Appendix E
Solvent Red 1

BACKGROUND

ALTERNATIVE NAMES for solvent red 1 include color index sudan red G, oil soluble red G, and α­methoxybenzenazo-ß-naphthol (MBN). Solvent red 1 is a component of the new red-dye mixture.

TOXICOKINETICS

No studies have been conducted on the toxicokinetics of solvent red 1.

TOXICITY SUMMARY

Effects in Humans

There have been no reports of humans exposed either accidentally or in controlled laboratory environments to solvent red 1.

Effects in Animals

A minimal number of toxicity studies have been conducted with solvent red 1. Those studies are summarized in Table E-1. Acute-toxicity studies of oral exposure in rats or dermal exposure in rabbits determined the



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Toxicity of Military Smokes and Obscurants: Volume 3 Appendix E Solvent Red 1 BACKGROUND ALTERNATIVE NAMES for solvent red 1 include color index sudan red G, oil soluble red G, and α­methoxybenzenazo-ß-naphthol (MBN). Solvent red 1 is a component of the new red-dye mixture. TOXICOKINETICS No studies have been conducted on the toxicokinetics of solvent red 1. TOXICITY SUMMARY Effects in Humans There have been no reports of humans exposed either accidentally or in controlled laboratory environments to solvent red 1. Effects in Animals A minimal number of toxicity studies have been conducted with solvent red 1. Those studies are summarized in Table E-1. Acute-toxicity studies of oral exposure in rats or dermal exposure in rabbits determined the

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Toxicity of Military Smokes and Obscurants: Volume 3 TABLE E-1 Summary of Toxicity Studies Conducted with Solvent Red 1 Study Type Species Exposure Conditions End Points and Comments Reference Acute toxicity Rat, Sprague-Dawley, M, F Oral, acute, 5 g/kg 0/10 died at 14d, LD50 >5 g/kg Manthei et al. 1983 Acute toxicity Rat, Fischer 344, M, F Oral, acute, 5 g/kg 0/10 died at 14d, LD50 >5 g/kg Smith et al. 1986 Acute toxicity Rabbit, New Zealand White, M, F Dermal, acute, 2 g/kg for 24 hr 0/10 died at 14d, LD50 >2 g/kg Manthei et al. 1983 Acute toxicity Rabbit, New Zealand White, M, F Dermal, acute, 2 g/kg for 24 hr 0/10 died at 14d, LD50 >2 g/kg Smith et al. 1986 Eye irritation Rabbit, New Zealand White, M, F 0.1 g/eye 0/6 responded at 24 hr, 48 hr, 72 hr, 7 d; negative Manthei et al. 1983 Eye irritation Rabbit, New Zealand White, M, F 0.1 g/eye 3/3 positive; redness, chemosis, discharge, iritis; no irritation by d 7 Smith et al. 1986 Dermal irritation Rabbit, New Zealand White, M, F Clipped skin, 0.5 g/kg for 24 hr 24, 72 hr; 6/6 erythema; primary irritation score 2.08; moderate irritant Manthei et al. 1983 Dermal irritation Rabbit, New Zealand White, M, F Clipped skin, 0.05 g/kg for 24 hr Nonirritant Smith et al. 1986 Sensitization Guinea pig, Hartley, M Injection 0.0001g/d for 22 d Negative Manthei et al. 1983 Contact hypersensitivity Mice, Balb/c, F Mouse ear-swelling test: 0.00005 g/d shaved back, 2 d); challenge on d 5 Contact sensitizer Sailstead et al. 1994 Contact hypersensitivity Mice, Balb/c, F Local lymph node assay: 0.0005 g/d both ears, 3 d) Weak contact sensitizer Sailstead et al. 1994 Abbreviations: M, male; F, female.

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Toxicity of Military Smokes and Obscurants: Volume 3 lethal dose for 50% of the test animals (LD50) to be greater than 5 grams per kilogram (g/kg) of body weight after oral administration and greater than 2 g/kg of body weight after dermal administration. Those doses (5 g/kg and 2 g/kg) were the highest doses used (Manthei et al. 1983; Smith et al. 1986). Results regarding the eye-irritation potential of solvent red 1 are conflicting. Manthei et al. (1983) reported that this chemical did not cause ocular irritation in rabbits; however, Smith et al. (1986) reported positive results in the same species. Conflicting results were also obtained for the dermal-irritation potential of solvent red 1. Manthei et al. (1983) suggested that it was moderately irritating, and Smith et al. (1986) suggested that it was nonirritating. The dose used in the Smith et al. (1986) study was 10 times higher than that in the Manthei et al. (1983) study. Studies using either an eye-swelling test or a local lymphoid assay to evaluate contact hypersensitivity in mice exposed to solvent red 1 showed that this chemical was a contact sensitizer (Sailstad et al. 1994). Mutagenicity Mutagenicity tests conducted with solvent red 1 are summarized in Table E-2. Mammalian studies have yielded conflicting results. For example, in vivo mutagenicity studies using Swiss albino mice showed no increase in micronucleated femoral polychromatic erythrocytes after intraperitoneal (i.p.) injections of solvent red 1 at up to 0.1 g/kg of body weight (Manthei et al. 1983). In contrast, in vitro studies using a mouse lymphoma cell line showed increases in thymidine kinase mutants and increases in micronuclei (Harrington-Brock et al. 1991). Experiments conducted in Chinese hamster ovary cells showed that solvent red 1 was cytotoxic and induced an increase in sister-chromatid-exchange frequency but was not mutagenic or clastogenic (Brooks et al. 1989). Studies on the mutagenicity of solvent red 1 in the bacterial system Salmonella typhimurium (Ames test) have also yielded conflicting results. Some investigators determined that solvent red 1 was not mutagenic in this system (Manthei et al. 1983; Brooks et al. 1989). Another investigator determined that it was positive in one strain (TA100) when a mammalian bioactivating system was used (Moore et al. 1989). Taken together, these mutagenicity studies suggest that solvent red 1 is a weak mutagen. The possibility that a contaminant in the dye is responsible for the mutagenic effect cannot be dismissed.

