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    QUINTOZENE       JMPR 1973

    Explanation

         This soil fungicide was evaluated at the 1969 Joint Meeting
    (FAO/WHO, 1970). A temporary acceptable daily intake of 0-0.001 mg/kg
    bw was established with the requirement that the results If
    carcinogenicity studies on two species of animal should be made
    available by June 1973. Studies to explain the cause of growth
    depression and the effects on bone marrow and liver in dogs and
    studies on the metabolism of quintozene and on the activity of the
    metabolites, particularly pentachloroaniline were requested.

         It is noted that most recent studies on this fungicide have given
    emphasis not only to quintozene per se, but also to some related
    chemical substances and impurities, which may be present in the
    technical product, especially hexachlorobenzene.

         Further data made available are summarized in this monograph
    addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    Biochemical aspects

    Absorption, distribution and excretion

         Groups of three cows were administered quintozene orally at
    dosage levels equivalent to 0, 0.1, 1 and 10 ppm in the diet for 12-16
    weeks. One cow received 1000 ppm for one month. Milk, biopsy and
    autopsy samples of fat and autopsy samples of other tissues were
    analysed. The results of the analyses using a highly sensitive method
    demonstrated that tissue storage of quintozene and the principal
    metabolites did not occur, nor were they excreted in milk (Borzelleca
    et al., 1971).

         No quintozene, pentachloroaniline or methyl pentachlorophenol
    sulphide were detected in milk from a cow administered quintozene
    orally at a level equivalent to 5 ppm in the diet for three days.
    Forty-five per cent. of the administered dose was eliminated as
    pentachloroaniline within four days of the last dose (St. John et al.,
    1965).

         Quintozene was administered orally to mice as a solution in corn
    oil/acetone mixture. Only low serum quintozene levels (< 1 ppm) were
    found, the highest levels being found two to six hours after dosing.
    Analysis of tissues after single or multiple doses of quintozene
    showed that the highest concentrations occurred two to six hours after
    dosage but these fell rapidly. Pentachloroaniline was also found but
    the highest concentration of this occurred in bile; this possibly
    accounts for the high concentration of this metabolite in faeces.
    Methyl pentachlorophenol sulfide was also found in tissues and the

    high concentration in liver two hours after dosage suggests that
    quintozene is rapidly converted to this metabolite, which is then
    rapidly excreted. Quintozene and its metabolites did not build up in
    tissues on repeated dosage. No data were presented on the
    hexachlorobenzene content of tissues. In pregnant mice more methyl
    pentachlorophenol sulfide passed the placenta than the other compounds
    and high concentrations were found in the fetus and uterus (Courtney,
    1973).

    Biodegradation

         The major metabolite of quintozene in mice is pentachloroaniline.
    After repeated dosage the urinary content of this increases in male
    but not in female animals. Methyl pentachlorophenol sulfide is
    excreted mainly in the conjugated form (Courtney, 1973).

    TOXICOLOGICAL STUDIES

    Special studies on carcinogenicity

         A group of 10 male and 10 female mice was painted twice weekly
    for 12 weeks with an 0.3% solution of quintozene in acetone. A similar
    group of control animals was painted with acetone. All mice were then
    painted with croton oil for 20 weeks and surviving mice were killed
    after a further 20 weeks without treatment. Papillomata appeared in
    test animals after five to eight weeks treatment with croton oil and
    became more numerous until 5-10 weeks after cessation of treatment,
    after which some of them regressed. One test animal was found to have
    a single squamous cell carcinoma at the end of the experiment (Searle,
    1966).

    Special studies on teratogenicity

         An unstated number of C57 black/6 mice received up to 500
    mg/kg/day quintozene (containing 1% hexachlorobenzene) in 0.1 ml of
    oil on days 7-11 of gestation and were killed and examined on day 19.
    Fetal weight and mortality were unaffected but the incidence of eye
    abnormalities which normally affect 107 of young was increased. In
    addition there was a 49% increase in renal agenesis and cleft palates
    occurred in some litters from treated mothers. Dosage levels of 100
    and 200 mg/kg/day were without ill-effect.

