- Email: [email protected]
Foetal effects of methylmercury and cadmium Fuyuta, M., Fujimoto, T. & Hirata, S. (1978). Embryotoxic effects of methylmercuric chloride administered to mice and rats during organogenesis. Teratology18, 353.
324
Environmental
contaminants-Fd
of which was greatest in foetuses of dams treated on day 9. Normal palatogenesis in the hamster begins on day 12 of pregnancy and is completed early on day 13. Therefore, assuming that chromium acts directly on the differentiating tissues, the lack of effect of chromium administered on days 10 and 11 is surprising. The authors suggest that at the dose level used in the experiment, it may have taken several days for the amount of chromium required to disrupt palatogenesisat the appropriate time to accumulate in the palatal region. A study of the severity of the abnormality indicated that while there was considerable variation in the degree of palatal development, the majority of the abnormal palates had reached a relatively late stage of development-that at which the middle and posterior thirds of the hard palate were used. There were indications in this study that a delay in foetal growth may be a major factor in chromiuminduced cleft palate. The crown-rump lengths of chromium-exposed foetuses with cleft palates were significantly shorter than those of chromium-exposed foetueseswithout palatal abnormalities. Furthermore, the foetuses with normal palates from treated females had shorter crown-rump lengths than the corresponding controls, although the difference in size was only significant in foetuses from dams treated on days 7 and 10. However the site of action of chromium in producing embryotoxicity is still in need of clarification. Foebl etkcts of methylmercury aod cadmium Grady, R. R., Kitay, J. I., Spyker, J. M. & Avery, D. L. (1978). Postnatal endocrine dysfunction induced by prenatal methylmercury or cadmium exposure in mice. J. enoir. Path. Toxicol. 1, 187.
Cosmet. Toxicol. Vol. 18, no. 3
after exposure to MeHg. In males, total liver capacity to metabolize corticosterone was impaired, but in females only the metabolism of the corticosterone side chain was significantly reduced. Adrenal weight was unchanged in both sexes.Corticosteroid production was not significantly impaired but there were indications that MeHg did affect adrenal secretory capacity although the wide variation in results did not permit a firm conclusion to be drawn, and no alteration in plasma corticosteroid concentration was detected. Cd-exposed female offspring showed significant increasesin body and liver weights after 277 days, but no effects were observed in males at this age. At 460-480 days of age a sexdifference in response to Cd was noted. In females there was a doubling of adrenal steroidogenesis and a significant increase in plasma corticosterone concentration, while in males the major effect was enhancement of hepatic reductive capacity. The second paper describes the effects of giving methylmercuric chloride orally to mice on days 6-13 of gestation at dose levels of 75, 60, 50 or 25 mg/kg/ day. Foetuses were examined on day 18. In a parallel experiment pregnant rats were given 75, 5.0 or 2.5 mg MeHgCl/kg/day from day 7 to day 14 of gestation and foetuses were examined on day 20. Treatment with 7.5 mg MeHgCl/kg caused death or resorption in 98.7% of foetuses in mice and 42.4% of foetuses in rats. At 6.0 mg MeHgCl/kg foetal death occurred at a rate of 34.2% in mice, with a significant decrease in mean weight of male foetuses and a markedly increased incidence of malformations. In rats at 50mg MeHgCl/kg foetal weight decreased and the malformation rate increased.The commonest malformations seen were cleft palate and fused thoracic vertebrae in mice, and cleft palate, generalized oedema, brain lesions and wavy ribs in rats. Hormoaal elTectsof pbthalic acid esters
