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Toxicity of Military Smokes and Obscurants: Volume 3 Appendix A Benzanthrone BACKGROUND ALTERNATIVE NAMES for benzanthrone (BZA) include 7H-benz(de)-anthracen-7-one, 1,9-benzanthrone, benzanthrenone, and mesobenzanthrone. BZA is a component of the old yellow-and green-dye mixtures. TOXICOKINETICS In rabbits administered BZA intraperitoneally at 0.2 grams per kilogram (g/kg) of body weight, 26% to 30% of the dose was excreted unchanged in the urine over a 5-day period (Pandya et al. 1976). TOXICITY SUMMARY Effects in Humans BZA is reported to cause an itching and burning sensation, erythema, dermatitis, and skin pigmentation (Uebelin and Buess 1951; Singh and Zaidi 1969; Trivedi and Niyogi 1968; Schwartz et al. 1957; Schwartz 1939; Horakova and Merhaut 1966, as cited in Dacre et al. 1979). In sensitive individuals, actinic dermatitis or leukoderma can develop because of a photodynamic effect (Singh and Zaidi 1969; Trivedi and
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Toxicity of Military Smokes and Obscurants: Volume 3 Niyogi 1968; Schwartz et al. 1957; Schwartz 1939; Horakova and Merhaut 1966; Isaev et al. 1957; Hueper 1942, as cited in Dacre et al. 1979). Itching, precocious generalized eczema, pigmentation, and photosensitization have been observed in workers exposed to BZA (Horakova and Merhaut 1966). Systemic effects result from liver damage (Slutskii 1958), nervous-system damage (Piskunova et al. 1956), and disturbance of the autonomic-nervous-system regulatory function (Slutskii 1958). More recent studies indicate that BZA, upon exposure to light, can generate active oxygen species that might be responsible for the photocontact dermatitis caused by BZA in industrial workers exposed to this chemical (Dabestani et al. 1992). Because of the toxic nature of BZA, the U.S. Army Environmental Health Agency advised substituting BZA with a less toxic chemical in smoke mixtures (AEHA 1970). Effects in Animals ONE-TIME EXPOSURE The intraperitoneal (i.p.) lethal dose for 50% of the test animals (LD50) is 1.5 g/kg in rats and 0.29 g/kg in mice exposed to BZA (Lundy and Eaton 1994). BZA did not cause clinical signs of toxicity in rats given oral doses of up to 7.1 g/kg (Payne 1976). The dye was not irritating to the skin of the albino rabbit (Payne 1976) or the clipped, intact, or abraded skin of the guinea pig (Parent 1964; Weeks and Yevich 1963). There were no indications of photoallergy in guinea pigs or phototoxicity in mice or swine (Payne 1976). White male rabbits injected i.p. at 0.2 g/kg of body weight and guinea pigs injected i.p. at 0.03 g/kg of body weight caused an inflammatory process in the urinary bladder (Pandya et al. 1976; Singh and Tripathi 1973). Intratracheal instillation of BZA (particle size, less than 5 micrograms (µg)) in guinea pigs caused a hemorrhagic edema (Singh 1971). REPEATED EXPOSURE Daily i.p. doses of BZA administered to rats at 0.05 g/kg of body weight led to a normocytic anemia due to hemolysis in 10-20 days (Chandra and Singh 1968). There was a significant increase in plasma fibrinogen and
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Toxicity of Military Smokes and Obscurants: Volume 3 a decrease in blood coagulation time (Mehrotra et al. 1975). BZA injected biweekly i.p. in rats at 0.03 g/kg of body weight for 6 months led to damage of the gametogenic function of rat testis (Singh and Khanna 1976). CARCINOGENICITY AND MUTAGENICITY Initial studies do not indicate that BZA is carcinogenic in mice (Parent 1964). Tests for mutagenicity in the dominant lethal mouse assay were negative (Epstein et al. 1972). BZA was not mutagenic in Salmonella typhimurium or Escherichia coli strains in some reports (Brown and Brown 1976; Gibson et al. 1978; Bond and Gilleland 1955), but Epler (1979) reported BZA to be mutagenic in the Salmonella assay. SUBCOMMITTEE EVALUATION OF DYE TOXICITY The dermal toxicity of BZA, as reported in workers exposed to the dye, precludes any use of the dye in colored smokes unless the exposed personnel make use of effective respiratory and dermal protection. REFERENCES AEHA (U.S. Army Environmental Hygiene Agency). 1970. 2nd Ind. Subject: Proposed Military Specification MIL-D-50074D, Dye Benzanthrone. Project No. 6820-0049. From the Surgeon General of the Department of the Army to Edgewood Arsenal, Edgewood, MD. Dec. 10. Bond, T.J., and J.L. Gilleland. 1955. The influence of some polycyclic hydrocarbons on the nucleic acid concentrations in Escherichia coli. Arch. Biochem. Biophys. 58:189-193. Brown, J.P., and R.J. Brown. 1976. Mutagenesis by 9,10-anthraquinons derivatives and related compounds in Salmonella typhimurium. Mutat. Res. 40(3): 203-224. Chandra, S.V., and G.B. Singh. 1968. Effect of benzanthrone on haemopoietic system of rats. Indian J. Ind. Med. 14:102-106. Dacre, J.C., W. D. Burrows, C.W.R. Wade, A.F. Hegyeli, T.A. Miller, D.R. Cogley. 1979. Problem Definition Studies on Potential Environmental
