Biomonitoring Data for 2,4-Dichlorophenoxyacetic Acid in the United States and Canada: Interpretation in a Public Health Risk Assessment Context Using Biomonitoring Equivalents

Abstract

BackgroundSeveral extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published.ObjectiveWe reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group.Data sourcesData on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized.Data synthesisThe biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values.ConclusionsBiomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D.

2,4-D Exposure and risk assessment: Comparison of external dose and biomonitoring based approaches

“…As a result, biomonitoring for 2,4-D is generally based on measurement of 2,4-D (both parent and conjugated forms) in urine (Knopp and Glass, 1991;Knopp, 1994;CDC, 2005). The available biomonitoring literature for 2,4-D was reviewed by Aylward et al (2010). Urinary biomonitoring data for 2,4-D are available for several groups (see Tables 2 and 3 for additional details of each source of biomonitoring data).…”

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

“…Biomonitoring equivalent determinations in this and other populations similarly demonstrate conservatively large MOEs (Aylward et al 2010;Hays et al 2012). Since the inflection points for onset of non-linear TK in male and female rats are in the range of 15-40 mg/kg/day, toxicity studies such as the EOGRT fulfilled recent dose selection guidance recommending use of a KMD dose selection strategy, i.e.…”

“…The influence of dosedependent 2,4-D toxicokinetics (TK) as an important determinant for expression of toxicity has also been characterized in multiple species, including humans. 2,4-D has been the subject of several epidemiological studies and comprehensive reviews as well as multiple studies to characterize potential human and environmental exposure levels (reviewed in Munro et al 1992;USDA 1998;Garabrant & Philbert 2002;US EPA 2005;Bus & Hammond 2007;Aylward et al 2010;Burns & Swaen 2012).…”

Phenoxy Herbicides (2,4-D)

“…In a biomonitoring study of 135 preschool-aged children and their adult caregivers, Morgan et al (2008) estimated the maximum absorbed dose in the chlidren as 0.28 g/kg/day, which, using a Biomonitoring Equivalents exposure analysis, were concluded as well below exposure guidance values developed by the US Environmental Protection Agency (Aylward et al, 2009). 84.6 toxIcologIcal studIes 84.6.1 absorption 2,4-D is rapidly absorbed through the gastrointestinal tract following oral exposure, with peak plasma levels being reached in as little as 10 minutes or up to 24 hours depending on the dose and chemical form of 2,4-D (Erne, 1966a;Khanna and Fang, 1966;Knopp and Schiller, 1992;Kohli et al, 1974;Pelletier et al, 1989;Sauerhoff et al, 1977). The rate of absorption is related to dose, with absorption occurring more rapidly at lower doses (i.e., 0.4 mg/kg body weight/day) than at higher doses (i.e., 1 mg/kg body weight/day) (Pelletier et al, 1989).…”