Age-Related Differences in Acetylcholinesterase Inhibition Produced by Organophosphorus and N-Methyl Carbamate Pesticides

Abstract

The concern that infants and children may be more susceptible to the toxic effects of chemicals, including pesticides, has received much attention in the scientific literature and the public media. Greater toxicity may be evident as long-term adverse outcomes, e.g., neurological and IQ deficits from early exposure to lead, or else as increased toxicological effects of acute or short-term exposures. A National Academy of Science panel reported in 1993 on the scientific and regulatory issues regarding relative sensitivity of the young (National Research Council 1993). This report stressed how little is understood regarding the magnitude and mechanisms of these differences, and called for systematic research on pesticide toxicity in developing organisms. The concern that regulatory practices may not adequately protect these subpopulations further led to the passage of the Food Quality Protection Act in 1996 (FQPA, Public Law 104-170, August 1996), which required the US Environmental Protection Agency (EPA) to take extra steps to protect infants and children in the regulation of pesticides. Specifically, the FQPA instructed that “an additional tenfold margin of safety” be applied for non-cancer effects of pesticides “to take into account potential pre-and postnatal toxicity and completeness of data with respect to exposure and toxicity to infants and children”. Currently, the EPA Office of Pesticide Programs addresses this additional margin of safety during the risk characterization process (Lowit, 2006; US EPA, 2002). With pesticides for which direct or acute effects drive the assessment, one approach for determining this factor has often been an evaluation of relative sensitivity of young compared to adult animals (US EPA, 2006). There are several factors impacting greater pesticide toxicity in children (Faustman et al. 2000). Exposures from intake of water contaminants and food residues are higher, because children take in considerably more food and water than adults on a per body weight basis (NRC, 1993). Behaviors of infants and toddlers (e.g., crawling, hand-to-mouth) also increase the likelihood of coming into contact with pesticides through dust and soil. Greater exposure levels in children have been documented in children of agricultural workers, comparisons of organic and standard diets, and in numerous housing surveys (e.g., Curl et al. 2003; Fenske et al. 1990; Loewenherz et al. 1997; Lu et al. 2001; Simcox et al. 1995). Higher