title: Humans appear no more sensitive than laboratory animals to the inhibition of red blood cell cholinesterase by dichlorvos.
abstract: Inhibition of red blood cell (RBC) cholinesterase is a consistent and sensitive indicator of exposure to dichlorvos (DDVP). Absent human data, default 10-fold adjustment factors for potential interspecies and intraspecies sensitivity differences would be used in developing a reference dose from the no observed effect levels for this endpoint obtained in toxicological assessments of laboratory animals. However, many studies of the cholinesterase-inhibiting effects associated with DDVP exposure have been conducted in humans, including healthy male volunteers, other healthy subpopulations, and diverse clinical subpopulations. Indeed, ample human data exist to permit a data-based assessment of potential interspecies sensitivity differences in RBC cholinesterase inhibition associated with DDVP exposure. In aggregate, these data demonstrate that the DDVP doses producing inhibition in humans are virtually identical to those eliciting the same levels of inhibition in laboratory rats, mice, monkeys, and dogs. Thus, healthy humans appear to be no more sensitive than laboratory animals to DDVP's effects on RBC cholinesterase, and an interspecies uncertainty factor of 1 is appropriate and scientifically warranted for use in DDVP risk assessments.
authors.affiliation: Toxicology Consulting Services, Arnold, MD, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: MacGregor
authors.forename: Laura M
authors.initials: LM
authors.lastname: Plunkett
authors.forename: Susan Hunter
authors.initials: SH
authors.lastname: Youngren
authors.forename: Ann
authors.initials: A
authors.lastname: Manley
authors.forename: James Barry
authors.initials: JB
authors.lastname: Plunkett
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Starr
mesh_terms: D000465:Algorithms; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004006:Dichlorvos / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D000882:Haplorhini; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D011247:Pregnancy; D051381:Rats; D013045:Species Specificity
chemical_list: D002800:Cholinesterase Inhibitors; D004006:Dichlorvos