U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 SCREENING-LEVEL HAZARD CHARACTERIZATION C.I. Pigment Red 48 and 52 Category SPONSORED CHEMICALS C.I. Pigment Red 48 Calcium C.I. Pigment Red 48 Barium C.I. Pigment Red 52 Calcium CASRN 7023-61-2 CASRN 7585-41-3 CASRN 17852-99-2 SUPPORTING CHEMICALS C.I. Pigment Red 57 C.I. Pigment Red 48:4 (Manganese) CASRN 5281-04-9 CASRN 5280-66-0 The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary initiative aimed at developing and making publicly available screening-level health and environmental effects information on chemicals manufactured in or imported into the United States in quantities greater than one million pounds per year. In the Challenge Program, producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship entailed the identification and initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data did not exist, and making both new and existing data and information available to the public. Each complete data submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Setl'2) endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the environment. The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of the quality and completeness of the data set provided in the Challenge Program submissions. They are not intended to be definitive statements regarding the possibility of unreasonable risk of injury to health or the environment. The evaluation is performed according to established EPA guidance2'3 and is based primarily on hazard data provided by sponsors; however, in preparing the hazard characterization, EPA considered its own comments and public comments on the original submission as well as the sponsor's responses to comments and revisions made to the submission. In order to determine whether any new hazard information was developed since the time of the HPV submission, a search of the following databases was made from one year prior to the date of the HPV Challenge submission to the present: (ChemID to locate available data sources including Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.), STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS, 1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm. 2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm. 3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm. ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Merck, etc.), Science Direct and ECHA4. OPPT's focus on these specific sources is based on their being of high quality, highly relevant to hazard characterization, and publicly available. OPPT does not develop HCs for those HPV chemicals which have already been assessed internationally through the HPV program of the Organization for Economic Cooperation and Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are presented in an international forum that involves review and endorsement by governmental authorities around the world. OPPT is an active participant in these meetings and accepts these documents as reliable screening-level hazard assessments. These hazard characterizations are technical documents intended to inform subsequent decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general public. However, they do provide a vehicle for public access to a concise assessment of the raw technical data on HPV chemicals and provide information previously not readily available to the public. 