Fuyuta, M., Fujimoto, T. & Hiram, S. (1978). Oishi, S. & Hiraga, K. (1979). Effect of phthalic acid Embryotoxic effects of methylmercuric _ -._ -.._ -_-chloride ad- esters on gonadal function in male rats. Bull. enuir. ministered to nii?% and rats durmg organogeneis. Contam. Toxicol. 21,65. Teratology 18, 353. Phthalic acid esters are used as plasticizers for a Both in man and in animals Hg is transferred wide range of synthetic polymers. Di-(2-ethylhexylt across the placenta and accumulates in foetal tissues phthalate (DEHP) is the phthalate most extensively (Cited in F.C.T. 1978, 16,622). In animals, particularly used in polyvinyl chloride manufacture, and is known high levels of Hg are found in the foetal brain. In to be widely distributed in the environment. DEHP addition, perinatal carbohydrate metabolism has been has a low acute toxicity in experimental animals but it shown to be deranged in the offspring of rats exposed has been reported to have antifertility and mutagenic briefly to low doses of methylmercury (MeHg) during effects in mice at high dose levels (Cited in F.C.T. gestation (Snell et al. Toxicology 1977, 8, 277). In the 1975, 13, 587) and its administration to rats had been first study cited above, the effects of MeHg exposure shown to cause testicular atrophy (Gray et al. Fd Coson the pituitary-adrenal axis were examined. met. Toxicol. 1977, 15, 389). In the study cited above Mice were given orally 2 mg MeHg dicyandiamidel hormonal changes occurring in the rat testis after kg or 2 mg CdClr/kg on days 15, 17 and 19 of gesta- DEHP treatment were investigated. tion and their offspring were exposed to MeHg and Male Wistar rats were injected ip with 1.25g Cd via milk from mothers that were dosed on alter- DEHP/kglday for 5 days. Control rats were injected nate days after delivery until day 20. When they were with olive oil. Testicular venous blood was collected between 460 and 480 days old the offspring exposed from about half the rats in both the treated and conto MeHg and the corresponding controls were killed trol groups 24 hr after the last injection. The remainand examined. Some of the Cd-exposed mice were ing animals were given 100 IU human chorionic killed on day 277, and the rest were killed between gonadotrophin (HCG) by iv injection and testicular days 460 and 480. Male offspring showed a 30% venous blood was collected 15 min later. The blood reduction and females a 20”/, reduction in liver weight samples were centrifuged and the testosterone concen-
Environmental
contaminants-Fd
of which was greatest in foetuses of dams treated on day 9. Normal palatogenesis in the hamster begins on day 12 of pregnancy and is completed early on day 13. Therefore, assuming that chromium acts directly on the differentiating tissues, the lack of effect of chromium administered on days 10 and 11 is surprising. The authors suggest that at the dose level used in the experiment, it may have taken several days for the amount of chromium required to disrupt palatogenesisat the appropriate time to accumulate in the palatal region. A study of the severity of the abnormality indicated that while there was considerable variation in the degree of palatal development, the majority of the abnormal palates had reached a relatively late stage of development-that at which the middle and posterior thirds of the hard palate were used. There were indications in this study that a delay in foetal growth may be a major factor in chromiuminduced cleft palate. The crown-rump lengths of chromium-exposed foetuses with cleft palates were significantly shorter than those of chromium-exposed foetueseswithout palatal abnormalities. Furthermore, the foetuses with normal palates from treated females had shorter crown-rump lengths than the corresponding controls, although the difference in size was only significant in foetuses from dams treated on days 7 and 10. However the site of action of chromium in producing embryotoxicity is still in need of clarification. Foebl etkcts of methylmercury aod cadmium Grady, R. R., Kitay, J. I., Spyker, J. M. & Avery, D. L. (1978). Postnatal endocrine dysfunction induced by prenatal methylmercury or cadmium exposure in mice. J. enoir. Path. Toxicol. 1, 187.
