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Vitamin and heart disease
760
Information Section--Fd Chem. Toxic. Vol. 34, No. 8
"a substantial proportion of the benefits of wine, beer or spirits are attributable to the alcohol content rather than to other components of each drink" and that "all alcoholic drinks are linked with lower risk" of heart disease (Rimm et al., ibid. 1996, 312, 731). Me|Qx LOW-DOSE INDUCTION OF P R E C A N C E R O U S LESIONS
The mutagen MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) is produced during the cooking of food and has previously been shown to be a potent carcinogen in rodents. It has now been shown to induce clear increases in the levels of a precancerous liver lesion and D N A liver adducts in rats fed a diet containing 0.8 ppm for only 6 wk. The rats were receiving about 35 lag/kg body weight/day; human exposures have been estimated to be in the order of 0.2-2.6 lag/person/day (Kato et al., Japanese Journal o f Cancer Research 1996, 87, 127). CALCIUM SUPPLEMENTATION DURING PREGNACY
A review of the effects of calcium supplementation during pregnancy re-examined data from 14 randomized trials (involving a total of almost 2500 women). Data pooled from all 14 studies showed blood pressure to be significantly and markedly reduced in those taking supplementary calcium during pregnancy. Analysis of the nine studies which provided adequate data on pregnancy outcome also showed a significant reduction in pre-eclampsia (Bucher et al., Journal o f the American Medical Association 1996, 275, 1113). An editorial notes that "dietary calcium intake fails to meet recommended levels in virtually all categories of Americans" and that over half the [US] population consumes inadequate calcium (McCarron and Hatton, ibid. 1996, 275, 1128). VITAMIN E AND HEART DISEASE
A British study has concluded that ct-tocopherol supplementation substantially reduces the rate of non-fatal heart attacks in patients with established heart disease, with beneficial effects apparent after 1 year of treatment. In a double-blind study, 1035 patients were given either 400 or 800 IU ~t-tocopherol/day (268 or 537mg/day). A further 967 patients received placebo capsules. The median follow-up time was 510 days. a-Tocopherol significantly reduced the risk of non-fatal myocardial infarction [14 v. 41 events; relative risk (RR) 0.23, 95% confidence interval (CI) 0.11-0.47], but had no effects on cardiovascular deaths, of which there was a slight, but non-statistically significant excess in the treated group (27 v. 23; RR 1.18, 95% CI 0.62-2.27) (Stephens et al., Lancet 1996, 347, 781).
CARCINOGENIC POTENTIAL OF T H I R A M
Thiram, a dithiocarbamate fungicide, increased the incidence of local tumours in a series of skin painting studies in mice. Tumours were seen when mice were given 100 mg/kg body weight (either as a single exposure, or three times/wk for 3 wk) followed by long-term treatment with a standard promotor. The thiram tested was of Indian commercial grade. There was no evidence of a carcinogenic potential when thiram was applied alone at 100 mg/kg body weight, three times/wk for 52 wk, although the high mortality (only six of the 40 mice remained alive at 52 wk) would have reduced the power of this study to detect a carcinogenic effect (Shukla et al., Food and Chemical Toxicology 1996, 34, 283). ENZYMES AND HYPERSENSITIVITY-ALL OVER AGAIN
A recent report describes hypersensitivity reactions and flu-like symptoms among 36 employees at a US biotechnology plant producing industrial and foodgrade enzymes. Difficulties were encountered with hypersensitivity reactions and enzymes in the detergent industry two or more decades ago (Biagini et al., Journal of Applied Toxicology 1996, 16, 139). PURPURIN---CARCINOGENICITY IN RATS
Purpurin, a natural hydroxyanthraquinone, when given at 1% in the diet of male rats for 17 months (a dose of about 500 mg/kg body weight/day) produced kidney damage and bladder tumours (in five of the 27 animals). Lower doses were not tested (Moil et al., Cancer Letters 1996, 102, 193). C H L O R O P H E N E - - - I N H A L A T I O N TOXICITY IN RODENTS
Mild anaemia, damage to the liver and nasal tissues and reduced sperm motility were seen in rats exposed to 200 ppm (720 mg/m3), 6 hr/day, 5 days/wk for 13 wk. The nasal tissues were also affected at 80 ppm, leading to a no-effect level of 32 ppm. The same no-effect level was reported in mice, forestomach hyperplasia resulting from exposure to 80 ppm (200 ppm was fatal to all mice within 2 wk). The authors concluded that "at similar exposure concentrations [chloroprene] is much more toxic to rodents than are butadiene and isoprene". On the basis of the above findings, exposure concentrations of 0, 12.5, 32 and 80 ppm were selected for 2-yr inhalation studies in rats and mice (Melnick, Toxicology 1996, 108, 79). 3-DIMETHYLAMINOPROPYLAMINE~ALLERGENIC IMPURITY IN SURFACTANTS?
