Exploration into the developmental toxicity of organophosphate insecticides in zebrafish (Danio rerio)

Organophosphates (OP) are a class of compounds utilized as insecticides for agricultural application in the United States. Effective at controlling such insect populations as mites, aphids, and caterpillars, OPs have greatly contributed to increased crop productions since their early 20th century development. OPs are toxic to many non-target organisms through their primary mechanism of action as acetylcholinesterase (AChE) inhibitors. Precipitation often facilitates the distribution of OPs which contaminates surface waters. These insecticides are inadvertently introduced to aquatic ecosystems, recreational areas, and freshwater sources. Zebrafish (ZF) are a useful for investigations into the potential adverse effects of OP exposure, because they are a complimentary vertebrate model for the study of human health. The neurobehavioral and molecular alterations in embryo-larval ZF post exposure to OPs are well documented, but few studies observe the comparative effects across multiple compounds or generations. This thesis research comprises the comparative analyses of four predominant OPs (diazinon, dichlorvos, methyl-parathion, and dichlorvos) and a transgenerational examination of the OP metabolite chlorpyrifos-oxon developmental exposure in wild-type ZF. Investigations included a combination of neurobehavioral, biochemical, molecular, and epigenetic endpoints to assess both cholinergic and noncholinergic effects. This research contributes to previously limited data on the comparative and long-term effects of prenatal OP exposure in controlled laboratory conditions.