Screening Assessment - Synopsis

Aromatic Azo and Benzidine-based Substance Grouping
Certain Benzidine-based Dyes and Related Substances

Environment Canada
Health Canada
November 2014

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Table of Contents

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 on 9 Benzidine-based Acid Dyes, 24 Benzidine-based Direct Dyes, 2 Benzidine-based Cationic Indicators, 2 Benzidine-based Precursors and 5 Benzidine Derivatives. These 42 substances constitute 5 subgroups of the Aromatic Azo and Benzidine-based Substances 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)Footnote[1], Domestic Substances List (DSL) name, and Colour Index generic name or acronym of the 42 substances are presented in the following tables, by subgroup. 

Identity of the 9 Benzidine-based Acid Dyes in the Aromatic Azo and Benzidine-based Substance Grouping
CAS RNDSL nameColour Index  name or acronym
3701-40-42,7-Naphthalenedisulfonic acid, 4-hydroxy-3-[[4′-[(2-hydroxy-1-naphthalenyl)azo]-2,2′-dimethyl[1,1′-biphenyl]-4-yl]azo]Acid Red 99
6459-94-51,3-Naphthalenedisulfonic acid, 8-[[3,3′-dimethyl-4′-[[4-[[(4-methylphenyl)sulfonyl]oxy]phenyl]azo][1,1′-biphenyl]-4-yl]azo]-7-hydroxy-, disodium saltAcid Red 114
6470-20-8[1,1′-Biphenyl]-2,2′-disulfonic acid, 4-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-4′-[(2-hydroxy-1-naphthalenyl)azo]-, disodium saltAcid Orange 56
6548-30-71,3-Naphthalenedisulfonic acid, 8-[[3,3′-dimethoxy-4′-[[4-[[(4-methylphenyl)sulfonyl]oxy]phenyl]azo][1,1′-biphenyl]-4-yl]azo]-7-hydroxy-, disodium saltAcid Red 128
68318-35-42,7-Naphthalenedisulfonic acid, 4-amino-3-[[4′-[(2,4-dihydroxyphenyl)azo]-3,3′-dimethyl[1,1′-biphenyl]-4-yl]azo]-5-hydroxy-6-[(4-sulfophenyl)azo]-, trisodium saltAcid Black 209
68400-36-22,7-Naphthalenedisulfonic acid, 4-amino-5-hydroxy-6-[[4′-[(4-hydroxyphenyl)azo]-3,3′-dimethyl[1,1′-biphenyl]-4-yl]azo]-3-[(4-nitrophenyl)azo]-, disodium saltNAAHD
83221-63-02,7-Naphthalenedisulfonic acid, 4-amino-3-[[4′-[(2,4-diaminophenyl)azo]-2,2′-disulfo[1,1′-biphenyl]-4-yl]azo]-5-hydroxy-6-(phenylazo)-, sodium saltNAADD
89923-60-4Benzenesulfonic acid, 3,3′-[(2,2′-dimethyl[1,1′-biphenyl]-4,4′-diyl)bis[azo(4,5-dihydro-3-methyl-5-oxo-1H-pyrazole-4,1-BADB
10169-02-5[1,1′-Biphenyl]-2,2′-disulfonic acid, 4,4′-bis[(2-hydroxy-1-naphthalenyl)azo]-, disodium saltAcid Red 97
Identity of the 24 Benzidine-based Direct Dyes in the Aromatic Azo and Benzidine-based Substance Grouping
CAS RNDSL nameColour Index name or acronym
72-57-12,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethyl[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[5-amino-4-hydroxy-, tetrasodium saltDirect Blue 14
573-58-01-Naphthalenesulfonic acid, 3,3′-[[1,1′-biphenyl]-4,4′-diylbis(azo)]bis[4-amino-, disodium saltDirect Red 28
992-59-61-Naphthalenesulfonic acid, 3,3′-[(3,3′-dimethyl[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[4-amino-, disodium saltDirect Red 2
2150-54-12,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethyl[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[4,5-dihydroxy-, tetrasodium saltDirect Blue 25
2429-71-21-Naphthalenesulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[4-hydroxy-, disodium saltDirect Blue 8
2429-74-52,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[5-amino-4-hydroxy-, tetrasodium saltDirect Blue 15
6420-06-01-Naphthalenesulfonic acid, 4-hydroxy-3-[[4′-[(1-hydroxy-5-sulfo-2-naphthalenyl)azo]-3,3′-dimethyl[1,1′-biphenyl]-4-yl]azo]-, disodium saltDirect Violet 28
6420-22-02,7-Naphthalenedisulfonic acid, 5-amino-3-[[4′-[(6-amino-1-hydroxy-3-sulfo-2-naphthalenyl)azo]-3,3′-dimethyl[1,1′-biphenyl]-4-yl]azo]-4-hydroxy-, trisodium saltDirect Blue 295
6449-35-01-Naphthalenesulfonic acid, 3-[[4′-[(6-amino-1-hydroxy-3-sulfo-2-naphthalenyl)azo]-3,3′-dimethoxy[1,1’′-biphenyl]-4-yl]azo]-4-hydroxy-, disodium saltDirect Blue 151
