc, kg
OC/kg), the sorptive capacity of suspended sediment’s organic carbon (Aoc, L/kg OC)
and the octanol–water partition coefficient of the diarylide yellow pigments (Kow,
dimensionless):
Ksw = Foc × Aoc × Kow
Gobas (2010) suggested a value of 0.1 kg OC/kg for the OC fraction of suspended
sediment (i.e., Foc = 0.1 kg OC/kg). Karickhoff (1981) proposed a value of 0.41 L/kg OC
for the sorptive capacity of suspended sediment OC based on a set of 17 sediment and
soil samples and various hydrophobic non-polar organic compounds. The log (Soct/Sw)
value, representing octanol–water partition coefficient for diarylide yellow pigments (as
described in the Physical and Chemical Properties section), varies within 0.4–2.1 (see
Table 5). The higher-end value of this range (log (Soct/Sw) of 2.1, i.e., Soct/Sw of 126) is
selected in order to derive a conservative sediment PEC. Based on these values, the
sediment–water partition coefficient is estimated as:
Ksw = Foc × Aoc × Soct/Sw = 0.1 kg OC/kg × 0.41 L/kg OC × 126 = 5.2 L/kg
As indicated in Ecological Exposure Assessment section, the highest aquatic PEC for
the deinking sector is 28.5 µg/L. This value is used to derive the highest conservative
sediment PEC:
Sediment PEC = Ksw × PECaquatic = 5.2 L/kg × 28.5 µg/L = 148 µg/kg ≈ 0.15
mg/kg
The sediment risk quotient can therefore be calculated by dividing this PEC by the
PNEC of 100 mg/kg:
Sediment RQ = PEC/PNEC = 0.15 mg/kg/100 mg/kg = 0.0015
97
Soil Exposure Calculations for Deinking Operations
The exposure to the diarylide yellow pigments in soil is estimated under a conservative
scenario, i.e., assuming that the pigment-containing biosolids generated from the
deinking sector are applied on agricultural land at the maximum allowable rate of 4.4
tonnes/ha (Crechem 2005) over a substantial number of years (i.e., 10 years), and also
assuming that the pigments are accumulated in soil and do not incur any degradation,
volatilization, soil runoff or leaching losses. This conservative scenario yields a soil PEC
of 6.8 mg/kg and, therefore, a risk quotient of approximately 0.07 when compared with a
PNEC of 100 mg/kg. Detailed calculations are presented below.
1. Total annual quantity of diarylide yellow pigments
The total annual quantity of the diarylide yellow pigments imported to and
manufactured in Canada is less than 500 000 kg/year for use as ink, toner and
colorant based on the 2006 and 2010 section 71 surveys.
Total annual quantity of diarylide yellow pigments: 500 000 kg/year
2. Quantity of diarylide yellow pigments in recycled paper
According to the Pulp and Paper Products Council, in Canada, the paper recycling
rate in 2010 was 69% (Christine Burow Consulting 2011). Based on this rate, the
quantity of the diarylide yellow pigments in recycled paper can be estimated:
Quantity of pigments in recycled paper: 500 000 kg/year × 0.69 = 345 000 kg/year
3. Quantity of diarylide yellow pigments in biosolids
As a conservative estimate, it is assumed that the entire quantity of the diarylide
yellow pigments in recycled paper ends up in biosolids.
Quantity of diarylide yellow pigments in biosolids: 345 000 kg/year
4. Fraction of deinked pulp in total pulp
The deinking sector processes two types of pulp: recycled pulp and virgin pulp. For
these two types of pulp, the deinking and total pulp capacities of the seven deinking
facilities evaluated for aquatic PECs (see Lockwood-Post Directory of Pulp and
Paper Mills 2011) are found to be 1 081 300 tonnes/year and 2 357 100 tonnes/year,
98
respectively. The fraction of deinked pulp in total pulp for the Canadian deinking
sector is thus estimated as:
Fraction of deinked pulp in total pulp: 1,081,300 t/yr/2,357,100 t/yr = 0.45 (or 45%)
5. Paper production from deinking sector
In 2010, the paper recycling rate in Canada reached 4 170 000 tonnes (2012 email
from Christine Burow Consulting, unreferenced). Since this rate represents 45% of
the total paper produced from the deinking sector, the latter can therefore be
estimated as:
Total paper production: 4,170,000 t/yr/45% = 9,267,000 t/yr
6. Sludge or biosolids quantity
The sludge can be generated from various sources, such as on-site wastewater
treatment and deinking operations. As a default value for assessment purposes, the
sludge generation rate is 10% (or 0.1) of the paper production (OECD 2009, p. 63).
