Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 2010 Mar;114(1):113-23. doi: 10.1093/toxsci/kfp286. Epub 2009 Nov 24.
N-Methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterase (ChE). Despite their widespread use, there are few studies of neurotoxicity in young animals. To study potential age-related differences, we evaluated seven carbamates (carbaryl, carbofuran, formetanate, methiocarb, methomyl, oxamyl, and propoxur) in preweanling (17 days old or postnatal day [PND] 17) male rats. Motor activity was monitored, and ChE inhibition was measured in brain and red blood cells (RBCs) using a radiometric assay that minimized reactivation of ChE. First, we conducted time-course studies in PND17 Long-Evans male rats, using a single oral dose of each carbamate. Almost all carbamates showed maximal ChE inhibition at a 45-min time point; only methomyl showed an earlier peak effect (15 min). At 24 h, most inhibition had recovered. Next, dose-response data were collected for each carbamate, using four doses and control, with motor activity testing beginning 15 min after dosing and tissue collection at 40-45 min. RBC ChE was generally inhibited to a greater degree than brain. Motor activity was not as sensitive a measure for some of the carbamates, with some differences across carbamates in the shapes of the dose-response curves. Additional studies documented age-related differences by comparing ChE inhibition in PND11, PND17, and adult rats following administration of carbaryl or carbofuran. Only the youngest (PND11) rats were more sensitive than adults to carbaryl, but both younger ages showed more effects than adults with carbofuran. Comparisons of the other carbamates to previous studies in adult rats suggest similar age-related sensitivity. Thus, these data show the time-course and dose-response characteristics for each carbamate and document greater sensitivity of the young for carbofuran and carbaryl.
N-甲基氨基甲酸酯类杀虫剂是中枢和外周乙酰胆碱酯酶（ChE）的可逆抑制剂。尽管它们被广泛使用，但对年轻动物的神经毒性研究甚少。为了研究潜在的年龄相关差异，我们评估了七种氨基甲酸酯（西维因、呋喃丹、甲萘威、涕灭威、灭多威、涕灭砜和残杀威）在新生（17 天大或出生后第[PND] 17 天）雄性大鼠中的毒性。使用放射性测定法监测运动活动，并测量大脑和红细胞（RBC）中的 ChE 抑制，该测定法最大限度地减少了 ChE 的再激活。首先，我们在 PND17 长耳雄性大鼠中进行了时间过程研究，使用每种氨基甲酸酯的单次口服剂量。几乎所有氨基甲酸酯在 45 分钟时达到最大 ChE 抑制；只有灭多威显示出更早的峰值效应（15 分钟）。24 小时后，大部分抑制已恢复。接下来，对每种氨基甲酸酯进行了剂量反应数据收集，使用四个剂量和对照，在给药后 15 分钟进行运动活动测试，并在 40-45 分钟时收集组织。RBC ChE 的抑制程度通常比大脑高。对于某些氨基甲酸酯，运动活性不是一个敏感的测量指标，一些氨基甲酸酯的剂量反应曲线形状存在差异。通过比较 PND11、PND17 和成年大鼠在给予西维因或呋喃丹后的 ChE 抑制，进一步研究记录了年龄相关的差异。只有最年轻的（PND11）大鼠比成年大鼠对西维因更敏感，但两个较年轻的年龄对呋喃丹的影响都比成年大鼠大。将其他氨基甲酸酯与成年大鼠的先前研究进行比较表明，它们具有相似的年龄相关敏感性。因此，这些数据显示了每种氨基甲酸酯的时间过程和剂量反应特征，并记录了年轻大鼠对呋喃丹和西维因的更高敏感性。
