U.S. Environmental Protection Agency Draft, 12/9/2009 04/06/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

Dyes Derived from Benzidine and Its Congeners (DCB) Action Plan

I. Overview

This Action Plan addresses the use of benzidine-based dyes and benzidine congenerbased dyes, both metalized and non-metalized, in products that would result in consumer exposure, such as for use to color textiles. Based on the There is a well-established concern for the potential carcinogenic effects presented by exposure to benzidine-based and benzidine congener-based dyes, and this Action Plan focuses on human carcinogenicity issues. EPA

intends to reduc e address risk concerns from such exposure potential exposures by p r epar ing a

pr opos al initiating rulemaking to add four benzidine-based dy es to an existing TSCA section 5(a)(2) significant new use ru le (SNUR) for benzidine-base d substances at 40 CFR 721.1660; and by initiating rulemaking to establish a new pro pose d TSCA section 5(a)(2) SNUR for benzidine congener-based dyes, in cluding 44 specific such dyes.

Because there may be concern for exposure to these dyes on imported finished textiles, EPA may also consider eliminating proposing to eliminate the article exemption applied to

SNURs. If EPA learns that such activities are ongoing, EPA intends to consider initiating action

under TSCA section 6.

If

Furthermore, should EPA determine s that there are othe r ongoing uses for the se dyes,

EPA intends to consider addi tional regulatory action to obtai n information necessary to determine whether the uses present con cerns which need to be addressed.

As part of the Agency's efforts to addre ss benzidine-based and be nzidine congener-based dyes, EPA also intends to evaluate the potential for disproportionate impact on children and other sub-populations.

II. Introduction

As part of EPA's efforts to enhance th e existing chemicals program under the Toxic Substances Control Act (TSCA) 1 , the Agency identified an ini tial list of widely recognized chemicals, including benzidine-based and benz idine congener-based dyes, for action plan development based on their presence in human blood; persistent, bioaccumulative, and toxic (PBT) 2 characteristics; use in consumer products; production volume; and other similar factors.

This Action Plan is based on EPA’ s initial review of readily avai lable use, exposure, and hazard

information 3 on the dyes. EPA considered which of th e various authorities provided under TSCA and other statutes might be appr opriate to address potential con cerns with the dyes in developing

1 15 U.S.C. §2601 et seq.
2 Information on PBT chemicals can be found on the EPA website at http://www.epa.gov/pbt/

. 3 Information sources customarily employed include Inventory Update Reporting (IUR) submissions; Toxic Release Inventory (TRI) reporting; data submitted to the HPV Challenge Program; existing hazard and risk assessments performed by domestic and international authorities includi ng but not limited to U.S. Federal government agencies, the Organization for Economic Cooperation and Development, the Stockholm Convention on Persistent Organic Pollutants, Health and Environment Canada, the European Union; and others. Action plans will reference specific

sources used.U.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

2 the Action Plan. The Action Plan is intended to de scribe the courses of action the Agency plans to pursue in the near term to address its con cerns. The Action Plan does not constitute a final Agency determination or other final Agency action. Regulatory procee dings indicated by the Action Plan will include appropriate opportunitie s for public and stakeholder input, including through notice and comment rulemaking processes.

III. Scope of Review

Benzidine and its congeners constitute a family of similar synthetic aromatic amines which are important precursors in the synthesis of dyes. Some of these dyes have the potential to metabolize to aromatic amines that are considered to be carcinogenic

. (NTP, 2005). Benzidine and dyes metabolized to benzidine are consid ered "known human carcinogens". Benzidine's congeners, 3,3'-dichlorobenzidine, 3,3'-dim ethylbenzidine, and 3,3'-dimethoxybenzidine and dyes metabolized to the latter two congeners have all been classified as "reasonably anticipated to be human carcinogens" (NTP, 2005).

The 2006 Inventory Update Report (IUR) indicat ed that a number of benzidine-based or congener-based dyes and pigments were being produced in high volumes. This observation

resulted in a decision to review the current status of the categ ory of dyes and pigments derived from benzidine and its congeners in products that could result in potential consumer exposure. In reviewing the benzidine c ongener-based pigments, EPA determined believes that the presence of pigments in such consumer products as printing i nks, paints, plastics, and textiles was unlikely to present an exposure concern, becaus e the pigments are not bioavailab le and are not absorbed into the body ( Environment Canada, 2009, Golka, et al, 2004 , OECD, 2003, ). Additionally EPA

determined believes that some of the congener-based dye s reported to the 2006 IUR were not likely to degrade to carcinogenic amines (Jung, R., et al, 1992).