The total annual quantity of sludge from deinking is then estimated as:
Total annual quantity of sludge: 9 267 000 tonnes/year × 0.1 = 926 700 tonnes/year
This sludge quantity is assumed to be equal to the biosolids quantity, i.e.:
Total annual quantity of biosolids = 926 700 tonnes/year
7. Concentration of diarylide yellow pigments in biosolids
The concentration of the diarylide yellow pigments in biosolids is estimated by
dividing the quantity of the pigments in biosolids by the total biosolids quantity:
Concentration of pigments in biosolids: 345,000 kg/yr/926,700 t/yr = 0.37 kg/t = 370
mg/kg
8. Land application rate
In Canada, the land application rate of biosolids from publicly-owned wastewater
systems is regulated by the provinces and territories. The allowable annual limits on
a dry weight basis are 1.6 tonnes/ha in Ontario, 3.4 tonnes/ha in British Columbia
and 4.4 tonnes/ha in Quebec (Crechem 2005). Considering that deinking mills are
mainly located in Ontario and Quebec, and assuming that these application rates are
applicable to biosolids generated from deinking activities, Quebec’s annual
99
application rate of 4.4 tonnes/ha would be an appropriate conservative rate for use
in the soil exposure assessment. Since 1 ha = 10 000 m2 and 1 tonne = 1000 kg, the
annual land application rate is:
Annual land application rate = 4.4 tonnes/ha = 0.44 kg/m2
9. Quantity of diarylide yellow pigments upon 10 years of biosolids application
The European Chemicals Agency (ECHA 2010, p. 73) suggests using 10
consecutive years as a length of accumulation in evaluating soil exposure resulting
from biosolids application. The quantity of the diarylide yellow pigments received per
square metre of the amended soil during this 10-year period would be:
Quantity of pigments per square metre of soil = biosolids application rate × 10 years
× concentration of pigments in biosolids = 0.44 kg/m2 per year × 10 years × 370
mg/kg = 1628 mg/m2
10. Mass of ploughing-layer soil per square metre
The European Chemicals Agency (ECHA 2010, p. 75) also suggests using 20 cm
(i.e., 0.2 m) as the ploughing depth in determining a mixing layer. Using a dry soil
density of 1200 kg/m3 (Williams 1999), the mass of the top 20 cm soil layer per
square metre is:
Mass of ploughing layer per square metre = 1200 kg/m3 × 1 m2 × 0.2 m = 240 kg
11. Soil PEC
The soil PEC is determined by dividing the quantity of the pigments upon 10-year
land application by the mass of ploughing-layer soil per square metre:
Soil PEC = 1,628 mg/m2/240 kg/m2 = 6.8 mg/kg
12. Risk quotient
The risk quotient is determined by dividing the PEC by the PNEC:
Soil RQ = PEC/PNEC = 6.8 mg/kg/ 100 mg/kg = 0.07
100
Appendix E: Upper-Bounding Estimates of Oral Exposure
Table E-1: Upper-bounding estimates of oral exposure from ingestion of lipstick