4 European Chemicals Agency, http://echa.europa.eu. 2 ------- U.S. Environmental Protection Agency September, 2014 Hazard Characterization Document Chemical Abstract Service Registry Number (CASRN) Sponsored Chemicals 7023-61-2 7585-41-3 17852-99-2 Supporting Chemicals 5281-04-9 5280-66-0 Chemical Abstract Index Name Sponsored Chemicals 2-Naphthalenecarboxylic acid, 4-[(5-chloro-4-methyl-2- sulfophenyl) azo]-3-hydroxy-, calcium salt (1:1) 2-Naphthalenecarboxylic acid, 4-[(5-chloro-4-methyl-2- sulfophenyl) azo]-3-hydroxy-, barium salt (1:1) 2-Naphthalenecarboxylic acid, 4-[(4-chloro-5-methyl-2- sulfophenyl) azo]-3-hydroxy-, calcium salt (1:1) Supporting Chemicals 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2- sulfophenyl) azo]-, calcium salt (1:1) Manganate(l-), [4-[[5-chloro-4-methyl-2-(sulfo-.kappa.O) phenyl] azo-.kappa.N l]-3-(hydroxy-.kappa.O)-2- naphthalenecarboxylato(3-)] -, hydrogen Structural Formula See Appendix Summary The C.I. Pigment Red 48 and 52 category is composed of three substances: 2- naphthalenecarboxylic acid, 4-[2-(5-chloro-4-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 48 Calcium); 2-naphthalenecarboxylic acid, 4-[2-(5- chloro-4-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, barium salt (1:1) (C.I. Pigment Red 48 Barium); and 2-naphthalenecarboxylic acid, 4-[2-(4-chloro-5-methyl-2-sulfophenyl)diazenyl]- 3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 57). The substances are red solids possessing negligible vapor pressure and low water solubility. They are expected to have low mobility in soil. A surrogate substance, 2-naphthalenecarboxylic acid, 3-hydroxy-4-[2-(4-methyl-2- sulfophenyl) diazenyl]-, calcium salt (1:1) (C.I. Pigment Red 57) is expected to be not readily biodegradable. In general, azo dyes and pigments are considered recalcitrant under aerobic conditions; however, a variety of microorganisms can reduce the azo bond under anaerobic conditions. Volatilization is expected to be low given that these are ionic substances. The rate of hydrolysis is negligible. These substances may be subject to direct and indirect photolysis in sunlit surface waters. The rate of atmospheric photooxidation is moderate; however, this is 3 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 not expected to be an important environmental fate process since these substances are not likely to exist in the vapor phase in the ambient atmosphere. The constituents of the C.I. Pigment Red 48 and 52 category are expected to have high (P3) persistence except in anaerobic environments and low (Bl) bioaccumulation potential. The acute oral toxicity of C.I. Pigment Red 48 and 52 category members in rats is low. No data are available for the repeated-dose/reproductive/developmental toxicity endpoints. C.I. Pigment Red 48 barium and C.I. Pigment Red 48 calcium were not mutagenic in bacteria in vitro and are not irritating to rabbit skin or eyes. Based on the supporting chemical (C.I. Pigment Red 57), the fish 96-h LCso for the sponsored chemicals (C.I. Pigment Red 48 Calcium, C.I. Pigment Red 48 Barium, and C.I. Pigment Red 52 Calcium) is 33 mg/L. Based on the supporting chemical, the 72-h ECso for the sponsored chemicals to aquatic plants is 190 mg/L (biomass),. There are no adequate data available for acute toxicity to aquatic invertebrates. Data gaps for repeated-dose, reproductive, developmental and genetic (gene mutations and chromosomal aberrations) toxicity and acute toxicity to aquatic invertebrates were identified under the HPV Challenge Program. 4 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 The sponsor, Color Pigments Manufacturers Association, Inc., submitted a Test Plan and Robust Summaries to EPA for the C.I. Pigment Red 48 and 52 category on August 15, 2006. EPA posted the submission on the ChemRTK HPV Challenge website on August 29, 2006 (http://www.epa.gov/hpv/pubs/summaries/cird4852/cl6302tc.htm). EPA comments on the original submission were posted to the website on March 31, 2009. Public comments were also received and posted to the website. The sponsor submitted a response to EPA comments and the Organisation for Economic Cooperation and Development (OECD) SIDS Initial Assessment Report (SIAR) for the supporting chemical, C.I. Pigment Red 57 on May 27, 2009. Category Justification C.I. Pigment Red 48 Calcium (CASRN 7023-61-2) and C.I. Pigment Red 48 Barium (CASRN 7023-41-3) are different salts of the same organic compound (2-naphthalenecarboxylic acid, 4- [(5-chloro-4-methyl-2-sulfophenyl) azo]-3-hydroxy-). The