Appendix F
Disperse Red 9

BACKGROUND

DISPERSE RED 9 is also called 1-(methylamino)-9,10-anthracenedione (MAA) (after 1972) and 1-N-methylamino-9,10-anthraquinone (before 1972). This compound is a component of the old red-and violet-dye mixtures.

TOXICOKINETICS

Oral administration of disperse red 9 to sheep at a concentration of 0.05 grams per kilogram (g/kg) of body weight showed that 40% of the total dose could be accounted for as unmetabolized disperse red 9 or its colored metabolites (Martin et al. 1983). Those colored metabolites were approximately 90% glucuronide conjugates. Greater than 50% of the remaining dose was represented as noncolored metabolites. Sendelbach (1989) concluded that disperse red 9 was essentially nontoxic and rapidly metabolized in mammals.



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Toxicity of Military Smokes and Obscurants: Volume 3 Appendix F Disperse Red 9 BACKGROUND DISPERSE RED 9 is also called 1-(methylamino)-9,10-anthracenedione (MAA) (after 1972) and 1-N-methylamino-9,10-anthraquinone (before 1972). This compound is a component of the old red-and violet-dye mixtures. TOXICOKINETICS Oral administration of disperse red 9 to sheep at a concentration of 0.05 grams per kilogram (g/kg) of body weight showed that 40% of the total dose could be accounted for as unmetabolized disperse red 9 or its colored metabolites (Martin et al. 1983). Those colored metabolites were approximately 90% glucuronide conjugates. Greater than 50% of the remaining dose was represented as noncolored metabolites. Sendelbach (1989) concluded that disperse red 9 was essentially nontoxic and rapidly metabolized in mammals.

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Toxicity of Military Smokes and Obscurants: Volume 3 TOXICITY SUMMARY Effects in Humans DERMAL EXPOSURE Disperse red 9 is reported to be a skin irritant and sensitizer in humans (Dacre et al. 1979; Owens and Ward 1974). Exposure concentrations were not reported. Effects in Animals INHALATION EXPOSURE Disperse red 9 has been assigned a toxicity rating of 1 when inhaled or swallowed (Parent 1964). A rating of 1 is defined as a slightly toxic material whose effects are temporary and disappear upon termination of exposure (Parent 1964). DERMAL EXPOSURE Application of disperse red 9 at a concentration of 2 g/kg of body weight on the shaved and abraded backs of rabbits resulted in negligible effects (Martin et al. 1983). OCULAR EXPOSURE Martin et al. (1983) exposed rabbits to disperse red 9 at a concentration of 0.05 g per eye. The exposure caused no toxic effects. ORAL EXPOSURE Griswold et al. (1968) administered disperse red 9 at a dose of 0.5 g per rat by gastric tube for 10 doses over a 30-day period (total dose, 5 g per

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Toxicity of Military Smokes and Obscurants: Volume 3 rat) to female Sprague-Dawley rats. The rats were observed for 9 months, and little toxicity was observed. Disperse red 9 administered orally to dogs at up to 8 grams per kilogram (g/kg) of body weight resulted in "minimal toxicity" (Martin et al. 1983). Disperse red 9 has a toxicity rating of 1 which means that it is slightly toxic and its effects are temporary. MUTAGENICITY AND CARCINOGENICITY STUDIES Studies have used the Ames assay to test disperse red 9 for mutagenicity. Lundy and Eaton (1994) reported a positive response. Dacre et al. (1979) cited a study that concluded that there was no evidence of mutagenicity. A review of anthraquinone dyes as candidates for nomination to the National Cancer Institute's Chemical Selection Working Group for carcinogenesis bioassay is described by Sigman et al. (1985). Disperse red 9 was considered for study because it gave positive results for mutagenicity in mouse lymphoma cells with and without activation and positive effects in the unscheduled DNA synthesis assay with mouse liver S9. Other mutagenicity tests (i.e., Ames, dominant lethal, mitotic gene conversion) gave negative results. In a carcinogenicity study by Griswold et al. (1968), one kidney tumor was identified in a female rat 9 months after disperse red 9 was administered at 5 g per rat (total dose) by gavage. The results produced inadequate evidence of carcinogencity. SUBCOMMITTEE EVALUATION OF DYE TOXICITY The experimental data are insufficient to assess the toxic effects of disperse red 9. REFERENCES Dacre, J.C., W.D. Burrows, C.W.R. Wade, A.F. Hegyeli, T.A. Miller, and D.R. Cogley. 1979. Problem Definition Studies on Potential Environmental Pollutants. V. Physical, Chemical, Toxicological, and Biological Properties of

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Toxicity of Military Smokes and Obscurants: Volume 3 Seven Chemicals Used in Pyrotechnic Compositions. Technical Report No. 7704. AD A090631. U.S. Army Medical Bioengineering Research and Development Laboratory, Fort Detrick, Frederick, MD. Griswold Jr., D.P., A.E. Casey, E.K. Weisburger, E.K., and J.H. Weisburger. 1968. The carcinogenicity of multiple intragastric doses of aromatic and heterocyclic nitro or amino derivatives in young female Sprague-Dawley rats. Cancer Res. 28:924-933. Lundy, D., and J. Eaton. 1994. Occupational Health Hazards Posed by Inventory U.S. Army Smoke/Obscurant Munitions (Review Update). WRAIR/RT-94-0001. AD A276774. U.S. Army Medical Research Detachment, Wright-Patterson Air Force Base, OH. Martin, B.W., G.W. Ivie, E.M. Bailey. 1983. The acute toxicity of 1-methyl-aminoanthraquinone in dogs and rabbits and its metabolism in sheep . Arch Environ. Contam. Toxicol. 12(4):499-507. Owens, E.J., and D.M. Ward 1974. A Review of the Toxicology of Colored Chemical Smokes and Colored Smoke Dyes. AD A003827. Edgewood Arsenal, Aberdeen Proving Ground, Edgewood, MD. Parent, P.A. 1964. Biological Effects of Colored Smoke Ingredients. CRDL Special Publication 4-59. AD 451092. Edgewood Arsenal, Aberdeen Proving Ground, Edgewood, MD. Sendelbach, L.E. 1989. A review of the toxicity and carcinogenicity of anthraquinone derivatives. Toxicology 57(30):227-240. Sigman, C. C., P.A. Papa, M.K. Doeltz, L.R. Perry, A.M. Twhigg and C.T. Helmes. 1985. A study of anthraquinone dyes for the selection of candidates for carcinogen bioassay. J. Environ. Sci. Health A20(4):427-484.