For 2003–2004, a total of 2,494 samples were available for statistical analysis. Geometric means could not be calculated for any analyte but DMTP because all the other analytes had a detection frequency of less than 60%. The geometric mean concentration and various percentiles stratified by age groups (6–11, 12–19, 20–39, 40–59, and ≥60 years), race/ethnicity (MA, NHB, NHW) and sex (male, female) for all three NHANES cycles are given in –. We analyzed 7,456 samples during the six-year period (1999–2004). No significant differences were noted in analyte concentrations from urine samples collected at different times during the day.
Table 1. Dimethylphosphate. Geometric mean and selected percentiles of urine concentrations for the U.S. population from the National Health and Nutrition Examination Surveys. Units are μg/L for unshaded values and μg/g creatinine for shaded values. (more ...)
Table 6. Diethyldithiophosphate. Geometric mean and selected percentiles of urine concentrations for the U.S. population from the National Health and Nutrition Examination Surveys. Units are μg/L for unshaded values and μg/g creatinine for shaded (more ...)
When examining the 2003–2004 data by multiple regression, the final model for DMTP included sex (p = 0.056), age (continuous, p < 0.001), age-square (p < 0.01), race (p = 0.058), and log creatinine (p < 0.0001). We observed a curvilinear relationship between the log-transformed DMTP concentration and age (). We found both a linear increase and positive quadratic trend with age (β for linear = 0.008, β for quadratic = 0.0005). In the model where age was treated categorically, the LSGM covariate-adjusted concentration of DMTP was highest among those ages 60 years and older (3.2 μg/L) while the second highest level was among children ages 6–11 years old (2.45 μg/L). NHB participants had the highest LSGM covariate-adjusted concentration of DMTP (3.57 μg/L), which was significantly higher than for NHW (1.97 μg/L, p = 0.02). Similarly, NHB had a higher LSGM covariate-adjusted concentration than MA (1.94. μg/L, p = 0.02). MA and NHW had similar LSGM covariate-adjusted concentrations for DMTP. The LSGM covariate-adjusted concentration of DMTP for females (2.46 μg/L) was marginally higher than the one for males (p = 0.055).
A curvilinear relationship was observed between age and the least squares geometric mean (LSGM) dimethylthiophosphate concentrations.
Regarding potential pathways of exposure, we noted that all analytes except DMP and DEDTP were significantly correlated with each other (). DMTP and DMDTP had the highest significant correlation (r = 0.59), whereas the significant correlations between other analytes ranged from 0.06 to 0.39 (all p-values < 0.0001).
Spearman correlation coefficients between dialkylphosphate metabolites of organophosphorus pesticides (correlation, p value, number of observations).
In examining the likelihood for those participants whose concentrations were above the 95th percentile, urine concentrations of DEP was significantly associated with age (p = 0.045), but not sex and race/ethnicity. Adolescents were 2.96 and 2.4 times more likely to be above the total population 95th percentile than senior adults (60 and older) (odds ratio [OR] [95% CI]: 2.96 [1.7, 5.2]) and other adults (20–59 years old) (OR [95% CI]: 2.4 [1.1, 5.1]), respectively. Similarly, for DMDTP, age was significantly associated with the chance to be above the 95th percentile (p=0.05). Participants aged 60 years and older were 3.8 times more likely to be above the 95th percentile than that for adolescents aged 12–19 years old (OR [95% CI]:3.8 [1.2, 11.9]) and 1.8 times more likely than adults aged 20–59 years old (OR [95% CI]: 1.8 [1.02, 3.2]). Also, adults aged 20–59 years old were 2.1 times more likely than adolescents ages 12–19 years old to be above the 95th percentile (OR [95% CI]: 2.1 [1.0, 4.4]). No differences were found for the chance to be above the 95th percentile in any other age categories or for any other analytes.
During the three two-year NHANES cycles, the 75th, 90th, and 95th percentile estimates for DMDTP and DEDTP in 1999–2000 were 3 to 5 times higher than for the following two NHANES cycles in the total population. This observation was consistent across demographic groups. We also observed a reduction in DETP median concentrations in 2003–2004 from the 2001–2002 and 1999–2000 median estimates; however, upper distribution percentiles were similar with the ones in year 1999–2000 and appeared to be lower as compared to the ones in year 2001–2002.
DAP metabolites of OP pesticides have been measured in a random subset of three NHANES cycles since 1999. These data from 2001–2004 represent the first time reference DAP concentrations have been reported for adults >60 years old. Additionally, these are the first data reported on the sample sets collected before and after a voluntary withdrawal of registrations for chlorpyrifos and diazinon. Although the DAP metabolite measurements are not specific for one OP pesticide in particular and a sizeable proportion probably derives from exposure to the preformed DAP metabolite in the environment, these data may be useful. They may serve as an indicator for the maximum potential of OP pesticide exposure over time.
Interestingly, the most vulnerable age groups, children and the elderly, had the highest concentrations of DMTP in 2003–2004, while adolescents and other adults had much lower levels. These data suggest that older adults and children share common behaviors or activities. For example, time spent indoors may contribute to their high urinary DAP concentrations. However, adolescents were more than twice as likely to have concentrations of DEP above the 95th percentile estimate than senior adults and adults. For DMDTP, senior adults were 3.8 times more likely to be above the 95th percentile than adolescents and 1.8 times more likely than adults. Also, adults were marginally more likely than adolescents to be above the 95th percentile. Understanding the predictors of exposure of the upper tail of the distribution is particularly important for regulatory mitigation efforts, so adolescents may be a good subpopulation to target for reducing exposure.
The significant correlation of all of the DAP metabolites in urine suggests common pathways for both exposure and excretion. Because the use of diethyl OP pesticides in applications with dimethyl pesticides is unexpected, the correlation among these likely points to dietary exposures from produce where both groups of OP pesticides were used regularly. The strongest correlation was between DMTP and DMDTP, both potential metabolites of the common OP pesticide malathion.
These data sets collectively suggest that human exposure to OP pesticides has decreased during the last six years. For example, the median and 95th percentile estimates of DMTP concentrations from NHANES 2003–2004 appeared to be one-third less than that found in NHANES 1999–2000 even though the frequency of detection only decreased by about 20%. Urinary concentrations of DETP were detected significantly less in samples collected in 2003–2004 than in those collected in 2001–2002; however, DEP concentrations were largely unaffected. Because DETP can be derived from chlorpyrifos and diazinon, strategies targeting residential pesticide use to reduce exposure may have contributed to the decrease. DEP is common to all diethyl-substituted OP insecticides which perhaps is why we may not have observed a similar decrease.
As noted earlier, the biggest limitation of our study is the lack of specificity of DAP metabolites for a given OP pesticide. According to some estimates, 70% or more of urinary OP metabolite concentrations may be attributable to exposure to the preformed metabolite in the environment, which is not known to be toxic [38
]. Thus, we caution that the concentrations reported here be used as a maximum possible estimate of OP pesticide exposures. Regardless, reducing the use or tolerance levels of OP pesticides would also result in reduced preformed metabolite concentrations in the environment so that changes in urinary DAP concentrations over time may parallel exposure mitigation strategies demonstrating their effectiveness.