title: Percutaneous absorption of 2,4-dichlorophenoxyacetic acid from soil with respect to soil load and skin contact time: in vivo absorption in rhesus monkey and in vitro absorption in human skin.
abstract: The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), used for control of weeds in agriculture, forestry, and rights of way, can accumulate as a residual chemical in soil. The objective was to determine percutaneous absorption of 2,4-D from soil, with emphasis on soil load and skin contact time. With control acetone vehicle, in vivo absorption of 2,4-D in the rhesus monkey was 8.6 +/- 2.1% of the dose, which compared closely to published human absorption of 6.0 +/- 2.4%. Percutaneous absorption from soil loads of 1 and 40 mg/cm2 were 9.8 +/- 4.0 and 15.9 +/- 4.7%, respectively, values similar to acetone vehicle. In vitro absorption in human skin calculated from skin contact accumulation over 24 h was 1.8 +/- 1.7, 1.7 +/- 1.3, and 1.4 +/- 1.2% for soil loads of 5, 10, and 40 mg/cm2, respectively. Thus, soil load did not affect 24-h percutaneous absorption. Current Environmental Protection Agency (EPA) recommended calculated reductions due to soil load are not supported by these results with 2,4-D. Percutaneous absorption of 2,4-D from acetone vehicle for 8 h dosing period was 3.2 +/- 1.0%, one-third the value of 8.6 +/- 2.1% over 24 h. With soil vehicle, absorption for 8 h was only 0.03 +/- 0.02% for 40 mg/cm2 soil load and 0.05 +/- 0/.004% for 1 mg/cm2 soil load. Absorption for 16 h was 2.2 +/- 1.2%. Absorption over time was linear for acetone vehicle, where total dose is deposited on skin, but not linear for soil vehicle, which had an 8-h delay (lag time). This equates with a normal 8-h work day where most of the contaminated soil can be washed off the skin. The apparent partition coefficient of 2,4-D between soil and water changed over time. This suggests there is a "mobility" phase for 2,4-D in soil that will change with time. For soil vehicle, percutaneous absorption of 2,4-D was not linear in respect to soil load or to skin contact time. Calculation based on assumed linearity can falsely estimate potential human health hazard. Clearly, the dermatokinetics with soil and skin represent complex interactive forces that require detailed evaluation before overgeneralizing rules for interpretation in terms of risk assessment.
authors.affiliation: Department of Dermatology, University of California School of Medicine, San Francisco, 94143, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Wester
authors.forename: J
authors.initials: J
authors.lastname: Melendres
authors.forename: F
authors.initials: F
authors.lastname: Logan
authors.forename: X
authors.initials: X
authors.lastname: Hui
authors.forename: H I
authors.initials: HI
authors.lastname: Maiback
authors.forename: M
authors.initials: M
authors.lastname: Wade
authors.forename: K C
authors.initials: KC
authors.lastname: Huang
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000818:Animals; D003666:Decontamination; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008253:Macaca mulatta; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012869:Skin Absorption / Q000502:physiology*; D012987:Soil / Q000032:analysis; D012989:Soil Pollutants / Q000032:analysis / Q000493:pharmacokinetics*; D012995:Solubility; D013997:Time Factors
chemical_list: D006540:Herbicides; D012987:Soil; D012989:Soil Pollutants; D015084:2,4-Dichlorophenoxyacetic Acid