FINAL DRAFT United States ECAO-CIN-P220 Environmental Protection May 1987 Agency J' -/EPA Research and Development HEALTH AND ENVIRONMENTAL EFFECTS PROFILE FOR DIRECT SKY BLUE 6B Prepared for OFFICE OF SOLID WASTE AND EMERGENCY RESPONSE Prepared by Environmental Criteria and Assessment Office Office of Health and Environmental Assessment U.S. Environmental Protection Agency Cincinnati, OH 45268 DRAFT: DO NOT CITE OR QUOTE NOTICE This document is a preliminary draft. It has not been formally released by the U.S. Environmental. Protection Agency and should not at this stage be construed to represent Agency policy. It Is being circulated for comments on its technical accuracy and policy implications. ------- DISCLAIMER This report Is an external draft for review purposes only and does not constitute Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. 11 ------- PREFACE Health and Environmental Effects Profiles (HEEPs) are prepared for the Office of Solid Waste and Emergency Response by the Office of Health and Environmental Assessment. The HEEPs are Intended to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA), as well as to provide health-related limits for emergency actions under Section 101 of the Compre- hensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and Information obtained from Agency program office files are evaluated as they pertain to potential human health, aquatic life and environmental effects of hazardous waste constituents. The literature searched and the dates of the searches are Included In the section titled "Appendix: Literature Searched.' The literature search material 1s current through November, 1985. Quantitative estimates are presented provided sufficient data are available. For systemic toxicants, these Include Reference doses (RfDs) for chronic exposures. An RfD 1s defined as the amount of a chemical to which humans can be exposed on a dally basis over an extended period of time (usually a lifetime) without suffering a deleterious effect. In the case of suspected carcinogens, RfDs are not estimated In this document series. Instead, a carcinogenic potency factor of q-j* Is provided.. These potency estimates are derived for both oral and Inhalation exposures where possible. In addition, unit risk estimates for air and drinking water are presented based on Inhalation and oral data, respectively. Reportable quantities (RQs) based on both chronic toxldty and cardno- genlclty are derived. The RQ 1s used to determine the quantity of a hazard- ous substance for which notification 1s required 1n the event of a release as specified under CERCLA. These two RQs (chronic toxldty and carcinogen- 1c1ty) represent two of six scores developed (the remaining four reflect 1gn1tab1l1ty, reactivity, aquatic toxldty and acute mammalian toxlclty). The first draft of this document was prepared by Syracuse Research Corporation under EPA Contract No. 68-03-3228. The document was subse- quently revised after reviews by staff within the Office of Health and Environmental Assessment: Carcinogen Assessment Group, Reproductive Effects Assessment Group, Exposure Assessment Group, and the Environmental Criteria and Assessment Office 1n Cincinnati. The HEEPs will become part of the EPA RCRA and CERCLA dockets. Ill ------- EXECUTIVE SUMMARY Direct Sky Blue 6B 1s a common name for the commercial azo dye Direct Blue 1, which Is produced by the dlazotlzatlon of o-d1an1s1d1ne with 4-am1no-5-hydroxy-l,3-naphthalened1sulfon1c add under alkaline conditions (Society of Dyers and Colourlsts, 1971a). It 1s very soluble 1n water but Insoluble 1n most organic solvents. It can be used to dye. stain or print cellulose, nylon, leather, paper, silk, wool, cotton or biological materials and to produce writing Inks and pigments (Society of Dyers and Colourlsts, 1971a). In 1980, four U.S. manufacturers produced 0.115 million pounds of Direct Sky Blue 6B (USITC, 1981), but only one U.S. manufacturer reported production In 1984 (USITC. 1985). Four U.S. companies currently market Direct Sky Blue 6B under various tradenames (AATCC, 1985). In 1983, -40.000 pounds of the dye was Imported Into the United States through principal customs districts (USITC, 1984). The only available data specifically regarding the environmental fate of Direct Sky Blue 68 Is a report that sorptlon to activated sludge 1s effec- tive In removing H from dye wastewaters (Leb1edowsk1 and Przyblnskl, 1980). If released to water. Direct Sky Blue 6B may be susceptible to significant adsorption because dyestuffs by their substantive nature (ability to be exhaustively deposited from aqueous baths to fibers) are likely to be adsorbed onto both sewage works sludge and silts and sediment of rivers and lakes (Brown and Laboureur, 1983). Removal of adsorbed Direct Blue 6B may occur by blodegradatlon since a number or azo dyes have been found to be substantially blodegraded under anaerobic and aerobic conditions (Brown and Laboureur, 1983; Leb1edowsk1 and Przyblnskl, 1980). In general, direct dyes are expected to be relatively stable to direct photolysis In natural waters 1v ------- (Porter, 1973), although humlc materials present In natural water may Indirectly accelerate the photodecomposUlon of azo dyes (Haag and Mill, 1985). In reducing environments, like natural water, reduction of the azo dyes to the corresponding amines Is possible (Takemura et al.. 1965). Hydrolysis, volatilization and bloconcentratlon are not expected to be significant. Therefore, Indirect photolysis, microblal degradation and adsorption are the most Important processes determining dye fate 1n water. If released to the atmosphere. Direct Sky Blue 6B will probably be associated with partlculate matter and dusts that are subject to wet and dry deposition. Based on Its reactivity with other aromatic amines (Atkinson, 1985), H 1s speculated that oxidation of this dye by HO radical 1n the atmosphere may be a significant process. If released to soil, Direct Sky Blue 6B may not leach significantly since It Is significantly adsorbed by soil. Microblal degradation or transformation within soil may occur. Photodegradatlon beyond the surface layer of soil 1s not likely. Occupational exposure to Direct Sky Blue 6B occurs during Us production and Us use 1n dyeing. Wastewater effluents are probably the major source of release to the environment. Ambient monitoring data could not be located 1n the available literature as dted 1n the Appendix. EN CAS Analytical Labs (1977a,b) reported 96-hour LC5Q values of 240 and 290 mg/i for two batches of Dlphenyl Brill Blue FF Supra for blue- gills. On the basis of CAS number, this 1s the same compound as Direct Sky Blue 6B. EN CAS Analytical Labs (1977c) also reported that waste treatment plant bacteria were unaffected by concentrations of <300 mg/l. Kon1sh1 and Hldaka (1969) found that Direct Sky Blue 6B stimulated carp chemo- receptors ]_n vitro. ------- Oral absorption of Direct Sky Blue 68 can be Inferred from toxldty data (Section 5.6.). Data concerning the distribution of Direct Sky Blue 68 after oral or Inhalation exposure could not be located In the available literature. Beaudoln and Pickering (1960) gave pregnant rats Intraperlto- neal Injections of Direct Sky Blue 68 and observed