structure of the organic portion of C.I. Pigment Red 52 Calcium (CASRN 17852-99-2) differs from the organic portion of C.I. Pigment Red 48 only by the position of the chlorine atom and methyl group on one of the rings. Because the three sponsored chemicals are expected to have similar physicochemical and toxicological properties, EPA agrees with the grouping of these 3 chemicals into a category. Justification for Supporting Chemicals The sponsor proposed the use of two supporting chemicals, C.I. Pigment Red 57 (CASRN 5281- 04-9) and C.I. Pigment Red 48:4 (Manganese), (CASRN 5280-66-0). EPA accepted the use of melting point data for C.I. Pigment Red 48:4 (Manganese) due to its structural similarity to the sponsored substance. C.I. Pigment Red 48:4 (Manganese), (CASRN 5280-66-0) was not used as an analog for either the health or eco endpoints. EPA accepted the use of C.I. Pigment Red 57 to satisfy aquatic toxicity endpoints because it shares a similar chemical structure with the category members and has a similar octanol/water partition coefficient, which influences toxicity to aquatic species. EPA did not accept the use of C.I. Pigment Red 57 for the human health endpoints because it does not possess the chlorine substituent that is present in all of the category members. The chlorine substituent may influence the toxicity of the sponsored substances such that toxicity differs between C.I. Pigment Red 57 and the category members. EPA has requested that the sponsor provide evidence that the chlorine substituent will not alter the basic biological effects of the sponsored chemicals (e.g., pharmacokinetic or metabolism data; comparative repeated-dose toxicity data). The comparative data for acute toxicity to mammals was not sufficient to determine whether or not C.I. Pigment Red 57 and the category members can be expected to produce similar toxicity in repeated-dose, reproductive or developmental toxicity studies or in genotoxicity studies. Although the sponsor, in their response to EPA's comments on the original submission, claimed that C.I. Pigment Red 57 is more reactive than the sponsored substances and therefore represents a worst-case scenario for toxicity, the sponsor provided no evidence to support this claim, other than higher solubility of C.I. Pigment Red 57 in water and octanol. Given that the toxicity of a substance to humans is not merely dependent upon its solubility, EPA did not accept this argument for the use of C.I. Pigment Red 57 as a supporting chemical for human health endpoints. Furthermore, the sponsor's argument that the breakdown products of C.I. Pigment Red 57 are similar to those of the category members was not an 5 ------- U.S. Environmental Protection Agency September, 2014 Hazard Characterization Document acceptable justification for the use of C.I. Pigment Red 57 as a supporting chemical because the breakdown products would still differ by the absence of the chlorine substituent. 1. Chemical Identity 1.1 Identification and Purity The purity of the substance for the health effects studies was not stated. 1.2 Physical-Chemical Properties The physical-chemical properties of the three constituents of the C.I. Pigment Red 48 and 52 category and two supporting chemicals are summarized in Table 1. The structures of these compounds are provided in the Appendix. 2-Naphthalenecarboxylic acid, 4-[2-(5-chloro-4-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 48 Calcium); 2-naphthalenecarboxylic acid, 4-[2-(5-chloro- 4-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, barium salt (1:1) (C.I. Pigment Red 48 Barium); and 2-naphthalenecarboxylic acid, 4-[2-(4-chloro-5-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 57) are red solids possessing negligible vapor pressure and low water solubility. These substances are used as pigments in inks, paints, and other materials. 