6548-29-42,7-Naphthalenedisulfonic acid, 4,4′-[(3,3′-dichloro[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[3-amino-, tetrasodium saltDirect Red 46
6655-95-4Acetic acid, 2,2′-[[4,4′-bis[[1-hydroxy-6-[(4-methoxyphenyl)amino]-3-sulfo-2-naphthalenyl]azo][1,1′-biphenyl]-3,3′-diyl]bis(oxy)]bis-, tetrasodium saltDirect Blue 158
16071-86-6Cuprate(2−), [5-[[4′-[[2,6-dihydroxy-3-[(2-hydroxy-5-sulfophenyl)azo]phenyl]azo][1,1′-biphenyl]-4-yl]azo]-2-hydroxybenzoato(4-)]-, disodiumDirect Brown 95
67923-89-12,7-Naphthalenedisulfonic acid, 5-amino-4-hydroxy-3-[[4′-[(1-hydroxy-4-sulfo-2-naphthalenyl)azo]-3,3′-dimethoxy[1,1′-biphenyl]-4-yl]azo]-, trilithium saltNAAH·3Li
70210-28-5Benzoic acid, 5-[[4′-[[6-amino-5-(1H-benzotriazol-5-ylazo)-1-hydroxy-3-sulfo-2-naphthalenyl]azo]-3,3′-dimethoxy[1,1′-biphenyl]-4-yl]azo]-2-hydroxy-4-methyl-, disodium saltBABHS
71215-83-3Benzoic acid, 5-[[4′-[(2-amino-8-hydroxy-6-sulfo-1-naphthalenyl)azo]-2,2′-dichloro[1,1′-biphenyl]-4-yl]azo]-2-hydroxy-, disodium saltBAHSD
71550-22-62,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[5-amino-4-hydroxy-, tetralithium saltNADB·4Li
72252-59-6[1,1′-Biphenyl]-3,3′-dicarboxylic acid, 4-[[5-[[5-(aminosulfonyl)-2-hydroxyphenyl]azo]-1-hydroxy-6-(phenylamino)-3-sulfo-2-naphthalenyl]azo]-4′-[[1-[[(3-carboxy-4-hydroxyphenyl)amino]carbonyl]-2-oxopropyl]azo]-, tetrasodium saltBDAAH
75659-72-22,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[5-amino-4-hydroxy-, monolithium trisodium saltNADB·Li·3Na
75659-73-32,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[5-amino-4-hydroxy-, dilithium disodium saltNADB·2Li·2Na
75673-18-62,7-Naphthalenedisulfonic acid, 5-amino-4-hydroxy-3-[[4′-[(1-hydroxy-4-sulfo-2-naphthalenyl)azo]-3,3′-dimethoxy[1,1′-biphenyl]-4-yl]azo]-, monolithium disodium saltNAAH·Li·2Na
75673-19-72,7-Naphthalenedisulfonic acid, 5-amino-4-hydroxy-3-[[4′-[(1-hydroxy-4-sulfo-2-naphthalenyl)azo]-3,3′-dimethoxy[1,1′-biphenyl]-4-yl]azo]-, dilithium monosodium saltNAAH·2Li·Na
75673-34-61-Naphthalenesulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[4-hydroxy-, dilithium saltNADB·2Li
75673-35-71-Naphthalenesulfonic acid, 3,3′-[(3,3′′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[4-hydroxy-, monolithium monosodium saltNADB·Li·Na
75752-17-92,7-Naphthalenedisulfonic acid, 3,3′-[(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis(azo)]bis[5-amino-4-hydroxy-, trilithium monosodium saltNADB·3Li·Na
Identity of the two Benzidine-based Cationic Indicators in the Aromatic Azo and Benzidine-based Substance Grouping
CAS RNDSL nameColour Index  name or acronym
298-83-92H-Tetrazolium, 3,3′-(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis[2-(4-nitrophenyl)-5-phenyl-, dichlorideTDBPD
1871-22-32H-Tetrazolium, 3,3′-(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis[2,5-diphenyl-, dichlorideTDBD
Identity of the two Benzidine-based Precursors in the Aromatic Azo and Benzidine-based Substance Grouping
CAS RNDSL nameColour Index  name or acronym
91-92-9Naphthalenecarboxamide, N,N′-(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis[3-hydroxy-Naphthol AS-BR
93940-21-71-Triazene-1-carbonitrile, 3,3′-(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)bis-TCDB
Identity of the five Benzidine Derivatives in the Aromatic Azo and Benzidine-based Substance Grouping
CAS RNDSL nameColour Index  name or acronym
91-97-41,1′-Biphenyl, 4,4′-diisocyanato-3,3′-dimethyl-TODI
119-90-41,1′-Biphenyl]-4,4′-diamine, 3,3′-dimethoxy-3,3′-DMOB
119-93-7Footnote Table 0e [a]1,1′-Biphenyl]-4,4′-diamine, 3,3′-dimethyl-3,3′-DMB
366-29-0[1,1′-Biphenyl]-4,4′-diamine, N,N,N′,N′-tetramethyl-4N-TMB
612-82-8[*]1,1′-Biphenyl]-4,4′-diamine, 3,3′-dimethyl-, dihydrochloride3,3′-DMB·2HCl
Footnote Table 0e 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. 