staining of nuclei of macrophages of maternal tissue. The yolk sac also contained a small amount of the dye. Lynn et al. (1980) orally dosed rats and dogs with Direct Sky Blue 68 and observed 3,3'-d1methoxybenz1d1ne In the urine of both these species, and the rat urine also contained N-acetyl-3,3'-d1methoxybenz1d1ne. The rats and dogs excreted small amounts of 3,3'-d1methoxybenz1d1ne after 72 and 48 hours, respectively. Pertinent data regarding the carclnogenldty of Direct Sky Blue 6B could not be located In the available literature as cited In the Appendix. How- ever, 3,3'-d1methoxybenz1d1ne (o-d1an1s1d1ne) 1s found In urine of workers & occupatlonally exposed to dyes derived from o-dlanlsldlne (NIOSH, 1980; OSHA/NIOSH, 1980). Positive results were obtained for S. typhlmurlum strain TA98 with metabolic activation by S-9 (Prlval et al., 1982, 1984; Prlval and Mitchell, 1982). Mutagenlc activity was enhanced when FHN was added as a reducing agent. Prlval and Mitchell (1982) found unlnduced hamster S-9 enhanced mutagenlcUy to a greater extent than did Induced rat S-9. Direct Sky Blue 68 did not Induce UDS j£ vivo or Iji vitro (Joachim and Decad, 1984). No data regarding the teratogenlc effects of Direct Sky Blue 68 after oral or Inhalation exposure were available; a few studies by the Intra- peMtoneal route were available. Beaudoln (1968) observed dose-relaled Increased resorptlons and malformations In rats at >140 mg/kg/day. Amels et al. (1977) observed a dose-related Increase 1n ocular malformations In rats given 1ntraper1toneal doses >100 mg/kg of Direct Sky Blue 68. Maternal v1 ------- toxldty was observed In mice given 250 mg/kg/day IntraperHoneally (Chernoff and Kavlock, 1983). Pertinent data regarding other reproductive effects or subchronlc and chronic toxldty of Direct Sky Blue 6B could not be located In the available literature as cited In the Appendix. The oral LD-- Is >5 mg/kg (M.B. Research Laboratories, 1978), and rats exposed by Inhalation to 18.94 mg/l for 4 hours were essentially unaffected by Direct Sky Blue 68, except for hyperact1v1ty (Southwest Foundation for Research and Education, 1979). The lack of chronic and subchronlc toxldty and carclnogenldty data precludes the derivation of an RfD, RQ, q * and F factor. Although carclnogenldty data In humans and animals are Inadequate, the fact that 3,3'-d1methoxybenz1d1ne, a known EPA Group B2 carcinogen, 1s a metabolite of the dye warrants placing Direct Sky Blue 6B 1n EPA Group B2: probable human carcinogen. This category Includes all agents with sufficient evidence on cardnogenldty In animals and Inadequate evidence or no data of cardno- genlclty In humans (U.S. EPA, 1986c). vll ------- TABLE OF CONTENTS 1. INTRODUCTION 1 1.1. STRUCTURE AND CAS NUMBER 1 1.2. PHYSICAL AND CHEMICAL PROPERTIES 1 1.3. PRODUCTION DATA 2 1.4. USE DATA 4 1.5. SUMMARY 4 2. ENVIRONMENTAL FATE AND TRANSPORT PROCESSES 5 2.1, HATER 5 2.1.1. Hydrolysis 5 2.1.2. Oxidation/Reduction .... 5 2.1.3. Photolysis 5 2.1.4. Mlcroblal Degradation 6 2.1.5. Volatilization 6 2.1.6. Adsorption 6 2.1.7. B1oconcentrat1on 7 2.2. AIR 7 2.3. SOIL 7 2.4. SUMMARY 8 3. EXPOSURE 10 3.1. WATER 10 3.2. FOOD . . . 11 3.3. INHALATION 11 3.4. DERMAL 11 3.5. SUMMARY 11 4. PHARMACOKINETCS 12 4.1. ABSORPTION 12 4.2. DISTRIBUTION 12 4.3. METABOLISM 12 4.4. EXCRETION 13 4.5. SUMMARY 13 5. EFFECTS 14 5.1. CARCINOGENICITY 14 5.2. MUTAGENICITY 14 5.3. TERATOGENICITY 14 5.4. OTHER REPRODUCTIVE EFFECTS 17 5.5. CHRONIC AND SUBCHRONIC TOXICITY 17 5.6. OTHER RELEVANT INFORMATION 17 5.7. SUMMARY 18 ------- TABLE OF CONTENTS (cont.) Page 6. AQUATIC TOXICITY 20 6.1. ACUTE 20 6.2. CHRONIC. 20 6.3. PLANTS 20 6.4. RESIDUES 20 6.5. OTHER RELEVANT INFORMATION 20 6.6. SUMMARY 20 7. EXISTING GUIDELINES AND STANDARDS 22 7.1. HUMAN 22 7.2. AQUATIC 22 8. RISK ASSESSMENT 23 9. REPORTABLE QUANTITIES 25 9.1. REPORTABLE QUANTITY (RQ) RANKING BASED ON CHRONIC TOXICITY 25 9.2. WEIGHT OF EVIDENCE AND POTENCY FACTOR (F=1/ED-|0) FOR CARCINOGENICITY 25 10. REFERENCES. . - 27 APPENDIX: LITERATURE SEARCHED 34 ------- LIST OF ABBREVIATIONS BOD Biochemical oxygen demand CAS Chemical Abstract Service DHSO Dimethyl sulfoxlde DNA Deoxyr1bonucle1c add FMN Flavin mononucleotlde GC Gas chromatography Kow Octanol/water partition coefficient LCso Concentration lethal to 50% of recipients LD50 Dose lethal to 50% of recipients MS Mass sectrometry ppm Parts per million RfD Reference dose RQ Reportable quantity UDS Unscheduled DNA synthesis ------- 1. INTRODUCTION 1.1. STRUCTURE AND CAS NUMBER Direct Sky Blue 68 1s commonly referred to as Direct Blue 1. The Colour Index reference number 1s C.I. 24410 (Society of Dyers and Colourlsts, 1971a,b). The current CAS designation for Direct Sky Blue 68 1s 1,3-naph- thalenedlsulfonlc add, 6,6'-[3,3'-d1methoxy[l,1'-b1phenyl]-4,4'-d1yl)b1s- azo]-b1s[4-am1no-5-hydroxy-]tetrasod1um salt. It Is a 3,3'-d1methoxybenz1- dlne (o-d1an1s1d1ne) based dye. Direct Blue 1 Is currently marketed 1n the United States under the tradenames Atlantic Direct Sky Blue 68 Ex. 300X (Atlantic Indust.}, Cylcofast Sky Blue (C. Lever Co. Inc.), Direct Brilliant Sky Blue 6B Concentrate (Crompton and Knoules Corp.) and Elcomlne Sky Blue 68 (International Dyestuffs Corp.) (AATCC, 1985). Various synonyms and trade names for this compound are Direct Blue 68, Direct Blue 6BS, Direct Sky Blue 6B. Direct Sky Blue 6BS and Niagara Sky Blue 6B (RTECS, 1981-1982). The structure, empirical formula and CAS- Registry number for Direct Sky Blue 68 are as follows: CH.O PCM, SO.NI N-N SO,Ma Molecular weight: 992.8 Empirical formula: C04H0.N,01,S.Na,l 34 24 o ID 4 4 CAS Registry number: 2610-05-1 1.2. PHYSICAL AND CHEMICAL PROPERTIES Direct Sky Blue 68 1s very soluble 1n water where 1t forms a bright blue solution, slightly soluble 1n ethylene glycol monoethyl ether and Insoluble In most other organic solvents (Society of Dyers and Colourlsts, 1971a). All direct dyes are water soluble and form anlons by dissociation (Kuehnl et 0854p -1- 04/29/87 ------- al., 1979). In aqueous solution, the molecules of direct dyestuffs are linked by hydrogen bonds forming larger agglomerates or colloidal solutions, which reduces their solubility and promotes disposition on celluloslc fibers. The structure of these agglomerates allows firm linkage to the cellulose molecule by multiple hydrogen bonds (Kuehnl et al., 1979). Physical properties such as melting point, boiling point, vapor pres- sure, density and log K could not be located In the available litera- ture. Lack of appropriate parameter values precluded the computer calcula- tion of log KQW (U.S. EPA, 1986a). The air conversion factor for Direct Sky Blue 6B 1s 1 ppm = 41 mg/m3. The manufacture and testing of Direct Sky Blue 6B probably do not conform to rigid chemical specifications, and Us composition may vary In order to meet shade and Intensity requirements. 1.3. PRODUCTION DATA Direct Sky Blue 68 1s produced by coupling o-d1an1s1d1ne to 2 mol of Chicago add (4-am1no-5-nydroxy-l.3-naphthalened1sulfon1c add) under alkaline conditions (Society of Dyers and Colourlsts, 1971a). In 1980, four U.S. manufacturers produced 0.115 million pounds of Direct Sky Blue 6B (USITC, 1981), the most recent production figure available; In 1984, Atlantic Industries was the only manufacturer listed (USITC, 1985). Four U.S. companies currently market Direct Sky Blue 6B under various trade- names (AATCC, 1985). The production data available from the public portion of the U.S. EPA TSCA production file for 1977 are listed 1n.Table 1-1. 