Cosmet. Toxicol. Vol. 18, no. 3
after exposure to MeHg. In males, total liver capacity to metabolize corticosterone was impaired, but in females only the metabolism of the corticosterone side chain was significantly reduced. Adrenal weight was unchanged in both sexes.Corticosteroid production was not significantly impaired but there were indications that MeHg did affect adrenal secretory capacity although the wide variation in results did not permit a firm conclusion to be drawn, and no alteration in plasma corticosteroid concentration was detected. Cd-exposed female offspring showed significant increasesin body and liver weights after 277 days, but no effects were observed in males at this age. At 460-480 days of age a sexdifference in response to Cd was noted. In females there was a doubling of adrenal steroidogenesis and a significant increase in plasma corticosterone concentration, while in males the major effect was enhancement of hepatic reductive capacity. The second paper describes the effects of giving methylmercuric chloride orally to mice on days 6-13 of gestation at dose levels of 75, 60, 50 or 25 mg/kg/ day. Foetuses were examined on day 18. In a parallel experiment pregnant rats were given 75, 5.0 or 2.5 mg MeHgCl/kg/day from day 7 to day 14 of gestation and foetuses were examined on day 20. Treatment with 7.5 mg MeHgCl/kg caused death or resorption in 98.7% of foetuses in mice and 42.4% of foetuses in rats. At 6.0 mg MeHgCl/kg foetal death occurred at a rate of 34.2% in mice, with a significant decrease in mean weight of male foetuses and a markedly increased incidence of malformations. In rats at 50mg MeHgCl/kg foetal weight decreased and the malformation rate increased.The commonest malformations seen were cleft palate and fused thoracic vertebrae in mice, and cleft palate, generalized oedema, brain lesions and wavy ribs in rats. Hormoaal elTectsof pbthalic acid esters
Fuyuta, M., Fujimoto, T. & Hiram, S. (1978). Oishi, S. & Hiraga, K. (1979). Effect of phthalic acid Embryotoxic effects of methylmercuric _ -._ -.._ -_-chloride ad- esters on gonadal function in male rats. Bull. enuir. ministered to nii?% and rats durmg organogeneis. Contam. Toxicol. 21,65. Teratology 18, 353. Phthalic acid esters are used as plasticizers for a Both in man and in animals Hg is transferred wide range of synthetic polymers. Di-(2-ethylhexylt across the placenta and accumulates in foetal tissues phthalate (DEHP) is the phthalate most extensively (Cited in F.C.T. 1978, 16,622). In animals, particularly used in polyvinyl chloride manufacture, and is known high levels of Hg are found in the foetal brain. In to be widely distributed in the environment. DEHP addition, perinatal carbohydrate metabolism has been has a low acute toxicity in experimental animals but it shown to be deranged in the offspring of rats exposed has been reported to have antifertility and mutagenic briefly to low doses of methylmercury (MeHg) during effects in mice at high dose levels (Cited in F.C.T. gestation (Snell et al. Toxicology 1977, 8, 277). In the 1975, 13, 587) and its administration to rats had been first study cited above, the effects of MeHg exposure shown to cause testicular atrophy (Gray et al. Fd Coson the pituitary-adrenal axis were examined. met. Toxicol. 1977, 15, 389). In the study cited above Mice were given orally 2 mg MeHg dicyandiamidel hormonal changes occurring in the rat testis after kg or 2 mg CdClr/kg on days 15, 17 and 19 of gesta- DEHP treatment were investigated. tion and their offspring were exposed to MeHg and Male Wistar rats were injected ip with 1.25g Cd via milk from mothers that were dosed on alter- DEHP/kglday for 5 days. Control rats were injected nate days after delivery until day 20. When they were with olive oil. Testicular venous blood was collected between 460 and 480 days old the offspring exposed from about half the rats in both the treated and conto MeHg and the corresponding controls were killed trol groups 24 hr after the last injection. The remainand examined. Some of the Cd-exposed mice were ing animals were given 100 IU human chorionic killed on day 277, and the rest were killed between gonadotrophin (HCG) by iv injection and testicular days 460 and 480. Male offspring showed a 30% venous blood was collected 15 min later. The blood reduction and females a 20”/, reduction in liver weight samples were centrifuged and the testosterone concen-