Return to footnote Table 0e a referrer

For the purpose of this Screening Assessment, four subgroups (Benzidine-based Acid Dyes, Direct Dyes, Cationic Indicators and Precursors) are collectively referred to as “Benzidine-based Substances” while Benzidine-based Acid Dyes and Benzidine-based Direct Dyes are collectively referred to as “Benzidine-based Dyes.”

The majority of the Benzidine-based Substances and Benzidine Derivatives in this grouping were not reported to be manufactured or imported in Canada in quantities above 100 kg/year according to recent surveys under section 71 of CEPA 1999.

Environment

Benzidine-based Dyes are anionic molecules that have relatively high water solubility (greater than 1 g/L) and are expected to dissociate at environmentally relevant pH levels. When considering potential releases of Benzidine-based Dyes to the environment, it is expected that the chemistry of these substances results in their partitioning to water, sediment and soil. Benzidine-based Dyes have low experimental log octanol–water partition coefficients (Kow) and low fish bioconcentration factors (BCFs), indicating that these dyes are not likely to bioconcentrate in aquatic organisms. According to empirical and modelled data, Benzidine-based Dyes are expected to biodegrade very slowly in aerobic environments (water, sediment and soil); however, they may degrade and transform to certain benzidine derivatives if they reach anaerobic environments. Based on aquatic and terrestrial ecotoxicity data (including both empirical and read-across data), Benzidine-based Dyes have the potential to cause harm to aquatic and terrestrial organisms at low concentrations. A conservative aquatic exposure analysis of the textile wet processing sector and a conservative terrestrial exposure analysis of the application of biosolids to land were done because they were anticipated to present the highest potential ecological risks related to the industrial release of these substances. Predicted environmental concentrations (PECs) for Benzidine-based Dyes in aquatic and terrestrial environments were compared with predicted no-effect concentrations (PNECs) for each compartment, and calculated risk quotients were all below one. Considering all available lines of evidence with respect to the persistence, potential bioaccumulation, ecotoxicity, industrial uses and potential releases of the substances, it is concluded that Benzidine-based Dyes have a low potential to cause ecological harm in Canada.