2. General Information on Exposure 2.1 Production Volume and Use Pattern The C.I. Pigment Red 48 & 52 Category chemicals had an aggregated production and/or import volume in the United States between 2 and 11.5 million pounds during calendar year 2005. CASRN 7023-61-2: Non-confidential information in the IUR indicated that the industrial processing and uses of the chemical include synthetic dye and pigment manufacturing as coloring agents, pigments. Non- confidential commercial and consumer uses of this chemical include rubber and plastic products and "other." CASRN 7585-41-3: No industrial processing and use, and commercial and consumer uses were reported for the chemical. • CASRN 7023-61-2: • CASRN 7585-41-3: • CASRN 17852-99-2: 1 to < 10 million pounds ; < 500,000 pounds ; 1 to < 10 million pounds ; 6 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 1. Physical-Chemical Properties of C.I. Pigment Red 48 and 521 Property SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, calcium salt (1:1) SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, barium salt (1:1) SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(4-chloro-5- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, calcium salt (1:1) SUPPORTING CHEMICAL Manganate(l-), [4-[2-[5- chloro-4-methyl-2-(sulfo- .kappa.O)phenyl|diazenyl- .kappa.N 1 |-3-(hydroxy- .kappa.O)-2- naphthalenecarboxylato(3- )|-, hydrogen (1:1) SUPPORTING CHEMICAL 2- Naphthalenecarboxylic acid, 3-hydroxy-4-[2- (4-methyl-2- sulfophenyl)diazenyl|-, calcium salt (1:1) CASRN 7023-61-2 7585-41-3 17852-99-2 5280-66-0 5281-04-9 Molecular Weight 458.89 556.14 458.89 473.75 424.44 Physical State Red solid Red solid Red solid Red solid Red solid Melting Point No data2 No data2 No data2 360°C (measured) 357.5 (measured) Boiling Point No data2 No data2 No data2 No data2 No data2 Vapor Pressure <1.0xl0"10mm Hg at 25°C (estimated)3'4 <1.0xl0"10mm Hg at 25°C (estimated)3'4 <1.0xl0"10mm Hg at 25°C (estimated)3'4 <1.0><10"10mm Hg at 25°C (estimated)3'4 <1.0xl0"10mm Hg at 25°C (estimated)3'4 Dissociation Constant pKa = 9.07 (estimated for phenol moiety)5 pKa = 9.07 (estimated for phenol moiety)5 pKa = 9.00 (estimated for phenol moiety)5 pKa = 9.07 (estimated for phenol moiety)5 pKa = 9.24 (estimated for phenol moiety)5 7 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 1. Physical-Chemical Properties of C.I. Pigment Red 48 and 521 Property SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, calcium salt (1:1) SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, barium salt (1:1) SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(4-chloro-5- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, calcium salt (1:1) SUPPORTING CHEMICAL Manganate(l-), [4-[2-[5- chloro-4-methyl-2-(sulfo- .kappa.O)phenyl|diazenyl- .kappa.N 1 |-3-(hydroxy- .kappa.O)-2- naphthalenecarboxylato(3- )|-, hydrogen (1:1) SUPPORTING CHEMICAL 2- Naphthalenecarboxylic acid, 3-hydroxy-4-[2- (4-methyl-2- sulfophenyl)diazenyl|-, calcium salt (1:1) Henry's Law Constant <1.0><10"10 atm-m3/mol (estimated)3'4 <1.0><10"10 atm-m3/mol (estimated)3'4 <1,0x 10"10 atm-m3/mol (estimated)3'4 <1.0xl0"10 atm-m3/mol (estimated)3'4 <1.0xl0"10 atm-m3/mol (estimated)3'4 Water Solubility 3.6xl0"3 mg/L at 25°C (estimated)3'4 1.8xl0"4 mg/L at 25°C (estimated)3'4 3.6xl0"3 mg/L at 25°C (estimated)3'4 6.1xl0"4 mg/L at 25°C (estimated)3'4 8.9 mg/L at 25°C (measured); 0.02 mg/L at 25°C (estimated)3'4 Log Kow 5.38 (estimated)3'4 6.18 (estimated)3'4 5.38 (estimated)3'4 6.18 (estimated)3'4 2.5 at pH 3 (measured); 1.1 at pH 7 (measured); 4.73 (estimated)3'4 'Color Pigment Manufacturers Association. 2007. Revised Test Plan and Robust Summary for CI Pigment Red 48 and 52. Available online at http://www.epa. gov/hpv/pubs/summaries/cird4852/c 16302tc.htm as of August 14, 2012. 2Azo pigments tend to thermally decompose; if they melt, the melting point would most likely be above 300°C. Similarly, any boiling points for these substances would be well above 300°C. 3U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental Protection Agency, Washington, DC, USA. Available online at http://www.epa. gov/opptintr/exposure/pubs/episuitedl.htm as of August 14, 2012. 