Insecticides developmental toxicity

As with most organophosphorus insecticides, acute toxicity is predominant. However tolerance to repeated exposures can occur. The no-observed-adverse-effect level (NOAEL) established from a rabbit developmental toxicity study was 50 mg kg day based on maternal toxicity (i.e., reduced body weight gain). Developmental toxicity studies were negative in rats and rabbits. A two-generation reproductive toxicity study in rats showed no increased sensitivity in pups compared to dams. Repeated exposure to malathion does not cause delayed neurotoxicity. The NOAEL of 2.4 mg kg day was established based on plasma cholinesterase inhibition in a long-term dosing study in rats. 

Another section of the EPA, the Office of Prevention, Pesticides, and Toxic Substances (OPPT), has recently updated and harmonized its testing guidelines for evaluating the developmental and reproductive effects of pesticides and industrial chemicals to include an assessment of endocrine disrupting properties. These guidelines will be used in future testing of pesticides under both the Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). 

Seikai, T. 1982. Acute toxicity of organophosphorous insecticides on the developmental stages of eggs, larvae and juveniles of Japanese striped knifejaw Oplegnathus fasciatus. Bull. Japan. Soc. Sci. Fish. 48 599-603. 

Slotkin, T.A., Levin, E.D. and Seidler, F.J. (2006) Comparative developmental neurotoxicity of organophosphate insecticides effects on brain development are separable from systemic toxicity. Environ. Health Perspect., 114 (5), 746-751. 

As mentioned previously, maternal and/or fetal stress associated with sublethal exposures to OP insecticides could lead to an increased incidence of abortions or pre-term births in intoxicated pregnant women and animals. Because of lower levels of detoxifying enzymes (i.e. paraoxonase), the fetus appears to be more susceptible to OP intoxication than adults, and developmental neurotoxicity and growth retardation have been associated with low-level, prenatal exposures of humans to OP insecticides (Desaiah, 1998 Eskanazi et ah, 2008 Peiris-John and Wickremasinghe, 2008). In addition to the maternal and fetal effects, OP insecticides can also have direct toxic effects on the placenta, possibly involving (depending on the species) AChE inhibition within the placental cholinergic system (Pelkonen et ah, 2006). 

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