Benzidine-based Cationic Indicators also have relatively high water solubility and are expected to dissociate at environmentally relevant pH levels. Given their high water solubility and affinity for negatively charged organic particles, potential releases would be expected to partition to water, sediment and soil. Since Benzidine-based Cationic Indicators are charged, they have low experimental log Kow values. While BCFs were not available for these substances, they are similar enough in physical and chemical properties to Benzidine-based Dyes to suggest that they are not likely to bioconcentrate in aquatic organisms. Benzidine-based Cationic Indicators are expected to biodegrade very slowly in aerobic environments (water, sediment and soil); however, Benzidine-based Cationic Indicators may degrade and transform to certain benzidine derivatives if they reach anaerobic environments. Based on aquatic and terrestrial ecotoxicity data (including both empirical and read-across data), Benzidine-based Cationic Indicators have the potential to cause harm to aquatic organisms at low concentrations. However, considering all lines of evidence for these two Benzidine-based Cationic Indicators, particularly as no commercial activity in Canada was reported, it is believed that the substances would not present a risk to the environment. Therefore, it is concluded that these Benzidine-based Cationic Indicators have a low potential to cause ecological harm in Canada.

The Benzidine-based Precursors, Naphthol AS-BR and TCDB, were assessed individually, since their physical and chemical properties and chemical structures are very different. Models were used to predict most results, as no close analogues with relevant data could be found. Naphthol AS-BR is sparingly soluble and not expected to dissociate under environmentally relevant pH levels, so it is expected to reside mostly in soil or sediment if released to the environment. TCDB is moderately soluble and is expected to dissociate readily and stay in the water column or bind with particles, given its acidic character. Both Benzidine-based Precursors have moderate to high estimated log Kowvalues and moderate to high modelled aquatic BCFs. Despite some tendency to bioaccumulate, modelled data show that these substances may metabolize significantly. These Benzidine-based Precursors are expected to biodegrade very slowly in aerobic environments (water, sediment and soil). Based on two sets of modelled aquatic toxicity data for acute and chronic endpoints, both TCDB and Naphthol AS-BR have the potential to cause harm to aquatic organisms at low concentrations (pivotal values less than  1 mg/L). Considering all lines of evidence, including the fact that TCDB and Naphthol AS-BR are not known to be in commerce in Canada, it is believed that these substances would not present a risk to the environment. Therefore, it is concluded that these Benzidine-based Precursors have a low potential to cause ecological harm in Canada.

Benzidine Derivatives are generally moderately soluble, have low to moderate log Kow values and will ionize at low pH levels. Based on these properties, as well as their high potential for binding to particulate matter and sediment, these substances are expected to be found in water, sediment and soil if released to the environment. Empirical and modelled data indicate that Benzidine Derivatives biodegrade slowly in aerobic environments (water, sediment and soil). Moderate to high water solubility, low to moderate log Kow values as well as a low empirical BCF for 3,3′-DMB indicate that Benzidine Derivatives will not bioconcentrate in aquatic organisms. Empirical and modelled data indicate that Benzidine Derivatives are moderately to highly toxic to aquatic organisms. However, given that these substances do not have the potential to be released to the environment in high volumes, as they were not reported to be manufactured or imported in Canada in quantities above 100 kg/year, according to recent regulatory surveys; therefore, it is believed that Benzidine Derivatives would not present a risk to the environment. Therefore, it is concluded that these five Benzidine Derivatives have a low potential to cause ecological harm in Canada.

