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    QUINTOZENE       JMPR 1977

    Explanation

    Quintozene was last evaluated in 1975 (FAO/WHO 1976). An ADI of 0.007
    mg/kg b.w. was established. Further research to elucidate the
    formation of subcutaneous fibrosarcomas in female mice was recorded as
    desirable. Since then Information on carcinogenicity and mutagenicity
    studies has become available and is discussed below.

    Questions raised at the ninth (1977) Session of the Codex Committee on
    Pesticide Residues are also considered.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    TOXICOLOGICAL STUDIES

    Special studies on mutagenicity

    Quintozene was studied in a dominant lethal test with mice. When given
    for 7 weeks in the diet (no concentrations mentioned) quintozene did
    not induce dominant lethal effects (Jorgenson et al., 1976)~

    The mutagenicity of quintozene was studied in a test system consisting
    of several bacterial strains, activated with a system using the liver
    of rats which had been treated with Arochlor 1254. No effect was found
    with quitozene (Simmon et al., 1976).

    Special studies on carcinogenicity

    Fifty male and 50 female mice were fed two increasing dose-levels of
    quintozene (> 98%, with 0.15% pentachlorobenzene, 0.25%
    2,3,4,5-tetrachloronitrobenzene and 1% or hexachlorobenzene, HCB) in
    the diet, starting with 1075 and 2150 ppm for male and 2320 and
    4640 ppm for female animals. During the last 315 days of the exposure
    period of 546 days (78 weeks) these dose levels were 3000 and 6000 ppm
    for males and 4500 and 9000 ppm for females. The control group,
    consisting of 20 male and 20 female mice was given only the vehicle
    (2% of corn oil). The total duration of the study was 92 weeks, but
    some mice were killed and autopsied earlier.

    In control male mice a frequency of 50% malignant tumours, in 25% of
    the number of the animals was found. For the low quintozene dose group
    these figures were 33% (in 29%) and for the high dose group 29% (in
    20). In the female mice 20% (in 10%), 18% (in 6%) and 57% (in 19%)
    were found for control, low and high dose groups respectively. Only in
    the females of the high dose group was the frequency in the.number of
    malignancies statistically higher then could be expected. However, in
    this case many malignant histiocytic lymphomas were found in numerous
    organs of the same animal. When considering the numbers of animals
    with tumours no statistical differences were found between the groups.
    No particular type of tumour could be ascribed to the administration
    of quintozene (Wedig et al., 1976). Fifty male and fifty female rats

    were fed two dose levels of quintozene (> 98% with 0.15%
    pentachlorobenzene, 0.25% 2,3,4,5-tetrachloronitrobenzene and 1% HCB)
    in the diet. During the first 98 days the males were fed 7,500 or
    15,000 ppm the females 11,000 or 22,000 ppm. These levels were reduced
    later: during the last 448 days they were 5,000 or 10,000 ppm for the
    male and 7,250 or 14,500 for the female rats. The control group,
    consisting of 20 male and 20 female animals was only given the vehicle
    (2% of corn oil). Total exposure time was 546 days (78 weeks) and
    total duration of the study 85-117 weeks.

    In control male rats a frequency of 16% malignant tumours in 10% of
    the number of the animals was found. For the low quintozene dose group
    this was 13% (in 8.5%) and for the high dose group 23% (in 12.5%). In
    the female rats 10% (in 10%), 8% (in 6%) and 9% (in 6.5%) were found
    for control, low and high dose groups respectively. No statistical
    difference between the groups was found for total number of tumours or
    number of animals with tumours. No particular type of tumour could be
    ascribed to the administration of quintozene (Wedig at al., 1976).

    COMMENTS

    In two mutagenicity studies, one with bacteria and one with mice, no
    indication of a mutagenic action of quintozene was obtained. At the
    1975 Meeting it was found desirable that further work on the influence
    of quintozene on the formation of subcutaneous fibrosarcomas in female
    mice should be made available. In two carcinogenicity studies with
    very high dose levels of quintozene no increased numbers of tumours
    was found in the treated groups. There is no indication, therefore,
    that administration of quintozene resulted in carcinogenic activity.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

    Rat: 25 mg/kg in the diet, equivalent to 1.25 mg/kg bw
    Dog: 30 mg/kg in the diet, equivalent to 0.175 mg/kg bw

    ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR HUMANS

    0-0.007 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    The Meeting discussed questions raised at the 9th Session of the Codex
    Committee on Pesticide Residues (1977) relating to the composition of
    quintozene residues, and decided that the compounds included in the
    MRLs for quintozenc should be quintozene, pentachloroaniline and
    methyl pentachlorophanyl sulphide. HOB and pentachlorobenzene should
    be dealt with separately as extraneous residue limits.

    REFERENCES

    Jorgensen, T.A., Rushbrook, C.J. and Newell, G.W. (1976) In vivo
    mutagenesis investigations of ten commercial pesticides,
    Toxicol. Appl. Pharmacol., 37, abstract no. 41.

    Simmon V F, Poole, D.C. and Newelly G.W. (1976), In vitro mutagenic
    studies of twenty pesticides. Toxicel. Appl. Pharmacol., 37,
    abstract no. 42.

    Wedig, J.H., Sperling, P. and Miller, R. (1976) Olin Corporation,
    unpublished report of an analysis of data submitted by the National
    Cancer Institute.

    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
       Quintozene (EHC 41, 1984)
       Quintozene (HSG 23, 1989)
       Quintozene (ICSC)
       Quintozene (FAO/PL:1969/M/17/1)
       Quintozene (WHO Pesticide Residues Series 3)
       Quintozene (WHO Pesticide Residues Series 4)
       Quintozene (WHO Pesticide Residues Series 5)
       Quintozene (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)