EPA therefore decided to focus on dyes derive d from benzidine and its congeners that are

listed on the non- CBI confidential business information (CBI) TSCA Inventory and have the potential to degrade to carcinogenic amines. A search of the non-CBI TSCA Inventory found 48 substances not already subject to TSCA SNUR authority. These are divided among two lists (see Appendix 1.):

 List 1. Benzidine Based Dyes -- 4 substances

 List 2. Benzidine Congener-Bas ed Dyes -- 44 substances

As these benzidine and congener

- based dyes all have the potential to degrade to carcinogenic metabolites benzidine or a benzidine congener , EPA chose to consider whether there are concerns about consumer exposure to the dy es in products that ne ed to be addressed.

IV. Uses and Substitutes Summary

Benzidine-based and congener-based dyes (also called azo dyes) are used in the production of textiles, paints , printing inks, paper, and pharmaceuticals. They are also used as reagents and biological stains in laboratories, are used in the food industries, and have moreU.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

3 recent uses in laser, liquid crystal displays, ink- jet printers, and electro- optical devices (Dapson, 2009, Kamboh, et al, 2009, Oomen, et al, 2004).

Dye production in the U.S. has been steadily de clining for the past decade, largely due to the increase in imported finished textiles. Most of the imported volume comes from China and

India

. and other less developed countries which may have less stringent regulations on dye intermediates (Dapson, 2009). No List 1 dyes were reported and only two List 2 dyes were reported on the 2006 IUR and since their volume was below 500,000 pounds per year, no exposure and use data was reported. Only 12 of the List 2 and none of the List 1 dyes were believed to be available in the U.S., and two othe rs are available internat ionally but could end up in U.S. products. Given that dyes are quite ofte n available from importers, reformulators and others who distribute in small volumes, it is a ssumed that there are a number that were not readily identified, because they are produced in volumes below the 2006 IUR reporting threshold (25,000 pounds per year). Because the European Union has had a ban on the use of certain azo dyes, such as those on Lists 1 and 2, in textiles and leather that are in prolonged contact with human skin, there are readily avai lable substitutes for the use of benzidine and congener dyes in

textiles and leather.

V. Hazard Identification Summary

The 1980 EPA Preliminary Risk Assessment on derivatives of benzidine and its congeners established that the primary hazard concern was for the carcinogenic effects to humans from exposure to specific metabolites of the dyes (EPA, 1980). Therefore, the hazard

review for this Action Plan focuses on human carcinogenicity issues. Azo dyes are biologically active through their metabolites. Azoreduction of these compounds occurs in humans by an enzyme-mediated reaction. Azoreduc tases are found in the liver, in gut bacteria, and in skin

bacteria. The result of this azo reduction is the release of the ca rcinogenic aromatic amine from the dye. Studies have demonstrated that the azo reduction of benzidine-based dyes occurs in the human body as well as on the skin (Golka, et al, 2004). Therefore, the primary human health concern for consumers is exposure to the benz idine-based and benzid ine-congener-based dyes through oral, dermal or inhalation routes. Evidence from animal studi es suggests that there is early life susceptibility to benzidine carcinog enesis. Cancer potency for benzidine was substantially increased when the dose was given in early life as compared to adults (EPA, 2005).

It appears that metal chela tion does not completely eliminate the carcinogenic effects of metalized dyes derived from bendizine congeners ; therefore, the metalized congener dyes have been included in List 2 (Morga n, et al, 1994). The four dyes on List 1 have the potential to degrade to benzidine. List 2 includes 17 dime thylbenzidine-based dyes, 26 dimethoxybenzidinebased dyes and 1 dichlorobenzidin e-based dye, all of which would be expected to degrade to their carcinogenic precursors a nd would therefore present a po tential exposure concern in consumer products

VI. Fate Characterization Summary

Azo dyes have been expected to resist biodegradation, because they are synthetic. However, the problems of discharge of dye cont ents to wastewaters from textile and otherU.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

4 industries have resulted in extensive research for biological methods to degrade dyes and other organic pollutants. Under certain environmental conditions, various fungi, bacteria, yeasts and algae have been found to be capable of deco lorizing and sometimes completely mineralizing many azo dyes. Different trophic groups of micr oorganisms are capable of degrading azo dyes under anaerobic, anoxic and aerobic conditions (Pandey, et al, 2007).

VII. Exposure Characterization Summary

The main routes of consumer exposure to azo dyes are : (Zeilmaker, et al, 1999, Zeilmaker, et al, 2000):

 Dermal absorption is the primary route fr om wearing azo-dyed cl othing or footwear and using azo-dyed materials such as paper and inks.

 Oral ingestion is an additional route for babies and young children who suck on clothing, blankets or other textiles , and other non-food products which might contain azo dyes

.

