Dermal absorption of chlorpyrifos in human volunteers

Objective: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). Methods: Two dermal, single, doses of CPF were applied in two study groups ( A and B) each comprising three apparently healthy male volunteers who gave their written informed consent. The clinical part of the study was conducted in compliance with the ICH Guideline and the EC principles of good clinical practice (GCP). An approximately 0.5 ml dilution of CPF in ethanol was applied to an area of similar to 100 cm(2) of the volar aspect of the forearm, resulting in doses of either 5 mg ( A) or 15 mg ( B) of CPF per study subject. Duration of dermal exposure was 4 h, after which the non-absorbed fraction was washed off. The following samples were collected at pre-determined intervals for the determination of either CPF or its metabolite TCP: dosing solutions, wash-off fractions and urine samples collected up to 120 h after dosing. Results: A relatively large fraction of CPF (42% - 67% of the applied dose) was washed off from the exposed skin area. Application of either 5 mg ( A) or 15 mg CPF ( B) resulted in the total urinary excretion of 131.8 mug ( A) or 115.6 mug ( B) of TCP 120 h after dosing. This indicated that 4.3% of the applied dose has been absorbed ( A), while in group ( B) no significant increase in urinary TCP (115.6 mug) was established. The latter indicates that an increase in the dermal dose at a fixed area does not increase absorption, which suggests that the percutaneous penetration rate was constant. Further, it was observed that the clearance of CPF by the body was not completed within 120 h, suggesting that CPF or TCP was retained by the skin and/or accumulated in the body. A mean elimination half-life of 41 h was established. Conclusion: The results show that daily occupational exposure to CPF may result in accumulation of CPF and/or its metabolites, possibly resulting in adverse effects.