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Toxicity of Military Smokes and Obscurants: Volume 3 Pollutants. V. Physical, Chemical, Toxicological, and Biological Properties of Seven Chemicals Used in Pyrotechnic Compositions. Tech. Rep. No. 7704 AD A090631 U.S. Army Medical Bioengineering Research and Development Laboratory, Fort Detrick, Frederick, MD. Dabestani R., R.H. Sik, A.G. Motten, and C.F. Chignell. 1992 Spectroscopic studies of cutaneous photosensitizing agents . XVII. Benzanthrone. Photochem. Photobiol. 55(4):533-539. Epler, J.L. 1979. U.S. Army Project Order No. 9600. Oak Ridge National Laboratory, Oak Ridge, TN. Epstein, S.S., E. Arnold, J. Andrea, W. Bass, and Y. Bishop. 1972. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol. Appl. Pharmacol. 23:288-325. Gibson, T.L., V.B. Smart, and L.L. Smith. 1978. Non-enzymic activation of polycyclic aromatic hydrocarbons as mutagens. Mutat. Res. 49(2):153-161. Hueper, W.C. 1942. Pp. 211-212 in Occupational Tumors and Allied Diseases. Springfield, IL: Charles C Thomas. Horakova, E., and J. Merhaut. 1966. Health of workers producing benzathrone [in Polish]. Prac. Lek. 18(2):78-81. Isaev, N.S., Z.B. Smelyanskii, L.K. Kotsyanov, and E.V. Khukhrin. 1957. Proposed new sanitary standards for projected industrial plants. Gig. Tr. Prof. Zabol 1(4):3-11. Lundy, D., and J. Eaton. 1994. Occupational Health Hazards Posed by Inventory U.S. Army Smoke/Obscurant Munitions (Review Update). WRAIR/RT-94-001. AD-A276-774. Prepared by U.S. Army Medical Research Detachment, Wright-Patterson Air Force Base, Ohio for Walter Reed Army Institute of Research, Washington, DC. Mehrotra, N.K., G.B. Singh, and S.K. Khanna. 1975. Blood coagulation disturbances due to benzanthrone. Ind. Health 13:101-103. Pandya, K.P., G.B. Singh, and A. Dhasmana. 1976. Urinary excretion of benzanthrone. Toxicol. Appl. Pharmacol. 38(1):217-219. Parent, P. 1964. Biological Effects of Colored Smoke Ingredients. CRDL Special Publication 4-59. AD 451092. Edgewood Arsenal, Aberdeen Proving Ground, Edgewood, MD. Payne, W.R. 1976. Letter from W.R. Payne, Toms River Chemical Corp., Toms River, NJ, to Capt. R.N. Shiotsuka, USAMBRDL. Oct. 25. Piskunova, V.G., V.S. Anatovskaya, G.D. Korotkova, A.B. Nerubenko, V.I. Danilov, M.E. Erman, and Z.I. Eremina. 1956. Industrial hygiene in production and use of benzanthrone [in Russian]. Gig. Sanit. 21(7):22-26. Schwartz, L. 1939. Occupational Diseases of the Skin. Pp. 390-429 in Industrial Hygiene, A.J. Lanza and J.A. Goldberg, eds. New York: Oxford University Press.
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Toxicity of Military Smokes and Obscurants: Volume 3 Schwartz, L., L. Tulipan, and D.J. Birmingham. 1957. Occupational Diseases of the Skin, 3rd Ed. Philadelphia: Lea & Febiger. Singh, G.B. 1971. Effect of benzanthrone on lung parenchyma of experimental animals. J. Sci. Labour (Part 2) 47(7):423-425. Singh G.B., and S.K. Khanna. 1976. Effect of benzanthrone on testis and male accessory sex glands. Environ. Res. 12(3):327-333. Singh, G.B. and V.N. Tripathi. 1973. Effect of benzanthrone on the urinary bladder of guinea pig. Experientia 29(6):683-684. Singh, G.B., and S.H. Zaidi. 1969. Preliminary clinical and experimental studies on benzanthrone toxicity. J. Indian Med. Assoc. 53(12):558-560. Slutskii, L.I. 1958. Role of the autonomic nervous system during functional disturbances in liver and intoxication by benzanthrone. Uch. Zap. Naucho-Issled. Inst. Gig. Tr. Profzabol. 27:78-79. Trivedi, D.H., and A.K. Niyogi. 1968. Benzanthrone hazard in dye-factory. Indian J. Ind. Med. 14(1):13-22. Uebelin, F., and H. Buess. 1951. Skin blackening by benzanthrone [in French]. Arch. Mal. Prof. 12(16):655-657. Weeks, M.H., and P. Yevich. 1963. The toxicity of combustion products of pyrotechnics. Ind. Hyg. J. 24:622-629.
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