RESUMEN
A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.
Asunto(s)
Metoxicloro/toxicidad , Útero/efectos de los fármacos , Alimentación Animal , Animales , Peso Corporal/efectos de los fármacos , Sistema Endocrino/efectos de los fármacos , Estrógenos/metabolismo , Conducta Alimentaria/efectos de los fármacos , Femenino , Humanos , Insecticidas/toxicidad , Masculino , Plaguicidas/toxicidad , Embarazo , Preñez , Ratas , Reproducción/efectos de los fármacos , Factores Sexuales , Pruebas de Toxicidad CrónicaRESUMEN
DDT, an organochlorine pesticide, has been cited as a representative chemical suspected of having endocrine disrupting effects. In this study, the potential endocrine disrupting activities of p,p'-DDT, a major component of DDT, were investigated in rats in a 2-generation reproduction toxicity study in accordance with the most current test guidelines of the Ministry of Agriculture, Forestry and Fisheries in Japan, Organization for Economic Cooperation and Development (OECD) and United States Environmental Protection Agency (USEPA) with some modifications and additions. p,p'-DDT was given to parental rats at dietary levels of 0, 5, 50 or 350 ppm. Systemic toxicities in the parental animals consisted of tremors and subsequent deaths (females only) and/or pathological alterations of the liver (both sexes of animals) of the 2 higher dose groups. Reproductive and postnatal developmental toxicities were not evident up to the highest dose level except for the decreased pup viability index on postnatal day 21 in the 350 ppm group. Changes in serum estradiol and progesterone levels and/or a delay in male sexual maturation were noted in the 2 higher dose groups in a dose-dependent fashion, suggesting alterations of endogenous endocrine functions. However, these changes never resulted in substantial reproductive disorders.
Asunto(s)
DDT/toxicidad , Plaguicidas/toxicidad , Anomalías Inducidas por Medicamentos , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Estrógenos/metabolismo , Femenino , Hígado/efectos de los fármacos , Masculino , Embarazo , Preñez , Progesterona/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
A two-generation reproductive toxicity study was conducted with 2,4-dichlorophenol (2,4-DCP), an agent suspected of exerting endocrine disrupting effects. Wistar-Hannover rats, 24/sex/group, were given diet containing 2,4-DCP at dose levels of 0, 500, 2000 or 8000 ppm to examine the potential effects of the test substance on parental animals and their offspring over 2 successive generations. Neither clear systemic nor reproductive toxicity of 2,4-DCP was apparent in the 500 ppm group. In the 2000 ppm group, mean body weight gain and food consumption of females were lowered significantly during the treatment period. Effects on body weights and food consumption were more serious in the 8000 ppm group, both males and females being significantly affected. Reproductive effects of the test substance were also observed in the 2000 and 8000 ppm groups dose-dependently. Observations included significantly increased uterine weights of F1 and/or F2 female weanlings and reduced numbers of implantation sites and live births of F1 parental females. These results suggest that 2,4-DCP has weak reproductive toxicity, possibly based on endocrine activity. However, the basic mechanisms for apparent estrogenic effects of 2,4-DCP remain to be elucidated.