Wang Helen Ying, Olmstead Allen W, Li Hong, Leblanc Gerald A
Department of Environmental & Molecular Toxicology, North Carolina State University, Raleigh, NC 27695, USA.
Aquat Toxicol. 2005 Sep 10;74(3):193-204. doi: 10.1016/j.aquatox.2005.05.010.
U.S. Environmental Protection Agency is charged with developing a screening and testing paradigm for detecting endocrine toxicity of chemicals that are subject to regulation under the Food Quality Protection and the Safe Drinking Water Acts. In this study, we developed and evaluated a screening assay that could be employed to detect juvenoid-related endocrine-modulating activity in an invertebrate species. Juvenoid activity, anti-juvenoid activity, and juvenoid potentiator activity of chemicals was assessed using the water flea Daphnia magna. Male sex determination is under the regulatory control of juvenoid hormone, presumably methyl farnesoate, and this endpoint was used to detect juvenoid modulating activity of chemicals. Eighteen chemicals were evaluated for juvenoid agonist activity. Positive responses were detected with the juvenoid hormones methyl farnesoate and juvenile hormone III along with the insect growth regulating insecticides pyriproxyfen, fenoxycarb, and methoprene. Weak juvenoid activity also was detected with the cyclodiene insecticide dieldrin. Assays performed repetitively with compounds that gave either strong positive, weak positive, or negative response were 100% consistent indicating that the assay is not prone to false positive or negative responses. Five candidate chemicals were evaluated for anti-juvenoid activity and none registered positive. Four chemicals (all trans-retinoic acid, methoprene, kinoprene, bisphenol A) also were evaluated for their ability to potentiate the activity of methyl farnesoate. All registered positive. Results demonstrate that an in vivo assay with a crustacean species customarily employed in toxicity testing can be used to effectively screen chemicals for juvenoid-modulating activity.
美国环境保护局负责制定一种筛选和测试模式，以检测受《食品质量保护法》和《安全饮用水法》监管的化学品的内分泌毒性。在本研究中，我们开发并评估了一种筛选试验，该试验可用于检测无脊椎动物物种中与保幼激素相关的内分泌调节活性。使用大型溞评估化学品的保幼激素活性、抗保幼激素活性和保幼激素增强活性。雄性性别决定受保幼激素（可能是法尼酸甲酯）的调节控制，该终点用于检测化学品的保幼激素调节活性。评估了18种化学品的保幼激素激动剂活性。保幼激素法尼酸甲酯和保幼激素III以及昆虫生长调节剂杀虫剂吡丙醚、苯氧威和烯虫酯均检测到阳性反应。环二烯类杀虫剂狄氏剂也检测到微弱的保幼激素活性。对产生强阳性、弱阳性或阴性反应的化合物进行的重复试验100%一致，表明该试验不易出现假阳性或假阴性反应。评估了5种候选化学品的抗保幼激素活性，均未显示阳性。还评估了4种化学品（全反式维甲酸、烯虫酯、烯虫炔酯、双酚A）增强法尼酸甲酯活性的能力。均显示阳性。结果表明，一种使用毒性测试中常用的甲壳类物种的体内试验可有效筛选具有保幼激素调节活性的化学品。