(adult)
Substance
PY83 (CAS RN 5567-15-7)
Assumptions/ (EF) Exposure frequency: 2.4/day (Loretz et al. 2005)
algorithm
(PA) Product amount: 0.01 g/application (Loretz et al. 2005)
(BW) Adult body weight (20–59 years): 70.9 kg-bw (Health Canada
1998)
(WF) Maximum weight fraction of PY83: 0.001 (personal
communication, email from the Consumer Products Safety Directorate
[Health Canada] to the Existing Substances Risk Assessment Bureau
[Health Canada], dated 2011; unreferenced)
Exposure estimate (per event)
= [(PA) × (WF)] ÷ [BW]
= [0.01 g × 0.001] ÷ [70.9 kg-bw]
= 0.14 µg/kg-bw per event
Amortized exposure estimate (daily)
= [External exposure estimate (per event)] × [EF]
= (0.14 µg/kg-bw) × (2.4/day)
Exposure
estimate
= 0.34 µg/kg-bw per day
Oral exposure estimate (daily): 0.34 µg/kg-bw per day
Table E-2: Upper-bounding estimates of oral exposure from ingestion of finger
paint (toddler)
Substances
PY12 (CAS RN 6358-85-6); PY13 (CAS RN 5102-83-0); PY83 (CAS
RN 5567-15-7); PY176 (CAS RN 90268-24-7)
101
Assumptions/
algorithm
(ED) Exposure duration: 45 min (Bremmer and van Veen 2002)
(IR) Ingestion rate: 30 mg/min (Bremmer and van Veen 2002)
(WF) Weight fraction of pigment: 0.01–0.03 (Delta Creative 2008)
(BW) Toddler body weight (0.5–4 years): 15.5 kg-bw (Health Canada
1998)
(EF) Exposure frequency: 0.27/day (i.e., 100/year; Bremmer and van
Veen 2002)
Exposure estimate (per event)
= [(ED) × (IR) × (WF)] ÷ [BW]
= [(45 min) × (30 mg/min) × (0.01–0.03)] ÷ [15.5 kg-bw]
= 0.87 - 2.6 mg/kg-bw per event
Amortized exposure estimate (daily)
= [External exposure estimate (per event)] × [EF]
= [0.87 - 2.6 mg/kg-bw] × (0.27/day)
= 0.24 - 0.7 mg/kg-bw per day
102
Appendix F: Upper-Bounding Estimates of Inhalation Exposure
Table F-1: Upper-bounding estimates of inhalation exposure from temporary hair
dye spray (children)
Substances
PY12 (CAS RN 6358-85-6); PY83 (CAS RN 5567-15-7)
Assumptions/ Child body weight (5–11 years): 31 kg-bw (Health Canada 1998)
algorithm
Exposure frequency: 0.016/day (i.e., 6/year; Bremmer et al. 2006)
Weight fraction of PY12: 0.001–0.003 (CNS 2011)
Weight fraction of PY83: 0.001–0.03 (CNS 2011)
Child inhalation rate (5–11 years): 14.5 m3/day (Health Canada
1998)
Temporary hair dye sprays may be particularly relevant to special
occasions such as sporting events, carnivals and children’s parties
(Bremmer et al. 2006). As children may be exposed to such
temporary hair dye sprays, a child body weight was assumed for this
exposure scenario.
ConsExpo v4.1, a consumer product exposure model developed by
the National Institute for Public Health and the Environment (RIVM) in
the Netherlands, was used to determine the inhalation and oral (nonrespirable) estimates of exposure to PY12 and PY83 in temporary
hair dye spray (ConsExpo 2006).