 Inhalation exposure is a more important ro ute in occupational settings; however, it can also occur from the use of azo-dyed inks during "air brus hing" or from offgassing from azo-dyed carpe ts to indoor air.

 Contact with azo dyes entering the envir onment through the whol e life cycle of azo dyes in textiles is an additional potential source of exposure.

Actual dermal exposure does occur from th e leaching of azo dyes by sweat in contact with the dyed textiles. Studies have shown that various types of human sk in bacteria possess the azo reductases necessary to breakdown azo dyes to release the carcinogenic amines, which can be absorbed. Additionally, once on the skin, the dye itself may be absorbed. It is well established

that azoreduction also occurs inte rnally in the gut and the liver

. (Zeilmaker, et al, 1999, Zeilmaker, et al, 2000).

Three European studies experimentally ex amined the leaching of amines and azo dyes from consumer textile products, including leathe r. Two of the studies used a variety of assumptions to estimate life-long daily uptake va lues for dermal exposure to various pieces of azo-dyed clothing and footwear shown to contai n benzidine or a congener. When comparing their values to EPA's acceptable 10 -6 level for benzidine (and extrapolated to the other congeners), they determined that exposure to the azo-dyed clothing and f ootwear would result in

a cancer risk above the "n egligible risk level" (N RL). (Zeilmaker, et al, 1999, Zeilmaker, et al, 2000). In addition to the fact that the studies reported data from dyed products purchased in Europe, many assumptions were used, often worst cases assumptions which may overestimate exposure. Also, it was noted that the main factor s determining dye releases from textiles to the skin include the type of dyed textile, contact w ith other substrates, amount of dye applied to the textile, and number of previous washings.

Nevertheless, during a similar time period as the studies discussed above, a risk committee for the European Commission reviewed a report on consumer exposure to diazo textile dyes (unavailable) and agr eed with the report's conclusion that while consumer exposure is likely to be very low, the associated cancer ri sks give enough cause for concern that the use ofU.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

5 azo dyes which can degrade to 22 carcinogenic arom atic amines be restricted to the lowest possible levels or banned (European Commission, 1999).

VIII. Risk Management Considerations

Current Regulatory Status in North America and Europe

Occupational exposure to some dyes derived from benzidine and its congeners has been regulated for many years; however, the potential for consumer exposure to products containing these products is still a potential concern. The EU has banned in textile and leather articles which may come into direct and prol onged contact with humans the us e of azo dyes which can break down to release any of 22 listed carcinogenic ar omatic amines (includes benzidine and its congeners) in amounts above 30 ppm in finished arti cles or the dyed parts (See Restriction 43 in REACH Annex XVII, European Commission, 2009). Ca nada has also expressed concern about the potential release of benzidine or its congeners from azo dyes and is evaluating potential approaches for addressing azo dyes (Environment Canada, 2009).

In 1995, when EPA proposed a significant new use rule (SNUR) on benzidine-based substances, EPA indicated that this was the first step in a risk management strategy to reduce the

risks associated with the manu facture and use of benzidine-based and benzidine congener-based dyes and pigments (60 FR 45119, 8/30/95). The S NUR at 40 CFR §721.1660 is for any use of 22

benzidine-based substances. These substances we re not included in th is Action Plan. Exempt from the SNUR were minor ongoing specified uses as analytical reagents a nd biological stains.

When EPA finalized that first SNUR, EPA recognized that additional benzidine-based

substances would need to be added. The four benzidine-based dyes on List 1 had been included in draft additions to §721.1660 which were ne ver finalized (61 FR 52287, 10/7/96). With the exception of the seven metalized congener dye s and the one DCB-based dye, the other 37 dyes

on List 2 had been included in a draft of a proposed SNUR for non-metalized dyes based on dimethylbenzidine and dimethoxybenzid ine that was never finalized.

Benzidine-based and congener-based dyes -- Potential concerns for humans

Risk from consumer use of products containing dyes . Because of the azoreductases present in the human body and in bacteria on the skin, consumer products using the dyes could present a concern. The main products presenting a concern would be textiles and leather products that are in prolonged contact with human skin. Th e other products are either not available to consumers (laboratory chemicals) or would not likely be readily accessible in significant quantities (printing ink or LCD displa ys) to present an exposure concern.

Risk to the general population from dyes released to the environment . Biodegradation studies indicate that the dyes w ould be expected to biodegrade at negligible to slow rates under aerobic conditions in the environment. However, in anaerobic soils the dyes are likely to undergo

azo reduction to benzidine and/ or congeners depending on struct ure. It is unclear whetherU.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

6 metabolites from these reductions would be available in large concentrations or locations to be of concern to the general population.