4Salts are typically outside the estimation domain of EPIWIN. 5SPARC; pKa/property server. Ver 4.6, Oct. 2011. Available at http://archemcalc.com/sparc as of August 14, 2012. 8 ------- Environmental Protection Agency Hazard Characterization Document September, 2014 CASRN 17852-99-2: Non-confidential information in the IUR indicated that the industrial processing and uses of the chemical include printing and printing ink manufacturing as coloring agents, pigments. Non- confidential commercial and consumer uses of this chemical include glass and ceramic products, paper products, and rubber and plastic products. 2.2 Environmental Exposure and Fate The constituents of the C.I. Pigment Red 48 and 52 category are expected to have low mobility in soil. A surrogate substance, 2-naphthalenecarboxylic acid, 3-hydroxy-4-[2-(4-methyl-2- sulfophenyl)diazenyl]-, calcium salt (1:1) (C.I. Pigment Red 57) achieved 9-12% of its theoretical biochemical oxygen demand (BOD) over a 28-day incubation period using an activated sludge inoculum and the MITI (OECD 301C) test. In general, azo dyes and pigments are considered recalcitrant under aerobic conditions; however, a variety of microorganisms can reduce the azo bond in the absence of oxygen. Volatilization is expected to be low given that these are ionic substances. The rate of hydrolysis is negligible. The rate of atmospheric photooxidation is moderate; however, this is not likely to be an important environmental fate process since these substances are not likely to exist in the vapor phase in the ambient atmosphere. Direct and indirect photolysis studies have been conducted on a number of azo dyes. The azo dyes were susceptible to indirect photolysis in natural waters containing humic acid. The direct photolysis half-life of supporting chemical 2-naphthalenecarboxylic acid, 3- hydroxy-4-[2-(4-methyl-2-sulfophenyl) diazenyl]-, calcium salt (1:1) was estimated to be about 18 days in water. Therefore, photolysis in sunlit natural waters containing humic materials may be an important environmental fate process for category members. The constituents of the C.I. Pigment Red 48 and 52 category are expected to have high (P3) persistence and low (Bl) bioaccumulation potential. The environmental fate properties are provided in Table 2. Conclusion: The C.I. Pigment Red 48 and 52 category is composed of three substances: 2- naphthalenecarboxylic acid, 4-[2-(5-chloro-4-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 48 Calcium); 2-naphthalenecarboxylic acid, 4-[2-(5-chloro- 4-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, barium salt (1:1) (C.I. Pigment Red 48 Barium); and 2-naphthalenecarboxylic acid, 4-[2-(4-chloro-5-methyl-2-sulfophenyl)diazenyl]-3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 57). The substances are red solids possessing negligible vapor pressure and low water solubility. They are expected to have low mobility in soil. A surrogate substance, 2-naphthalenecarboxylic acid, 3-hydroxy-4-[2-(4-methyl-2-sulfophenyl) diazenyl]-, calcium salt (1:1) (C.I. Pigment Red 57) is expected to be not readily biodegradable. In general, azo dyes and pigments are considered recalcitrant under aerobic conditions; however, a variety of microorganisms can reduce the azo bond under anaerobic conditions. Volatilization is expected to be low given that these are ionic substances. The rate of hydrolysis is negligible. 