Dermal penetration of14C‐labeled diisopropyl methylphosphonate in swine

Abstract

Diisopropyl methylphosphonate (DIMP) has been identified as a groundwater contaminant on or near sites of former chemical warfare production facilities. The material is a by-product of GB (or Sarin) manufacture and does not occur naturally in the environment. The present study measured the dermal absorption of 14C-labeled DIMP in swine to establish the basis for estimating health risk from this portal of entry. Yorkshire cross swine were treated by sc injection of labeled DIMP to measure the efficiency of bioelimination. Additional pigs each received a single percutaneous (pc) exposure of 400, 40, or 4 micrograms/cm2 of labeled DIMP. Absorption through 7 d was measured by the appearance of 14C label in the urine and feces. Tissue specimens, collected at necropsy, were assessed for residual radioactivity. The results showed that between 3 and 7% of cutaneous DIMP was absorbed through 7 d. Urinary elimination accounted for about 95% of the absorbed dose in the first 24 h. No significant tissue deposition was observed. Pigs treated by the sc route excreted nearly 100% of the injected material demonstrating an extremely efficient metabolic process. It was concluded that humans may be expected to absorb less than 10% of an unoccluded single dermal exposure to DIMP. Absorbed dose would likely be metabolized to isopropyl methylphosphonic acid and excreted primarily in the urine within 24 h. Significant evaporation of the material from the open skin surface would be expected to occur.