0854p -2- 04/29/87 ------- TABLE 1-1 Direct Sky Blue 6B Production Data for 1977* Producer/Location Manfacturer or Importer Production Range (thousands of pounds) FabMcolor Inc. Paterson, NJ Hobay Chemical Bayonne. NJ Atlantic Chemical Nutley, NJ American Research Products South Euclid. OH Toms River Chemical Toms River, NJ Hilton-Davis Chemical Cincinnati, OH Harshaw Lowell. NC GAF Corp. Rensselaer, NY DuPont Deepwater. NJ Marubeni American Corp. New York, NY Uglne Kuhlmann of America Paramus, NJ American Hoechst BMdgewater, NJ manufacturer manufacturer manufacturer manufacturer manufacturer manufacturer manufacturer manufacturer manufacturer Importer Importer Importer none confidential 10-100 confidential confidential none 1-10 10-100 none confidential confidential confidential 'Source: U.S. EPA, 1977 0854p -3- 09/26/86 ------- Importation of Direct Sky Blue 68 through principal U.S. customs districts 1n recent years was reported as follows (USITC, 1982, 1983, 1984): Import Volume Year _ (pounds) 1983 39,991 1982 13,229 1981 14,189 1.4. USE DATA Direct Sky Blue 6B 1s a dye that can be used to dye cellulose, nylon, leather and paper; print cellulose and nylon; stain silk, wool, cotton and biological materials; and produce writing Inks and pigments (Society of Dyers and Colourlsts, 1971b). 1.5. SUMMARY Direct Sky Blue 6B Is a common name for the commercial azo dye Direct Blue 1, which Is produced by the dlazotlzatlon of o-d1an1s1d1ne with 4-am1no-5-hydroxy-l,3-naphthalened1sulfon1c add under alkaline conditions (Society of Dyers and Colourlsts, 1971a). It Is very soluble 1n water but Insoluble In most organic solvents. It can be used to dye, stain or print cellulose, nylon, leather, paper, silk, wool, cotton or biological materials and to produce writing Inks and pigments (Society of Dyers and Colourlsts, 1971b). In 1980, four U.S. manufacturers produced 0.115 million pounds of Direct Sky Blue 6B (USITC, 1981), but only one U.S. manufacturer reported production 1n 1984 (USITC, 1985). Four U.S. companies currently market Direct Sky Blue 68 under various tradenames (AATCC, 1985). In 1983, -40,000 pounds of the dye was Imported Into the United States through principal customs districts (USITC, 1984). 0854p -4- 04/29/87 ------- 2. ENVIRONMENTAL FATE AND TRANSPORT PROCESSES 2.1. WATER 2.1.1. Hydrolysis. Experimental hydrolysis data could not be located In the available literature; however, Direct Sky Blue 68 does not contain functional groups that are readily susceptible to environmental hydrolysis. Therefore, hydrolysis 1s not expected to be environmentally relevant. 2.1.2. Oxidation/Reduction. Specific experimental data on oxidation/ reduction of Direct Sky Blue 68 could not be located In the available literature. Takemura et al. (1965) reported that bubbling H_S through a pure azo-dye solution yields aromatic amines and suggested that azo dyes 1n wastewater may be reduced at the azo linkage (by H.S or S02 In the water) to form Intermediates such as benzldlne or naphthylamlne from which the dye was produced. One possible source of aromatic amines detected In a polluted river water In Japan was speculated to be due to the reduction of azo dyes discharged In the river by H^S or SO- 1n the river (Takemura et al., 1965). 2.1.3. Photolysis. Porter (1973) examined the photodegradatlon rate In aqueous solution of 8 direct dyes and 12 other azo dyes In artificial light and 1 direct and 1 add dye In natural sunlight. Based on the experimental results, the author concluded that direct dyes are relatively stable to direct photolysis 1n natural waters. Although Direct Sky Blue 68 was not one of the dyes studied, Us structure 1s similar to several dyes that were tested. Haag and Mill (1985) examined the aqueous photodegradatlon rate of 15 azo days by simulated or natural sunlight. Significant direct photolysis was observed for some dyes; however, humlc materials In natural water were 0854p -5- 03/25/87 ------- found to strongly accelerate the Indirect photodecomposltlon rate of all the dyes. Therefore, Indirect photolysis may be an Important removal mechanism for azo dyes In the aquatic environment. 2.1.4. M1crob1al Degradation. Mlcroblal degradation data specific to Direct Sky Blue 6B are limited. An abstract of a Polish study {Lebledowskl and Przyb1nsk1, 1980) reported that activated sludge treatment of dyeing wastewaters containing this dye reduced the BOD by 30-50% In 2-2.5 hours. Brown et al. (1981) reported that Direct Sky Blue 6B Is not likely to have a significantly Inhibiting effect during sewage treatment. Brown and Laboureur (1983) reported that a number of azo dyes were substantially blodegraded under anaerobic test conditions and suggested that the breakdown of dyestuffs 1n the environment may be Initiated under anaerobic conditions. 2.1.5. Volatilization. Experimental volatilization data could not be located In the available literature; however, since Direct Sky Blue 6B Is soluble In water (Society of Dyers and Colourlsts, 1971a) and Is expected to have a relatively low vapor pressure because of Its lonlzatlon ability, a relatively small Henry's Law constant 1s expected. Therefore, volatiliza- tion from water Is not expected to be significant In the environment. 2.1.6. Adsorption. Oyestuffs by their substantive nature (ability to be exhaustively deposited from aqueous baths to fibers) are likely to be adsorbed onto both sewage works sludge and onto silts and sediments of rivers and lakes (Brown and Laboureur, 1983). In conventional biological waste treatment systems, soluble dye removal usually occurs when the dye 1s adsorbed onto sludge (Porter, 1973). It was reported that the sorptlon properties of activated sludge contribute to the purification of Sky Blue 68 from dyeing wastewaters (Lebledowskl and Przyblnskl, 1980). Sewage works sludge Is usually treated by anaerobic digestion or landfllUng. 0854p -6- 03/25/87 ------- Removal of dye from the sludge must therefore occur by anaerobic blodegrada- tlon. Similar anaerobic conditions exist 1n many lakes and rivers with respect to adsorbed material on silts and sediments and, therefore, adsorbed dyes may be subject to anaerobic blodegradatlon 1n the environment (Brown and Laboureur, 1983). 2.1.7. B1oconcentrat1on. Experimental bloconcentratlon data could not be located 1n the available literature. Since Direct Sky Blue 6B 1s water soluble {Society of Dyers and Colourlsts, 1971a), bloconcentratlon 1n aquatic organisms Is not expected to be significant. 2.2. AIR Direct Sky Blue 6B 1n the atmosphere Is most likely to be associated with partlculate matter and dusts, especially from atmospheric effluents resulting from Us production and use. These partlculate matter and dusts are subject to wet and dry deposition. Aromatic amines are known to be very reactive (half-life of a few hours) with HO radical' In the atmosphere (Atkinson. 1985). Therefore, since this dye also contains aromatic amlne groups, H may also react with atmospheric HO radical. 