Assumptions and Uncertainties

Based on market information and the fact that the 2006 IUR had no reports for the benzidine-based dyes, it appears that if the dyes ar e used at all, they would be used in small volumes, making it difficult to access production a nd use information. Additionally, it appears that new uses of azo dyes in high tech applic ations have been developed since EPA last examined the market. Although it is unclear whethe r the dyes on Lists 1 and 2 are used in these applications, it is assumed that these new uses would be less likely to result in significant consumer exposure to the dyes.

As many of the Direct Blue dyes on List 2 ha ve been identified as having potential uses as biological stains and as ha ving anti-viral activit y, it is unknown how mu ch of the production volume would be attributed to those uses, which would generally not be a concern for consumers or not subject to TSCA (e.g., pharmaceuticals). Th e only consumer exposure data available for analysis comes from a few Europe an studies which may or may not be applicable in the U.S. Those studies also used many a ssumptions to prepare their estimates and identified important variables which affect the amount of dye released from textiles to the skin. However, given the evidence for early life susceptibility to benzidine, EPA believes that it is important to consider actions to address children's pot ential exposure to dyes which can metabolize to benzidine and benzidine-based congeners.

Given that dye production has been shifting to Asia and importation of finished textiles has increased, it is possible that th e risk of exposure to azo dyes in the U.S. would be more from dyes on imported finished textiles than from dyes manufactured or imported and used to finish

textiles in the U.S.

IX. Next Steps

List 1 Benzidine-Based Dyes

EPA intends to p repare a proposal initiate rulemaking to add the four List 1 dyes to the existing TSCA section 5(a)(2) significant new use rule for benzidine-based substances at 40 CFR

721.1660.

 In order to use the SNUR authority, EPA must be aware that the uses it chooses to regulate are not ongoing or exempt ongoing uses.

 The existing SNUR at 40 CFR 721.1660 already covers listed benzidine-based substances.

EPA could choose to add the four List 1 benzidine-based dyes to that SNUR.

 Request comment on whether there are for ongoing uses as analyti cal reagents and lab stains and indicate that the exemption at 721.1660 would likely continue to apply.U.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

7  There is some uncertainty about the extent of current uses; however, the market profile did not find information indicating that any of the four List 1 substa nces are available in the U.S. Therefore, it is clear that any uses would be very small quantities.

 If public comments on the proposed SNUR indicate that there are existi ng uses beyond minor laboratory uses, EPA may need to consider additional action such as TSCA section 6 rulemaking , depending on the potential exposure s cenarios presented by any existing uses

. In making such a consideration, EPA would eval uate whether those existing uses indicated the potential to present an unreasonable risk, in coordination with CPSC and/or other agencies where appropriate

.

List 2 Benzidine Congener-Based Dyes

EPA intends to prepare a new proposed TSCA section 5(a)(2) significant new use rule for benzidine congener-based dyes a nd include the List 2 dyes.

 In order to use the SNUR authority, EPA must be aware that the uses it chooses to regulate are not ongoing or exempt ongoing uses.

o Some of the Direct Blues a ppear to have application as biological stains and pharmaceuticals. The stain uses could be exempted and the pharmaceutical uses are not subject to TSCA.

o There is much uncertainty about the uses of and potential exposures to the dyes in

both textiles and the ne wer high tech fields.

 EPA could draft a proposed benzidine congener- based SNUR for the List 2 dyes, indicating an intention to exempt minor laboratory uses that are reported during the comment period.

 If ongoing uses in high technology applications, such as LCD displays, are reported, EPA could further evaluate potential exposure concerns before addressing those uses.

EPA will search the CBI TSCA Inventory to identify benzidine-based and benzidine congener-based dyes that could be added to List 1 or List 2 a nd included in the above SNURs.

Because there is concern for exposure to azo dyes on imported finished textiles, EPA could propose eliminating the article ex emption applied to the above SNURs.

If EPA determines that List 1 and/or 2 dyes are currently coming into the U.S. on imported finished textiles, EPA could intends to consider initiating regulatory action under TSCA

section 6. In making such a consideration, EPA woul d evaluate whether those existing uses indicated the potential to present an unreasonable risk, in coordination with CPSC and/or other Agencies where appropriate.

When EPA proposes the SNURS, EPA will re quest comment on using TSCA section 6 as an alternative approach to the SNUR process.

X. References

Dapson, R.W. 2009. Benzidine-based dyes: effects of industrial practices, regulations, and world trade on the biological stains market. Biotechnic & Histochemistry 84(3): 95-100.U.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

8 Environment Canada. 2009. Strategic options for the management of toxic substances benzidine and 3,3-
dichlorobenzidine. Accessed 10/9/09 at: http://www.ec.gc.ca/toxics/docs/sor/bdine/EN/sum.cfm

EPA. 1980. Preliminary Risk Assessment: Phase I. Benzidine, its congeners, and their derivative dyes and pigments. EPA-560/11-80-019, June 1980.

