Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada H3G 1Y6.
Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada K1A 0K9.
Toxicology. 2014 Jun 5;320:56-66. doi: 10.1016/j.tox.2014.03.005. Epub 2014 Mar 23.
Brominated flame retardants are incorporated into a wide variety of consumer products and are known to enter into the surrounding environment, leading to human exposure. There is accumulating evidence that these compounds have adverse effects on reproduction and development in humans and animal models. Animal studies have generally characterized the outcome of exposure to a single technical mixture or congener. Here, we determined the impact of exposure of rats prior to mating and during gestation to a mixture representative of congener levels found in North American household dust. Adult female Sprague-Dawley rats were fed a diet containing 0, 0.75, 250 or 750mg/kg of a mixture of flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane) from two weeks prior to mating to gestation day 20. This formulation delivered nominal doses of 0, 0.06, 20 and 60mg/kg body weight/day. The lowest dose approximates high human exposures based on house dust levels and the dust ingestion rates of toddlers. Litter size and resorption sites were counted and fetal development evaluated. No effects on maternal health, litter size, fetal viability, weights, crown rump lengths or sex ratios were detected. The proportion of litters with fetuses with anomalies of the digits (soft tissue syndactyly or malposition of the distal phalanges) was increased significantly in the low (0.06mg/kg/day) dose group. Skeletal analysis revealed a decreased ossification of the sixth sternebra at all exposure levels. Thus, exposure to an environmentally relevant mixture of brominated flame retardants results in developmental abnormalities in the absence of apparent maternal toxicity. The relevance of these findings for predicting human risk is yet to be determined.
溴系阻燃剂被广泛应用于各类消费品，已知会进入周围环境，导致人类接触。越来越多的证据表明，这些化合物对人类和动物模型的生殖和发育有不良影响。动物研究通常描述了单一技术混合物或同系物暴露的结果。在这里，我们研究了在交配前和妊娠期暴露于代表北美的家庭灰尘中同系物水平的混合物对大鼠的影响。成年雌性 Sprague-Dawley 大鼠在交配前两周至妊娠第 20 天期间，喂食含阻燃剂（多溴二苯醚、六溴环十二烷）混合物的饮食，浓度分别为 0、0.75、250 或 750mg/kg。这种配方提供了 0、0.06、20 和 60mg/kg 体重/天的名义剂量。最低剂量基于房屋灰尘水平和幼儿的灰尘摄入量，近似于高人体暴露。计算了窝仔数和吸收部位，并评估了胎儿发育情况。未发现母体健康、窝仔数、胎儿存活率、体重、头臀长或性别比例受到影响。在低剂量（0.06mg/kg/天）组中，具有手指异常（软组织并指或远端指骨位置异常）的胎儿的窝仔比例显著增加。骨骼分析显示，在所有暴露水平下，第六胸骨的骨化程度降低。因此，在没有明显母体毒性的情况下，暴露于环境相关的溴系阻燃剂混合物会导致发育异常。这些发现对于预测人类风险的相关性尚待确定。
