A sequence of different classes of synthetic insecticides have been used over the past 70 years. Over this period, the widely-used organochlorines were eventually replaced by organophosphates, with dichlorodiphenyltrichloroethane (DDT) and chlorpyrifos (CPF) as the principal prototypes. Considerable research has characterized the risks of DDT and CPF individually, but little is known about the toxicology of transitioning from one class of insecticides to another, as has been commonplace for agricultural and pest control workers. This study used adult zebrafish to investigate neurobehavioral toxicity following 5-week chronic exposure to either DDT or CPF, to or their sequential exposure (DDT for 5 weeks followed by CPF for 5 weeks). At the end of the exposure period, a subset of fish were analyzed for brain cholinesterase activity. Behavioral effects were initially assessed one week following the end of the CPF exposure and again at 14 months of age using a behavioral test battery covering sensorimotor responses, anxiety-like functions, predator avoidance and social attraction. Adult insecticide exposures, individually or sequentially, were found to modulate multiple behavioral features, including startle responsivity, social approach, predator avoidance, locomotor activity and novel location recognition and avoidance. Locomotor activity and startle responsivity were each impacted to a greater degree by the sequential exposures than by individual compounds, with the latter being pronounced at the early (1-week post exposure) time point, but not 3–4 months later in aging. Social approach responses were similarly impaired by the sequential exposure as by CPF-alone at the aging time point. Fleeing responses in the predator test showed flee-enhancing effects of both compounds individually versus controls, and no additive impact of the two following sequential exposure. Each compound was also associated with changes in recognition or avoidance patterns in a novel place recognition task in late adulthood, but sequential exposures did not enhance these phenotypes. The potential for chemical x chemical interactions did not appear related to changes in CPF metabolism to the active oxon, as prior DDT exposure did not affect the cholinesterase inhibition resulting from CPF. This study shows that the effects of chronic adult insecticide exposures may be relevant to behavioral health initially and much later in life, and that the effects of sequential exposures may be unpredictable based on their constituent exposures.

过去 70 年来，人们使用了一系列不同类别的合成杀虫剂。在此期间，广泛使用的有机氯最终被有机磷酸盐所取代，其中二氯二苯基三氯乙烷（DDT）和毒死蜱（CPF）为主要原型。大量研究分别描述了 DDT 和 CPF 的风险，但对从一类杀虫剂过渡到另一类杀虫剂的毒理学知之甚少，这对于农业和害虫防治工作者来说是司空见惯的事情。本研究使用成年斑马鱼来研究慢性暴露于 DDT 或 CPF 5 周或连续暴露（DDT 5 周，随后 CPF 5 周）后的神经行为毒性。在暴露期结束时，对一部分鱼的脑胆碱酯酶活性进行了分析。行为影响最初在 CPF 暴露结束后一周进行评估，并在 14 个月大时再次使用行为测试组进行评估，涵盖感觉运动反应、类焦虑功能、捕食者回避和社交吸引力。研究发现，成人单独或连续接触杀虫剂会调节多种行为特征，包括惊吓反应、社交方式、躲避捕食者、运动活动以及新位置识别和回避。与单个化合物相比，连续暴露对运动活动和惊吓反应性的影响程度更大，后者在早期（暴露后 1 周）时间点很明显，但在衰老后 3-4 个月则不明显。在衰老时间点，顺序暴露与单独 CPF 类似地都会损害社会方法反应。捕食者测试中的逃跑反应表明，与对照组相比，两种化合物单独具有增强逃跑的作用，并且两种化合物在连续暴露后没有附加影响。每种化合物还与成年晚期新地点识别任务中识别或回避模式的变化相关，但连续暴露并没有增强这些表型。化学间相互作用的可能性似乎与 CPF 对活性氧的代谢变化无关，因为之前接触 DDT 并不影响 CPF 引起的胆碱酯酶抑制。这项研究表明，成人长期接触杀虫剂的影响可能与生命初期和以后的行为健康有关，并且根据其成分暴露，连续接触的影响可能是不可预测的。