EPA. 2005. Supplemental Guidance for Assessing Suscep tibility from Early Life Exposu re to Carcinogens. EPA 630/R-03/003F, March 2005.

European Commission. 1999. Opinion of risk of cancer caused by textiles and leather goods coloured with azo-dyes expressed at the 7th CSTEE plenary meeting, Br ussels, 18 January 1999. Accessed 9/18/09 at http://ec.europa.eu/health/ph_risk/committees/sct/docshtml/sct_out27_en.htm

European Commission. 2009. Commission Regulation EC No. 552/2009 Commission Regulation (EC) No 552/2009 of 22 June 2009 amending Regulation (EC) No 1907/2006 of the European Parliament and of the Council on REACH as regards Annex XVII.

Golka, K., Kopps, S., Myslak, Z.W. 2004. Carcinogenc itiy of azo colorants: influence of solubility and bioavailability. Tox Lett 151:203-210.

Jung, R., D. Steinle, R. Anliker. 1992. A compilation of genotoxicity and carcinogenicity data on aromatic aminosulphonic acids. Fd.Chem.Toxic. 30(7):635-660.

Kamboh, M.A., Solangi, I.B., Sherazi, S.T.H., Memon, S. 2009. Synthesis and application of caliz[4]arene based resin for the removal of azo dyes.

Morgan, D.L., J.K. Dunnick, T. Goehl, M.P. Jokinen, H.B. Matthews, E. Zeiger, J.H. Mennear. 1994. Summary of the National Toxicology Program Benzidine Dye Initiativ e. Environ.HealthPerspect. 102(Suppl 2):63-78.

NTP. 2005. Report on Carcinogens, 11th edition.

OECD. 2003. SIDS Initial Assessment Profile for Diary lide Yellow Pigment Category, SIAM 16, 27-30 May 2003.

Oomen, A.G., Versantvoort, C.H.M., Duits, M.R., van de Ka mp, E., van Twillert, K. 2004. Application of in vitro digestion models to assess release of lead and phthalate from toy matrices and azo dyes from textile. RIVM Report

320102003/2004. Netherlands.

Pandey, A., Singh, P., Iyengar, L. 2007. Bacterial decolorization and degradat o i o n of azo dyes. Int. Biodeterioration & Biodegradation 59:73-84.

Zeilmaker, M.J., Rosese, E.D., van Haperen, P., van V een, M.P., Bremmer, H.J., van Kranen, H.J., Wouters, M.F.A., Janus, J.A. 1999. Cancer risk assessment of azo dyes and aromatic amines from garment and footwear. RIVM Report 601503014. Netherlands.

Zeilmaker, M.J., van Kranen, H.J., van Veen, M.P., Janus, J.A. 2000. Cancer risk assessment of azo dyes and aromatic amines from tattoo bands, folders of paper, toys, bed clothes,U.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

9 Appendix 1. Benzidine-Based and Congener-Based Dyes With Potential to Degrade to Carcinogenic Amines

List 1: Benzidine-Based Dyes on the Non-CBI TSCA Inventory

CAS NO CHEMICAL NAME 1

117-33-9 1,3-Naphthalenedisulfonic acid, 7-hydr oxy-8-[[4'-[(4-hydroxyphenyl )azo][1,1'-biphenyl]- 4-yl]azo]- 65150-87-0 1,3,6-Naphthalenetrisulfoni c acid, 8-hydroxy-7-[[4'-[(2-hydroxy-1-naphthalenyl)azo][1,1'- biphenyl]-4-yl]azo]-, trilithium salt 68214-82-4 2,7-Naphthalenedisulfonic acid, 5-am ino-3-[[4'-[(7-amino-1-hydroxy-3-sulfo-2- naphthalenyl) azo][1,1'-biphenyl]-4-yl] azo]-4-hydroxy-, disodium salt [ CI Direct Navy

BH ] 72379-45-4 2,7-Naphthalenedisulfonic acid, 4-amino-5-hydroxy-3-[[4 '-[[2-hydroxy-4-[(2- methylphenyl) amino]phenyl]azo] [1,1' -biphenyl]-4-yl]azo]-6-(phenylazo)-