2.3. SOIL Pertinent experimental data on the fate of Direct Sky Blue 6B 1n soil could not be located 1n the available literature. Chemical degradation may not occur significantly since dyes, 1n general, are resistant to common oxldants such as ozone, chlorine and nitrogen oxides (Porter, 1973) and hydrolysis Is not expected to be environmentally relevant. If significant removal cf Direct Sky Blue 6B 1s to occur 1n soil, mlcroblal degradation may be the environmental fate process Involved. A number of azo dyes have been shown to be susceptible to anaerobic blodegradatlon (Brown and Laboureur, 1983). Photodegradatlon of Direct Sky Blue 68 beyond the surface layers may not be significant. 0854p -7- 03/25/87 ------- Since Direct Sky Blue 68 Is water soluble (Society of Dyers and Colour- 1sts, 1971a), leaching In soil might be expected; however, the substantive nature of dyestuffs (Brown and Laboureur, 1983), Including the direct dyes (Kuehnl et al.t 1979), Indicates that significant adsorption to soil may occur. Therefore, significant leaching In soil may not occur. 2.4. SUMMARY The only available data specifically regarding the environmental fate of Direct Sky Blue 6B 1s a report that sorptlon to activated sludge 1s effec- tive 1n removing 1t from dye wastewaters (Leb1edowsk1 and Przyblnslcl, 1980). If released to water, Direct Sky Blue 6B may be susceptible to significant adsorption because dyestuffs by their substantive nature (ability to be exhaustively deposited from aqueous baths to fibers) are likely to be adsorbed onto both sewage works sludge and onto silts and sediment of rivers and lakes (Brown and Laboureur, 1983). Removal of adsorbed Direct Blue 6B may occur by blodegradatlon since a number of azo dyes have been found to be substantially blodegraded under anaerobic and aerobic conditions (Brown and Laboureur, 1983; Lebledowskl and Przyblnskl, 1980). In general, direct dyes are expected to be relatively stable to direct photolysis In natural waters (Porter, 1973), although humlc materials present In natural water may Indirectly accelerate the photodecompos1t1on of azo dyes (Haag and Mill, 1985). In reducing environments, like natural water, reduction of the azo dyes to the corresponding amines Is possible (Takemura et a!., 1965). Hydrolysis, volatilization and bloconcentratlon are not expected to be significant. Therefore, Indirect photolysis, mlcroblal degradation and adsorption are the Important fate processes In water. 0854p -8- 03/26/87 ------- If released to the atmosphere, Direct Sky Blue 68 will probably be associated with partlculate matter and dusts that are subject to wet and dry deposition. Based on Its reactivity with other aromatic amines (Atkinson, 1985), H Is speculated that oxidation of this dye by HO radical In the atmosphere may be a significant process. If released to soil, Direct Sky Blue 68 may not leach significantly since dyestuffs are susceptible to significant adsorption. M1crob1al degradation or transformation within soil may occur. Photodegradatlon beyond the surface layer of soil Is not likely. 0854p -9- 03/25/87 ------- 3. EXPOSURE Direct Sky Blue 68 has not been reported to occur In nature; therefore, exposure from natural sources 1s not expected to occur. Occupational exposure to Direct Sky Blue 6B occurs during Us production and use for the dyeing of various products. Likely routes of exposure are Inhalation of partlculates and dermal exposure. A National Occupational Hazard Survey conducted during 1972-1974 estimated that 1141 U.S. workers are potentially exposed to Direct Sky Blue 6B 1n an occupational setting (NIOSH, 1984). 3.1. HATER Pertinent monitoring data for Direct Sky Blue 68 could not be located In the available literature as cited 1n the Appendix. For the organic dye Industry, In general, H was estimated that -90% of the dye Is taken up by the fabric, while 10% 1s lost to wastewater effluents during dye operations (Porter, 1973; Brown et al., 1981). Loss of dyes to wastewater effluents during manufacture were estimated to be 1-2% (Brown et al., 1981). Haste streams from dye manufacture contain dissolved Inorganic salts and small amounts of dye and dye Intermediates (Steadman et al., 1977). Hastewater effluents are therefore the major source of release to water; the efficiency of wastewater treatment operations will determine the amount of dye that reaches natural water. Release of dye from textile fabrics may occur from commercial or consumer washing; however, dyes In most finished products are considered to be essentially "fast* (they do not migrate or wash out) (Jones, 1979). Various after-treatments are commonly applied to fabrics dyed with direct dyes to Improve their colorfastness (Kuehnl et al., 1979). 0854p -10- 03/25/87 ------- 3.2. FOOD Pertinent monitoring data regarding exposure to Direct Sky Blue 68 through food could not be located 1n the available literature as dted In the Appendix. 3.3. INHALATION Ambient air or occupational monitoring data could not be located 1n the available literature as dted 1n the Appendix. Ambient atmospheric emissions may occur from ventilation of effluents at production and use sites. In addition, air effluents from production opera- tions, such as spray drying, may be sources of release. Partlculate emis- sions from these sources are usually filtered at plant sites, which should reduce significantly the amount of partlculate matter actually reaching the ambient atmosphere. 3.4. DERMAL Pertinent dermal exposure data could not be located 1n the available literature as dted .In the Appendix. The general public 1s exposed mainly to finished dyes after they have been applied to the product; however, according to one author there 1s little chance of dyes coming off 1n perspiration, saliva or washings 1f label Instructions are followed (Jones, 1979). 3.5. SUMMARY Occupational exposure to Direct Sky Blue 6B occurs during Its production and Us use 1n dyeing. Hastewater effluents are probably the major source of release to the environment. Ambient monitoring data could not be located In the available literature as cited In the Appendix. 0854p -11- 04/29/87 ------- 4. PHARHACOKINETICS 4.1. ABSORPTION Pertinent data regarding the absorption of Direct Sky Blue 6B could not be located In the available literature as cited In the Appendix. Oral absorption can be Inferred from toxUHy data (Section 5.6.). 