Page 5: Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Chlorpyrifos
Chlorpyrifos is readily absorbed from the gastrointestinal tract and is rapidly metabolized. Metabolites are excreted principally in the urine and to a lesser extent in the faeces; the main metabolites are 3,5,6-trichloro-2-pyridylphosphate and 3,5,6-trichloro-2-pyridinol.Footnote 17 Small amounts of unmetabolized chlorpyrifos have been detected in the blood, brain and liver after accidental human ingestion.Footnote 18
Chlorpyrifos is a cholinesterase inhibitor. Human volunteers (four men per group) were administered oral doses of chlorpyrifos of 0.014 mg/kg bw per day for 27 days, 0.03 mg/kg bw per day for 20 days or 0.10 mg/kg bw per day for nine days.Footnote 19 Red blood cell cholinesterase activity was not affected at any level.
Beagle dogs were fed diets containing chlorpyrifos at dose levels of 0, 0.01, 0.03, 0.1, 1.0 or 3.0 mg/kg bw per day for two years.Footnote 20 Red blood cell cholinesterase was inhibited in males and females at 1.0 and 3.0 mg/kg bw per day. In a similar study,Footnote 21 rats were fed diets containing chlorpyrifos at concentrations of 0, 0.01, 0.03, 0.1, 1.0 and 3.0 mg/kg bw per day for two years. Brain cholinesterase activity was inhibited at 3.0 mg/kg bw per day and slightly depressed at 1.0 mg/kg bw per day. Based on these results, the no-observed-adverse-effect level (NOAEL) for red blood cell and brain cholinesterase inhibition is considered to be 0.1 mg/kg bw per day. The NOAEL in Rhesus monkeys receiving 0.08 mg/kg bw per day of chlorpyrifos by gavage for six months was similar; animals exhibited no depression in red blood cell cholinesterase activity.Footnote 22
In a carcinogenicity study in CD-1 mice, chlorpyrifos was not oncogenic when administered at dose levels up to 15 ppm (1.5 mg/kg bw per day) in food for 105 weeks.Footnote 23 Chlorpyrifos was not found to be mutagenic in five microbial assay systems.Footnote 24 In a CF-1 mouse teratogenicity study, chlorpyrifos was not teratogenic at doses up to 25 mg/kg bw per day, although significant reductions in plasma and erythrocyte cholinesterase levels were observed in maternal mice at 1 mg/kg bw per day or greater and in foetuses at 10 mg/kg bw per day or more.Footnote 25
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