List 2: Benzidine Congener-Based Dyes on the Non-CBI TSCA Inventory

CAS NO CHEMICAL NAME 1

72-57-1 2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3'-d imethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5- amino-4-hydroxy-, tetrasodium salt [ CI Direct Blue 14 , tetrasodium salt; Trypan Blue] 117-32-8 1,3-Naphthalenedisulfonic acid, 7- hydroxy-8-[[4'-[(4-hydr oxyphenyl)azo]-3,3'- dimethyl[1,1'-biphenyl]-4-yl]azo]- 314-13-6 1,3-Naphthalenedisulfonic acid, 6,6'-[(3,3'-d imethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[4- amino-5-hydroxy-, tetrasodium salt [ CI Direct Blue 53 , tetrasodium salt; Evans Blue] 992-59-6 1-Naphthalenesulfonic acid, 3,3'-[(3,3'-dim ethyl [1,1'-biphenyl]-4,4' -diyl)bis(azo)] bis[4- amino-, disodium salt [ CI Direct Red 2, disodium salt ; Benzopurpurin 4B] 2150-54-1 2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3' -dimethyl [1,1'-biphenyl] -4,4'-diyl)bis(azo)] bis[4,5-dihydroxy-, tetrasodium salt [ CI Direct Blue 25, tetrasodium salt ;p Benzo Sky Blue] 2429-71-2 1-Naphthalenesulfonic acid, 3,3'-[(3,3'-dim ethoxy [1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis [4- hydroxy-, disodium salt [ CI Direct Blue 8, disodium salt; Benzoazurine G] 2429-74-5 2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3'-dimethoxy[1,1'-biphenyl]-4,4'- diyl)bis(azo)]bis[5-amino-4- hydroxy-, tetras odium salt [ CI Direct Blue 15 , tetrasodium salt; Direct Sky Blue] 2586-57-4 1,3-Naphthalenedisulfonic acid, 4-ami no-5-hydroxy-6-[[4'-[(2-hydr oxy-1-naphthalenyl) azo]-3,3'-dimethoxy [1,1'-biphenyl]-4- yl]azo]-, disodium salt [ CI Direct Blue 22, disodium salt ; Chicago (Niagra) Blue RW] 2610-05-1 1,3-Naphthalenedisulfonic acid, 6,6'-[(3,3'-dimethoxy[1,1'-biphenyl]-4,4'-U.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

10 List 2: Benzidine Congener-Based Dyes on the Non-CBI TSCA Inventory

CAS NO CHEMICAL NAME 1

diyl)bis(azo)]bis[4-amino-5- hydroxy-, tetras odium salt [ CI Direct Blue 1, tetrasodium salt; Chicago/Sky Blue 6B] 3841-14-3 1,3-Naphthalenedisulfonic acid, 6,6'-[(3,3'-dimethoxy[1,1'-biphenyl]-4,4'- diyl)bis(azo)]bis[4-amino-5-hydroxy- [ CI Direct Blue 1, free acid ; Chicago Sky Blue 6B] 4198-19-0 2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3' -dimethoxy [1,1'-biphenyl ]-4,4'-diyl)bis(azo)] bis[4,5-dihydroxy-, tetrasodium salt [ CI Direct Blue 10 ; Dianil Blue G] 6358-29-8 1,3-Naphthalenedisulfonic acid, 8- [[4'-[(4-ethoxyphenyl) azo]-3,3'-dimethyl[1,1'- biphenyl]-4-yl]azo]-7-hydroxy-, disodium salt [ CI Direct Red 39, disodium salt ] 6405-94-3 Benzenesulfonic acid, 3,3'-[(3,3'-dime thyl [1,1'-biphenyl]-4,4' -diyl)bis(azo)] bis[2,4- diamino-5-methyl-, disodium salt [ CI Direct Orange 10 ] 6449-35-0 1-Naphthalenesulfonic ac id, 3-[[4'-[(6-amino-1-hydroxy-3- sulfo-2-naphthalenyl) azo]-3,3'- dimethoxy[1,1'-biphenyl]-4-yl]azo ]-4-hydroxy-, disodium salt [ CI Direct Blue 151, disodium salt ] 6459-94-5 1,3-Naphthalenedisulfonic acid, 8-[[3,3' -dimethyl-4'-[[4-[[(4-methylphenyl)sulfonyl] oxy]phenyl]azo] [1,1'-biphenyl]-4-yl ]azo]-7-hydroxy-, disodium salt [ CI Acid Red 114, disodium salt ; Milling Red B] 6548-29-4 2,7-Naphthalenedisulfonic acid, 4,4'-[(3,3' -dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)] bis[3-amino-, tetrasodium salt [ CI Direct Red 46, tetrasodium salt ] 6739-62-4 Benzoic acid, 2-[[2-amino-6-[[4'-[( 3-carboxy-4-hydroxyphenyl)azo]-3,3'-dimethoxy[1,1'- biphenyl]-4-yl]azo]-5-hydroxy- 7-sulfo-1-naphthalenyl]azo]- 5-nitro-, trisodium salt [ CI Direct Black 91 ] 12222-00-3 Cuprate(4-), [.mu.-[[4,4 '-[[3,3'-di(hydroxy-.kappa.O) [ 1,1'-biphenyl]-4,4'-diyl]bis(azo- .kappa.N1)]bis[3-(hydroxy-.kappa.O )-2,7-naphthalenedisulfonato]]( 8-)]]di-, tetrasodium [ CI Direct Blue 80 ] 17011-51-7 Ethanesulfonic acid, 2,2'-[(3,3'-dimet hoxy-4,4'-biphenylylene)bis[ azo(methylimino)]]di-,

