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Reproductive toxicity of methoxychlor in rats
150
Information Section
vascular diseases was 30-40% lower among men and women taking at least one drink per day than among non-drinkers. On the other hand, mortality from cancers of the breast, gastrointestinal tract and liver, and cirrhosis of the liver was higher among those admitting to two or more drinks per day. Overall, the risk of death was lowest among men and women who reported one drink daily (Thun M.J. et aI., New EnglandJournal ofMedicine 1997, 337,1705).
Alcohol, coffee and Helicobacter pylori
reduced in patients who supplemented their diet with retinol (25,000IV) for up to 5 years. All the participants had a prior history of skin cancer. The 1157 subjects who took retinol supplements had a hazard ratio for time to first new squamous cell carcinoma of 0.74 (95% CI 0.56-0.99) when compared with the 1140 taking the placebo. A total of 249 subjects developed skin cancer of the squamous cell type in the study period (Moon T .E. et aL, Cancer Epidemiology, Biomarkers & Prevention 1997,6,949).
Helicobacter pylori is a bacterial infection associated
Heart disease In the elderly
with an increased risk of gastritis and other gastrointestinal complaints, including cancer. A study of 447 German patients on routine visits to their general practitioners suggests that alcohol consumption (beer or wine) may afford some protection against H pylori infection, while coffee may have the opposite effect. The odds ratio for active H pylori infection associated with the consumption of three or more cups of coffee a day (compared with those drinking no coffee) was 2.49 [95% confidence interval (Cl) 1.23-5.03] (Brenner H. et al., British MedicalJournal1997, 315, 1489).
A study of very old Seventh-Day Adventists indicates that even at the age of 85 or more the effects of previous dietary habits and traditional risk factors are still important predictors of death from heart disease. An analysis of nearly 1400 deaths (364 from coronary heart disease) following 12,000 person-years of observation revealed that the frequent consumption of nuts had a protective effect against heart disease, as did regular exercise, while the consumption of one or more doughnuts each week (presumably an indicator of poor dietary patterns) was associated with an increased risk of heart disease mortality (Fraser G.E. and Shavlik D.]., Archives ofInternalMedicine 1997, 157,2249).
An accompanying editorial from a professor of nutritional sciences and medicine at the University of Toront, notes that a recent study of over 47,000 men found no increased risk of duodenal ulcer associated with coffee or alcohol consumption and warns of the dangers of premature conclusions in this important area (jenkins D.J.A., ibid. 1997,315, 1481).
Drinking-water calcium and colon cancer A study comparing 1714 residents of Taiwan who died from colon cancer with an equal number of controls has found a reduced cancer risk to be associated with calcium in the drinking water. The odds ratio for colon cancer death for water calcium levels between 24.4 and 42.3 mg/litre was 0.79 (95% CI 0.64-0.98) relative to the reference group who were exposed to 24 mg/litre or less. In areas with calcium levels of 42.4 mg/litre or more, the odds ratio was lower still at 0.58 (0.47-0.73) (Yang C.-Y. et al.,Japanese Journal ofCancer Research 1997, 88, 928).
Retinol supplementation suppresses recurrence of skin cancer The recurrence of one type of skin cancer (squamous cell carcinoma) has been shown to be
Oestrogenic activity of DDT isomers in human cells in culture In a human breast cancer cell line, the two DDT isomers, p,p'-DDT and o,p'.DDT, were shown to enhance oestrogen-stimulated cell growth and to induce the expression of oestrogen-sensitive genes. When the DDT isomers were mixed together, they were active at concentrations 10o-fold lower than those required when each was administered alone. When tested individually, p,p'.DDT was more effective than o,p'·DDT (Shekhar P.V.M. et al., Journal oftheNationalCancer Institute 1997, 89, 1774).
Reproductive toxicity of methoxychlor in rats An oral study has failed to establish a clear no-effect level for developmental toxicity. This pesticide was administered to female rats at doses of 5-150 mg/kg body weight/day for the week before and the week after birth and then for a short period to the pups. There were no clear effects in the adult females at the lowest dose, but the female pups showed a slight decrease in ovary weight (statistically significant at higher doses) and a significant reduction in serum levels of follicle stimulating hormone. The low-dose male pups showed a
Information Section
significant reduction in seminal vesicle weight, while testis weight was reduced at 50 mg/kg body weight/day and above (Chapin R.E. et al., Fundamental and Applied Toxicology 1997, 40,138).
