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评估流行病学和动物数据进行风险评估:毒死蜱发育神经行为结果。

Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos developmental neurobehavioral outcomes.

机构信息

Exponent Health Sciences Group, Menlo Park, California, USA.

出版信息

J Toxicol Environ Health B Crit Rev. 2012;15(2):109-84. doi: 10.1080/10937404.2012.645142.

Abstract

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring.

摘要

为了进行风险评估,对 2010 年 6 月之前发表的流行病学和动物研究中与接触毒死蜱(CPF)有关的发育神经行为结果进行了综述。对于流行病学研究,本综述考虑了(1)研究设计的整体强度,(2)CPF 暴露生物标志物的特异性,(3)潜在的偏倚,以及(4)因果推理的希尔准则。对于动物研究,本综述侧重于评估在断奶前使母体和/或后代暴露于 CPF 的体内哺乳动物研究中发育神经行为终点的结果的一致性。还评估了发育神经药理学和神经病理学结果。实验设计和方法作为证据权重的一部分进行了检查。没有足够的证据表明人类在不同队列研究中的发育性 CPF 暴露会对婴儿和儿童产生不良的神经行为影响,这些影响可能与 CPF 暴露有关。在动物中,在 1mg/kg-d 的妊娠期暴露后,很少有行为参数受到影响,但不同实验室并未一致报告。对于产后暴露,在 1mg/kg-d 时,超过一个研究发现的行为影响是雌性大鼠在放射臂迷宫中的错误减少和雄性大鼠在皮下给药(从出生后第 1 天到第 4 天)中的错误增加。在从出生后第 1 天到第 21 天口服暴露于 1、2 和 4mg/kg-d 的递增剂量水平的大鼠中也观察到了类似的发现,但在以 1mg/kg-d 的恒定剂量水平给药的大鼠中没有观察到。神经发育行为、药理学和形态学效应发生在导致母体或后代大脑或红细胞乙酰胆碱酯酶抑制显著的剂量下。

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