title: Lack of carcinogenicity of chlorpyrifos insecticide in a high-dose, 2-year dietary toxicity study in Fischer 344 rats.
abstract: Chlorpyrifos (CPF) was administered daily in the feed to evaluate toxicity and oncogenicity potential in male and female Fischer 344 rats, according to U.S. EPA guidelines. Doses for the 2-year study were based on findings in a 13-week feeding study in which lower body weights, urinary perineal staining, adrenal cortical vacuolization, and inhibition (slightly more than 60%) of brain cholinesterase (ChE) occurred at 15 mg/kg/day. The high dose in the subsequent 2-year study was 10 mg/kg/day, with lower doses of 0, 0.05, 0.1, or 1.0 mg/kg/day chosen to define dose-response patterns. Rats given 10 mg/kg/day for 2 years were healthy and there was no evidence of premature deaths. Mild toxicity occurred only in rats given 10 mg/kg/day and consisted of perineal urine soiling in females and a 6-8% body-weight decrease in males. Males given 10 mg/kg/day also had increased adrenal weights and vacuolation of the adrenal zona fasciculata. ChE was considered a measure of exposure. Plasma, RBC, and brain ChE activities were inhibited in rats given 10 mg/kg/day, and the plasma and RBC ChE activities were inhibited in rats given 1.0 mg/kg/day. Chronic exposure to 0.1 mg/kg/day was considered a threshold exposure level for inhibition of plasma ChE. Rats given 10 mg/kg/day, considered a maximum-tolerated dose, had approximately 60% chronic inhibition of brain ChE. This group had similar numbers and types of neoplasms as control rats. Consequently, CPF was not carcinogenic at dose levels up to 10 mg/kg/day.
authors.affiliation: Health and Environmental Research Laboratories, The Dow Chemical Company, Midland, Michigan 48674, USA. blyano@dow.com
authors.forename: B L
authors.initials: BL
authors.lastname: Yano
authors.forename: J T
authors.initials: JT
authors.lastname: Young
authors.forename: J L
authors.initials: JL
authors.lastname: Mattsson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000378:metabolism; D004032:Diet; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015383:Zona Fasciculata / Q000187:drug effects / Q000473:pathology
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D002802:Cholinesterases; D004390:Chlorpyrifos