No association between benzene exposure and multiple myeloma On the basis of a small number of case reports, it has been suggested that multiple myeloma (a malignant proliferation of plasma cells in the bone marrow) may be another benzene-induced disease. An analysis of 22 mortality studies involving over 250,000 petroleum workers in the USA, UK, Canada and Australia provides no evidence to support the contention. There were 205 deaths from this rare type of tumour, compared with an expected number (based on national mortality rates) of 221 (Wong O. and Raabe G.K., Regulatory ToxicologyandPhannacology 1997,26,188).
Solvent exposure impairs colour vision Impaired colour vision in the blue-green range was found in 24 workers at a German car factory. The workers were exposed to a mixture of solvents including xylene, toluene, ethyl benzene, propyl benzene, ethyl toluene, methyl ethyl ketone, methyl isobutyl ketone and perchloroethylene. Workplace levels of the solvents were below the appropriate German occupational threshold limit values (Muttray A. et al., International Archives of Occupational and EnvironmentalHealth 1997, 70, 407).
Respiratory disease after exposure to triphenylmethane triisocyanate A case is presented of an Irishman who developed both asthma and lung inflammation (alveolitis) after occupational exposure to one of the less common isocyanates, triphenylmethane triisocyanate. Five months earlier, he had spent 4 days applying an adhesive in a confined space, with no respiratory or skin protection. While the development of asthma after isocyanate exposure is well recognized, the concurrent development of alveolitis was said to be unusual. The investigators were not aware of any other reports of acute or chronic respiratory disease in humans after exposure to this particular isocyanate (Buick J.B. and Todd G.R.G., Occupational Medicine 1997, 47, 504).
Respiratory and local effects from colophony fumes A HSE study of female workers in four UK electronics factories "highlights the health problems
151
arising from a known but sometimes neglected hazard", the fumes generated from cored solder wire containing the flux colophony. Among the 88 workers exposed for 37 hours each week or longer, over 60% complained of wheeziness, while over 30% and 20%, respectively, had nose and eye symptoms. These incidences were more than double those seen in the 44 workers exposed for less than 20 hours per week (palmer K. and Crane G., Occupational Medicine 1997, 47, 491).
Hexamethylphosphoramide-repeated oral toxicity in rats In a 9o-day study, respiratory tract lesions occurred in rats given 15 mg/kg body weight/day or greater orally, either via the drinking water or by stomach tube. There was some evidence of injury to the trachea (regenerated epithelium) in the rats receiving the lowest tested dose (about 1.5 mg/kg body weight/day). Testes injury was reported at 120 mg/kg body weight/day (Keller D.A. et aL, Fundamental and AppliedToxicology 1997, 40, 15).
Subchronic oral toxicity of p-nonylphenol In rats This high-volume chemical intermediate, which has shown weak oestrogenic activity in various in vitro and in vivo screening assays, gave no evidence of any hormonal action in a 9O-day feeding study in rats. The rats receiving up to 2000 ppm in the diet (around 150 mg/kg body weight/day) showed no treatment-related changes in the endocrine organs (weight or morphology), or in sperm parameters or oestrous cycling. Because there were signs of weak toxic effects at the top dose, the no-effect level was 50 mg/kg body weight/day (Cunny H.C. et aL, Regulatory Toxicology and Pharmacology 1997, 26, 172).
"Divinylbenzene" inhalation toxicity in mice Treatment-related changes in the nasal cavity, liver and kidneys (and some deaths) occurred when mice were exposed, 6 hrlday, 5 days/week for 2 weeks, to atmospheres containing a mixture of 75 ppm divinylbenzene and 60 ppm ethylvinylbenzene. Damage to the nose was evident even at the lowest tested concentration of 25 ppm d.ivinylbenzene and 20 ppm ethylvinylbenzene (Morgan D.L. et al., Fundamental and AppliedToxicology 1997, 39, 89).