ConsExpo v4.1: “Exposure, spray model, spraying towards
exposed person”
Spray duration: 0.24 min (Bremmer et al. 2006)
Exposure duration: 5 min (Bremmer et al. 2006)
Room volume: 10 m3 (Bremmer et al. 2006)
Room height: 2.5 m (Bremmer et al. 2006)
Ventilation rate: 2/h (Bremmer et al. 2006)
Cloud volume: 0.0625 m3 (Bremmer et al. 2006)
Mean mass generation rate: 0.4 g/s (RIVM 2010)
Airborne fraction: 1 g/g (Bremmer et al. 2006)
Weight fraction non-volatile: 0.03 g/g (Bremmer et al. 2006)
Density non-volatile: 1.5 g/cm3 (Bremmer et al. 2006)
Initial particle distribution median diameter (C.V.): 35 µm (Bremmer et
al. 2006)
Inhalation cut-off diameter: 15 µm (Bremmer et al. 2006)
Inhalation exposure estimates for PY12:
Inhalation mean event concentration: 1.18 × 10−3 to 3.53 × 10−3
mg/m3
103
Inhalation mean concentration on day of exposure: 4.08 × 10−6 to 1.22
× 10−5 mg/m3
Oral exposure estimate (non-respirable fraction) for PY12:
Oral acute external dose: 5.78 × 10−4 to 1.74 × 10−3 mg/kg-bw
Inhalation exposure estimates for PY83:
Inhalation mean event concentration: 1.18 × 10−3 to 0.0353 mg/m3
Inhalation mean concentration on day of exposure: 4.08 × 10−6 to 1.22
× 10−4 mg/m3
Exposure
estimates
Oral exposure estimate (non-respirable fraction) for PY83:
Oral acute external dose: 5.78 × 10−4 to 0.0173 mg/kg-bw
Inhalation mean concentration of PY12 on day of exposure:
4.08 × 10−6 to 1.22 × 10−5 mg/m3
Inhalation mean concentration of PY83 on day of exposure:
4.08 × 10−6 to 1.22 × 10−4 mg/m3
Table F-2: Upper-bounding estimates of inhalation exposure from hair spray
(adult)
Substance
PY83 (CAS RN 5567-15-7)
Assumptions/ Adult body weight (20–59 years): 70.9 kg-bw (Health Canada 1998)
algorithm
Exposure frequency: 1.49/day (Loretz et al. 2006)
Maximum weight fraction of PY83: 0.001 (CNS 2011)
Adult inhalation rate (20–59 years): 16.2 m3/day (Health Canada
1998)
ConsExpo v4.1, a consumer product exposure model developed by
RIVM in the Netherlands, was used to determine the inhalation and
oral (non-respirable) estimates of exposure to PY83 in hair spray
(ConsExpo 2006).
ConsExpo v4.1: “Exposure, spray model, spraying towards
exposed person”
Spray duration: 0.24 min (Bremmer et al. 2006)
Exposure duration: 5 min (Bremmer et al. 2006)
Room volume: 10 m3 (Bremmer et al. 2006)
Room height: 2.5 m (Bremmer et al. 2006)
Ventilation rate: 2/h (Bremmer et al. 2006)
Cloud volume: 0.0625 m3 (Bremmer et al. 2006)
Mean mass generation rate: 0.4 g/s (RIVM 2010)
Airborne fraction: 1 g/g (Bremmer et al. 2006)
104
Weight fraction non-volatile: 0.03 g/g (Bremmer et al. 2006)
Density non-volatile: 1.5 g/cm3 (Bremmer et al. 2006)
Initial particle distribution median diameter (C.V.): 35 µm (Bremmer et
al. 2006)
Inhalation cut-off diameter: 15 µm (Bremmer et al. 2006)
Inhalation exposure estimates for PY83:
Inhalation mean event concentration: 1.18 × 10−3 mg/m3
Inhalation mean concentration on day of exposure: 6.08 × 10−6 mg/m3
Inhalation air concentration year average: 6.08 × 10−6 mg/m3 per day
Exposure
estimates
Oral exposure estimates (non-respirable fraction) for PY83:
Oral acute dose: 2.82 × 10−4 mg/kg-bw
Oral daily dose: 4.21 × 10−4 mg/kg-bw per day
Inhalation air concentration year average exposure: 6.08 × 10−6
mg/m3 per day
Oral chronic dose: 4.21 × 10−4 mg/kg-bw per day
Table F-3: Upper-bounding estimates of inhalation exposure from painting walls
using an airless sprayer (adult)
Substances
PY12 (CAS RN 6358-85-6); PY13 (CAS RN 5102-83-0); PY83 (CAS
RN 5567-15-7); PY176 (CAS RN 90268-24-7)
Assumptions/ (BW) Adult body weight (20–59 years): 70.9 kg-bw (Health Canada
algorithm
1998)
(EF) Exposure frequency: 0.0027/day (i.e., 1/year; Prud’homme de
Lodder et al. 2006)
(BZC) Breathing zone concentration of respirable paint aerosols: 5.14
mg/m3 (Reinhardt and Fendick 2004)
(WF) Weight fraction of pigment: 0.03–0.6 (IARC 2010a)
(FPR) Fraction of pigment remaining after use of particle filter: 0.05
Individuals applying paint through an airless sprayer were assumed to
use a respirator with particle filter, removing 95% of respirable paint
aerosol (PMRA 2000; 3M OHSD 2012). The use of appropriate
respiratory protection is recommended for any spray application of
paint.