         Quintozene in corn oil/acetone was administered to an unstated
    number of random bred CH1 mice from day 7-17 of gestation. Fetal
    mortality was unaffected at the 200 mg/kg dosage level but animals
    receiving 500 mg/kg produced young with a high incidence of cleft
    palate; kidney abnormalities were not found.

         An unstated dose of quintozene of 99% purity was administered
    orally each day to random bred CB rats from days 7-18 of gestation.
    Animals were killed on the nineteenth day. No effect on maternal
    weight, liver weight, weight of fetuses, fetal viability and
    morphological development was seen (Courtney, 1973).

         Groups of at least 20 pregnant Charles River rats were
    administered orally by gavage 8, 20, 50 or 125 mg/kg of quintozene
    dissolved in corn oil once daily on days 6-15 of gestation. Negative
    control groups received corn oil or were intubated without being
    administered vehicle and a positive control group received
    chlorcyclizine. No abnormalities were found which could be attributed
    to quintozene treatment in the numbers of corpora lutea,
    implantations, dead and resorbed fetuses, viable fetuses, fetal
    weights and sex or in skeletal or soft tissue malformations (Jordan
    and Borzelleca, 1973).

    Special studies on metabolites

         An unstated number of C57 black/6 mice received up to 500 mg
    pentachloroaniline/kg in 0.1 ml oil on days 7-18 of gestation and were
    killed and examined on day 19. Maternal weight was decreased and fetal
    mortality increased at the 100 mg/kg dosage level but not at higher
    levels.

         Pentachloroaniline in corn oil/acetone mixture was administered
    to an unstated number of random bred CHl mice from days 7-17 of
    gestation. Fetal mortality and development were unaffected at the 200
    mg/kg dosage level.

         An unstated dose of pentachloroaniline was administered orally to
    random bred CB rats from days 7-18 of gestation. Animals were killed
    on the nineteenth day. Maternal weight was depressed but all other
    indices were normal (Courtney, 1973).

    Acute toxicity

         No further data.

    Short-term studies

         No further data.

    Long-term studies

         No data are yet available.

    Comments

         Further studies have confirmed that quintozene is absorbed from
    the gastrointestinal tract and rapidly excreted, the main metabolites
    being pentachloroaniline and methyl pentachlorophenol sulfide. The
    latter was found at higher concentrations than other metabolites in
    the fetuses of mothers exposed to quintozene.

         Studies have shown that pentachloroaniline has no teratogenic
    activity. An increased number of eye abnormalities, cleft palates and
    renal agenesis was reported in one mouse strain and cleft palates in
    another strain in teratogenicity studies in which 300 mg/kg doses of
    quintozene were administered, Lower dosage levels produced no
    abnormalities in mice and no teratogenic abnormalities were found in
    studies on rats. The reason for this difference has not been
    established.

         No studies have been carried out to explain the effects reported
    to occur in dogs and no other studies on pentachloroaniline have been
    made available. It was noted that long-term feeding studies in rats
    and mice are in progress and that results may soon be available. The
    Meeting considered that a temporary acceptable daily intake could be
    set for a further two years.

    TOXICOLOGICAL EVALUATION

    Level causing no significant toxicological effect

         Rat: 25 ppm in diet equivalent to 1.25 mg/kg bw

    Estimate of temporary acceptable daily intake for man

         0-0.001 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    Purity of quintozene

         Detailed gas-chromatographic analyses of technical quintozene,
    including its chemically related impurities, have been established
    (Olin Mathieson Co., 1973). The ranges covered by 10 samples from five
    different manufacturers are given as follows:

         Quintozene (PCNE)                  : 88.4-98.6
         Tetrachloronitrobenzene (TCNB)     : 0.3-3.9
         Hexachlorobenzene (HCB)            : n.d.-10.8
         Pentachlorobenzene (PCB)           : n.d.-1.2
         Others, high boilers               : n.d.-0.6

    The high boiling fraction is identified, from one producer, as mainly
    consisting of tetrachlorodinitrobenzene, whereas attempts to detect
    any tetra- or octa-chlorodibenzo-p-dioxin have proved negative, within
    a detection limit of 0.05 ppm (Griffith and Thomas, 1972).

