Title
Dermal absorption of chlorpyrifos in human volunteers
Author
Meuling, W.J.
Ravensberg, L.C.
Roza, L.
van Hemmen, J.J.
TNO Kwaliteit van Leven
Publication year
2005
Abstract
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 ∼100 cm2 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 μg (A) or 115.6 μg (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 μg) 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. Conc lusion: The results show that daily occupational exposure to CPF may result in accumulation of CPF and/or its metabolites, possibly resulting in adverse effects. © Springer-Verlag 2004.
Subject
Health
Analytical research
Occupational exposure
Percutaneous penetration
Pesticide
Urinary metabolites
Volunteers
alcohol
chlorpyrifos
pyridinol
adult
article
clinical study
controlled study
dilution
forearm
fractionation
good clinical practice
human
human experiment
informed consent
male
methodology
occupational exposure
practice guideline
skin absorption
skin penetration
urinalysis
urinary excretion
volunteer
Adult
Chlorpyrifos
Human Experimentation
Humans
Male
Occupational Exposure
Pesticides
Skin Absorption
To reference this document use:
http://resolver.tudelft.nl/uuid:f30d61d8-b6fa-4bb9-8706-17af12280793
DOI
https://doi.org/10.1007/s00420-004-0558-6
TNO identifier
238366
ISSN
0340-0131
Source
International Archives of Occupational and Environmental Health, 78 (1), 44-50
Document type
article