Please note that the “inhalation mean event concentration” estimated
below is the air concentration of pigment in inspired air, after 95%
removal of respirable paint aerosol.
Inhalation mean event concentration
= [(BZC) × (WF) × (FPR)]
= [(5.14 mg/m3) × (0.03–0.6) × (0.05)]
105
Exposure
estimate
= 0.008–0.15 mg/m3
Inhalation mean event concentration: 0.008–0.15 mg/m3
106
Appendix G: Upper-Bounding Estimate of Short-Term Exposure from
Tattoo Ink
Table G-1: Upper-bounding estimate of short-term exposure from intra-dermal
injection of tattoo ink
Substances
PY12 (CAS RN 6358-85-6); PY83 (CAS RN 5567-15-7)
Assumptions/ Exposure factors were derived based on a study that examined the
loss of a monoazo tattoo pigment from mouse skin in vivo due to
algorithm
biological dissemination and photochemical decomposition (Engel
et al. 2009). While this study was specifically on Pigment Red 22
(PR22), a generic approach is taken as a conservative approach to
estimate short-term exposure to any pigments including PY12 and
PY83 in this assessment.
Exposure scenario
•
Route of exposure: Injection into the dermis
•
Average skin concentration: 2.53 mg pigment/cm2 ex vivo
human or pig skin (Engel et al. 2008; Danish EPA 2012)1
•
Realistic worst-case skin concentration: 9.42 mg
pigment/cm2 (Danish EPA 2012)
•
Skin area covered for average tattoo: 430 cm2 (Danish EPA
2012)
•
Skin area covered for realistic worst-case tattoo (i.e., whole
back): 1090 cm2 (Danish EPA 2012)
•
(AV) Amount of azo pigment in average tattoo potentially
available for absorption: 1.09 g (Danish EPA 2012)
•
(AW) Amount of azo pigment in realistic worst-case tattoo
potentially available for absorption: 10.3 g (Danish EPA 2012)
•
(BW) Adult body weight: 70.9 kg-bw (Health Canada 1998)
•
(FP) Fraction of intact pigment in dermis that is mobilized into
the lymphatic system: 32% over 42 days (Engel et al. 2009) 1
Exposure to pigment
= [(AV–AW) × (FP)] ÷ [(BW) × (Length of study)]
= [(1.09–10.3 g) × (0.32)] ÷ [(70.9 kg-bw) × (42 days)]
= 0.12–1.1 mg/kg-bw per day
Therefore, the short-term systemic daily exposure to PY12 and
PY83 in tattooed individuals is assumed to be 0.12 mg/kg-bw per
day on average and 1.1 mg/kg-bw per day as an upper-bounding
estimate.
1
In Engel et al. (2009), 19 hairless female SKH-1 mice, divided into
four groups, were tattooed on their dorsa with PR22. Exposure to
107
Exposure
estimate
normal ambient light for 32 days after 10 days of recovery following
the initial injection (total of 42 days) resulted in a 32% reduction of
PR22 in skin. The loss percentage was considered predominantly
attributable to biological dissemination of the tattoo pigment into the
lymphatic system. A separate group of mice exposed to simulated
solar radiation instead of normal ambient light resulted in a 60%
reduction in the initial skin pigment concentration. The fraction of
photodecomposed Pigment Red 22 that resulted in the formation of
aromatic amines is unknown for simulated solar radiation.
Therefore, this exposure scenario focuses on systemic exposures of
the intact pigment only.
0.12–1.1 mg/kg-bw per day
108
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