3-Methyl-l-butanol and 2-methyl-lpropanol-90-day toxicity studies in rats Mild effects on the blood were observed in rats given the industrial solvent 3-methyl-l-butanol in
Information Section
vascular diseases was 30-40% lower among men and women taking at least one drink per day than among non-drinkers. On the other hand, mortality from cancers of the breast, gastrointestinal tract and liver, and cirrhosis of the liver was higher among those admitting to two or more drinks per day. Overall, the risk of death was lowest among men and women who reported one drink daily (Thun M.J. et aI., New EnglandJournal ofMedicine 1997, 337,1705).
Alcohol, coffee and Helicobacter pylori
reduced in patients who supplemented their diet with retinol (25,000IV) for up to 5 years. All the participants had a prior history of skin cancer. The 1157 subjects who took retinol supplements had a hazard ratio for time to first new squamous cell carcinoma of 0.74 (95% CI 0.56-0.99) when compared with the 1140 taking the placebo. A total of 249 subjects developed skin cancer of the squamous cell type in the study period (Moon T .E. et aL, Cancer Epidemiology, Biomarkers & Prevention 1997,6,949).
Helicobacter pylori is a bacterial infection associated
Heart disease In the elderly
with an increased risk of gastritis and other gastrointestinal complaints, including cancer. A study of 447 German patients on routine visits to their general practitioners suggests that alcohol consumption (beer or wine) may afford some protection against H pylori infection, while coffee may have the opposite effect. The odds ratio for active H pylori infection associated with the consumption of three or more cups of coffee a day (compared with those drinking no coffee) was 2.49 [95% confidence interval (Cl) 1.23-5.03] (Brenner H. et al., British MedicalJournal1997, 315, 1489).
A study of very old Seventh-Day Adventists indicates that even at the age of 85 or more the effects of previous dietary habits and traditional risk factors are still important predictors of death from heart disease. An analysis of nearly 1400 deaths (364 from coronary heart disease) following 12,000 person-years of observation revealed that the frequent consumption of nuts had a protective effect against heart disease, as did regular exercise, while the consumption of one or more doughnuts each week (presumably an indicator of poor dietary patterns) was associated with an increased risk of heart disease mortality (Fraser G.E. and Shavlik D.]., Archives ofInternalMedicine 1997, 157,2249).
An accompanying editorial from a professor of nutritional sciences and medicine at the University of Toront, notes that a recent study of over 47,000 men found no increased risk of duodenal ulcer associated with coffee or alcohol consumption and warns of the dangers of premature conclusions in this important area (jenkins D.J.A., ibid. 1997,315, 1481).
Drinking-water calcium and colon cancer A study comparing 1714 residents of Taiwan who died from colon cancer with an equal number of controls has found a reduced cancer risk to be associated with calcium in the drinking water. The odds ratio for colon cancer death for water calcium levels between 24.4 and 42.3 mg/litre was 0.79 (95% CI 0.64-0.98) relative to the reference group who were exposed to 24 mg/litre or less. In areas with calcium levels of 42.4 mg/litre or more, the odds ratio was lower still at 0.58 (0.47-0.73) (Yang C.-Y. et al.,Japanese Journal ofCancer Research 1997, 88, 928).
Retinol supplementation suppresses recurrence of skin cancer The recurrence of one type of skin cancer (squamous cell carcinoma) has been shown to be
Oestrogenic activity of DDT isomers in human cells in culture In a human breast cancer cell line, the two DDT isomers, p,p'-DDT and o,p'.DDT, were shown to enhance oestrogen-stimulated cell growth and to induce the expression of oestrogen-sensitive genes. When the DDT isomers were mixed together, they were active at concentrations 10o-fold lower than those required when each was administered alone. When tested individually, p,p'.DDT was more effective than o,p'·DDT (Shekhar P.V.M. et al., Journal oftheNationalCancer Institute 1997, 89, 1774).
Reproductive toxicity of methoxychlor in rats An oral study has failed to establish a clear no-effect level for developmental toxicity. This pesticide was administered to female rats at doses of 5-150 mg/kg body weight/day for the week before and the week after birth and then for a short period to the pups. There were no clear effects in the adult females at the lowest dose, but the female pups showed a slight decrease in ovary weight (statistically significant at higher doses) and a significant reduction in serum levels of follicle stimulating hormone. The low-dose male pups showed a
Information Section
significant reduction in seminal vesicle weight, while testis weight was reduced at 50 mg/kg body weight/day and above (Chapin R.E. et al., Fundamental and Applied Toxicology 1997, 40,138).