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 42 Benzidine-based Dyes and Related Substances evaluated in this assessment. It is concluded that these Benzidine-based Dyes and Related Substances 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

A critical effect for certain Benzidine-based Substances is potential carcinogenicity via reductive cleavage of the azo bonds and release of aromatic amines, which can be converted to reactive intermediates through metabolic oxidation. Therefore, Benzidine-based Substances are evaluated by examining their hazard potential (e.g., ability to undergo reductive cleavage and hazard potential of the corresponding aromatic amines), together with their potential for exposure of the general population of Canada. Similarly, the Benzidine Derivatives are evaluated for their hazard potential, together with their potential for exposure of the general population.

Exposure of the general population to Benzidine-based Substances and derivatives from environmental media is not expected due to limited commercial quantities in Canada. Therefore, risk to human health from these sources is not expected.

Available information indicates that residual3,3′-DMB may leach into foods being prepared with polyamide cooking utensils. Margins between the estimated daily oral exposure from use of polyamide cooking utensils and critical effect levels are considered adequate to address uncertainties in the health effects and exposure databases.

The Benzidine Derivatives 3,3′-DMB and 3,3′-DMOB are regulated in textiles in the European Union. Two European surveys, as well as a Japanese study, indicate that 3,3′-DMB and 3,3′-DMOB are occasionally detected in some textiles and leather products, some of which were reported to be imported from other countries. Accordingly, these two Benzidine Derivatives could be present in imported products in Canada, as the Canadian textile market is predominantly composed of imported products. Testing of products on the Canadian market, however, did not identify these two Benzidine Derivatives in imported and domestic textile and leather products. Exposure to 3,3′-DMB and 3,3′-DMOB from textiles and leather is considered to be limited; direct and prolonged skin contact is not expected. Therefore, risk to human health is not expected.

Exposure of the general population to the other three Benzidine Derivatives (3,3′-DMB·2HCl, TODI and 4N-TMB) is not expected. Therefore, risk to human health is not expected.

Three of the five Benzidine Derivatives in this assessment (3,3′-DMB, 3,3′-DMB·2HCl and 3,3′-DMOB) have human health effects of concern based on their potential carcinogenicity.

Potential for general population exposure due to dermal contact with textile clothing and leather articles was identified for one of the Benzidine-based Acid Dyes, Acid Red 97. Although exposure to Acid Red 97 is expected for the general population, the hazard potential, based on available information, is considered low. Accordingly, the risk to human health is considered to be low.

For the remaining Benzidine-based Acid Dyes in this assessment, and all of the benzidine-based Direct Dyes in this assessment, available information (including surveys conducted under section 71 of CEPA 1999 and information on uses pursuant to the Food and Drugs Act) indicates that exposure from textiles and leather is considered to be limited; direct and prolonged skin contact is not expected. Therefore, risk to human health is not expected.

Exposure of the general population to the two Benzidine-based Precursors and two Benzidine-based Cationic Indicators in this assessment is not expected. Therefore, risk to human health is not expected.

Some of the Benzidine-based Acid Dyes, Benzidine-based Direct Dyes, and Benzidine-based Precursors in this assessment have human health effects of concern based on potential carcinogenicity. These include the Benzidine-based Substances which may release benzidine, 3,3′-dichlorobenzidine (3,3′-DCB), 3,3′-DMB, 3,3′-DMOB, 2,2′-dimethylbenzidine (2,2′-DMB) or 2,2′-dichlorobenzidine (2,2′-DCB).

Based on the information presented in this Screening Assessment, it is concluded that the Benzidine-based Dyes and Related Substances 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 Benzidine-based Dyes and Related Substances evaluated in this assessment do not meet any of the criteria set out in section 64 of CEPA 1999.

Footnotes

Footnote 1

CAS RN: Chemical Abstracts Service Registry Number

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Footnote 2

Twenty-two aromatic amines listed in Appendix 8 of Regulation (EC) No. 1907/2006 (EU 22).

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Footnote 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 is not relevant to, nor does it preclude, an assessment against the hazard criteria specified in the Controlled Products Regulations, which is 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.

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Footnote 4

The List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist) is 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 2011a).

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Footnote 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 its 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, industry-generated data and monitoring data.

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Footnote 6

Twenty-two aromatic amines are listed in Appendix 8 of Regulation (EC) No. 1907/2006 (EU 2006).

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