title: Occupational exposure limits for 30 organophosphate pesticides based on inhibition of red blood cell acetylcholinesterase.
abstract: Toxicity and other relevant data for 30 organophosphate pesticides were evaluated to suggest inhalation occupational exposure limits (OELs), and to support development of a risk assessment strategy for organophosphates in general. Specifically, the value of relative potency analysis and the predictability of inhalation OELs by acute toxicity measures and by repeated oral exposure NOELs was assessed. Suggested OELs are based on the prevention of red blood cell (RBC) acetylcholinesterase (AChE) inhibition and are derived using a weight-of-evidence risk assessment approach. Suggested OEL values range from 0.002 to 2 mg/m(3), and in most cases, are less than current permissible exposure levels (PELs) or threshold limit values(R) (TLVs(R)). The available data indicate that experimental data for most organophosphates evaluated are limited; most organophosphates are equally potent RBC AChE inhibitors in different mammalian species; NOELs from repeated exposure studies of variable duration are usually equivalent; and, no particular grouping based on organophosphate structure is consistently more potent than another. Further, relative potency analyses have limited usefulness in the risk assessment of organophosphates. The data also indicated that equivalent relative potency relationships do not exist across either exposure duration (acute vs. repeated) or exposure route (oral vs. inhalation). Consideration of all variable duration and exposure route studies are therefore usually desirable in the development of an OEL, especially when data are limited. Also, neither acute measures of toxicity nor repeated oral exposure NOELs are predictive of weight-of-evidence based inhalation OELs. These deviations from what is expected based on the common mechanism of action for organophosphates across exposure duration and route - AChE inhibition - is likely due to the lack of synchrony between the timing of target tissue effective dose and the experimental observation of equivalent response. Thus, comprehensive interpretation of all toxicity data in the context of available toxicokinetic, toxicodynamic and exposure information for each individual organophosphate in a weight-of-evidence based risk assessment is desirable when deriving inhalation OELs.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 66160, Kansas City, KS, USA. jes19@health.state.ny.us
authors.forename: J E
authors.initials: JE
authors.lastname: Storm
authors.forename: K K
authors.initials: KK
authors.lastname: Rozman
authors.forename: J
authors.initials: J
authors.lastname: Doull
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure; D009943:Organophosphorus Compounds
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds