In vitro percutaneous absorption and stratum corneum binding of alachlor: effect of formulation dilution with water

The effect of vehicle dilution on the percutaneous absorption of alachlor, 2-chloro-2',6'-diethyl-N-(methoxymethyl)acetanilide, through excised human skin was determined using flowthrough design glass penetration cells and 14C radiotracer methodology. Three dilutions of alachlor (in the solubilizing commercial formulation) with distilled water were utilized: 1:20, 1:40, and 1:80 (v/v); corresponding to concentrations of 23.0, 11.8, and 5.98 mg alachlor per milliliter, respectively. Skin from the penetration studies and human powdered stratum corneum from the binding studies demonstrated a high capacity for alachlor. A soap and water (1:1, v/v) solution effectively decontaminated powdered stratum corneum. Using plasma as the receptor solution, penetration ranged from 0.5 to 4% of the applied dose for an 8-hr exposure period. Lag times of 1.2 to 1.8 hr were observed. Increasing dilution resulted in significant enhancement (p less than 0.01) in the rate and extent of alachlor penetration. Although the biological significance of this observation is unclear, this phenomenon might be explored in future studies because of its ramifications for human toxicity and for decontamination opportunities.