Venerosi Aldina, Ricceri Laura, Scattoni Maria Luisa, Calamandrei Gemma
Section of Neurotoxicology and Neuroendocrinology Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
Environ Health. 2009 Mar 30;8:12. doi: 10.1186/1476-069X-8-12.
Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy.
Late gestational exposure [gestational day (GD) 14-17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs) 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10). Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration.
As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking) and explorative (wall rearing) responses.
Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants.
毒死蜱(CPF)是一种广泛用作杀虫剂的非持久性有机磷酸酯(OP)。动物模型研究表明,毒死蜱是一种发育性神经毒物,能够在远低于全身毒性阈值的剂量水平下作用于未成熟的中枢神经系统。到目前为止,关于产前和婴儿期低水平接触毒死蜱对儿童潜在的短期和长期不良影响的数据很少。
在CD-1小鼠的早期发育过程中,评估其在妊娠晚期(妊娠第14 - 17天)以6 mg/kg的剂量接触毒死蜱的情况,通过评估躯体和感觉运动成熟度[出生后第3、6、9、12和15天的反射组]以及与母亲和兄弟姐妹隔离后的超声发声情况(出生后第4、7和10天)。在出生后第12天的自发活动测试中评估幼崽的运动技能。在出生后第4天,对哺乳母鼠在笼内的母性行为以及对先前从巢中取出的幼崽的反应进行评分,以验证毒死蜱给药直接引起的母性照料潜在变化。
关于对后代的影响,结果表明,在出生后第10天,毒死蜱显著减少了超声发声的次数和持续时间,同时增加了隔离后发出第一声呼叫的潜伏期。产前接触毒死蜱还降低了出生后第12天的运动行为,而通过反射组评分在接触毒死蜱的幼崽中观察到低反射倾向。在妊娠期给予毒死蜱的母鼠显示出与对照组相当的母性照料基线水平,但对幼崽的定向(舔舐)和探索(靠墙站立)反应水平更高。
总体而言,我们的结果与先前关于有机磷酸酯神经行为毒性的流行病学数据一致,并且还表明超声发声是啮齿动物研究中毒死蜱发育过程中接触的早期标志物,对人类婴儿具有潜在的转化价值。