Exposure to the Widely Used Fungicide Mancozeb Causes Thyroid Hormone Disruption in Rat Dams but No Behavioral Effects in the Offspring
Exposure to the Widely Used Fungicide Mancozeb Causes Thyroid Hormone Disruption in Rat Dams but No Behavioral Effects in the Offspring
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DOI：
10.1093/toxsci/kfr006
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发表时间：
2011-04-01
影响因子：
3.8
通讯作者：
Hass, Ulla
中科院分区：
文献类型：
--
作者：
Axelstad, Marta;Boberg, Julie;Hass, Ulla
广泛使用的杀菌剂代森锰锌已被证明会在成年实验动物中引起低甲状腺素血症和对甲状腺激素系统的其他不利影响。在人类中，怀孕早期的低甲状腺素血症会对神经系统发育产生不利影响，并可能导致儿童认知功能和运动发育受损。因此，本研究的目的是评估围产期代森锰锌暴露是否会导致大鼠发育神经毒性。 9-21 只交配时间的 Wistar 大鼠组从妊娠第 7 天 (GD) 到出生后第 16 天 (PND) 每天通过管饲法给予 0、50、100 或 150 mg 代森锰锌/kg 体重 (bw)，并在妊娠期间测量母鼠的总甲状腺素 (T-4) 水平。在 PND 16 时，测量了后代的激素水平和多个器官重量，同时评估了成年后代的运动活动、惊吓反应和认知功能。 150 mg/kg/天的剂量会对怀孕母鼠产生神经毒性，因此在研究中期将剂量减少至100 mg/kg体重/天。在 GD 15 时，所有三个剂量组的母鼠 T-4 水平均呈现剂量依赖性且显着下降，而后代 T-4 水平、甲状腺重量和组织学在 PND 16 时未受影响。未观察到对生殖器官重量的影响，也未观察到行为变化。综上所述，这些结果表明，在大鼠中，妊娠期间中度的母体低甲状腺素血症并不一定会导致后代多动或特殊学习能力下降。然而，接触代森锰锌确实会降低母鼠的 T-4 水平，因此可能仍然是人类甲状腺破坏的潜在因素，从而对发育中的大脑产生不利影响。
The widely used fungicide mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100, or 150 mg mancozeb/kg body weight (bw)/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T-4) levels were measured in dams during gestation. On PND 16, hormone levels and several organ weights were measured in the offspring, whereas motor activity, startle response, and cognitive function were assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams and was therefore reduced to 100 mg/kg bw/day in mid study. T-4 levels showed a dose-dependent and significant decrease in dams from all three dose groups on GD 15, whereas offspring T-4 levels, thyroid weights, and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did, however, reduce T-4 levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affects the developing brain.