Flynn K M, Delclos K B, Newbold R R, Ferguson S A
Divisions of Neurotoxicology and Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
J Agric Food Chem. 2001 Mar;49(3):1658-65. doi: 10.1021/jf0008893.
Vinclozolin is a fungicide used on food crops with human exposure estimated at approximately 2 microg/kg/day from ingestion; occupational exposure, however, may be greater. The metabolites of vinclozolin have been reported to act as antiandrogens and have adverse effects on reproductive physiology and behavior in animals. Here, pregnant rats were fed soy-free diets containing 0, 10, 150, or 750 ppm of vinclozolin (approximately 0, 0.8, 12, and 60 mg/kg/day for an adult) beginning on gestational day 7, and offspring were continued on these diets through sacrifice at postnatal day 77. Male and female offspring were assessed for changes in several nonreproductive sexually dimorphic behaviors: open field and running wheel locomotor activity, play behavior, and consumption of saccharin- and sodium chloride-flavored solutions. There was a significant interaction of sex with vinclozolin exposure on running wheel activity, which indicated that females in the high-dose exposure group were hypoactive compared to same-sex controls. There was a significant overall effect of vinclozolin exposure on fluid consumption, and high-dose animals showed increased intake of the saccharin solution and decreased intake of plain water while saccharin was available. Effects were more pronounced in females, which drank 40.8% more saccharin than control females, whereas males drank 6.2% more than control males. There were no effects of vinclozolin treatment on play behavior or sodium solution intake. Gestational duration, total and live pups per litter, litter sex ratios, and birth weight were also not significantly affected, nor were body weight and food intake for dams and offspring. These results indicate that long-term dietary exposure to vinclozolin does not have severe toxicological consequences on the nonreproductive behaviors measured here. However, exposure may cause subtle alterations in locomotor activity and consumption of saccharin-flavored solution.
乙烯菌核利是一种用于粮食作物的杀菌剂，据估计，人类通过摄入接触该物质的量约为2微克/千克/天；然而，职业接触量可能更高。据报道，乙烯菌核利的代谢产物具有抗雄激素作用，并对动物的生殖生理和行为产生不良影响。在此，从妊娠第7天开始，给怀孕大鼠喂食不含大豆、分别含有0、10、150或750 ppm乙烯菌核利的饲料（对成年大鼠而言，分别约为0、0.8、12和60毫克/千克/天），并让后代继续食用这些饲料，直至在出生后第77天处死。对雄性和雌性后代的几种非生殖性两性异形行为的变化进行了评估：旷场和转轮运动活动、玩耍行为以及对甜味素和氯化钠口味溶液的消耗。在转轮活动方面，性别与乙烯菌核利暴露之间存在显著的交互作用，这表明高剂量暴露组中的雌性与同性对照组相比活动不足。乙烯菌核利暴露对液体消耗有显著的总体影响，在有甜味素的情况下，高剂量组动物的甜味素溶液摄入量增加，而纯水摄入量减少。这种影响在雌性中更为明显，饮用甜味素的雌性比对照雌性多40.8%，而雄性比对照雄性多6.2%。乙烯菌核利处理对玩耍行为或钠溶液摄入量没有影响。妊娠期、每窝的总仔数和存活仔数、窝仔性别比例以及出生体重也没有受到显著影响，母鼠和后代的体重及食物摄入量也未受影响。这些结果表明，长期通过饮食接触乙烯菌核利对这里所测量的非生殖行为没有严重的毒理学后果。然而，接触可能会导致运动活动和甜味素口味溶液消耗出现细微变化。
