背景:人类暴露于有机磷酸酯阻燃剂是由于它们在许多消费品中用作添加剂。这些试剂是溴化阻燃剂的替代品,但尚未面临类似的发育神经毒性审查。我们研究了一种具有代表性的有机磷酸酯阻燃剂,磷酸三苯酯(TPP)及其对行为发育和多巴胺能功能的潜在影响。
方法:雌性Sprague-Dawley大鼠通过皮下渗透泵给予低剂量的TPP(16或32mgkg-1day-1),开始孕前,并持续到产后早期。后代从青春期到成年期接受了一系列行为测试,和同窝动物用于评估多巴胺能突触功能。
结果:在新颖性抑制喂养测试中,TPP暴露的后代显示开始进食的潜伏期增加,受损物体识别记忆,视觉信号检测测试中的选择准确性受损,和性别选择对青春期(男性)而不是成年期的运动活动的影响。男性,但不是女性,后代显示纹状体中多巴胺利用率显著增加,主要多巴胺代谢物(3,4-二羟基苯乙酸)相对于多巴胺水平的比例增加。
结论:这些结果表明,TPP的不利影响在某些方面与有机磷农药相似,由于它们的发育神经毒性而受到限制。
Human exposures to organophosphate flame retardants result from their use as additives in numerous consumer products. These agents are replacements for brominated flame retardants but have not yet faced similar scrutiny for developmental neurotoxicity. We examined a representative organophosphate flame retardant, triphenyl phosphate (TPP) and its potential effects on behavioral development and dopaminergic function.
Female Sprague-Dawley rats were given low doses of TPP (16 or 32 mg kg-1 day-1 ) via subcutaneous osmotic minipumps, begun preconception and continued into the early postnatal period. Offspring were administered a battery of behavioral tests from adolescence into adulthood, and littermates were used to evaluate dopaminergic synaptic function.
Offspring with TPP exposures showed increased latency to begin eating in the novelty-suppressed feeding test, impaired object recognition memory, impaired choice accuracy in the visual signal detection test, and sex-selective effects on locomotor activity in adolescence (males) but not adulthood. Male, but not female, offspring showed marked increases in dopamine utilization in the striatum, evidenced by an increase in the ratio of the primary dopamine metabolite (3,4-dihydroxyphenylacetic acid) relative to dopamine levels.
These results indicate that TPP has adverse effects that are similar in some respects to those of organophosphate pesticides, which were restricted because of their developmental neurotoxicity.