CHLORPYRIFOS JMPR 1977
Explanation
Chlorpyrifos was considered by the Joint Meetings of 1972, when an ADI
of 0.0015 mg/kg/day was established, 1974 and 1975 (FAO/WHO, 1973,
1975, 1976). The present evaluation is in the light of new biochemical
and toxicological information and of discussions at the 9th (1977)
Session of the Codex Committee on Pesticide Residues.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOCHEMICAL ASPECTS
Biotransformation
Twelve male rats (about 330 g each) were orally dosed once (stomach
tube) with 5 mg of chlorpyrifos (2.97 µ Ci per rat) in 0.5 ml of
ethanol.
The urine was collected at 12-hr intervals, and the faeces were
collected daily. The rats were sacrificed 48 hr after dosing. The
radioactivity in the urine (88% of the dose) represented at least six
metabolites.
Three metabolites, accounting for 97% of the urinary radioactivity,
were identified by mass spectrometry of their trimethylsilyl (TMS)
derivatives as the glucuronide of 3,5, 6-trichloro-2-pyridinol (80%),
a glucoside of 3,5,6-trichloro-2-pyridinol (4%) and
3,5,6-trichloro-2-pyridinol (12%) (Bakke et al., 1976).
TOXICOLOGICAL STUDIES
Special studies on mutagenicity
Chlorpyrifos showed no mutagenic activity in the histamine reverse
mutation system in five strains of Salmonella typhimurium (TA 1535,
TA 1537, TA 1538, TA 98, and TA 180), the tryptophan mutation system
in Escherichia coli WP2, the mitotic recombination assay in
Saccharomyces cerevisiae D3, and the relative toxicity essays in
Escherichia coli and Bacillus subtilis (Poole et al., 1977).
COMMENTS
New data on biotransformation indicate that the main metabolite of
chlorpyrifos in the urine is the glucoronide of
2,5,6-trichloro-2-pyridinol (80%), instead of
2,5,6-trichloro-2-pyridyl phosphate. At least four other metabolites
were found. One of these was identified as the glycoside of
2,5,6-trichloro-2-pyridinol.
Chlorpyrifos showed no mutagenic activity in a metabolically activated
microbiological assay system.
Although no further information has become available about the
possible increased sensitivity to plasma cholinesterase depression
after withdrawal from an initial dose regime, there is no base to
justify a change of the ADI for humans other than in accordance with
comments in this report to round this off to one significant figure
(see section 2.2).
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 0.03 (mg/kg bw)/day
Dog: 0.01 (mg/kg bw)/day
Humans: 0.014 mg/kg bw orally for 1 month
ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR HUMANS
0-0.001 mg/kg bw
RESIDUES IN FOOD AND THEIR EVALUATION
At the 9th (1977) Session of the Codex Committee on Pesticide Residues
(ALINORM 78/24, par. 77), it was agreed that the MRL for peppers
should be raised from 0.2 mg/kg to 0.5 mg/kg, since the retention of
the residue on peppers was similar to that on tomatoes for which a
maximum residue limit of 0.5 mg/kg had been recommended. The
delegation of Israel undertook to provide data to the Joint Meeting.
Although no data were received, the Meeting concurred with the
observations of the Codex Committee on Pesticide Residues and amended
the recommendation accordingly.
FURTHER WORK OR INFORMATION
Desirable
Elucidation of possible increased sensitivity to plasma cholinesterase
depression after withdrawal from an initial dose regime.
REFERENCES
Bakke, J.E., Feil, V.J. and Price, C.E. (1976) Rat urinary metabolites
from 0,0-diethyl-0 (3,5,6-trichloro-2-pyridyl) phosphortioate.
J. Environ. Sci. Health, Bull. (3), 225-230.
Poole, D.C., Simmon, V.F., and Newell, Co. W. (1977) In vitro
mutagenic activity of fourteen pesticides, Stanford Research
Institute, Menlo Park, California, Abstracts: sixteenth annual
meeting. Tox. Appl. Pharm. 41, 196.
FAO/WHO (1973) 1972 evaluations of some pesticide residues in foods
AGP:1972/M/9/1; WHO Pesticide Residues Series, No. 2.
FAO/WHO (1975) 1974 evaluations of some pesticide residues in food.
AGP:1974/M/11; WHO Pesticide Residues Series, No. 4.
FAO/WHO (1976) 1975 evaluations of some pesticide residues in food.
AGP:1975/M/13; WHO Pesticide Residues Series, No. 5.