disodium salt

28407-37-6

(former = 10401-50-0) Cuprate(4-), [.mu.-[[3,3'-[[ 3,3'-di(hydroxy-.kappa.O) [1,1' -biphenyl]-4,4'-diyl]bis(azo- .kappa.N1)]bis[5-amino-4-(hydroxy-.kappa.O )-2,7-naphthalenedisulfonato]](8-)]] di-,

tetrasodium [ CI Direct Blue 218 ] 64743-15-3 Benzoic acid, 5-[[4'-[[ 2,6-diamino-3-methyl-5-[(4-s ulfophenyl)azo]phenyl]azo]-3,3'- dimethyl [1,1'-biphenyl]-4-yl] azo]-2-hydroxy-, disodium salt [ CI Direct Brown 222 ] 65151-33-9 2,7-Naphthalenedisulfonic acid, 4,4'-[(3,3'-dimethoxy[1,1'-biphenyl]-4,4'- diyl)bis(azo)]bis[3-hydroxy-, tetrasodium salt 65152-14-9 1,6-Naphthalenedisulfonic ac id, 4-amino-3-[[4'-[(1-amino- 4-sulfo-2-naphthalenyl)azo]- 3,3'-dimethyl[1,1'-biphenyl]-4-yl]azo]-, trisodium saltU.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

11 List 2: Benzidine Congener-Based Dyes on the Non-CBI TSCA Inventory

CAS NO CHEMICAL NAME 1

65152-15-0 1,7-Naphthalenedisulfonic ac id, 4-amino-3-[[4'-[(1-amino- 4-sulfo-2-naphthalenyl)azo]- 3,3'-dimethyl[1,1'-biphenyl]-4-yl]azo]-, trisodium salt 66214-51-5 2,7-Naphthalenedisulfonic acid, 5-am ino-3-[[4'-[(7-amino-1-hydroxy-3-sulfo-2- naphthalenyl) azo]-3,3'-dimethyl[1,1'-biphe nyl]-4-yl]azo]-4-hydroxy-, trisodium salt 66225-65-8 Cuprate(2-), [5 -[[4'-[[2,6-dihydroxy-3-[ (2-hydroxy-5-sulfophenyl)azo]phenyl]azo]-3,3'- dimethyl[1,1'-biphenyl]-4-yl]azo]- 2-hydroxybenzoato(4-)]-, disodium 66418-17-5 Cuprate(3-), [.mu.-[4 -[[4'-[(6-amino-1-hydroxy-3-sulf o-2-naphthalenyl)azo]-3,3'- dihydroxy[1,1'-biphenyl]-4-yl] azo]-3-hydroxy-2,7-naphthalene disulfonato(7-)]]di-,

trisodium 66418-18-6 Cuprate(4-), [. mu.-[3-[[3,3'-dihydroxy-4' -[(2-hydroxy-3,6-disulfo-1- naphthalenyl)azo][1,1'-biphenyl ]-4-yl]azo]-4-hydroxy-2,7-napht halene disulfonato(8-)]]di- , tetrasodium 67893-48-5 Benzoic acid, 5-[[4'-[( 2,4-diamino-5-sulfophenyl) azo]- 3,3'-dimethyl[1,1'-biphenyl]-4- yl]azo]-2-hydroxy-, disodium salt 68084-09-3 2,7-Naphthalenedisulfonic acid, 5-am ino-4-hydroxy-3-[[4'-[(2- hydroxy-3,6-disulfo-1- naphthalenyl)azo]-3,3'-dimethoxy[1,1'-biphe nyl]-4-yl]azo]-, tetrasodium salt 68084-21-9 1,3-Naphthalenedisulfonic acid, 4-am ino-5-hydroxy-6-[[4'-[(2- hydroxy-3,6-disulfo-1- naphthalenyl)azo]-3,3'-dimethoxy[1,1'-biphe nyl]-4-yl]azo]-, tetrasodium salt 68084-22-0 2,7-Naphthalenedisulfonic ac id, 4-[[4'-[(6-amino-1-hydroxy-3 -sulfo-2-naphthalenyl)azo]- 3,3'-dimethoxy[1,1'-biphenyl]-4-yl]azo ]-3-hydroxy-, trisodium salt 68084-23-1 1,3-Naphthalenedisulfonic acid, 4- amino-6-[[4'-[(1,8-dihydroxy-3,6-disulfo-2- naphthalenyl)azo]-3,3'-dimethoxy[1,1'-biphenyl ]-4-yl]azo]-5-hydroxy-,t etrasodium salt 68140-31-8 Cuprate(3-), [.mu.-[3 -[[3,3'-di(hydroxy-.kappa.O) -4 '-[[2-(hydroxy-.kappa.O)-8-hydroxy6-sulfo-1-naphthalenyl]azo-.kappa.N1][1,1 '-biphenyl]-4-yl]azo-.kappa.N1]-4-(hydroxy- .kappa.O)-5-hydroxy-2,7-naphthalenedisu lfonato(7-)]]di-, trisodium [ CI Direct Blue

