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.
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Authors | B L Yano, J T Young, J L Mattsson |
Journal | Toxicological sciences : an official journal of the Society of Toxicology
(Toxicol Sci)
Vol. 53
Issue 1
Pg. 135-44
(Jan 2000)
ISSN: 1096-6080 [Print] United States |
PMID | 10653531
(Publication Type: Journal Article)
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Chemical References |
- Cholinesterase Inhibitors
- Insecticides
- Cholinesterases
- Chlorpyrifos
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Topics |
- Administration, Oral
- Animals
- Body Weight
(drug effects)
- Carcinogenicity Tests
- Chlorpyrifos
(toxicity)
- Cholinesterase Inhibitors
(toxicity)
- Cholinesterases
(metabolism)
- Diet
- Female
- Insecticides
(toxicity)
- Kidney Glomerulus
(drug effects, pathology)
- Liver
(drug effects, pathology)
- Male
- Neoplasms, Experimental
(chemically induced, pathology)
- Organ Size
(drug effects)
- Rats
- Rats, Inbred F344
- Zona Fasciculata
(drug effects, pathology)
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