It has been shown that a semivolatile pesticide such as chlorpyrifos can volatilize days after its indoor application and can be adsorbed to various surfaces . Children’s felt toys, in particular, and, to a lesser extent, plastic toys accumulated significant levels of chlorpyrifos. For a young child exhibiting typical mouthing and hand-to-mouth behavior, dermal and nondietary oral exposure to such conditions were estimated to constitute a dose of 64 µg/ kg/d under the most conservative absorption assumptions and to contribute between 40 and 60% of the total dose. This greatly exceeds the allowable daily intake of 10 µg/kg/d proposed by the US EPA.Therefore, either environmental or biological monitoring is used. In recent years, environmental monitoring has yielded information on concentrations of OP pesticides in outdoor, indoor, and personal air; indoor dust; soil; and foods and beverages . All of the measured values vary considerably, but it is difficult to determine whether they reflect mostly methodological differences or represent true differences in pesticide concentrations. Note that many of the available studies have focused on chlorpyrifos and diazinon. The US EPA eliminated essentially all indoor residential uses of these pesticides by 2002, but they continue to be used in agriculture. Several important findings have emerged from these exposure assessment studies. OP pesticides are detectable in essentially all media analyzed, including food, indoor air, dust, and soil near the home. Interestingly, OP pesticides were not detected in duplicate beverage samples in two studies , whereas others reported their detection in 4 of 21 beverage samples; 4 of 9 of the samples that included apple juice contained azinphosmethyl . Comparisons of pesticide concentrations in dust, soil,cannabis curing and surface and hand wipes have clearly indicated that exposure of agricultural families is considerably greater than that of non-agricultural reference families . This higher exposure appears to result from both take-home pathways and proximity of the residence to farmland , although the association with proximity is not a consistent finding .

Using food consumption data from the Nurses Health Study and the Health Professionals’ Follow-Up Study combined with the data from the Food and Drug Administration Total Diet Study, researchers estimated that mean daily dietary intakes of chlorpyrifos, diazinon, and malathion were 0.8, 0.5, and 5.5 µg/d for women and 0.9, 0.5, and 6.1 µg/d for men, respectively . From duplicate diet samples, adult dietary chlorpyrifos and malathion exposure has been estimated to be 0.5 and 1.3 µg/d, respectively , and dietary chlorpyrifos intake in children was estimated to be 0.263 µg/d . Mean aggregate chlorpyrifos exposure from a total of six pathways was calculated to be 1.39 µg/d ; inhalation made the greatest contribution , whereas only between 7 and 13% was attributable to pesticide residues in solid food, and the dermal route was negligible . In two studies of children’s pesticide exposure, however, solid food made the greatest contribution to the cumulative intake of chlorpyrifos, malathion, and diazinon . Interestingly, despite the high contribution that food appeared to make to aggregate chlorpyrifos exposure in the Minnesota Children’s Pesticide Exposure Study, there was a much stronger correlation between urinary metabolites of this pesticide and concentrations in personal air than with levels in the ingested solid food . Additionally, note that the estimates of dermal absorption neglected to account for the volatilized portion of chlorpyrifos. The finding of a high correlation between chlorpyrifos in indoor air and in the corresponding dermal wipes suggests that this route of exposure may be important . The reported dietary pesticide intakes were generally well within the US EPA or similar reference values . However, it has been noted that dietary intake estimates greatly depend on the assumed value of nondetect samples, with assumption of a zero value underestimating exposure by a factor of 10 to 60 . Bio-monitoring of OP pesticide exposure most commonly involves measurement of their urinary metabolites or, much more rarely,quantification of the pesticides themselves and/or some of their metabolites in plasma .

Whereas urinary dialkylphosphate metabolites are nonspecific because they can be derived from a wide variety of OP compounds, certain other urinary metabolites are specific for one or two pesticides . Recall that urinary metabolites of OP pesticides can provide only rough estimates of exposure because the amount of absorption and the fractional excretion of specific metabolites are not really known, nor have all the metabolites been identified. Additionally, it cannot be determined whether and to what extent urinary metabolites represent exposure to one or more parent compounds or direct exposure to their metabolites. Furthermore, urinary metabolite concentrations should be corrected for dilution, but the appropriate method is still under debate , particularly because marked seasonal fluctuations in creatinine levels were observed in small children . Bio-monitoring of prenatal exposure involves the measurement of pesticides and their metabolites in umbilical cord blood, amniotic fluid, or meconium. A total of eight pesticides were detectable in 45 to 77% of maternal plasma samples obtained at delivery and in a similar percentage of cord plasma samples from 230 mother–infant pairs from New York City . Their concentrations in maternal and cord plasma were similar and highly correlated, indicating the occurrence of transplacental transfer and substantial in utero exposure . A further indication for transplacental transfer comes from the finding that the DAP metabolites DEP, dimethyl phosphate, and dimethylthiophosphate were detected in 10, 10, and 5% of amniotic fluid samples, respectively . Meconium consists of fetal bile secretions along with the content of the amniotic fluid that the fetus swallowed, representing exposure from the second trimester through delivery, and is usually not excreted by the fetus until after birth. DEP and diethylthiophosphate were present in 95 and 100% of 20 meconium samples from New York newborns, respectively, whereas other OP metabolites were detected in only one or none of the samples . Similarly, the detection of diazinon , malathion , parathion , and chlorpyrifos , along with various organochlorine compounds, has been reported in meconium samples from infants in the Philippines . Up to six or seven pesticides were detected in 4 and 5% of the samples, respectively. Some investigators detected an association between reported indoor residential pesticide use and urinary concentrations of specific pesticide metabolites, but this association was not detected in several other studies of children and adults . Reported pesticide use in the garden is also not consistently associated with urinary DAP levels .

