FAO Meeting Report No. PL/1965/10/1
    WHO/Food Add./27.65

    EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met in Rome,
    15-22 March 19651

    Food and Agriculture Organization of the United Nations
    World Health Organization
    1965

                
    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65

    CHLORPROPHAM

    Chemical names

         Isopropyl N-(3-chlorophenyl)carbmate; isopropyl
    chlorocarbanilate

    Synonyms

         CIPC

    Empirical formula

         C10H12O2N Cl

    Structural formula

    

    BIOLOGICAL DATA

    Acute toxicity
                                                                                  
    Animal         Route         LD50 mg/kg      References
                                 body-weight
                                                                              

    Rat            Oral           5000-8000      van Esch & van Genderen, 1956;
                                                 Westrick at al., 1953

    Rat       Intraperitoneal        700         van Esch & van Genderen, 1956

    Rabbit         Oral         approx. 5000     Westrick et al., 1953
                                                                              
    
    Short-term studies

         Mouse. Groups each of 30 mice, 15 females and 15 males, were
    given the following oral doses of chlorpropham : One group, a single
    dose of 750 mg/kg body-weight; a second group, once a week an oral
    dose of 750 mg/kg body-weight; and a third group, 1000 ppm in the diet
    for 6 months. Chlorpropham and also ethylurethane were used as
    initiators and croton oil was painted on the skin as a promoter.

    Although in some of the original experiments skin papillomas developed
    following applications of croton oil in mice fed clorpropham, this
    result could not be confirmed in a number or subsequent experiments
    carried on in the same institution. No lung tumours were found in
    these experiments. Positive controls given ethylurethane in the place
    of chlorpropham developed both skin papillomas and lung adenomas (van
    Esch et al., 1958; van Esch, 1965).

         Rat. Groups of 10 rats were fed diets containing 310, 1250,
    5000 and 20 000 ppm of chlorpropham for 90 days. All groups showed an
    increase in weight and food-intake as compared with the controls. The
    mean liver weights of the animals receiving 1250, 5000 and 20 000 ppm
    were significantly higher than those of the controls (no significant
    changes in kidney weight). No microscopic changes in the liver and the
    kidney after 90 days were found (Westrick et al., 1953).

         Dog. Groups of 4 dogs (2 male and 2 female) were given 200,
    2000 and 20 000 ppm of chlorpropham in their diet for one year. All
    animals showed initial weight loss, but only the animals receiving 20
    000 ppm failed to surpass the average starting weight for the group
    during the experimental period; no animals died and there was no
    apparent morbidity. Lower haemoglobin and haematocrit values were
    found in the first six-month feeding period on 20 000 ppm but not at
    the end of the 12-month feeding period. The weights of the liver and
    spleen relative to body-weight increased at the 20 000 ppm level
    (Larson et al., 1960).

         Pig. Pigs, 4 per group, received 3300 ppm of chlorpropham in
    their diet for 19 weeks. There was no effect on weight gain, and at
    autopsy no pathological abnormalities were observed. The liver, kidney
    and spleen were histologically normal. No changes in the blood
    picture, except a slight decrease in haemoglobin content in the
    nineteenth week, were present (van Esch & van Genderen, 1956).

    Long-term studies

         Rat. Groups each of 50 rats, 25 males and 25 females, were
    administered 200, 2000 and 20 000 ppm chlorpropham in their diet for 2
    years. No abnormalities were observed at concentrations of 200 and
    2000 ppm. At 20 000 ppm growth was depressed, the mortality rate of
    the males was increased, and the haematocrit and haemoglobin values
    were lowered; increases in liver and spleen weights relative to
    body-weight were observed. Tumour incidence in the treated animals was
    not greater than in the control animals (Larson et al., 1960).

    Comments on experimental work reported

         The suspicion that chlorpropham could be a co-carcinogen for mice
    could not be confirmed. In other species experiments purposely
    designed did not indicate any tumorigenic effect.

    EVALUATION

         Not enough toxicological data on animals are available at present
    to set no-effect levels.

    Further work required

         Biochemical studies; long-term feeding studies in other species
    than the rat.

    REFERENCES

    van Esch, G. J. (1965) Personal communication concerning data from the
    National Institute of Public Health, Utrecht, The Netherlands

    van Esch, G. J. & van Genderen. H. (1956) Preliminary report of the
    National Institute of Public Health

    van Esch, G. J., van Genderen, H. & Vink, H. H. (1958) Brit. J.
    Cancer, 3, 355

    Larson, F. S., Crawford, E. M., Blackwell Smith, R., Hennigar, G. R.,
    Haag, H. B. & Finnegan, J. K. (1960) Toxicol. Appl. Pharmacol., 2,
    659

    Westrick, M. L., Gross, P. & Schrenk, H. H. (1953) Report from Ind.
    Hyg. Foundation America to Pittsburgh Plate Glass Company,
    June/September and September/December
    

    See Also:
       Toxicological Abbreviations
       Chlorpropham (ICSC)
       Chlorpropham (JMPR Evaluations 2000 Part II Toxicological)
       Chlorpropham (JMPR Evaluations 2005 Part II Toxicological)