4.2. DISTRIBUTION Beaudoln and Pickering (1960) studied the distribution of Direct Sky Blue 6B In pregnant Sherman rats. Fifteen rats were Injected Intraperlto- neally on gestation day 8 with a dose of 14 mg/100 g (140 mg/kg) In a 2% aqueous solution. Rats were sacrificed on day 20 of gestation, and maternal lungs, liver, uterus, ovary, spleen, lymph nodes, kidneys and placenta were examined for the presence of dye. Direct Sky Blue 6B was sparsely distrib- uted 1n the macrophages of the tissues, often staining the nuclei, rather than being present as granules In the cytoplasm. In the kidney, all nuclei were stained Including the nuclei of the glomerull and Bowman's capsule. The yolk sac contained a small amount of Direct Sky Blue 6B. 4.3. METABOLISM Lowry et al. (1980) observed dlmethoxybenzldlne In the urine of workers occupatlonally exposed to 3,3'-d1methoxybenz1d1ne-based dyes. Similar results were reported by Genln (1977). Lynn et al. (1980) studied the metabolism of Direct Sky Blue 6B In rats and dogs. Four male Sprague-Dawley rats were given a single 100 mg/kg dose of Direct Sky Blue 68 by gavage. Urine was collected at 24-hour Intervals and analyzed for 3,3'-dlmethoxy- benzldlne by GC-MS. Two female mongrel dogs were given a single dose (100 mg/kg) of Direct Sky Blue 68 In the dtet. Urine was collected at 24-hour Intervals for 3 days and analyzed for 3,3'-d1methoxybenz1d1ne. Control urine was collected from all rats and dogs used 1n the study before they 0854p -12- 09/26/86 ------- were dosed. Urine from dosed rats and dogs contained 3,3'-dlmethoxy- benzldlne, and the rat urine was found to contain N-acetyl-3,3'-dlmethoxy- benzldlne. 4.4. EXCRETION After 72 hours rats excreted 0.55*0.37% (meanfSD from four animals) of the Direct Sky Blue 6B administered as 3.3'-dlmethoxybenzldlne (Lynn et al., 1980). In dogs, 0.08X (mean from two animals) of the administered dose was excreted as 3.3'-d1methoxybenz1d1ne 48 hours after dosing. 4.5. SUMMARY Oral absorption of Direct Sky Blue 6B can be Inferred from toxldty data (Section 5.6.). Data concerning the distribution of Direct Sky Blue 6B after oral or Inhalation exposure could not be located 1n the available literature. Beaudoln and Pickering (I960) gave pregnant rats Intraperlto- neal Injections of Direct Sky Blue 6B and observed staining of nuclei of macrophages of maternal tissue. The yolk sac also contained a small amount of the dye. Lynn et al. (1980) orally dosed rats and dogs with Direct Sky Blue 6B and observed 3.3'-dlmethoxybenz1d1ne 1n the urine of both these species, and the rat urine also contained N-acetyl-3,3'-d1methoxybenz1d1ne. The rats and dogs excreted small amounts of 3,3'-dlmethoxybenzldlne after 72 and 48 hours, respectively. 0854p -13- 03/25/87 ------- 5. EFFECTS 5.1. CARCINOGEMICITY Pertinent data regarding the carclnogenldty of Direct Sky Blue 66 to laboratory animals could not be located In the available literature as cited 1n the Appendix. Direct Sky Blue 6B was not scheduled for testing by the National Toxicology Program (NTP, 1986). Genln (1977) found five cases of bladder tumors In an unspecified number of workers occupational^ exposed to dyes with a latency period of -18-43 years. 3,3'-01methoxybenz1d1ne 1n quantities from trace amounts to 0.3 yg/mi were measured 1n the urine of 3/22 workers exposed to dlmethoxy- benzldlne-based dyes. Direct Sky Blue 6B was not specifically mentioned, however. 5.2. MUTAGENICITY Direct Sky Blue 6B has been tested for mutagen1c1ty and genotoxlclty; details of these tests are summarized 1n Table-5-1. PMval et al. (1982, 1984} and PMval and Mitchell (1982) found that the presence of FHN was required for Direct Sky Blue 6B to produce at least a 2-fold Increase of mutants compared with the control. Prlval and Mitchell (1982) found that unlnduced hamster S-9 greatly enhanced the number of mutations compared with Induced rat S-9. Joachim and Decad (1984) found that Direct Sky Blue 6B was negative 1n a rat hepatocyte UDS assay, both after the compound was given to rats by gavage and after the compound was Introduced Into the cell cultures. 5.3. TCRA7C6ENICITY Pertinent data regarding the teratogenlc effects of Direct Sky Blue 68 after oral or Inhalation exposure could not be located 1n the available literature as cited 1n the Appendix. 0854p -14- 04/29/87 ------- TABLE 5-1 Hulagenlctty Testing of Direct Sky Blue 6B Assay Reverse •illation Reverse oulalton Reverse •utatton UDS UOS Indicator Organ Urn Salconella typhlaur lua TA98 S. typhlnurlua TA9B S. tvDhlaurlua TA1538 rat hepatocytes rat hepatocytes Purity coonerctal grade connerclal grade technical grade technical grade technical grade Application plate Incorporation plate Incorporation plate Incorporation cell culture gavage. In vitro Concentration or Dose 0.1-1.0 lAol/plate 100-1000 vg/plale 50-500 Mg/«t SOO «g/kg Activating System »S-9. tfNN; »S-9. -ItW »S-9. »FHN iS-9 none NA Response Connents » FHN Increased nuta- » genlc activity » rat S-9 Induced or hamster S-9 unlnduced used; hamster S-9 enhanced autagentc activity ^ no reduction systea used •Icroscoplc exam Indicated that dye did not enter the cells only one dose tested Reference Prlval el al.. 198?. 1984 Prlval and Mitchell. 1982 Joachln and Oecad. 19U4 Joachla and Decad. I9U4 Joachla and Decad. 19U4 HR . Hot reported; NA - not applicable ------- A study by Beaudoln (1968) showed DUect Sky Blue 68 to be teratogenfc In Hlstar rats after Intraperltoneal Injection. Groups of 5-18 rats were Injected Intraperltoneally with a 2% aqueous solution of Direct Sky Blue 68 on gestation day 8 at doses of 70, 140 or 200 mg/kg. At the same time, 15 control rats were Injected with distilled water. Dams were killed on day 20, uteri were removed and the number of resorptlon sites and live fetuses were counted. Fetuses were fixed In Bouln's fluid or 95% alcohol for later examination. The resorptlon rate of the low-dose group was similar to that of the control, while the two highest dose groups showed a dose-related Increase In resorptlons. No malformed survivors were found In the lowest dose group, while the 140 and 208 mg/kg groups showed dose-related Increases 1n the number of malformations. Anomalies Included anophthalmla, hydro- cephalus, exencephaly, m1crophthalm1a and megalophthalmla. Fetal weights were significantly (p=0.01) reduced 1n the 200 mg/kg dye-treated group as compared with controls. Exposure to the highest dose caused maternal death. Eleven dams receiving an unspecified dose of Direct Sky Blue 68 showed a decrease 1n weight gain, which was most significant during days 8-13. Chernoff and Kavlock (1983) Injected 30 pregnant CD-I mice Intraperlto- neally on gestation day 8 with 250 mg/kg Direct Sky Blue 6B In distilled water. At the same time, 40 control mice received Injections of distilled water. Dams were allowed to give birth naturally, but dams that did not give birth by postnatal day 3 were sacrificed, and their uteri examined for Implantation sites. Mice treated with Direct Sky Blue 68 did not give birth to live offspring. The dose level used leu to maleinal death and a decrease In maternal weight gain. Amels et al. (1977) Injected an unspecified number of pregnant Hlstar rats and Houdet rats IntraperHoneally with 100, 150 or 200 mg/kg Direct Sky 0854p -16- 09/26/86 ------- Blue 68 In aqueous solution on day 9 of gestation. Rats were killed on days 12-18 and 20 of pregnancy. Fetuses were examined for abnormalities, particularly for ocular malformations. Treatment of control animals was not specified, and results were tabulated without the day of sacrifice speci- fied. The number of ocular malformations showed a dose-related Increase. Only two other unspecified structural abnormalities were noted In the 133 fetuses examined. No Information concerning maternal toxlclty was provided. 5.4. OTHER REPRODUCTIVE EFFECTS Pertinent data regarding the reproductive effects of Direct Sky Blue 6B could not be located 1n the available literature as cited 1n the Appendix. 