Introduction (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309544/)
Organophosphorous pesticides are widely used in agriculture in the United States(DPR, 2008); despite the voluntary phase out of residential uses of chlorpyrifos and diazinon between 2000 and 2004 (U.S. EPA, 2000; U.S. EPA, 2001), some organophosphate pesticides are still registered for home garden use (U.S. EPA, 2006). Acute exposure to organophosphate pesticides can lead to neurotoxic effects through inhibition of the enzyme acetylcholinesterase (Costa et al., 2008). Recent epidemiologic studies suggest associations of low dose chronic prenatal exposure to organophosphate pesticides with adverse birth and neurodevelopmental outcomes including reduced birth weight and length (Whyatt et al., 2004), shorter gestational duration (Eskenazi et al., 2004), increased number of abnormal reflexes in neonates (Engel et al., 2007; Eskenazi et al., 2008), higher risk of reported attention problems (Marks et al., 2010), and lower intelligence in 7 year olds (Bouchard et al., 2011).
Although the majority of animal data provide evidence of organophosphate toxicity through cholinergic pathways, some studies suggest potential mechanisms for the adverse effects of organophosphate pesticide exposures, even at dose levels below the threshold for acetylcholinesterase inhibition (Costa, 2006). For instance, exposures to low doses of diazinon and/or chlorpyrifos in rat and or mouse models were associated with changes in neuronal cell development (Slotkin et al., 2008), changes in emotional behaviors (Roegge et al., 2008), up regulation of serotonin neurotransmitters(Aldridge et al., 2003; Slotkin et al., 2006), and changes in thyroid hormone levels and the reproductive system(Buratti et al., 2006; De Angelis et al., 2009; Haviland et al., 2010). Recent studies also provide evidence that organophosphate pesticide exposure induces oxidative stress (Samarawickrema et al., 2008; Slotkin and Seidler, 2009), a condition associated with common diseases like cardiovascular disease and diabetes (Bhattacharyya et al., 2008; Li et al., 2003).
Estimating the internal dose of organophosphate pesticide exposure in biological specimens is particularly challenging because organophosphate pesticides have relatively short half-lives and are quickly metabolized and excreted from the body (Wessels et al., 2003). Organophosphate metabolites, including dialkyl phosphates, in urine have been used as biomarkers of organophosphate pesticide exposure in many studies (Bouchard et al., 2010; Eskenazi et al., 2004; Fenske et al., 2002; Grandjean et al., 2006; Lacasana et al., 2010; Ye et al., 2009). Collection of urine specimens from study participants is relatively noninvasive and methods for analyzing organophosphate pesticide metabolites are well established (Bradman and Whyatt, 2005). Analysis of organophosphate pesticide levels in blood allows for direct measurement of parent compounds rather than metabolites and may more accurately represent the dose that reaches the target tissue (Bradman and Whyatt, 2005). Although the rate of clearance from the blood is initially quite rapid, chlorpyrifos and diazinon are lipophilic so the portion of compound that partitions into body fat may be eliminated more slowly (Eaton et al., 2008). Therefore, levels in blood may represent a steady state concentration (Needham, 2005). However, since concentrations of organophosphate pesticides in blood are much lower (by orders of magnitude) than metabolite levels in urine, very sensitive analytical methods are required to measure them (Perez et al., 2010). Thus far, only a small number of studies have measured prenatal organophosphate pesticide exposure in maternal or umbilical cord blood (Neta et al., 2010; Whyatt et al., 2003). Only one study has compared chlorpyrifos levels in blood and urine from the same subjects (mothers and infants) and reported no association between chlorpyrifos in maternal or cord blood and levels of the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol in urine (Whyatt et al., 2009). Additionally, there are no published analytical methods for some organophosphate pesticides in blood, such as oxydemeton methyl and thus, blood measures may not fully capture exposure especially in populations exposed to multiple organophosphate pesticides. As there are strengths and weaknesses in using either of the two biological matrices, it remains unclear which measures will be more useful in epidemiological studies of prenatal organophosphate pesticide exposures and adverse health effects.
