Biomonitoring of 2,4-Dichlorophenoxyacetic Acid Exposure and Dose in Farm Families

Abstract

ObjectiveWe estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm.MethodsFarm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application.ResultsMedian urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 μ g/L for applicators, below the limit of detection, and 1.2 μ g/L for spouses, and 1.5 and 2.9 μ g/L for children. The younger children (4–11 years of age) had higher median post-application concentrations than the older children (≥ 12 years of age) (6.5 vs. 1.9 μ g/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4–11 years of age), and 0.12 (children ≥ 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators.ConclusionsWe observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D–exposed agricultural populations.

Immunohistochemical and Histopathological Evaluation of 2,4-Dichlorophenoxyacetic Acid-Induced Changes in Rat Kidney Cortex

“…Apart from a dose-dependent decrease in body and kidney weights, changes in the kidney morphology at light microscopical level (Table 2) was observed distinctly in this dose range, indicating the congruity of the dose range selected. Morover, a recent study has evaluated 2,4-D exposure in farm family members in Minnesota and South Carolina of United States on their farm and the geometric mean systemic doses were found 2.46, 0.8 and 0.22 lg/kg in applicators, spouses and children, respectively (Alexander et al 2007). This study has revealed a considerable heterogeneity of 2,4-D exposure among farm family members and showed that exposure to the spouses and children is primarily determined by direct contact with the application process and the number of acres treated.…”

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

“…Finally, a lack of biological plausibility is further affirmed by the extremely large margin of exposure between biomonitored 2,4-D doses reported for male farm-worker applicators in the Ag Health Study itself and the NOEL dose for thyroid effects in rats reported by Stoker. The Alexander et al (2007) study of farm families identified a geometric mean exposure dose for male applicators of 2.46 lg/kg/day, which is approximately 10 000X below the NOEL of 30 mg/kg/ day (30 000 lg/kg/day) for thyroid effects identified by Stoker and Zorrilla (2010). Importantly, the geometric mean dose for female spouses living in close proximity to active 2,4-D application operations was 0.08 lg/kg/day, and was substantially disparate (> 300 000) from the approximately 25 mg/kg/day dietary dose identified as the inflection point for onset of TSRC in female rats (a non-thyroid toxic dose in rats).…”

“…This NOAEL is based on renal toxicity, not on endocrine or reproductive effects. Alexander et al (2007) reported that children living on farms on which 2,4-D was being actively applied had systemic doses (geometric mean) of 0.32 (children 4-11) to 0.12 (children >12 years old) lg/kg based on five days of comprehensive urinary biomonitoring. These dose levels were 65 625-175 000-fold below the overall NOAEL of 21 mg/kg/day (21 000 lg/kg/ day) used to set the EPA chronic reference dose for 2,4-D. Large margins of exposure (MOEs) were similarly noted for both applicators and spouses (geometric mean systemic doses of 2.46 and 0.8 lg/kg/day, respectively).…”

“…"Increase #Decrease (Alexander et al 2007) and the AHS biomonitoring study ). As a result, the efforts to evaluate exposure-response in the AHS are very limited at best.…”

Neurobehavioral testing in human risk assessment

“…Children of agricultural workers may have a higher risk of exposure to pesticides compared to the general populations because of the close proximity of their homes to the fields where pesticides are applied and from take-home exposure (Fenske, et al, 2002;Loewenherz, et al, 1997). Although pesticide metabolite levels were not significantly increased in spouses and children living on a farm during pesticide applications, children who had contact or were observing the mixing or application had higher metabolite levels than those who were out of the area when pesticides were mixed or applied (Acquavella, et al, 2005;Alexander, et al, 2007). While information is available on the impact of acute exposure in adults and occupational exposure, little information is available examining the impact of exposures in children.…”