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Toxicity of Military Smokes and Obscurants: Volume 3 TABLE E-2 Summary of Mutagenicity Studies Conducted with Solvent Red 1 Experimental system Exposure Conditions End Points and Comments Reference Swiss albino male mice i.p. injections, 0.001, 0.01, 0.1 g/kg, at 30 hr and 6 hr before euthanasia No increase in micronucleated-femoral polychromatic erythrocytes Manthei et al. 1983 Mouse lymphoma cells 0-9 g/L, 4 hr +S9, 100 thymidine kinase mutants per 106 survivors; 16 micronuclei per 1,000 cells at 22% survival Harrington-Brock et al. 1991 Salmonella typhimurium (strains TA1535, TA1537, TA 1538, TA98, TA100) ± S9 0.0001-1 g/plate Not mutagenic Manthei et al. 1983 Salmonella typhimurium (strains TA1537, TA1538, TA98, TA100, TA102, TA104) ± S9 0-0.3 g/plate Positive in TA100 +S9 with mammalian bioactivating system Moore et al. 1990 Salmonella typhimurium (strains TA1535, TA1538, TA98, TA100) ± S9 0-0.8 g/plate, Not mutagenic Brooks, et al. 1989 Chinese hamster ovary cells 0-40 g/L, 3 hr Cytotoxic, increased sister-chromatid-exchange frequency, not mutagenic or clastogenic Brooks et al. 1989 Abbreviation: i.p., intraperitoneal.

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Toxicity of Military Smokes and Obscurants: Volume 3 SUBCOMMITTEE EVALUATION OF DYE TOXICITY Experimental data are insufficient to assess the toxic effects of solvent red 1. The studies on contact hypersensitivity suggest that additional studies in the area might be advisable given the demonstrated dermal-sensitization potential of other dyes. REFERENCES Brooks, A.L., F.A. Seiler, R.L. Hanson, and R.F. Henderson. 1989. In vitro genotoxicity of dyes present in colored smoke munitions. Environ. Mol. Mutagen. 13(4):304-313 Eastin, W.C., M.R. Elwell, S. Grumbein, and J.H. Yuan. 1996. Effects of D&C yellow no. 11 ingestion on F344/N rats and B6C3F1 mice. J. Toxicol. Environ. Health 48(2):197-213. Harrington-Brock, K., L. Parker, C. Doerr, M.C. Cimino, and M.M. Moore. 1991. Analysis of the genotoxicity of anthraquinone dyes in the mouse lymphoma assay. Mutagenesis 6(1):35-46. Krebs, J.S. 1980. Toxicity of D&C yellow 11: A literature review. SRI Project LSU-6465, Contract No. DAAK 11-17-C-0029. Chemical Systems Laboratory, Aberdeen Proving Ground, Edgewood, MD. Manthei, J.H., F.K. Lee, D.H. Heitkamp, and W.C. Heyl. 1983. Preliminary and Acute Toxicological Evaluation of Five Candidate Smoke Compounds. Tech. Rep. ARCSL-TR-82066. U.S. Army Armament Research and Development Command, Aberdeen Proving Ground, Edgewood, MD. Moore, M.M., L. Claxton, V. Houk, G.M. Nelson, and K. Harrington-Brock. 1989. Toxicity of Red and Violet Dyes in M18 Grenades: Mutagenic Screening of Three Dyes for Marker Grenades in the Salmonella Reversion Assay and the L5178Y/TK +/- Mouse Lymphoma Assay. Final Report ADA229021. U.S. Environmental Protection Agency, Health Effects Research Laboratory, Research Triangle Park, NC. Sailstad, D.M., J.S. Tepper, D.L. Doerfler, M. Qasim, and M.K. Selgrade, 1994. Evaluation of an azo and two anthraquinone dyes for allergic potential. Fundam. Appl. Toxicol. 23(4):569-577. Smith, S.H., G.L. Doyle, J.C. Kreuger, K.A. Mellon, D.A. Mayhew. 1986. Dermal, Eye and Oral Toxicological Evaluations, Phase IV Report with Disperse Red 11, Disperse Blue 3, Solvent Red 1, and Red and Violet Mixtures. ADA172758. Bioassay Systems Corp., Woburn, MA. Sun, J.D., R.F. Henderson, T.C. Marshall, Y.S. Cheng, J.S. Dutcher. J.A. Pickrell, J.L. Mauderly, F.F. Hahn, D.A. Banas, F.A. Seiler, and C.H. Hobbs. 1987. The inhalation toxicity of two commercial dyes: Solvent yellow 33 and solvent green 3. Fundam. Appl. Toxicol. 8(3):358-371.