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.
    

    See Also:
       Toxicological Abbreviations
       Chlorpyrifos (ICSC)
       Chlorpyrifos (WHO Pesticide Residues Series 2)
       Chlorpyrifos (WHO Pesticide Residues Series 5)
       Chlorpyrifos (Pesticide residues in food: 1981 evaluations)
       Chlorpyrifos (Pesticide residues in food: 1982 evaluations)
       Chlorpyrifos (Pesticide residues in food: 1983 evaluations)
       Chlorpyrifos (JMPR Evaluations 1999 Part II Toxicological)