A significant correlation was reported between levels of chlorpyrifos, diazinon, and the carbamate propoxur in personal air and the concentrations of these insecticides or their metabolites in plasma obtained within a month of the personal monitoring, but there was no correlation in plasma obtained at later time-points . Because of the relatively short half-lives of these pesticides, the relevance of these correlations is difficult to evaluate without further information about the regularity or chronicity with which the women were exposed to these pesticides. Several studies in which urinary pesticide metabolite levels were measured have confirmed the findings of environmental monitoring studies that farm children are exposed to higher levels of OP pesticides compared with children from non-agricultural reference families ,drying weed particularly during periods of pesticide application . In one of these studies, azinphosmethyl was the pesticide detected with the highest frequency and at the highest concentrations in house dust and was significantly correlated with dimethyl DAP metabolites in urine . Only the study that detectedan association between house dust levels of azinphosmethyl and phosmet and proximity to farmland also found higher dimethyl DAP levels in children living near treated orchards compared to those living at a greater distance . In the same group of subjects, however, urinary levels of the major chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol were not significantly different between children from agricultural and non-agricultural families and did not reflect distance from orchards, although chlorpyrifos was present at higher concentrations in house dust of farming families and was increased with increasing distance from pesticide-treated areas . Although studies of exposure to individual pesticides, even those considering aggregate exposure, have generally found the estimated exposure levels to be well below the RfD , there is increasing evidence from biological monitoring studies that exposure to OP pesticides overall may exceed reference doses in a substantial number of subjects from both agricultural and non-agricultural areas. Calculations of exposure using urinary DAP metabolites are difficult because these metabolites can originate from a large variety of OP pesticides with highly different chronic toxicity and RfD values. In 2- to 5-yr-old children from urban and suburban areas of Seattle, the percentage of exposure estimates exceeding US EPA guidelines ranged between 0 and 100%, depending on which pesticide was assumed to be responsible for the exposure . When pesticides commonly applied in an agricultural community in Washington were used to calculate the absorbed daily dose in children age 6 yr or younger, 9 to 56% of children from agricultural families and 0 to 44% of reference children exceeded the EPA RfD for azinphosmethyl and phosmet during the spray season . Similar calculations for the same age groups of children from Yuma County, Arizona, indicated that the highest daily dose values were 61 to 385 times higher than the EPA RfD . In a study of pregnant women in the Salinas Valley in California, the estimated exposure to OP pesticides exceeded the oral benchmark dose10 of the US EPA in 0 to 36% of the women, depending on the index chemical on which the estimate was based and exceeded the benchmark dose for 10% response in approx 15% of women regardless of the parent compound .

The benchmark doses for 10% response are doses expected to result in a 10% reduction in brain cholinesterase activity in rats. Notably, there is evidence from urinary DAP assessments that suggests that consumption of a predominantly organic diet can greatly reduce dietary exposure to OP pesticides as well as the associated risk . However, daily consumption of a single meal prepared with organically grown produce was not sufficient to significantly influence urinary levels of DAP metabolites .OP pesticides and carbamates inhibit acetylcholinesterase . Because AChE inactivates acetylcholine at neuronal junctions, its inhibition results in ACh accumulation and continued neurotransmission. Because the autonomic, the somatic, and the central nervous systems all use ACh, the symptoms of OP-mediated AChE inhibition are manifold and include dizziness, headache, confusion, convulsions, blurred vision, respiratory distress, bradycardia and hypotension, fatigue, weakness, ataxia, muscle cramps, and increased lacrimation and salivation. Although the effects of environmental OP exposure are milder, they can resemble those of acute poisoning and, incidentally, include some well-known SBS symptoms, such as tearing eyes, chest pressure/tightness, and feeling dazed . Numerous animal studies have documented the developmental neurotoxicity of gestational or early postnatal exposure to OP pesticides at relatively low levels that did not result in overt systemic toxicity and inhibited cholinesterase to a minor extent in the dam. Such exposure resulted in impairments in maze performance, locomotion, coordination and balance, righting reflexes, and cliff avoidance. The molecular and cellular changes in the fetal or newborn brain that could account for these effects include inhibition of brain AChE and choline acetyltransferase activity , alteration of muscarinic receptor function via inhibition of ligand binding and permanent reduction in the density of muscarinic cholinergic receptors , altered synaptic development and function that can persist into adulthood , decreased expression and activity of multiple components of the adenylyl cyclase cascade , impaired DNA and RNA synthesis , and reduced cellularity and brain weight in offspring. Most of these studies were performed using chlorpyrifos, but similar effects and mechanisms were observed with other OP pesticides as well as two different pyrethroids . Few studies have addressed possible neurodevelopmental effects of prenatal OP exposure in humans. Recently, the association between prenatal OP pesticide exposure and neonatal neurodevelopment as assessed by the Brazelton Neonatal Behavioral Assessment Scale was investigated in 381 full-term infants in the CHAMACOS project. Table 11 includes maternal DAP metabolite levels during pregnancy in this cohort of women, which contained a substantial portion of agricultural workers from the Salinas Valley and other women with rather high environmental exposure to pesticides because of their heavy use in this agricultural center.