Cassidy R A, Vorhees C V, Minnema D J, Hastings L
U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 78234.
Toxicol Appl Pharmacol. 1994 Jun;126(2):326-37. doi: 10.1006/taap.1994.1123.
Technical chlordane is a mixture of four main isomers (i.e., heptachlor, cis-chlordane, trans-chlordane, and trans-non-achlor) found in meat and dairy products as well as in indoor air of houses treated for termites. These isomers are metabolized to more potent epoxides (heptachlor epoxide and oxychlordane) which accumulate in lipid compartments of tissues and have been shown to reduce chloride influx through GABAA receptor complex channels and to alter steroid levels. However, considering the almost universal human exposure and the potential for accumulation of these agents, very little is known about how chronic, low-level exposures during development affect adult behavior and steroid-mediated processes. Time-pregnant Sprague-Dawley dams (Day 4 of gestation through Day 21 of lactation) and offspring (Day 22 of age through Day 80) were exposed to three levels of technical chlordane (100, 500, or 5000 ng/g) on a daily schedule. The low-exposure level generated heptachlor epoxide and oxychlordane plasma levels in the dam (Day 20) and in the offspring (Day 80) representative of those found in the U.S. populace. Chlordane-dosed offspring exhibited sex- and dose-dependent effects on testosterone levels, behavioral tests, and body weight conducted between postnatal Days 77 and 85. Chlordane-dosed females, but not males, had significant decreases in testosterone levels, significant improvements in spatial abilities (i.e., decreases in Cincinnati maze errors, navigation times, and failures to escape), and significant increases in body weight and in auditory startle-evoked responses. In two other tests, only males were used. These chlordane-dosed males showed significant increases in male-typical mating behaviors and decreases in 36Cl- uptake into brain microsacs. For all behavioral and body weight measurements, dose-response effects were observed for the 100 and 500 ng/g dosed groups. However, the 5000 ng/g dose group responses were closer to those of control values. These results suggest that these cyclodienes masculinize sexually dimorphic functions and behaviors by mimicking sex steroids and/or changing their levels.
工业氯丹是四种主要异构体（即七氯、顺式氯丹、反式氯丹和反式九氯）的混合物，存在于肉类和奶制品中，以及在经白蚁防治处理房屋的室内空气中。这些异构体代谢为更具活性的环氧化物（七氯环氧化物和氧氯丹），它们在组织的脂质区室中蓄积，并已显示会减少通过γ-氨基丁酸A型（GABAA）受体复合物通道的氯离子内流，并改变类固醇水平。然而，考虑到几乎所有人都接触这些物质以及它们有蓄积的可能性，对于发育期间慢性低水平接触如何影响成年行为和类固醇介导的过程，人们了解甚少。将处于孕期的斯普拉格-道利（Sprague-Dawley）母鼠（从妊娠第4天到哺乳期第21天）及其后代（从出生后第22天到第80天）每天暴露于三种水平的工业氯丹（100、500或5000纳克/克）。低暴露水平在母鼠（第20天）和后代（第80天）中产生的七氯环氧化物和氧氯丹血浆水平与在美国人群中发现的水平相当。给予氯丹的后代在出生后第77天至85天之间进行的睾酮水平、行为测试和体重方面表现出性别和剂量依赖性效应。给予氯丹的雌性，但不是雄性，睾酮水平显著降低，空间能力显著改善（即辛辛那提迷宫错误次数、导航时间和未能逃脱的次数减少），体重和听觉惊吓诱发反应显著增加。在另外两项测试中，只使用了雄性。这些给予氯丹的雄性表现出典型雄性交配行为显著增加，并且进入脑微粒体的36Cl摄取减少。对于所有行为和体重测量，在给予100和500纳克/克剂量的组中观察到剂量反应效应。然而，给予5000纳克/克剂量组的反应更接近对照值。这些结果表明，这些环二烯类化合物通过模拟性类固醇和/或改变其水平使两性异形功能和行为男性化。
