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Effect of feeding BHC on testicular tissue
Agricultural chemicals-Fd Cosmet.
Toxicol.
131
Vol. 19, no. 1
an increase only in males. The latter compound also latter extended downwards into the submucosa and significantly increased the lung tumour incidence were often atypical in appear&e. The mcldence of (Innes et al. J. natn. Cancer Inst. 1969, 42, 1101). The stomach tumours was not increased in mice fed results of this last study have now been analysed in safrole or isosafrole. Carcinomas of the liver were very frequent in safmore detail, and stomach tumours have for the first time been reported from dihydrosafrole. role-fed mice, 60% of the males and 100% of the females of strain X and 11% of the males and 75% of The two hybrid mouse strains, (C57BL/6 x C3HAnf)F, and (C57BL/6 x AKR)F, (referred to as the females of strain Y being affected. Dihydrosafrole strains X and Y. respectively),were given &role, iso- also caused a significant increase in such tumours in safrole or dihydrosafrole at the maximum tolerated , males: 60 and 41% of the strain X and Y males, redose levels of 464, 215 and 464 mg/kg, respectively, in spectively,developed liver carcinomas, compared with distilled water by stomach tube on days 7-27 of age. 6 and 0% of the corresponding controls. However, in dihydrosafrole-fed females the incidence of liver From 28 days of age the mice were given maximum tolerated doses of 1400 ppm safrole, 517 ppm isosa- tumours was no higher than in the controls. In isosafrole or 14OOppm dihydrosafrole in the diet. There frole-treated male mice liver carcinomas were somewere 15-18 mice in each treatment group and the what more frequent than in thi: controls but the animals were killed after 82 wk of treatment. In mice difference was not statistically significant. Only one fed dihydrosafrole, hyperplasia and carcinomas of the strain X female given dihydrosafrole developed liver forestomach were found in 18% .of the males and 88% carcinoma. of the females of strain X and in 41% of the males and Mice with neoplasms of the forestomach generally 78% of the females of strain Y. One of the strain Y did not have liver tumours, a finding similar to that in females had a haemangiosarcoma that metastasized chlorobenzilate-treated female mice (Reuber, Digesto the peritoneum. Of the controls, 23% of the males tion 1977, 16, 308). It is noted that in other, unpuband 28% of the females of strain X had stomach hy- lished, FDA studies oesophageal hyperplasia occurred perplasia or carcinoma, while there was a zero inci- in dogs fed dihydrosafrole for 2 yr, and carcinomas of dence among the strain Y controls. The increase in the skin and tongue developed in dogs given safrole such tumours produced by dihydrosafrole was thus for 6 yr. The author cites previous studies in hamsters highly statistically significant in all groups except the that have indicated that vitamin A deficiency may be strain X males. The neoplasms were sessilegrowths involved in the aetiology of tumours of the forestomach and other squamous epithelia. with an increase in squamous and basal cells; the
AGRICULTURAL Effect of feeding BHC on testicular tissue
Nigam, S. K., Lakkad, B. C., Kamik, A. B., Thakore, K. N., Bhatt, D. K., Babu, K. A. & Kashyap, S. K. (1979). Effect of hexachlorocyclohexane feeding on testicular tissue of pure inbred Swissmice. Bull. enuir. Contam.
Toxicol.
23, 43 1.
Commercial benzene hexachloride (lindane; BHC) consists predominantly of the y isomer but also contains some z and /I isomers. Testicular atrophy has previously been reported in rats ingesting lindane (100% y-BHC: Reuber, Enuir. Res. 1979, 19, 460). In addition, severe hypertrophy and the total arrest of spermatogenesis with the appearance of multinucleated cells have resulted from the testicular injection of 0.25 mg lindane (98% y-BHC) in rats (Dikshith & Datta, Acta pharmac. fox. 1972, 31, 1). However a three-generation reproduction study involving the feeding of lindane to rats at levels of 25-IOOppm showed no effects on reproductive function (Palmer et 01. Toxicology
1978,
10, 45).
This paper describes the testicular changes ob served following the dietary administration of 500 ppm technical grade BHC to 150 male inbred Swissmice over a period of 10 months. Six controls and six test animals were killed each month so that the organs could be weighed and a histological examination of the tissues could be made. From the third month onward the testes of the mice from the test group were significantly heavier than those of the
CHEMICALS controls and various histopathological changes were observed. These included degeneration and shrinking of the epithelia of the seminiferous tubules, some of which had become completely hyalinized, accompanied by the appearance of oedematous fluids in the lumen. Active ceil proliferation of the interstitial tissue was noted along with severe damage in the spermatogonic cells and a sparcity of spermatocytes. In extreme casesthe seminiferous tubules consisted of large numbers of multinucleated giant cells. The authors stress that these findings may be of importance to those involved in the manufacture and use of BHC. Pentachlorobenzene
metabolism
in monkeys
Rozman, K., Williams, J., Mueller, W. F., Coulston, F. & Korte, F. (1979). Metabolism and pharmacokinetics of pentachlorobenzene in the rhesus monkey. Bull. envir. Contam. Toxicol. 22, 190. Pentachlorobenzene is a contaminant of commercial hexachlorobenzene, which has been widely used as a fungicide. However in its 1878 recommendation that pentachlorobenzene be added to the list of sub stances for testing under the TSCA, the Interagency Testing Committee pointed out the lack of data on the effects of this compound on animals and man and cited a study that indicated that it was foetotoxic and teratogenic in rats (Federal Register 1978, 43, 50630). The metabolism and pharmacokinetics of penta-
Toxicol.