5.5. CHRONIC AND SUBCHRONIC TOXICITY Pertinent data regarding the chronic and subchronlc toxUHy of Direct Sky Blue 6B could not be located In the available literature as dted 1n the Appendix. 5.6. OTHER RELEVANT INFORMATION The acute oral toxUHy of Direct Sky Blue 6B was Investigated by M.B. Research Laboratories (1978). Five male and five female Wlstar rats received 5 g/kg Direct Sky Blue 6B by oral Intubation, and were observed for 14 days after dosing. No rats died during the study. Indicating that the acute oral LD5Q In rats 1s >5 g/kg. The acute Inhalation toxldty of Direct Sky Blue 6B was Investigated by Southwest Foundation for Research and Education (1979). Five male and five female Sprague-Dawley rats were exposed for 4 hours to the highest airborne concentration obtainable (18.94 mg/i). The rats were observed for 14 days after exposure. No deaths occurred, but nine of the rats appeared hyper- active. At necropsy, no abnormalities that could be considered chemically- related were observed. 0854p -17- 09/26/86 ------- Acute dermal toxUHy of Direct Sky Blue 68 was studied 1n New Zealand HhHe rabbits by M. B. Research Laboratories (1978). A dose of 2.0 g/kg Direct Sky Blue 6B was placed on the clipped and abraded backs of four rabbits and covered with gauze and Impervious material. After 24 hours, the dye was washed off with warm tap water; 1 hour later the sites were graded. Direct Sky Blue 68 was found to be minimally Irritating. Rabbits were observed for 14 days, then necropsled. At necropsy, no abnormalities were observed. Eye Irritation of Direct Sky Blue 68 was studied In six New Zealand White rabbits (M.B. Research Laboratories. 1978). A dose of 0.1 g was placed In the lower conjunctiva! sac of one eye of each rabbit and the lid shut for 1 second. The eyes were graded at 1, 24, 48 and 72 hours after dosing according to accepted protocol. The results of this study classified Direct Sky Blue 68 as moderately Irritating. 5.7. SUMMARY Pertinent data regarding the cardnogenlcHy of Direct Sky Blue 68 could not be located In the available literature as cited In the Appendix. Posi- tive results were obtained for £. typhlmurlum strain TA98 with metabolic activation by S-9 (Prlval et al., 1982, 1984; Prlval and Mitchell, 1982). Mutagenlc activity was enhanced when FMN was added as a reducing agent. Prlval and Mitchell (1982) found unlnduced hamster S-9 enhanced mutagenlclty to a greater extent than did Induced rat S-9. Direct Sky Blue 6B did not Induce UDS In. vivo or Vn vitro {Joachim and Decad, 1984). No data regarding the teratogenlc effects of Direct Sky Blue 6B after oral or Inhalation exposure were available; a few studies by the Intra- perltoneal route were available. Beaudoln (1968) observed dose-related Increased resorptlons and malformations In rats at >140 mg/kg/day. Amels et 0854p -18- 04/29/87 ------- al. (1977) observed a dose-related Increase In ocular malformations )n rats given Intraperltoneal doses >100 mg/kg of Direct Sky Blue 68. Maternal toxldty was observed In mice given 250 mg/kg/day IntraperHoneally (Chernoff and Kavlock, 1983). Pertinent data regarding other reproductive effects or subchronlc and chronic toxldty of Direct Sky Blue 68 could not be located In the available literature as cited 1n the Appendix. The oral LD-Q 1s >5 mg/kg (M.B. Research Laboratories, 1978), and rats exposed by Inhalation to 18.94 mg/8. for 4 hours were essentially unaffected by Direct Sky Blue 6B, except for hyperactWHy (Southwest Foundation for Research and Education. 1979). 0854p -19- 09/26/86 ------- 6. AQUATIC TOXICITY 6.1. ACUTE EN CAS Analytical Labs (1977a,b) reported 96-hour LC5Q values of 240 and 290 mg/i for two different batches of Dlphenyl Brill Blue FF Supra (CAS No. 2610-05-1) for bluegllls, Lepomls macrochlrus. 6.2. CHRONIC Pertinent data regarding the chronic toxlclty of Direct Sky Blue 6B to aquatic organisms could not be located 1n the available literature as cited In the Appendix. 6.3. PLANTS Pertinent data regarding the effects of Direct Sky Blue 68 on aquatic plants could not be located 1n the available literature as cited 1n the Appendix. 6.4. RESIDUES Pertinent data regarding Direct Sky Blue 6B residues In aquatic biota could not be located 1n the available literature as cited In the Appendix. 6.5. OTHER RELEVANT INFORMATION •i Kon1sh1 and Hldaka (1969) reported that Direct Sky Blue 6B stimulated carp, Cyprlnus carplo. chemoreceptors In vitro. Klyohara et al. (1984) reported that Direct Sky Blue 68 was used as a selective stain for tastebuds 1n various fish species. EN CAS Analytical Labs (1977c) reported that Dlphenyl Brill Blue FF Supra had no effect on waste treatment plant bacteria at concentrations <300 mg/i, the highest concentration tested. 6.6. SUMMARY EN CAS Analytical Labs (1977a,b) reported 96-hour LC5Q values of 240 and 290 mg/l for two batches of Dlphenyl Brill Blue FF Supra for blue- gllls. On the basis of CAS number, this Is the same compound as Direct Sky 0854p -20- 03/25/87 ------- Blue 6B. EN CAS Analytical Labs (1977c) also reported that waste treatment plant bacteria were unaffected by concentrations of <300 mg/i. Konlshl and Hldaka (1969) found that Direct Sky Blue 6B stimulated carp chemo- receptors hi vitro. 0854p -21- 09/26/86 ------- 7. EXISTING GUIDELINES AND STANDARDS 7.1. HUMAN OSHA/NIOSH (1980) concluded that 3,3'-dimethoxybenzldlne dyes may present a cancer risk to humans and recommend caution In handling and minimum exposure. U.S. EPA (1981) In response to ITC recommendations decided not to require testing of 3,3'-d1methoxybenz1d1ne-based dyes. 7.2. AQUATIC Guidelines and standards for the protection of aquatic biota from the toxic effects of Direct Sky Blue 68 could not be located In the available literature as cited In the Appendix. 0854p -22- 09/26/86 ------- 8. RISK ASSESSMENT Pertinent data regarding the cardnogenlcHy of Direct Sky Blue 68 could not be located 1n the available literature as cited 1n the Appendix. Posi- tive results were obtained for S_. typhlmurlum strain TA98 with metabolic activation by S-9 (PMval et al.. 1982, 1984; PMval and Mitchell, 1982; Joachim and Decad, 1984). Mutagenlc activity was enhanced when FHN was added. Prlval and Mitchell (1982) found unlnduced hamster S-9 enhanced mutagenldty to a greater extent than did Induced rat S-9. Direct Sky Blue 6B did not Induce UDS \r± vivo or hi vitro (Joachim and Decad, 1984). No data regarding the teratogenlc effects of Direct Sky Blue 6B after oral or Inhalation exposure were available; a few studies by the 1ntra- perltoneal route were available. Beaudoln (1968) observed dose-related Increased resorptlons and malformations In rats at >HO mg/kg/day. Amels et al. (1977) observed a dose-related Increase In ocular malformations 1n rats given IntraperUoneal doses >100 mg/kg of Direct Sky Blue 6B. Maternal toxldty was observed In mice given 250 mg/kg/day 1ntraper1toneally (Chernoff and Kavlock, 1983). Pertinent data regarding other reproductive effects and subchronlc or chronic toxldty of Direct Sky Blue 6B could not be located 1n the available literature as cited In the Appendix. The oral LDrQ 1s >5 mg/kg (M. B. Research Labs, 1978), and rats exposed to 18.94 mg/i were essentially unaffected by Direct Sky Blue 6B except for hyper- actlvlty. Thus, data are Insufficient to derive an RfD. Direct Sky Blue 6B 1s a 3-3'-d1methoxybenz1d1ne-based dye. 3,3-01- methoxybenzldlne, a recognized animal carcinogen (IARC. 1982). Is also a metabolite of the dye and was Identified In workers occupatlonally exposed to dyes (Lowry et al., 1980). Genln (1977) found several bladder cancer 0854p -23- 09/26/86 ------- cases upon examination of plant records of workers occupatlonally exposed to dyes, but Direct Sky Blue 86 was not specifically mentioned. Thus, Direct Sky Blue 68 may present a carcinogenic risk to man. 0854p -24- 09/26/86 ------- 9. REPORTABLE QUANTITIES 9.1. REPORTABLE QUANTITY (RQ) BASED ON CHRONIC TOXICITY No subchronlc or chronic oral or Inhalation toxldty studies of Direct Sky Blue 6B were located; therefore, data are Insufficient for deriving an RQ (Table 9-1). 