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1877. Carcinogenic effects of bis(chloromethyl) ether
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THE CHEMICAL ENVIRONMENT
1877. Carcinogenic effects of bis(chloromethyl) ether Gargus, J. L., Reese, W. H. Jr. & Rutter, H. A. (1969). Induction of lung adenomas in newborn mice by bis(chloromethyl) ether. Toxic. appl. Pharmac. 15, 92. In view of the occurrence of lung cancer among workers exposed to dimethyl sulphate, the effects of two other alkylating agents, bis(chloromethyl) ether (I) and chloromethyl methyl ether (II), on the incidence of lung adenoma has been studied in newborn mice. Groups of 100 ICR Swiss mice, aged between 1 and 3 days and approximately equally divided by sex, were given a single subcutaneous injection of I (12.5/zl/kg) or II (125/zl/kg) in 0.05 ml peanut oil. Groups of 50 mice receiving peanut oil (25 ml/kg) or urethane (1-5 g/kg) served, respectively, as negative and positive control groups. The percentage incidence of mice bearing lung adenomas 6 months after the injection was 14, 100, 45 and 17 in the negative and positive groups and test groups I and li, respectively. I also produced a papilloma and a fibrosarcoma at the site of injection in two mice. These data clearly indicate the carcinogenic potency of I and the inactivity of II, and the authors refer to further unpublished work in which similar findings have been obtained following chronic inhalation by mice. Long-term dermal studies (Van Duuren et al. Archs envir. Hlth 1968, 16, 472) showed I to be a potent carcinogen to mouse skin and to be active by the subcutaneous route. 1878. Another side to ethylene chlorohydrin Bleckat, G. & Strube, G. (1968). Die Klinik der akuten percutanen AthylenchlorhydrinIntoxikation. Int. Arch. Gewerbepath. Gewerbehyg. 25, 45. Ethylene chlorohydrin (EC) has figured in these pages mainly as a reaction product in foodstuffs fumigated with ethylene oxide (Cited in F.C.T. 1966, 4, 456) and attempts are being made to establish safe levels of ingestion of EC (Food Chemical News 1968, 10 (26), 19). A completely different and more acute problem arises in connexion with EC intoxication resulting from its industrial use. Cases of EC poisoning generally result from percutaneous absorption and, in addition to headache, vomiting and reduced vision, may show severe confusion and agitation, convulsions, coma, respiratory paralysis, lung oedema, haematuria and skin irritation. Pathological findings reported in the literature have included oedema of the brain and basal ganglia, degenerative changes in the liver and kidney and necrosis of the bronchial tree. The present authors describe a very severe case of poisoning which resulted from a large area of skin (about 25 ~o of the body surface) being in contact with the solvent for a short time. The neurotoxic effects of EC, and particularly its afl]nity for the ganglion cells of the central nervous system, are demonstrated by this case. The fact that 2 yr after the acute intoxication some neurological effects persisted although liver and kidney function had returned to normal is interpreted as indicating that EC acts directly upon the nervous system, and the effects on the liver and kidney are secondary effects of shock. The use of EC is connected with a few specific branches of the chemical industry, in which it may be used as a solvent for acetylcellulose, resins, gelatin, waxes and lacquers. Accidenls resulting in cases of poisoning by this solvent are fortunately rare and may well be eliminated altogether in the future by improved working conditions. The authors consider, however, that because of its high toxicity this solvent should be used only when there is no effective substitute.
THE CHEMICAL ENVIRONMENT
1877. Carcinogenic effects of bis(chloromethyl) ether Gargus, J. L., Reese, W. H. Jr. & Rutter, H. A. (1969). Induction of lung adenomas in newborn mice by bis(chloromethyl) ether. Toxic. appl. Pharmac. 15, 92. In view of the occurrence of lung cancer among workers exposed to dimethyl sulphate, the effects of two other alkylating agents, bis(chloromethyl) ether (I) and chloromethyl methyl ether (II), on the incidence of lung adenoma has been studied in newborn mice. Groups of 100 ICR Swiss mice, aged between 1 and 3 days and approximately equally divided by sex, were given a single subcutaneous injection of I (12.5/zl/kg) or II (125/zl/kg) in 0.05 ml peanut oil. Groups of 50 mice receiving peanut oil (25 ml/kg) or urethane (1-5 g/kg) served, respectively, as negative and positive control groups. The percentage incidence of mice bearing lung adenomas 6 months after the injection was 14, 100, 45 and 17 in the negative and positive groups and test groups I and li, respectively. I also produced a papilloma and a fibrosarcoma at the site of injection in two mice. These data clearly indicate the carcinogenic potency of I and the inactivity of II, and the authors refer to further unpublished work in which similar findings have been obtained following chronic inhalation by mice. Long-term dermal studies (Van Duuren et al. Archs envir. Hlth 1968, 16, 472) showed I to be a potent carcinogen to mouse skin and to be active by the subcutaneous route. 1878. Another side to ethylene chlorohydrin Bleckat, G. & Strube, G. (1968). Die Klinik der akuten percutanen AthylenchlorhydrinIntoxikation. Int. Arch. Gewerbepath. Gewerbehyg. 25, 45. Ethylene chlorohydrin (EC) has figured in these pages mainly as a reaction product in foodstuffs fumigated with ethylene oxide (Cited in F.C.T. 1966, 4, 456) and attempts are being made to establish safe levels of ingestion of EC (Food Chemical News 1968, 10 (26), 19). A completely different and more acute problem arises in connexion with EC intoxication resulting from its industrial use. Cases of EC poisoning generally result from percutaneous absorption and, in addition to headache, vomiting and reduced vision, may show severe confusion and agitation, convulsions, coma, respiratory paralysis, lung oedema, haematuria and skin irritation. Pathological findings reported in the literature have included oedema of the brain and basal ganglia, degenerative changes in the liver and kidney and necrosis of the bronchial tree. The present authors describe a very severe case of poisoning which resulted from a large area of skin (about 25 ~o of the body surface) being in contact with the solvent for a short time. The neurotoxic effects of EC, and particularly its afl]nity for the ganglion cells of the central nervous system, are demonstrated by this case. The fact that 2 yr after the acute intoxication some neurological effects persisted although liver and kidney function had returned to normal is interpreted as indicating that EC acts directly upon the nervous system, and the effects on the liver and kidney are secondary effects of shock. The use of EC is connected with a few specific branches of the chemical industry, in which it may be used as a solvent for acetylcellulose, resins, gelatin, waxes and lacquers. Accidenls resulting in cases of poisoning by this solvent are fortunately rare and may well be eliminated altogether in the future by improved working conditions. The authors consider, however, that because of its high toxicity this solvent should be used only when there is no effective substitute.