9 ------- Environmental Protection Agency Hazard Characterization Document September, 2014 Table 2. Environmental Fate Properties of C.I. Pigment Red 48 and 521 Property SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, calcium salt (1:1) SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, barium salt (1:1) SPONSORED CHEMICAL 2- Naphthalenecarboxylic acid, 4-[2-(4-chloro-5- methyl-2- sulfophenyl)diazenyl|- 3-hydroxy-, calcium salt (1:1) SUPPORTING CHEMICAL Manganate(l-), [4-[2-[5- chloro-4-methyl-2-(sulfo- .kappa.O)phenyl|diazenyl- .kappa.N 1 ]-3-(hydroxy- .kappa.O)-2- naphthalenecarboxylato(3- )|-, hydrogen (1:1) SUPPORTING CHEMICAL 2- Naphthalenecarboxylic acid, 3-hydroxy-4-[2- (4-methyl-2- sulfophenyl)diazenyl|-, calcium salt (1:1) CASRN 7023-61-2 7585-41-3 17852-99-2 5280-66-0 5281-04-9 Photodegradati on Half-life 11.5 hours (estimated)2'3 11.5 hours (estimated)2'3 11.5 hours (estimated)2'3 11.5 hours (estimated)2'3 11.2 hours (estimated)2'3 Hydrolysis Half- life Stable Stable Stable Stable Stable Biodegradation No data. This class of pigments are considered resistant to biodegradation under aerobic conditions, but microorganisms have been identified which reduce the azo bond under anaerobic conditions4 No data. This class of pigments are considered resistant to biodegradation under aerobic conditions, but microorganisms have been identified which reduce the azo bond under anaerobic conditions4 No data. This class of pigments are considered resistant to biodegradation under aerobic conditions, but microorganisms have been identified which reduce the azo bond under anaerobic conditions4 No data. This class of pigments are considered resistant to biodegradation under aerobic conditions, but microorganisms have been identified which reduce the azo bond under anaerobic conditions4 9-12% after 28 days (not readily biodegradable) Bioaccumulation Factor BAF = 65.2 (estimated)2'3 BAF = 51.8 (estimated)2'3 BAF = 65.2 (estimated)2'3 BAF = 83.8 (estimated)2'3 BCF = 0.7-1.8 (measured in carp at 0.3 ppb); BAF = 40.8 (estimated)2'3 Log Koc 4.1 (estimated)2'3 4.1 (estimated)2'3 4.1 (estimated)2'3 4.1 (estimated)2'3 3.9 (estimated)2'3 11 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 2. Environmental Fate Properties of C.I. Pigment Red 48 and 521 Property SPONSORED SPONSORED SPONSORED SUPPORTING SUPPORTING CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL 2- 2- 2- Manganate(l-), [4-[2-[5- 2- Naphthalenecarboxylic Naphthalenecarboxylic Naphthalenecarboxylic chloro-4-methyl-2-(sulfo- Naphthalenecarboxylic acid, 4-[2-(5-chloro-4- acid, 4-[2-(5-chloro-4- acid, 4-[2-(4-chloro-5- .kappa.O)phenyl|diazenyl- acid, 3-hydroxy-4-[2- methyl-2- methyl-2- methyl-2- .kappa.N 1 ]-3-(hydroxy- (4-methyl-2- sulfophenyl)diazenyl|- sulfophenyl)diazenyl|- sulfophenyl)diazenyl|- .kappa.O)-2- sulfophenyl)diazenyl|-, 3-hydroxy-, calcium 3-hydroxy-, barium 3-hydroxy-, calcium naphthalenecarboxylato(3- calcium salt (1:1) salt (1:1) salt (1:1) salt (1:1) )|-, hydrogen (1:1) Fugacity (Level III Model)2'3 <0.1 <0.1 <0.1 <0.1 <0.1 Air (%) 4.3 4.5 4.3 4.5 8.9 Water (%) 88.9 88.7 88.9 88.8 88.5 Soil (%) 6.8 6.7 6.8 6.7 5.6 Sediment (%) Persistence5 P3 (high) P3 (high) P3 (high) P3 (high) P3 (high) Bioaccumulation5 B1 (low) B1 (low) B1 (low) B1 (low) B1 (low) 'Color Pigment Manufacturers Association. 2007. Revised Test Plan and Robust Summary for CI Pigment Red 48 and 52. Available online at http://www.epa.gov/hpv/pubs/summaries/cird4852/cl6302tc.htm as of August 14, 2012. 2U.S.EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental Protection Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of August 14, 2012. 3Salts are typically outside the estimation domain of EPIWIN. 4LynchD. 2000. Estimating properties of synthetic organic dyes. In: Handbook of Property Estimation for Chemicals. Boethling RS; Mackay D. (eds.). Lewis Publishers, Boca Raton, FL. pp 447-467. 5Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Inderal Register 64. Number 213 (November4, 1999) pp. 60194- 60204. 12 ------- Environmental Protection Agency Hazard Characterization Document September, 2014 These substances may be subject to direct and indirect photolysis in sunlit surface waters. The rate of atmospheric photooxidation is moderate; however, this is not expected to be an important environmental fate process since these substances are not likely to exist in the vapor phase in the ambient atmosphere. The constituents of the C.I. Pigment Red 48 and 52 category are expected to have high (P3) persistence and low (Bl) bioaccumulation potential. 