9.2. WEIGHT OF EVIDENCE AND POTENCY FACTOR (F»1/ED1Q) FOR CARCINOGENICITY Pertinent data describing the carclnogenlclty of Direct Sky Blue 68 by the oral or Inhalation routes were not available. Genln (1977) found five cases of bladder tumors In an unspecified number of workers occupatlonally exposed to dyes, but Direct SKy Blue 6B was not specifically mentioned. Lowry et al. (1980) and Genln (1977) detected 3,3'-dlmethoxybenzldlne 1n the urine of workers occupatlonally exposed to dyes. 3,3'-Dlmethoxybenzldlne Is a known carcinogen with an IARC ranking of 2B and a EPA ranking of B2 (IARC, 1982; U.S. EPA, 1986b). Thus, Direct Sky Blue 6B may present a carcino- genic risk to humans; however, human and animal data are Inadequate. Since there 1s Inadequate evidence 'that Direct Sky Blue 6B 1s carcinogenic In humans or 1n animals, this dye could be classified In the EPA D category (U.S. EPA, 1986c), but the fact that Us metabolite Is a known carcinogen more appropriately places this dye In EPA Group B2. 0854p -25- 04/30/87 ------- TABLE 9-1 Direct Sky Blue 66 Minimum Effective Dose (MED) and Reportable Quantity (RQ) Route: Dose: Effect: Reference: RVd: RVe: Composite Score: RQ: Data are not sufficient for deriving an RQ 0854p -26- 09/26/86 ------- 10. REFERENCES AATCC (American Association of Textile Chemists and Colonists). 1985, AATCC buyers' guide. Text. Chem. Color. 17: 80. Amels, 0., M. Chedu and S. Sandor. 1977. Contributions to the study of blsazo dyes-Induced eye anomalies In rats. Rev. Roum. Horphol. Embryol. Physlol. Morphol Embryol. 23: 93-101. Atkinson, R. 1985. Kinetics and mechanisms of the gas-phase reaction of the hydroxyl radical with organic compounds under atmospheric conditions. Chem. Rev. 85: 69-201. Beaudoln, A.R. 1968. Teratogenlc activity of six dlsazo dyes 1n the Hlstar albino rat. Proc. Soc. Exp. B1ol. Hed. 127: 215-219. Beaudoln, A.R. and M.J. Pickering. 1960. Teratogenlc activity of several synthetic compounds structurally related to Trypan Blue. Anat. Rec. 137: 297-305. Brown, D. and P. Laboureur. 1983. The degradation of dyestuffs. Part I: Primary blodegradatlon under anaerobic conditions. Chemosphere. 12: 397-404. Brown, 0., H.R. H1tz and L. Schaefer. 1981. The assessment of the possible Inhibitory effect of dyestuffs on aerobic wastewater bacteria. Experience with a screening test. Chemosphere. 10(3): 245-261. 0854p -27- 09/26/86 ------- Chernoff, N. and R.J. Kavlock. 1983. A teratology test system which utilizes postnatal growth and viability In the mouse. Environ. Scl. Res. 27: 417-427. EN CAS Analytical Labs. 1977a. 96-Hour static fish bloassay test. Prepared for Clba-Gelgy Corp., Greensboro, NC. TSCA 8d Submission. OTS, U.S. EPA, Washington. DC. Flche No. OTS 0206480. EN CAS Analytical Labs. 1977b. 96-Hour static fish bloassay test. Prepared for C1ba-Ge1gy Corp., Greensboro, NC. TSCA 3d Submission. OTS, U.S. EPA, Washington, DC. Flche No. OTS 0206480. EN CAS Analytical Labs. 1977c. Toxlclty of dyestuffs to waste treatment bacteria. Laboratory Report 8. Prepared for C1ba-Ge1gy Corp., Greensboro, NC. TSCA 8d Submission. OTS, U.S. EPA, Washington, DC. Flche No. OTS 0206480. Genln, V.A. 1977. Formation of blastomogenlc dlphenylamlno derivatives as a result of the metabolism of direct azo dyes. Vopr. Onkol. 23(9): 50-52. (Rus.) (Cited In N10SH, 1980) Haag, W.R. and T. Mill. 1985. Direct and Indirect photolysis of azodyes. Summary Report, EPA 68-02-3968, Versar, Inc., Springfield, VA. Subcontract 867-1. 0854p -28- 09/26/86 ------- IARC (International Agency for Research on Cancer). 1982. Chemicals, Industrial Processes at Industries Associated with Cancer In Humans. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. WHO, IARC, Lyon, France. Vol. 1-29, Suppl. 4, p. 116-118. Joachim, F. and G.H. Oecad. 1984. Induction of unscheduled DMA synthesis In primary rat hepatocytes by benz1d1ne-congener-der1ved azo dyes 1n the hi vitro and 1n v1vo/1n vitro assays. Mutat. Res. 136: 147-152. Jones, T.C. 1979. Preliminary risk assessment. Phase I. Benzldlne, congeners and their derivative dyes and pigments. Office of Pesticides and Toxic Substances, U.S. EPA. EPA 560/11-80-019. p. 37-42. Klyohara. S.f J. Kltoh and S. YamashUa. 1984. A study on the rapid surface staining of fish tastebuds. Nippon Sulsan . Gakkalshl. 59(8): 1299-1304. [CA 102(1):2783f] Kon1sh1, J. and I. Hldaka. 1969. Stimulation of fish chemoreceptors by dilute solutions of polyelectrolytes. Jap. J. Physlol. 19(3): 315-326. Kuehnl, R.G., J.C. King, R.E. Phillips, et al. 1979. Dyes, application and evalutalon. Irr. K1rk-0thmer Encyclopedia of Chemical Technology, Vol. 8, 3rd ed., M. Grayson and D. Eckroth, Ed. John Wiley and Sons, Inc., New York. p. 302-305. Lebledowskl, H. and J. Przyb1nsk1. 1980. Use of the sorptlon properties of activated sludge for purification of dyeing effluents. Przegl. Wlok. 34(1): 51-53. (Pol.) (CA 093:1010295) 0854p -29- 03/25/87 ------- Lowry, L.K., W.P. Tolos, M.F. Boenlger, C.R. Nony and M.C. Bowmen. 1980. Chemical monitoring of urine from workers potentially exposed to benzldene- derlved azo dyes. Toxlcol. Lett. 7: 29-36. Lynn, R.K., D.W. Danlelson, A.M. IHas, J.M. Kennlsh. K. Wong and H.B. Mathews. 1980. Metabolism of blzazoblphenyl dyes derived from benzldlne, 3,3'-d1methylbenz1d1ne or 3,3'-d1methoxybenz1d1ne to carcinogenic aromatic amines In the dog and rat. Toxlcol. Appl. Pharmacol. 56: 248-258. M. B. Research Laboratories. 1978. Acute Oral Toxldty 1n Rats (Direct Blue 6B). Prepared for Toms River Chemical Corp., Toms River, NJ. 8d Submission 206237. F1che #237. NIOSH (National Institute for Occupational Safety and Health). 1980. Special Occupational Standard Review for Benz1d1ne-based Dyes. NIOSH, Washington, DC. NIOSH (National Institute for Occupational Safety and Health). 1984. Cur- rent Awareness File, RTECS (Registry of Toxic Effects of Chemical Substance. NIOSH, Cincinnati, OH. NTP (National Toxicology Program). 1986. Management Status Report. Dated 3/12/86. OSHA/NIOSH (Occupational Safety and Health Administration/National Institute for Occupational Safety and Health). 1980. Health Hazard Alert: Benzldlne, o-To!1d1ne and o-01an1s1d1ne-Based Dyes. DHHS (NIOSH) Publ. No. 81-106. 0854p -30- 03/25/87 ------- Porter, J.J. 1973. Stability of acid, basic and direct dyes to light and water. Text. Res. J. 43(12): 735-744. Prlval, M.J. and V.D. Mitchell. 