Ovarian toxicity

J. K. Doerr, S. B. Hooser, B. J. Smith, I. G. Sipes, Ovarian Toxicity of 4-Vinylcyclo-hexene and Related Olefins in B6C3F1 Mice Role of Diepoxides , Chem. Res. Toxicol. 1995, 8, 963 - 969. 

Toxicology. 4-Vinylcyclohexene (VCH) is a moderate skin irritant and causes ovarian toxicity in mice. It is carcinogenic in some animal species when metaholically activated. 

Toxicological studies have suggested that the species specificity for induction of ovarian tumors (produced in mice but not rats) occurs because the blood level of the ovotoxic VCH metabolite VCH-1,2-epoxide is dramatically higher in VCH-treated female mice compared with rats. VCH has been shown to be metabolized by the liver of mice to the ovotoxic metabolite (VCH-1,2-epoxide), which circulates in blood and is delivered to the ovary, where it destroys small oocytes. This destruction of small oocytes is considered to be an early event in carcinogenesis. Species difference in epoxidation of VCH by hepatic micro-somes correlates well with the differences observed in the blood concentration of VCH-1,2-epoxide and VCH ovarian toxicity. Further in vitro studies have found that the rate of VCH epoxidation in humans by human hepatic microsomes was 13- and 2-fold lower than epoxidation by mouse and rat systems respec-tively. Therefore, if the rate of hepatic VCH epoxidation is the main factor that determines the ovotoxicity of VCH, rats may be a more appropriate animal model for humans. 

Smith BJ, Mattison DR, Sipes IG The role of epoxidation in 4-vinylcyclohexene-induced ovarian toxicity. Toxicol Appl Pharmacol 105 372-381, 1990... 

Bolon B et al (1997) Differential follicle coimts as a screen for chemically induced ovarian toxicity in mice results from continuous breeding bioassays. Fimdam Appl Toxicol 39 1-10... 

Pelkonen. Ovarian toxicity of cigarette smoke exposure during pregnancy in mice. Toxicol Lett 1985 25(1) 75-80. 

Bolon, B., Bucci, T.J., Warbritton, A.R., Chen, J.J., Mattison, D.R. Heindel, J.J. (1997) Differential follicle counts as a screen for chemically induced ovarian toxicity in mice results from continuous breeding bioassays. FanJam. appl. Toxicol, 39, t-tO... 

Smith BJ, Plowchalk DR, Sipes IG, Mattison DR (1991) Comparison of random and serial sections in assessment of ovarian toxicity. Reprod Toxicol, 5 379-383. 

Doerr, J.K., Hollis, E.A. Sipes, I.G. (1996) Species differences in tine ovarian toxicity of 1,3-butadiene epoxides inB6C3F mice and Sprague-Dawley rats. Toxicology, 113, 128-136 Downs, T.D., Crane, M.M. Kim, K.W. (1987) Mortality among workers at a butadiene facility. 

Plowchalk DR Mattison DR (1991) Phosphoramide mustard is responsible for the ovarian toxicity of cyclophosphamide. Toxicol Appl Pharmacol, 107 472-481. 

Drugs with ovarian toxicity (busulfan, chlorambucil, cisplatin, cyclophosphamide, fluorouracil)... 

Mattison DR, Singh H, Takizawa K, et al. 1989. Ovarian toxicity of benzo(a)pyrene and metabolites in mice. Report Toxicol 3(2) 115-126. 

MattisonDR. 1985. Clinical manifestations of ovarian toxicity. In Dixon RL, ed. Target organ toxicology series. Reproductive Toxicology. New York Raven Press, 109-130. 

RACB Protocol for Detecting Ovarian Toxicity of Xenobiotics 521... 

Rehm S, Waalkes MP (1988) Cadmium-induced ovarian toxicity in hamsters, mice, and rats. Fund Appl Toxicol 10 635-647... 

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