Moser Virginia C, Barone Stanley, Phillips Pamela M, McDaniel Katherine L, Ehman Kimberly D
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
Neurotoxicology. 2006 May;27(3):409-20. doi: 10.1016/j.neuro.2005.12.003. Epub 2006 Jan 25.
Organotins such as monomethyltin (MMT) are widely used as heat stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for neurotoxicity produced by organotin exposure during development has been raised by published findings of a deficit on a runway learning task in rat pups perinatally exposed to MMT (Noland EA, Taylor DH, Bull RJ. Monomethyl and trimethyltin compounds induce learning deficiencies in young rats. Neurobehav Toxicol Teratol 1982;4:539-44). The objective of these studies was to replicate the earlier publication and further define the dose-response characteristics of MMT following perinatal exposure. In Experiment 1, female Sprague-Dawley rats were exposed via drinking water to MMT (0, 10, 50, 245 ppm) before mating and throughout gestation and lactation (until weaning at postnatal day [PND] 21). Behavioral assessments of the offspring included: a runway test (PND 11) in which the rat pups learned to negotiate a runway for dry suckling reward; motor activity habituation (PNDs 13, 17, and 21); learning in the Morris water maze (as adults). Other endpoints in the offspring included measures of apoptosis (DNA fragmentation) at PND 22 and as adults, as well as brain weights and neuropathological evaluation at PND 2, 12, 22, and as adults. There were no effects on any measure of growth, development, cognitive function, or apoptosis following MMT exposure. There was a trend towards decreased brain weight in the high dose group. In addition, there was vacuolation of the neuropil in a focal area of the cerebral cortex of the adult offspring in all MMT dose groups (1-3 rats per treatment group). In Experiment 2, pregnant rats were exposed from gestational day 6 until weaning to 500 ppm MMT in drinking water. The offspring behavioral assessments again included the runway task (PND 11), motor activity habituation (PND 17), and Morris water maze (as adults). In this second study, MMT-exposed females consumed significantly less water than the controls throughout both gestation and lactation, although neither dam nor pup weights were affected. As in Experiment 1, MMT-exposure did not alter pup runway performance, motor activity, or cognitive function. These results indicate that perinatal exposure to MMT, even at concentrations which decrease fluid intake, does not result in significant neurobehavioral or cognitive deficits. While mild neuropathological lesions were observed in the adult offspring, the biological significance of this restricted finding is unclear.
有机锡化合物，如单甲基锡（MMT），被广泛用作聚氯乙烯（PVC）和氯化聚氯乙烯（CPVC）管道的热稳定剂，这导致它们存在于饮用水供应中。围产期暴露于MMT的大鼠幼崽在跑道学习任务中出现缺陷的已发表研究结果，引发了人们对有机锡暴露在发育过程中产生神经毒性的担忧（诺兰德EA、泰勒DH、布尔RJ。单甲基和三甲基锡化合物导致幼鼠学习缺陷。神经行为毒理学与致畸学1982年；4：539 - 44）。这些研究的目的是重复早期的研究，并进一步确定围产期暴露后MMT的剂量反应特征。在实验1中，雌性斯普拉格 - 道利大鼠在交配前以及整个妊娠期和哺乳期（直到出生后第21天断奶）通过饮用水接触MMT（0、10、50、245 ppm）。对后代的行为评估包括：一项跑道测试（出生后第11天），在该测试中大鼠幼崽学习通过跑道以获得干乳奖励；运动活动习惯化（出生后第13、17和21天）；在莫里斯水迷宫中的学习（成年后）。后代中的其他终点指标包括出生后第22天和成年时的凋亡（DNA片段化）测量，以及出生后第2、12、22天和成年时的脑重量和神经病理学评估。MMT暴露后，对生长、发育、认知功能或凋亡的任何测量指标均无影响。高剂量组有脑重量下降的趋势。此外，在所有MMT剂量组（每个治疗组1 - 3只大鼠）成年后代大脑皮质的一个局部区域出现了神经毡空泡化。在实验2中，怀孕大鼠从妊娠第6天到断奶期间通过饮用水接触500 ppm的MMT。对后代的行为评估再次包括跑道任务（出生后第11天）、运动活动习惯化（出生后第17天）和莫里斯水迷宫（成年后）。在第二项研究中，暴露于MMT的雌性大鼠在整个妊娠期和哺乳期消耗的水明显少于对照组，尽管母鼠和幼崽的体重均未受到影响。与实验1一样，MMT暴露并未改变幼崽的跑道表现、运动活动或认知功能。这些结果表明，围产期暴露于MMT，即使在降低液体摄入量的浓度下，也不会导致明显的神经行为或认知缺陷。虽然在成年后代中观察到了轻度神经病理学病变，但这一有限发现的生物学意义尚不清楚。