214 ] 68345-21-1 2,7-Naphthalenedisulfonic acid, 3-[[3,3'-d imethyl-4'-[[4-[[(4-methylphenyl)sulfonyl]oxy] phenyl] azo][1,1'-biphenyl]-4- yl]azo]-4-hydroxy-5-[[(4-me thylphenyl) sulfonyl]oxy]-,

disodium salt 68966-43-8 2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3' -dimethoxy [1,1'-biphenyl ]-4,4'-diyl)bis(azo)] bis[5-amino-4-hydroxy-, sodium salt, compd. with 2,2'-iminobis[ethanol] 68966-50-7 2,7-Naphthalenedisulfonic acid, 3,3'-[( 3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)bis(azo)] bis[5-amino-4-hydroxy-, sodium salt 70210-32-1 Benzenesulfonic acid, 3-(benzoylamino )-4-hydroxy-5-[[1-[[[4'-[[ 2-[[2-hydroxy-5-(methyl sulfonyl)phenyl]azo]-1,3-dioxobut yl]amino]-3,3'-dimethoxy[1 ,1'-biphenyl]-4-yl]amino] carbonyl]-2-oxopropyl]azo]-, monosodium salt 70632-09-6 Benzoic acid, 5-[[4'-[[2, 6-diamino-3-[(4-sulfophenyl) az o]phenyl]azo]-3,3'-dimethyl [1,1'- biphenyl]-4-yl]azo]-2-hydroxy-, dilithium salt 71550-22-6 2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3' -dimethoxy[1,1'- biphenyl ]-4,4'-diyl)bis(azo)] bis[5-amino-4-hydroxy -, tetralithium salt [ CI Direct Blue 15 or Trypan Blue, tetralithium salt ] 71566-41-1 Benzoic acid, 2-[[2-ami no-5-hydroxy-6-[[4'-[( 2-hydroxy-6-sulfo-1-naphthalenyl)azo]-3,3'-U.S. Environmental Protection Agency Draft, 12/9/2009 03/05/2010 U.S. Government Internal Deliberative Document, Do Not Quote, Cite, or Release

12 List 2: Benzidine Congener-Based Dyes on the Non-CBI TSCA Inventory

CAS NO CHEMICAL NAME 1

dimethoxy[1,1'-biphenyl]-4-yl]azo ]-7-sulfo-1-naphthalenyl]azo ]-5-nitro-, trisodium salt

71701-30-9 2,7-Naphthalenedisulfonic acid, 3-[[ 3,3'-dimethyl -4'-[[4-[(phenylsulfonyl)oxy] phenyl]azo] [1,1'-biphenyl]-4-yl] azo]-4-hydroxy-, disodium salt

71873-63-7

(former = 12217-56-0) Cuprate(4-), [.mu.-[7-[[3,3' -di(hydroxy-.kappa.O) -4'-[[4-(hydroxy-.kappa.O)-2-sulfobenzo [a]phenazin-3-yl]azo-.kappa.N1] [1,1 '-biphenyl]-4-yl]azo-.kappa.N1]-8-(hydroxy- .kappa.O)-1,3,6-naphthalene trisul fonato(8-)]]di-, tetrasodium [ CI Direct Blue 90 ]

101200-51-

5 Benzoic acid, 2-[[2-amino-5-hydroxy-6-[[4'- [(2-hydroxy-6-sulfo-1-naphthalenyl)azo]-3,3'- dimethoxy[1,1'-biphenyl]-4-yl] azo]-7-sulfo-1-naphthalenyl]a zo]-5-nitro-, disodium salt

1 Common names are not unique identifiers as they may be applied to more than one CAS No.; however, they are frequently used, even in peer-reviewed literature.