131
Vol. 19, no. 1
an increase only in males. The latter compound also latter extended downwards into the submucosa and significantly increased the lung tumour incidence were often atypical in appear&e. The mcldence of (Innes et al. J. natn. Cancer Inst. 1969, 42, 1101). The stomach tumours was not increased in mice fed results of this last study have now been analysed in safrole or isosafrole. Carcinomas of the liver were very frequent in safmore detail, and stomach tumours have for the first time been reported from dihydrosafrole. role-fed mice, 60% of the males and 100% of the females of strain X and 11% of the males and 75% of The two hybrid mouse strains, (C57BL/6 x C3HAnf)F, and (C57BL/6 x AKR)F, (referred to as the females of strain Y being affected. Dihydrosafrole strains X and Y. respectively),were given &role, iso- also caused a significant increase in such tumours in safrole or dihydrosafrole at the maximum tolerated , males: 60 and 41% of the strain X and Y males, redose levels of 464, 215 and 464 mg/kg, respectively, in spectively,developed liver carcinomas, compared with distilled water by stomach tube on days 7-27 of age. 6 and 0% of the corresponding controls. However, in dihydrosafrole-fed females the incidence of liver From 28 days of age the mice were given maximum tolerated doses of 1400 ppm safrole, 517 ppm isosa- tumours was no higher than in the controls. In isosafrole or 14OOppm dihydrosafrole in the diet. There frole-treated male mice liver carcinomas were somewere 15-18 mice in each treatment group and the what more frequent than in thi: controls but the animals were killed after 82 wk of treatment. In mice difference was not statistically significant. Only one fed dihydrosafrole, hyperplasia and carcinomas of the strain X female given dihydrosafrole developed liver forestomach were found in 18% .of the males and 88% carcinoma. of the females of strain X and in 41% of the males and Mice with neoplasms of the forestomach generally 78% of the females of strain Y. One of the strain Y did not have liver tumours, a finding similar to that in females had a haemangiosarcoma that metastasized chlorobenzilate-treated female mice (Reuber, Digesto the peritoneum. Of the controls, 23% of the males tion 1977, 16, 308). It is noted that in other, unpuband 28% of the females of strain X had stomach hy- lished, FDA studies oesophageal hyperplasia occurred perplasia or carcinoma, while there was a zero inci- in dogs fed dihydrosafrole for 2 yr, and carcinomas of dence among the strain Y controls. The increase in the skin and tongue developed in dogs given safrole such tumours produced by dihydrosafrole was thus for 6 yr. The author cites previous studies in hamsters highly statistically significant in all groups except the that have indicated that vitamin A deficiency may be strain X males. The neoplasms were sessilegrowths involved in the aetiology of tumours of the forestomach and other squamous epithelia. with an increase in squamous and basal cells; the
AGRICULTURAL Effect of feeding BHC on testicular tissue
Nigam, S. K., Lakkad, B. C., Kamik, A. B., Thakore, K. N., Bhatt, D. K., Babu, K. A. & Kashyap, S. K. (1979). Effect of hexachlorocyclohexane feeding on testicular tissue of pure inbred Swissmice. Bull. enuir. Contam.
Toxicol.
23, 43 1.
Commercial benzene hexachloride (lindane; BHC) consists predominantly of the y isomer but also contains some z and /I isomers. Testicular atrophy has previously been reported in rats ingesting lindane (100% y-BHC: Reuber, Enuir. Res. 1979, 19, 460). In addition, severe hypertrophy and the total arrest of spermatogenesis with the appearance of multinucleated cells have resulted from the testicular injection of 0.25 mg lindane (98% y-BHC) in rats (Dikshith & Datta, Acta pharmac. fox. 1972, 31, 1). However a three-generation reproduction study involving the feeding of lindane to rats at levels of 25-IOOppm showed no effects on reproductive function (Palmer et 01. Toxicology
1978,
10, 45).
This paper describes the testicular changes ob served following the dietary administration of 500 ppm technical grade BHC to 150 male inbred Swissmice over a period of 10 months. Six controls and six test animals were killed each month so that the organs could be weighed and a histological examination of the tissues could be made. From the third month onward the testes of the mice from the test group were significantly heavier than those of the
CHEMICALS controls and various histopathological changes were observed. These included degeneration and shrinking of the epithelia of the seminiferous tubules, some of which had become completely hyalinized, accompanied by the appearance of oedematous fluids in the lumen. Active ceil proliferation of the interstitial tissue was noted along with severe damage in the spermatogonic cells and a sparcity of spermatocytes. In extreme casesthe seminiferous tubules consisted of large numbers of multinucleated giant cells. The authors stress that these findings may be of importance to those involved in the manufacture and use of BHC. Pentachlorobenzene
metabolism
in monkeys
Rozman, K., Williams, J., Mueller, W. F., Coulston, F. & Korte, F. (1979). Metabolism and pharmacokinetics of pentachlorobenzene in the rhesus monkey. Bull. envir. Contam. Toxicol. 22, 190. Pentachlorobenzene is a contaminant of commercial hexachlorobenzene, which has been widely used as a fungicide. However in its 1878 recommendation that pentachlorobenzene be added to the list of sub stances for testing under the TSCA, the Interagency Testing Committee pointed out the lack of data on the effects of this compound on animals and man and cited a study that indicated that it was foetotoxic and teratogenic in rats (Federal Register 1978, 43, 50630). The metabolism and pharmacokinetics of penta-