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Multigeneration carcinogenic action of diethylstilboestrol in mice
636
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asthma death" (Carino M. et al., Respiration 1997, 64, 111).
Is the OEL for hydrogen sulfide too high? A 30-minute exposure to hydrogen sulfide at the current UK/US 8-hour exposure limit of 10 ppm decreased oxygen uptake and increased blood lactate in exercising volunteers. Arterial blood gases, haemoglobin saturation, cardiovascular responses and enzyme activities in muscle tissue were unaffected. The Canadian investigators concluded that the findings "question the scientific validity of the current occupational exposure limits for hydrogen sulfide" (Bhambhani Y. et al., Journal of Occupational and Environmental Medicine 1997, 39, 122).
Cancer mortality and offset printing An increased risk of cancer has been reported among workers in an offset printing plant in France. The preliminary study concerned 262 men, 16 of whom had died, 10 from cancer. The death rate for all cancers [standardized mortality ratio (SMR) 213, 95% C198-405], and lung [SMR 381, 95% CI 104-975] and oesophageal cancers [SMR 1049, 95% CI 216-3065] were increased among those employed for more than 10 years. Pressmen were found to be particularly at risk. Because of inadequacies in the study design, the investigators felt that "definitive conclusions could not be reached" but "an increased risk of cancer, especially lung cancer," is suggested (Luce D. et aL, Occupational and Environmental Medicine 1997, 54, 264).
Germ cell genotoxicity of formaldehyde Formaldehyde has been reported in a Nigerian study to be genotoxic, affecting the male germ cells of rats treated with five daily intraperitoneal injections of 0.125 mg/kg body weight. As well as an increased level of sperm abnormality and a decreased sperm count, there was evidence of the induction of transmissible mutations (as indicated by positive results in a dominant lethal study) (Odeigah P.G.C., Mutation Research 1997, 389,
141).
generations on. According to the investigators, "if the high intensity of DES multigenerational carcinogenicity seen in mice is applicable to the human population, this is a health problem of major proportions." Furthermore, if, as in mice, the tumours appear late in life, "reliance on detecting human germ cell damage by waiting for an increased cancer rate could take over 50 years, by which time a country's germ cell pool could have become massively contaminated" (Walker B.E. and Haven M.I., Carcinogenesis 1997, 18, 791).
$ubchronic toxicity of DEHP and DNOP in rats In a study carried out under the auspices of the Canadian Government, rats were given DEHP or its straight-chained analogue di-n-octylphthalate (DNOP) at up to 5000 ppm in the diet for 13 weeks. Both produced effects in the thyroid and liver. Testes damage and peroxisome proliferation in the liver were seen in the DEHP-treated animals only. The no-observed-effect levels were 50 ppm 0.7 mg/kg body weight/day) for DEHP and 500 ppm 06.8 mg/kg body weight/day) for D N O P (Pooh R. et al., Food and Chemical Toxicology 1997, 35, 225).
Diisononyl phthalate m chronic toxicity and carcinogeniclty in rats Di-Cs-10 branched alkyl, Cg-rich, phthalate (referred to by the investigators as diisononyl phthalate) has been found to induce mononuclear cell leukaemia (MNCL) and associated non-tumour liver changes in male and female rats fed about 170 mg/kg body weight/day in the diet for 2 years. Liver, kidney and spleen weights, the blood, and urine were also affected. There was no peroxisome proliferation in the liver. The Exxon investigators concluded that the study indicated "a low potential for chronic toxicity and carcinogenic@ in... rats" with ~no clear evidence of any carcinogenic effects except for a marginal increase in the incidence of MNCL ... which is not considered a relevant risk for humans". The no-observed-effect level was about 17 mg/kg body weight/day (Lington A.W. et al., Fundamental and Applied Toxicology 1997, 36,
79).
Multigeneration carcinogenic action of diethylstilboestrol in mice
Carcinogenicity of 2-methylnaphthalene in mice
In a US study in which a group of pregnant mice was given a single injection of diethylstilboestrol, the carcinogenic action of this synthetic hormone was found still to be present in the female line three
The incidence of total lung tumours (bronchiolar/ alveolar adenomas and carcinomas) was increased in male mice fed about 55 or 115 mg/kg body weight/day in the diet for 81 weeks (20.4 and
Information Section
asthma death" (Carino M. et al., Respiration 1997, 64, 111).
