TOXICOLOGY
Phorate, an organophosphorus insecticide that inhibits cholinesterase, was first reviewed for toxicological effects by the Joint Meeting in 1977. A temporary ADI of 0-0.0002 mg/kg bw was established in 1982. In 1994, the Meeting re-evaluated phorate and allocated an ADI of 0-0.0005 mg/kg bw per day. Because in a limited study in rats it was reported that less than 40% of the administered 32P label was excreted within 144 h, adequate studies on absorption, distribution, excretion, and metabolism in rats were requested for review in 1996.
Studies on the absorption, distribution, metabolism, and excretion of phorate in rats were reviewed by the present Meeting. 14C-labelled phorate was rapidly absorbed and excreted by rats after a single dose in corn oil by gavage. The urine was the primary route of elimination, with approximately 80% of the administered radiolabel excreted within 24 h; faecal elimination accounted for about 10% of the label.
The current studies showed essentially total excretion of 14C after 192 h. The Meeting concluded that phorate and its metabolites are rapidly excreted and that accumulation of a toxic metabolite is not a concern. Thus, the new data did not indicate that the ADI allocated in 1994 should be reassessed. The ADI of 0-0.0005 mg/kg bw allocated on the basis of a NOAEL of 0.05 mg/kg bw per day in a one-year study of toxicity in dogs and a two-year study of toxicity and carcinogenicity in rats, with a 100-fold safety factor, was confirmed.
An addendum to the toxicological monograph was prepared.
TOXICOLOGICAL EVALUATION
Levels that cause no toxic effect
|
Mouse: |
1 ppm, equal to 0.18 mg/kg bw per day (13-week study of toxicity) |
|
Rat: |
1 ppm, equal to 0.05 mg/kg bw per day (two-year study of toxicity and carcinogenicity) |
|
Rabbit: |
0.15 mg/kg bw per day (study of developmental toxicity) |
|
Dog: |
0.05 mg/kg bw per day (one-year study of toxicity) |
Estimate of acceptable daily intake for humans
0-0.0005 mg/kg bw
Studies that would provide information useful for the continued evaluation of the compound
Further observations in humans.