The skin sensitizing activity of two commercial surfactants, cocamidopropylbetaine and cocamidopropylamine oxide, has been attributed to 3dimethylaminopropylamine (DMPA), an impurity
Information Section--Fd Chem. Toxic. Vol. 34, No. 8
"a substantial proportion of the benefits of wine, beer or spirits are attributable to the alcohol content rather than to other components of each drink" and that "all alcoholic drinks are linked with lower risk" of heart disease (Rimm et al., ibid. 1996, 312, 731). Me|Qx LOW-DOSE INDUCTION OF P R E C A N C E R O U S LESIONS
The mutagen MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) is produced during the cooking of food and has previously been shown to be a potent carcinogen in rodents. It has now been shown to induce clear increases in the levels of a precancerous liver lesion and D N A liver adducts in rats fed a diet containing 0.8 ppm for only 6 wk. The rats were receiving about 35 lag/kg body weight/day; human exposures have been estimated to be in the order of 0.2-2.6 lag/person/day (Kato et al., Japanese Journal o f Cancer Research 1996, 87, 127). CALCIUM SUPPLEMENTATION DURING PREGNACY
A review of the effects of calcium supplementation during pregnancy re-examined data from 14 randomized trials (involving a total of almost 2500 women). Data pooled from all 14 studies showed blood pressure to be significantly and markedly reduced in those taking supplementary calcium during pregnancy. Analysis of the nine studies which provided adequate data on pregnancy outcome also showed a significant reduction in pre-eclampsia (Bucher et al., Journal o f the American Medical Association 1996, 275, 1113). An editorial notes that "dietary calcium intake fails to meet recommended levels in virtually all categories of Americans" and that over half the [US] population consumes inadequate calcium (McCarron and Hatton, ibid. 1996, 275, 1128). VITAMIN E AND HEART DISEASE
A British study has concluded that ct-tocopherol supplementation substantially reduces the rate of non-fatal heart attacks in patients with established heart disease, with beneficial effects apparent after 1 year of treatment. In a double-blind study, 1035 patients were given either 400 or 800 IU ~t-tocopherol/day (268 or 537mg/day). A further 967 patients received placebo capsules. The median follow-up time was 510 days. a-Tocopherol significantly reduced the risk of non-fatal myocardial infarction [14 v. 41 events; relative risk (RR) 0.23, 95% confidence interval (CI) 0.11-0.47], but had no effects on cardiovascular deaths, of which there was a slight, but non-statistically significant excess in the treated group (27 v. 23; RR 1.18, 95% CI 0.62-2.27) (Stephens et al., Lancet 1996, 347, 781).
CARCINOGENIC POTENTIAL OF T H I R A M
Thiram, a dithiocarbamate fungicide, increased the incidence of local tumours in a series of skin painting studies in mice. Tumours were seen when mice were given 100 mg/kg body weight (either as a single exposure, or three times/wk for 3 wk) followed by long-term treatment with a standard promotor. The thiram tested was of Indian commercial grade. There was no evidence of a carcinogenic potential when thiram was applied alone at 100 mg/kg body weight, three times/wk for 52 wk, although the high mortality (only six of the 40 mice remained alive at 52 wk) would have reduced the power of this study to detect a carcinogenic effect (Shukla et al., Food and Chemical Toxicology 1996, 34, 283). ENZYMES AND HYPERSENSITIVITY-ALL OVER AGAIN
A recent report describes hypersensitivity reactions and flu-like symptoms among 36 employees at a US biotechnology plant producing industrial and foodgrade enzymes. Difficulties were encountered with hypersensitivity reactions and enzymes in the detergent industry two or more decades ago (Biagini et al., Journal of Applied Toxicology 1996, 16, 139). PURPURIN---CARCINOGENICITY IN RATS
Purpurin, a natural hydroxyanthraquinone, when given at 1% in the diet of male rats for 17 months (a dose of about 500 mg/kg body weight/day) produced kidney damage and bladder tumours (in five of the 27 animals). Lower doses were not tested (Moil et al., Cancer Letters 1996, 102, 193). C H L O R O P H E N E - - - I N H A L A T I O N TOXICITY IN RODENTS
Mild anaemia, damage to the liver and nasal tissues and reduced sperm motility were seen in rats exposed to 200 ppm (720 mg/m3), 6 hr/day, 5 days/wk for 13 wk. The nasal tissues were also affected at 80 ppm, leading to a no-effect level of 32 ppm. The same no-effect level was reported in mice, forestomach hyperplasia resulting from exposure to 80 ppm (200 ppm was fatal to all mice within 2 wk). The authors concluded that "at similar exposure concentrations [chloroprene] is much more toxic to rodents than are butadiene and isoprene". On the basis of the above findings, exposure concentrations of 0, 12.5, 32 and 80 ppm were selected for 2-yr inhalation studies in rats and mice (Melnick, Toxicology 1996, 108, 79). 3-DIMETHYLAMINOPROPYLAMINE~ALLERGENIC IMPURITY IN SURFACTANTS?
The skin sensitizing activity of two commercial surfactants, cocamidopropylbetaine and cocamidopropylamine oxide, has been attributed to 3dimethylaminopropylamine (DMPA), an impurity