3. Human Health Hazard A summary of health effects data submitted for SIDS endpoints is provided in Table 3. Acute Oral Toxicity C.I. Pigment Red 48 Barium (CASRN 7585-41-3) Rats (strain, sex and number per dose not specified) were administered C.I. Pigment Red 48 (barium) (purity unknown) via gavage at unspecified doses. No other details were provided. LDso > 5000 mg/kg C.I. Pigment Red 48 Calcium (CASRN 7023-61-2) and C.I. Pigment Red 52 Calcium (CASRN 17852-99-2) Rats (strain, sex and number per dose not specified) were administered C.I. Pigment Red 48 Calcium and C.I. Pigment Red 52 Calcium (purities unknown) via gavage at unspecified doses. It is not clear if the substances were tested as a mixture or individually. No other details were provided. LD50 > 5000 mg/kg Repeated-Dose Toxicity No data are available. Reproductive Toxicity No data are available. Developmental Toxicity No data are available. Genetic Toxicity - Gene Mutation In vitro 13 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 C.I. Pigment Red 48 Barium (CASRN 7585-41-3) and C.I. Pigment Red 48 Calcium (CASRN 7023-61-2) Salmonella typhimurium (strains not specified) were exposed to C.I. Pigment Red 48 Barium and C.I. Pigment Red 48 Calcium (purities not stated) with and without activation to test for mutagenicity. It is not clear if the substances were tested as a mixture or individually. Use of controls was not specified. No further details were provided. No evidence of mutagenicity was observed. C.I. Pigment Red 48 Barium and C.I. Pigment Red 48 Calcium were not mutagenic in this assay. Genetic Toxicity — Chromosomal Aberrations No data are available. Additional Information Skin Irritation C.I. Pigment Red 48 Barium (CASRN 7585-41-3) and C.I. Pigment Red 48 Calcium (CASRN 7023-61-2) Rabbits (strain, sex and number per dose not specified) were administered C.I. Pigment Red 48 Barium and C.I. Pigment Red 48 Calcium (purities not stated) via the dermal route at unspecified doses. It is not clear if the substances were tested as a mixture or individually. No further details were provided. C.I. Pigment Red 48 Barium and C.I. Pigment Red 48 Calcium were not irritating to rabbit skin in these studies. Eye Irritation C.I. Pigment Red 48 Barium (CASRN 7585-41-3) and C.I. Pigment Red 48 Calcium (CASRN 7023-61-2) Rabbits (strain, sex and number per dose not specified) were administered C.I. Pigment Red 48 Barium and C.I. Pigment Red 48 Calcium (purities not stated) in the eye at unspecified doses. It is not clear if the substances were tested as a mixture or individually. No further details were provided. C.I. Pigment Red 48 Barium and C.I. Pigment Red 48 Calcium were not irritating to rabbit eyes in these studies. Conclusion: The acute oral toxicity of C.I. Pigment Red 48 and 52 category members in rats is low. No data are available for the repeated-dose/reproductive/developmental toxicity endpoints. C.I. Pigment Red 48 barium and C.I. Pigment Red 48 calcium were not mutagenic in bacteria in vitro and are not irritating to rabbit skin or eyes. 14 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 3. Summary of Screening Information Data Set under the U.S. HPV Challenge Program - Human Health Data Endpoints SPONSORED CHEMICAL C.I. Pigment Red 48 Calcium (7023-61-2) SPONSORED CHEMICAL C.I. Pigment Red 48 Barium (7585-41-3) SPONSORED CHEMICAL C.I. Pigment Red 52 Calcium (17852-99-2) Acute Oral Toxicity LDso (mg/kg) >5000 >5000 >5000 Repeated-Dose Toxicity Oral (mg/kg-day) No Data No Data No Data Reproductive Toxicity Oral (mg/kg-day) No Data No Data No Data Developmental Toxicity Oral (mg/kg-day) No Data No Data No Data Genetic Toxicity - Gene Mutation Negative Negative No Data Negative (RA) Genetic Toxicity - Chromosomal Aberrations No