Is the OEL for hydrogen sulfide too high? A 30-minute exposure to hydrogen sulfide at the current UK/US 8-hour exposure limit of 10 ppm decreased oxygen uptake and increased blood lactate in exercising volunteers. Arterial blood gases, haemoglobin saturation, cardiovascular responses and enzyme activities in muscle tissue were unaffected. The Canadian investigators concluded that the findings "question the scientific validity of the current occupational exposure limits for hydrogen sulfide" (Bhambhani Y. et al., Journal of Occupational and Environmental Medicine 1997, 39, 122).
Cancer mortality and offset printing An increased risk of cancer has been reported among workers in an offset printing plant in France. The preliminary study concerned 262 men, 16 of whom had died, 10 from cancer. The death rate for all cancers [standardized mortality ratio (SMR) 213, 95% C198-405], and lung [SMR 381, 95% CI 104-975] and oesophageal cancers [SMR 1049, 95% CI 216-3065] were increased among those employed for more than 10 years. Pressmen were found to be particularly at risk. Because of inadequacies in the study design, the investigators felt that "definitive conclusions could not be reached" but "an increased risk of cancer, especially lung cancer," is suggested (Luce D. et aL, Occupational and Environmental Medicine 1997, 54, 264).
Germ cell genotoxicity of formaldehyde Formaldehyde has been reported in a Nigerian study to be genotoxic, affecting the male germ cells of rats treated with five daily intraperitoneal injections of 0.125 mg/kg body weight. As well as an increased level of sperm abnormality and a decreased sperm count, there was evidence of the induction of transmissible mutations (as indicated by positive results in a dominant lethal study) (Odeigah P.G.C., Mutation Research 1997, 389,
141).
generations on. According to the investigators, "if the high intensity of DES multigenerational carcinogenicity seen in mice is applicable to the human population, this is a health problem of major proportions." Furthermore, if, as in mice, the tumours appear late in life, "reliance on detecting human germ cell damage by waiting for an increased cancer rate could take over 50 years, by which time a country's germ cell pool could have become massively contaminated" (Walker B.E. and Haven M.I., Carcinogenesis 1997, 18, 791).
$ubchronic toxicity of DEHP and DNOP in rats In a study carried out under the auspices of the Canadian Government, rats were given DEHP or its straight-chained analogue di-n-octylphthalate (DNOP) at up to 5000 ppm in the diet for 13 weeks. Both produced effects in the thyroid and liver. Testes damage and peroxisome proliferation in the liver were seen in the DEHP-treated animals only. The no-observed-effect levels were 50 ppm 0.7 mg/kg body weight/day) for DEHP and 500 ppm 06.8 mg/kg body weight/day) for D N O P (Pooh R. et al., Food and Chemical Toxicology 1997, 35, 225).
Diisononyl phthalate m chronic toxicity and carcinogeniclty in rats Di-Cs-10 branched alkyl, Cg-rich, phthalate (referred to by the investigators as diisononyl phthalate) has been found to induce mononuclear cell leukaemia (MNCL) and associated non-tumour liver changes in male and female rats fed about 170 mg/kg body weight/day in the diet for 2 years. Liver, kidney and spleen weights, the blood, and urine were also affected. There was no peroxisome proliferation in the liver. The Exxon investigators concluded that the study indicated "a low potential for chronic toxicity and carcinogenic@ in... rats" with ~no clear evidence of any carcinogenic effects except for a marginal increase in the incidence of MNCL ... which is not considered a relevant risk for humans". The no-observed-effect level was about 17 mg/kg body weight/day (Lington A.W. et al., Fundamental and Applied Toxicology 1997, 36,
79).
Multigeneration carcinogenic action of diethylstilboestrol in mice
Carcinogenicity of 2-methylnaphthalene in mice
In a US study in which a group of pregnant mice was given a single injection of diethylstilboestrol, the carcinogenic action of this synthetic hormone was found still to be present in the female line three
The incidence of total lung tumours (bronchiolar/ alveolar adenomas and carcinomas) was increased in male mice fed about 55 or 115 mg/kg body weight/day in the diet for 81 weeks (20.4 and