1982. Analysis of a method for testing azo dyes for mutagenlc activity 1n Salmonella typhlmurlum In the presence of Flavin mononucleotlde and hamster liver S9. Mutat. Res. 97: 103-116. Prlval, M.J., V.D. Mitchell, M. Pelperl, V. Vaughan-Dellarco and S.J. Bell. 1982. Evaluation and application of a protocol for testing azo dyes for mutagenldty 1n Salmonella typhlmurlum. Environ. Mutagen. 4: 414. Prlval. M.J., S.J. Bell, V.D. Mitchell, M.D. Pelperl and V.L. Vaughan. 1984. Mutagenldty of benzldlne and benzldlne-congener dyes and selected monoazo dyes 1n a modified Salmonella assay. Mutat. Res. 136: 33-47. RTECS (Registry of Toxic Effects of Chemical Substances). 1981-1982. p. 799. Society of Dyers and Colourlsts. 1971a. Colour Index, Vol 4, 3rd ed. Lund Humphries. Bradford. United Kingdom, p. 4209. Society of Dyers and Colourlsts. 1971b. Colour Index, Vol 2, 3rd ed. Lund Humphries. Bradford. United Kingdom, p. 2221. Southwest Foundation for Research and Education. 1979. Evaluation of the Acute Inhalation ToxUHy of Direct Blue 6B. 8d Submission 206237. Prepared for Toms River Chemical Corp., Toms River, NJ. 0854p -31- 03/25/87 ------- Steadman, P.R., E.W. Helper, T. Parsons, G.E. Wlllklns and N.P. Phillips. 1977. Industrial process profiles for environmental use: Chapter 7. Organic dyes and pigment Industry. EPA 600/2-77-023g. p. 69. Takemura, N., T. Aklyama and C. Nakahama. 1965. A survey of the pollution of the Sumlda River, especially on the aromatic amines In the water. Inter. J. Air Pollut. 9(10): 665-670. U.S. EPA. 1977. Computer print-out of non-confidential production data from TSCA Inventory. OPTS, CIO, U.S. EPA, Washington, DC. U.S. EPA. 1981. Benzldlne, o-to!1d1ne and o-d1an1s1d1ne-based dyes response to the Interagency Testing Committee. Federal Register. 46(214): 55004-55006. U.S. EPA. 1986a. GEMS (Graphical Exposure Modeling System). CLOGP (Octanol Water Partition Coefficient) data base. U.S. EPA, Washington, DC. U.S. EPA. 1986b. Health and Environmental Effects Profile on 3,3'-01- methoxybenz1d1ne. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1986c. Guidelines for Carcinogen Risk Assessment. Federal Register. 51(185): 33992-34003. 0854p -32- 03/25/87 ------- USITC (U.S. International Trade Commission). 1981. Synthetic Organic Chemicals. U.S. Production and Sales, 1980. USITC Publ. 1183, Washington. DC. p. 67. USITC (U.S. International Trade Commission). 1982. Imports of Benzenold Chemicals and Products 1981. USITC Publ. 1272, Washington, DC. p. 52. USITC (U.S. International Trade Commission). 1983. Imports of Benzenold Chemicals and Products 1982. USITC Publ. 1401, Washington, DC. p. 50. USITC (U.S. International Trade Commission). 1984. Imports of Benzenold Chemicals and Products 1983. USITC Publ. 1548, Washington, DC. p. 51. USITC (U.S. International Trade Commission). 1985. Synthetic Organic Chemicals. U.S. Production and Sales, 1984. USITC Publ. 1745,. Washington, DC. p. 66. 0854p -33- 03/25/87 ------- APPENDIX LITERATURE SEARCHED This profile Is based on data Identified by computerized literature searches of the following: GLOBAL TSCATS CASR online (U.S. EPA Chemical Activities Status Report) CAS online STN International TOXLINE TOXBACK 76 TOXBACK 65 RTECS OHM TADS STORET SRC Environmental Fate Data Bases SANSS AQUIRE TSCAPP NTIS Federal Register These searches were conducted 1n Hay, 1986. In addition, hand searches were made of Chemical Abstracts (Collective Indices 6 and 7). and the following secondary sources were reviewed: ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986. Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH. ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1985-1986. TLVs: Threshold Limit Values for Chemical Substances and Physical Agents In the Workroom Environment with Intended Changes for 1985-1986. Cincinnati, OH. 114 p. Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed.. Vol. 2A. John Wiley and Sons, NY. 2878 p. Clayton, G.D. and F.E. Clayton. Ed. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 28. John Wiley and Sons, NY. p. 2879-3816. 0854p -34- 09/26/86 ------- Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and Sons, NY. p. 3817-5112. Grayson, H. and D. Eckroth, Ed. 1978-1983. K1rk-0thmer Encyclo- pedia of Chemical Technology. 3rd ed. John Wiley and Sons, NY. 23 Volumes. Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed. Publishing Sciences Group, Inc., Littleton, MA. 575 p. IARC (International Agency for Research on Cancer). IARC Mono- graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. WHO, IARC, Lyons, France. ITII (International Technical Information Institute). 1982. Toxic and Hazardous Industrial Chemicals Safety Manual for Handling and Disposal with Toxldty and Hazard Data. ITII, Tokyo, Japan. 700 p. Jaber, H.H., W.R. Mabey, S.T. L1u, T.W. Chow and H.L. Johnson. 1984. Data aqulsltlon for environmental transport and fate screen- Ing for compounds of Interest 1n the Office of Solid Waste. EPA 600/6-84-010. NTIS PB84-243906. SRI International. Menlo Park, CA. NTP (National Toxicology Program). 1986. Toxicology Research and Testing Program. Chemicals on Standard Protocol. Management Status. Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide Register. McGraw-Hill Book Co.. NY. Sax, N.I. 1979. Dangerous Properties of Industrial Materials, 5th ed. Van No-strand Relnhold Co.. NY. SRI (Stanford Research Institute). 1984. Directory of Chemical Producers. Menlo Park, CA. U.S. EPA. 1985. Status Report on Rebuttable Presumption Against Registration (RPAR) or Special Review Process. Registration Stan- dards and the Data Call In Programs. Office of Pesticide Programs. Washington, DC. U.S. EPA. 1985. CSB Existing Chemical Assessment Tracking System. Name and CAS Number Ordered Indexes. Office of Toxic Substances, Washington. DC. USITC (U.S. International Trade Commission). 1983. Synthetic Organic Chemicals. U.S. Production and Sales, 1982, USITC Publ. 1422. Washington, DC. Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals. 2nd ed. Van Nostrand Relnhold Co., NY. 0854p -35- 09/26/86 ------- Wlndholz. M.. Ed. 1983. The Merck Index, 10th ed. Merck and Co., Inc., Rahway, NJ. Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual. British Crop Protection Council. 695 p. In addition, approximately 30 compendia of aquatic toxldty data were reviewed, Including the following: Battelle's Columbus Laboratories. 1971. Water Quality Criteria Data Book. Volume 3. Effects of Chemicals on Aquatic Life. Selected Data from the Literature through 1968. Prepared for the U.S. EPA under Contract No. 68-01-0007. Washington, DC. Johnson, W.W. and M.T. Flnley. 1980. Handbook of Acute Toxldty of Chemicals to Fish and Aquatic Invertebrates. Summaries of Toxlclty Tests Conducted at Columbia National Fisheries Research Laboratory. 1965-1978. U.S. Dept. Interior, F1sh and Wildlife Serv. Res. Publ. 137, Washington, DC. HcKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed. Prepared for the Resources Agency of California. State Water Quality Control Board. Publ. No. 3-A. Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target Species. Prepared for the U.S. EPA, Washington, DC. PB-269605. Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S. EPA, Washington. DC. EPA 540/9-79-003. NTIS PB 80-196876. 0854p -36- 09/26/86 ------- |