No association between benzene exposure and multiple myeloma On the basis of a small number of case reports, it has been suggested that multiple myeloma (a malignant proliferation of plasma cells in the bone marrow) may be another benzene-induced disease. An analysis of 22 mortality studies involving over 250,000 petroleum workers in the USA, UK, Canada and Australia provides no evidence to support the contention. There were 205 deaths from this rare type of tumour, compared with an expected number (based on national mortality rates) of 221 (Wong O. and Raabe G.K., Regulatory ToxicologyandPhannacology 1997,26,188).
Solvent exposure impairs colour vision Impaired colour vision in the blue-green range was found in 24 workers at a German car factory. The workers were exposed to a mixture of solvents including xylene, toluene, ethyl benzene, propyl benzene, ethyl toluene, methyl ethyl ketone, methyl isobutyl ketone and perchloroethylene. Workplace levels of the solvents were below the appropriate German occupational threshold limit values (Muttray A. et al., International Archives of Occupational and EnvironmentalHealth 1997, 70, 407).
Respiratory disease after exposure to triphenylmethane triisocyanate A case is presented of an Irishman who developed both asthma and lung inflammation (alveolitis) after occupational exposure to one of the less common isocyanates, triphenylmethane triisocyanate. Five months earlier, he had spent 4 days applying an adhesive in a confined space, with no respiratory or skin protection. While the development of asthma after isocyanate exposure is well recognized, the concurrent development of alveolitis was said to be unusual. The investigators were not aware of any other reports of acute or chronic respiratory disease in humans after exposure to this particular isocyanate (Buick J.B. and Todd G.R.G., Occupational Medicine 1997, 47, 504).
Respiratory and local effects from colophony fumes A HSE study of female workers in four UK electronics factories "highlights the health problems
151
arising from a known but sometimes neglected hazard", the fumes generated from cored solder wire containing the flux colophony. Among the 88 workers exposed for 37 hours each week or longer, over 60% complained of wheeziness, while over 30% and 20%, respectively, had nose and eye symptoms. These incidences were more than double those seen in the 44 workers exposed for less than 20 hours per week (palmer K. and Crane G., Occupational Medicine 1997, 47, 491).
Hexamethylphosphoramide-repeated oral toxicity in rats In a 9o-day study, respiratory tract lesions occurred in rats given 15 mg/kg body weight/day or greater orally, either via the drinking water or by stomach tube. There was some evidence of injury to the trachea (regenerated epithelium) in the rats receiving the lowest tested dose (about 1.5 mg/kg body weight/day). Testes injury was reported at 120 mg/kg body weight/day (Keller D.A. et aL, Fundamental and AppliedToxicology 1997, 40, 15).
Subchronic oral toxicity of p-nonylphenol In rats This high-volume chemical intermediate, which has shown weak oestrogenic activity in various in vitro and in vivo screening assays, gave no evidence of any hormonal action in a 9O-day feeding study in rats. The rats receiving up to 2000 ppm in the diet (around 150 mg/kg body weight/day) showed no treatment-related changes in the endocrine organs (weight or morphology), or in sperm parameters or oestrous cycling. Because there were signs of weak toxic effects at the top dose, the no-effect level was 50 mg/kg body weight/day (Cunny H.C. et aL, Regulatory Toxicology and Pharmacology 1997, 26, 172).
"Divinylbenzene" inhalation toxicity in mice Treatment-related changes in the nasal cavity, liver and kidneys (and some deaths) occurred when mice were exposed, 6 hrlday, 5 days/week for 2 weeks, to atmospheres containing a mixture of 75 ppm divinylbenzene and 60 ppm ethylvinylbenzene. Damage to the nose was evident even at the lowest tested concentration of 25 ppm d.ivinylbenzene and 20 ppm ethylvinylbenzene (Morgan D.L. et al., Fundamental and AppliedToxicology 1997, 39, 89).
3-Methyl-l-butanol and 2-methyl-lpropanol-90-day toxicity studies in rats Mild effects on the blood were observed in rats given the industrial solvent 3-methyl-l-butanol in