Department of Physiological Sciences, Center for Environmental and Human Toxicology, UF, USA; Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611, USA.
Southern California Coastal Water Research Project Authority, Costa Mesa, CA, 92626, CA, USA.
Mol Cell Endocrinol. 2020 May 1;507:110764. doi: 10.1016/j.mce.2020.110764. Epub 2020 Feb 26.
Organochlorine pesticides (OCPs) are persistent environmental contaminants that act as endocrine disruptors and organ system toxicants. These pesticides (e.g. dichlorodiphenyltrichloroethane (DDT), dieldrin, toxaphene, among others) are ranked as some of the most concerning chemicals for human health. These pesticides (1) act as teratogens, (2) are neuroendocrine disruptors, (3) suppress the immune and reproductive systems, and (4) dysregulate lipids and metabolism. Using a computational approach, we revealed enriched endocrine-related pathways in the Comparative Toxicogenomics Database sensitive to this chemical class, and these included reproduction (gonadotropins, estradiol, androgen, steroid biosynthesis, oxytocin), thyroid hormone, and insulin. Insight from the Tox21 and ToxCast programs confirm that these agrochemicals activate estrogen receptors, androgen receptors, and retinoic acid receptors with relatively high affinity, although differences exist in their potency. We propose an adverse outcome pathway for OCPs toxicity in the fish testis as a novel contribution to further understanding of OCP-induced toxicity. Organochlorine pesticides, due to their persistence and high toxicity to aquatic and terrestrial wildlife as well as humans, remain significant agrochemicals of concern.
有机氯农药 (OCPs) 是持久性环境污染物，具有内分泌干扰物和器官系统毒物的作用。这些农药（例如，滴滴涕 (DDT)、狄氏剂、毒杀芬等）被列为对人类健康最令人担忧的化学物质之一。这些农药 (1) 具有致畸作用，(2) 是神经内分泌干扰物，(3) 抑制免疫系统和生殖系统，以及 (4) 使脂质和代谢失调。我们使用计算方法，在比较毒理学基因组数据库中揭示了对这一类化学物质敏感的丰富的内分泌相关途径，其中包括生殖（促性腺激素、雌二醇、雄激素、类固醇生物合成、催产素）、甲状腺激素和胰岛素。Tox21 和 ToxCast 计划的见解证实，这些农用化学品以相对较高的亲和力激活雌激素受体、雄激素受体和视黄酸受体，尽管它们的效力存在差异。我们提出了鱼类睾丸中 OCP 毒性的不良结局途径，作为进一步了解 OCP 诱导毒性的新贡献。由于有机氯农药具有持久性和对水生和陆地野生动物以及人类的高毒性，它们仍然是令人关注的重要农用化学品。