Data No Data No Data Additional Information Skin Irritation Eye Irritation Not Irritating Not Irritating Not Irritating Not Irritating - Measured data in bold text; (RA) = Read Across; - endpoint not addressed for this chemical 15 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 4. Hazard to the Environment A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 4. The table also indicates where data for the supporting chemical are read-across (RA) to untested members of the category. Acute Toxicity to Fish C.I. Pigment Red 57 (CASRN 5281-04-9; supporting chemical) (1) Japanese killifish (Oryzias latipes) were exposed to C.I. Pigment Red 57 at five nominal concentrations from 17.1 - 180 mg/L under static renewal conditions for 96 hours, using dimethyl sulfoxide (DMSO) as a dispersant. 96-h LCso = 33 mg/L (2) Japanese killifish (Oryzias latipes) were exposed to C.I. Pigment Red 57 at unspecified concentrations under flow-through conditions for 48 hours. 48-h LC50 = 50 mg/L Acute Toxicity to Aquatic Invertebrates No adequate data are available. Toxicity to Aquatic Plants C.I. Pigment Red 57 (CASRN 5281-04-9; supporting chemical) Green algae (Pseudokirchneriella subcapitata) were exposed to C.I. Pigment Red 57 at 13 nominal concentrations from 1 - 1000 mg/L under unspecified conditions for 72 hours. 72-h EC50 (biomass) = 190 mg/L Conclusion: Based on the supporting chemical (C.I. Pigment Red 57), the fish 96-h LC50 for the sponsored chemicals (C.I. Pigment Red 48 Calcium, C.I. Pigment Red 48 Barium, and C.I. Pigment Red 52 Calcium) is 33 mg/L. Based on the supporting chemical, the 72-h EC50 for the sponsored chemicals to aquatic plants is 190 mg/L (biomass),. There are no adequate data available for acute toxicity to aquatic invertebrates. 16 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 4. Summary of Screening Information Data Set under the U.S. HPV Challenge Program - Aquatic Toxicity Data Endpoints SPONSORED CHEMICAL C.I. Pigment Red 48 Calcium SPONSORED CHEMICAL C.I. Pigment Red 48 Barium SPONSORED CHEMICAL C.I. Pigment Red 52 Calcium SUPPORTING CHEMICAL C.I. Pigment Red 57 (7023-61-2) (7585-41-3) (17852-99-2) (5281-04-9) Fish 96-h LCso (mg/L) 33 (RA) 33 (RA) 33 (RA) 33 Aquatic Invertebrates 48-h ECso (mg/L) No adequate data. No adequate data. No adequate data. Aquatic Plants 72-h ECso (mg/L) Biomass 190 (RA) 190 (RA) 190 (RA) 190 Bold = experimentally-derived data; (RA) = Read Across; - endpoint not addressed for this chemical 17 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 APPENDIX Sponsored Chemicals Chemical Name CASRN Structure 2- Naphthalenecarboxyli c acid, 4-[2-(5-chloro- 4-methyl-2- sulfophenyl)diazenyl]- 3-hydroxy-, calcium salt (1:1) 7023-61-2 0=^ OH o" o-s=o 2+ II Ca o Representative SMILES: c 12c(N=Nc3 cc(Cl)c(C)cc3 S(=0)(=0)0[Ca] 5)c(0)c(C(=0)0 5)cclcccc2 2- Naphthalenecarboxyli c acid, 4-[2-(5-chloro- 4-methyl-2- sulfophenyl)diazenyl]- 3-hydroxy-, barium salt (1:1) 7585-41-3 0=^ OH o" o-s=o 2+ II Ba o Representative SMILES: c 12c(N=Nc3 cc(Cl)c(C)cc3 S(=0)(=0)0[Ba] 5)c(0)c(C(=0)0 5)cclcccc2 2- Naphthalenecarboxyli c acid, 4-[2-(4-chloro- 5-methyl-2- sulfophenyl)diazenyl]- 3-hydroxy-, calcium salt (1:1) 17852-99- 2 \ / CH, 0="( OH /=^ o" o-s=o 2+ II Ca o Representative SMILES: c 12c(N=Nc3 cc(C)c(Cl)cc3 S(=0)(=0)0[Ca]4)c(0)c(C(=0)0 4)cclcccc2 18 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Supporting Chemicals Chemical Name CASRN Structure Manganate(l-), [4-[2- [5-chloro-4-methyl-2- (sulfo- ,kappa.O)phenyl]diaze nyl-.kappa.Nl]-3- (hydroxy-.kappa.O)-2- naphthalenecarboxylat o(3-)]-, hydrogen (1:1) 5280-66-0 0=^ OH o" o-s=o 2+ II Mn O Representative SMILES: c 12c(N=Nc3 cc(Cl)c(C)cc3 S(=0)(=0)0[Mn] 5)c(0)c(C(=0)0 5)cclcccc2 2- Naphthalenecarboxyli c acid, 3-hydroxy-4- [2-(4-methyl-2- sulfophenyl)diazenyl]- , calcium salt (1:1) 5281-04-9 0=^ OH o" o-s=o 2+ II Ca 0 Representative SMILES: c 12c(N=Nc3 ccc(C)cc3 S(=0)(=0)0 [Ca] 5)c(0)c(C(=0)05)cc lcccc2 19 ------- |