Abstract:
OBJECTIVE:The aim of this study was to assess whether the joint effects of three androgen receptor antagonists (vinclozolin, flutamide, procymidone) on male sexual differentiation after in utero and postnatal exposures can be predicted based on dose-response data of the individual chemicals. METHODS:Test chemicals and mixtures were administered by gavage to time-mated nulliparous, young adult Wistar rats from gestational day 7 to the day before expected birth, and from postnatal days 1-16. Changes in anogenital distance (AGD) and nipple retention (NR) in male offspring rats were chosen as end points for extensive dose-response studies. Vinclozolin, flutamide, and procymidone were combined at a mixture ratio proportional to their individual potencies for causing retention of six nipples in male offspring. RESULTS:With AGD as the end point, the joint effects of the three anti-androgens were essentially dose additive. The observed responses for NR were slightly higher than those expected on the basis of dose addition. A combination of doses of each chemical, which on its own did not produce statistically significant AGD alterations, induced half-maximal mixture effects. At individual doses associated with only modest effects on NR, the mixture induced NR approaching female values in the males. CONCLUSIONS:Effects of a mixture of similarly acting anti-androgens can be predicted fairly accurately on the basis of the potency of the individual mixture components by using the dose addition concept. Exposure to anti-androgens, which individually appears to exert only small effects, may induce marked responses in concert with, possibly unrecognized, similarly acting chemicals.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Hass U,Scholze M,Christiansen S,Dalgaard M,Vinggaard AM,Axelstad M,Metzdorff SB,Kortenkamp Adoi
10.1289/ehp.9360subject
Has Abstractpub_date
2007-12-01 00:00:00pages
122-8eissn
0091-6765issn
1552-9924journal_volume
115 Suppl 1pub_type
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pub_type: 杂志文章,评审
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更新日期:1985-02-01 00:00:00
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