Tipping the Balance of Autism Risk

Potential Mechanisms Linking Pesticides and Autism

Janie F. Shelton; Irva Hertz-Picciotto; Isaac N. Pessah

Disclosures

Environ Health Perspect. 2012;120(7):944-951. 

In This Article

Conclusions

We have reviewed several mechanisms by which pesticides may increase the risk of autism, summarized in Table 2. Pesticides may or may not, however, play a role in the trend of increasing autism prevalence, which itself is likely due to a confluence of multiple phenomena, including changes in diagnostic practices, physician and lay awareness, the availability of treatments, and the prevalence of a variety of environmental chemical, medical, and food-related exposures. While pesticide use patterns have changed, home and ambient environments also include other exposures that have changed over time as a result of regulatory and economic factors (e.g., flame retardants, plasticizers, solvents, stabilizers, antimicrobials).

Pesticides are composed of a parent product, inert ingredients, and in some cases agonists that enhance the functionality of the parent compound, and all of these ingredients may be degraded to metabolites that also distribute throughout the body. Consequently, pesticide formulations represent a mixture of compounds that might contribute to observed effects. Difficulties in distinguishing the effects of metabolites versus parent compounds may have confounded associations observed in many studies of urinary metabolites and neurodevelopment, and very few studies have examined the main effects or effect modification of exposure to piperonyl butoxide, which slows the metabolism of several types of pesticides by inhibiting cytochrome P450 enzymes.

Although pesticides are a biologically plausible contributor to autism, research in several critical areas is needed to understand cognitive and behavioral consequences of gestational exposure in humans. First, animal studies suggest critical windows of exposure, yet in humans the window or windows of biologic susceptibility remain unknown, and would be expected to vary by mechanism. Second, studies of nontoxic, environmentally relevant doses are needed to understand the effects of developmental neurotoxicity in the context of a background of genetic susceptibilities. Third, the vast majority of exposures occur in combination with exposures to other ubiquitous and/or persistent compounds such as flame retardants, plasticizers, and other pesticides. More research on combinations of exposures may reveal interactions between environmental exposures, such as effect modification by chemical additives to pesticide compounds. In light of the recently revised prevalence estimates of autism (1 in 88), large birth cohorts, such as the National Children+s Study (NCS), which aim to enroll women at pregnancy and follow the children over time, are well positioned to obtain enough cases and to examine prenatal exposures prospectively. Pending accurate and reliable exposure estimates in critical time windows, and enrollment of approximately 100,000 children resulting in 1,000 or more cases of autism, NCS can contribute greatly to our understanding of these associations. Finally, more case–control studies with large populations of participants with confirmed diagnoses of autism that examine environmental exposures in relation to severity of the core domains of language impairment, social avoidance, and repetitive behaviors or insistence on sameness may shed light on possible exposure-related endophenotypes.

Although we have described several possible avenues by which pesticide exposure may influence autism, the dearth of studies on large occupational and pregnancy cohorts with adequate exposure assessment impedes our understanding of a) whether pesticides are consistently associated with autism risk, and b) if so, which pesticide compounds and which components of those compounds might actually contribute to autism risk. Grandjean and Landrigan (2006) hypothesized that our exposure to chemicals that have not been adequately tested for developmental neurotoxicity has led to a silent pandemic. Further research is warranted to provide the evidence base that can ultimately lead to reducing or eliminating these potentially damaging exposures through changes to regulatory policy, consumer behavior, or dietary choices.

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