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    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

    CHLORFENSON

    Chemical name

         p-chlorophenyl-p-chlorobenzene sulfonate;
    4-chlorophenyl-4-chlorobenzene-sulfonate.

    Synonyms

         Ovotram; Ovex; Mitran; Orthotran; Ovotex; Difenson; CPCBS.

    Empirical formula

         C12H8O3Cl2S

    Structural formula

    CHEMICAL STRUCTURE 

    BIOLOGICAL DATA

    Biochemical aspects

         Absorption from the alimentary tract of dogs and rats after
    single oral doses varying from 15 to 500 mg/kg body-weight was
    variable. Intravenous doses of 15 mg/kg body-weight in dogs
    disappeared from the plasma within 22 hours and less than 1% of the
    total dose was recovered in the urine. There is evidence that
    accumulation occurs in depot fat of dogs after the administration of
    50 mg/kg body-weight daily for 6 months. Only traces could be found in
    the fat depots and tissues or organs in dogs given doses of 15 and 5
    mg/kg body-weight per day for the same period (Dow, 1962).

         Female rats tended to accumulate chlorfenson in depot fat more
    than males after dose levels of 300 and 3000 ppm in the diet for 370
    days. Small quantities were also found in the liver and muscles. At
    the level of 100 ppm no traces could be found in tissues or organs of
    rats (Dow, 1962).

    Acute toxicity

                                             
    Animal    Route   LD50 mg/kg    References
                      body-weight
                                             

    Rat       Oral       2 000      Dow, 1951
                                    Dow, 1962
                                             

    Short-term studies

         Rat. Female rats (5 per group) were fed 300, 1000, 3000 and 
    10 000 ppm in the diet for 130 days. Those at 300 ppm showed no 
    evidence of adverse effects as judged by general appearance and 
    behaviour, mortality rate, growth, organ weights, and microscopic 
    examination of the tissues. The animals receiving 1000 and 3000 ppm 
    showed an increase in liver and kidney weights, and slight 
    histological degenerative changes in these organs. Those on the 
    highest dose level, 10 000 ppm, showed more pronounced effects (Dow,
    1962).

         Dog. Sixteen male and female dogs were divided into 4 groups
    and were given 5, 15 and 50 mg/kg body-weight per day for 6 months. At
    the lowest dose level, 5 mg, no effect was reported. At doses of 15
    and 50 mg/kg body-weight per day only a questionable increase in the
    average weights of the liver were found. No histological changes were
    noted in this organ (Dow, 1962).

    Long-term studies

         Rat. Groups of 80 rats (40 female and 40 male were maintained
    for one year on diets containing 100, 300 and 3000 ppm of chlorfenson.
    Growth retardation, increases in average liver and kidney weight and
    histological changes in these organs were found in the rats receiving
    300 and 3000 ppm. At 100 ppm only a slight increase in liver weight
    and histological changes in liver and kidneys were found (Dow, 1951).
    The slight changes in the liver were characterized by the presence of
    congestion and cloudy swelling, mainly in the portal areas which had
    the appearance of beginning portal cirrhosis without fibrosis. The
    kidneys showed some evidence of glomerular fibrosis with degeneration,
    vacuole formation, cloudy swelling of the tubular epithelium, and the
    presence of casts, oedema and congestion. Half the rats from this
    experiment were placed on the normal diet for 30 days. Gross
    examination at autopsy showed no abnormalities in the animals that had
    previously received 100 and 300 ppm of chlorfenson in the diet.
    Microscopic examination of the tissues of the rats that had received
    100 ppm showed slight pathological changes in the liver and kidney.
    The liver showed beginning portal cirrhosis and a few large fat
    vacuoles and areas of necrosis. The kidney showed glomerular and
    tubular fibrosis (Dow, 1962).

         Groups of 20 rats (10 females and 10 males) were given a diet
    containing 0.63, 1.25, 2.5, 5, 15 and 50 mg/kg body-weight per day for
    two years. Increases in the average weights of liver and kidney and
    histopathological changes in these organs were noted at doses of 2.5
    mg/kg and above. Microscopically there were fatty changes in the liver
    and chronic glomerulonephritis in the kidneys.

         In the groups of rats that had ingested doses of 1.25 and 0.63
    mg/kg per day, no significant effects were found as judged by general
    appearance and behaviour, growth, mortality rate, food consumption,


    average organ weights, and gross and microscopic examination of the
    tissues (Dow, 1962; Weil & McCollister, 1963).

    Comments on the experimental studies reports

         Adequate experimental data on the short-term and long-term
    toxicity in the rat and short-term toxicity in the dog have been
    presented. Almost all the information obtainable on long-term toxicity
    has been derived from one reliably conducted study with adequate
    numbers of animals. Biochemical data on the accumulation and excretion
    of chlorfenson have also been presented, but no information is
    available on its metabolism.

    EVALUATION

    Level causing no significant toxicological effect in the rat

         The maximum no-effect level in rats is 25 ppm equivalent to 1.25
    mg/kg body-weight per day.

    Estimate of acceptable daily intake for man

         0-0.01 mg/kg body-weight.

    Further work desirable

         Metabolic studies in animals. Short-and long-term studies in
    other species than the rat.

    REFERENCES

    Dow Chemical Company (1951) Midland Michigan, Technical Bulletin

    Dow Chemical Company (1962) Midland Michigan, Unpublished data

    Weil, C. S. & McCollister, D. D. (1963) Agric. Food Chem., 11, 486
    


    See Also:
       Toxicological Abbreviations