A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates

Citation
G. Carrier et Rc. Brunet, A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates, TOXICOL SCI, 47(1), 1999, pp. 23-32
Citations number
25
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
10966080 → ACNP
Volume
47
Issue
1
Year of publication
1999
Pages
23 - 32
Database
ISI
SICI code
1096-6080(199901)47:1<23:ATMTAT>2.0.ZU;2-V
Abstract
Azinphosmethyl (APM) is one of the most common insecticides used in fruit f arming. The object of this paper is to develop a quick and practical test f or assessing the risk for humans coming into contact with APM. It has been shown that the principal component of occupational and/or accidental exposu re is through the skin (C. A. Franklin et al., 1981, J. Toxicol. Environ. H ealth 7, 715-731), but our approach is applicable to exposures via any rout e or a combination of routes. The method proposed in the present paper can accommodate a single-event exposure or repeated exposures over long periods . Urinary alkylphosphate (AP) metabolites are reliable bioindicators of the presence of APM in the body; they are easily accessible and can be used to estimate APM body burden. We developed a simple toxicokinetic model to lin k the time varying APM body burden to absorbed doses and to rates of elimin ation in the form of AP urinary metabolites. Using this model and data avai lable in the literature, we are able to propose a "no observed adverse effe ct level" (NOAEL) for APM body levels and for corresponding absorbed doses. We have established that after a single exposure, the safe limit correspon ding to the NOAEL is reached at a cumulative 0.215 mu moles AP/kg bw elimin ated in urine in the first 24 hours following the beginning of exposure. Fo r repeated dairy exposures at steady state, the corresponding urinary AP me tabolite level is equal to a cumulative 0.266 mu moles AP/kg bw eliminated per 24 hours.