         From many additional samples analysed (CXPR, 1973) it is
    indicated that production procedures which favour a minimum content of
    MB, may give rise to increased amounts of pentachlorobenzene. Thus,
    three samples containing less than 0.1% HCE, contained up to 3.6%
    pentachlorobenzene.

    Use pattern

         While no significantly different use patterns have been
    described, some additional information on already established uses has
    been received.

    Residues resulting from supervised trials

         Kuchar et al. (1973) have supplied further data on residues found
    after field trials, setting out the analytical findings individually
    for quintozenep pentachlorobenzene and hexachlorobenzene (HCB), as
    well as for the metabolites pentachloroaniline (PCA) and methyl
    pentachlorophenyl sulfide (MPCPS). This information is summarized in
    Table 1 reporting the maximum residues only. The results indicate that
    total residues resulting from approved uses largely conform to the
    temporary residue limits recommended by the 1969 meeting, the
    exception being peanut kernels for which the composite residues
    following recommended use patterns suggest 2 ppm as a more realistic
    level.

         From information presented by the Netherland delegation to the
    sixth session of the Codex Committee on Pesticide Residues and later
    directly to the Joint Meeting, it has become evident that there exists
    an established and definite need for quintozene to control prevailing
    fungi complexes of Botrytis and Sclerotinia species which in some
    countries has justified a yearly preplanting soil treatment of 3 g
    a.i. per m2. Results from supervised trials (see Table 2) demonstrate
    that such registered use regularly gives residues in lettuce heads,
    which, however, only occasionally exceed 3 ppm.

         Results of analysis show that quintozene is not evenly
    distributed in the harvested crop. A three to four fold higher
    concentration is found in the outer leaves of individual heads than in
    the remaining inner parts. This leads to the conclusion that a major
    part of the residues results from vapour transfer from the soil under
    closed glasshouse conditions rather than by way of absorption through
    the roots.

    Fate of residues

    In plants

         The above residue data confirms a slight systemic uptake from
    soil into plants. Residues of impurities in the technical product
    (i.e. HCB and PCB) and the metabolites formed in soil and/or plants
    (i.e. PCA and MPCPS) usually comprise the greater part of total
    residues. A significant increase of PCB relative to HCB compared to
    the ratios in technical quintozene is noted simultaneously with the
    formation of PCA and MPCPS.


    
    TABLE 1. RESIDUES OF QUINTOZENE, METABOLITES AND IMPURITIES IN VARIOUS CROPS

                                                                                               

    Crop           Application     Quintozone      PCB          HCB          PCA           NPCPS
                   rate            
                                                                                                

    Beans, Lima      0.5-1.5 lb/     0.029         n.d.         n.d.         0.014         n.d.
                     acre

    Beans, Snap      2 lb/acre       n.d.          n.d.         n.d.         n.d.          n.d.

    Cabbage          15 lb/acre      0.004         n.d.         0.001        n.d.          0.015

    Peanuts          10 lb/acre      0.015-0.269   0.002-0.148  0.012-0.278  0.028-0.324   n.d.-0.42

    Peanut hulls     10 lb/acre      0.51-0.98     0.04-0.109   0.03-0.310   0.34-0.90     0.03-0.27

    Peas             1.5 lb/acre     0.007         n.d.         n.d.         n.d.          n.d.

    Potatoes         25 lb/acre      0.004         0.044        0.008        0.025         0.013

    Potatoes,        25 lb/acre      0.002         0.040        0.007        0.020         0.008
    peeled

    Potatoes,        25 lb/acre      0.026         0.080        0.018        0.066         0.057
    peel only

    Potatoes         50 lb/acre      0.024         0.059        0.014        0.031         0.033
                                                                                             

    TABLE 2. QUINTOZENE RESIDUES IN GLASSHOUSE LETTUCEa
             (Treatment: 3 g a.i./m2, before planting)

                                                                                          

                                                                              13
    Weeks after planting:              9            10.5          12          (Harvest)
                                                                                          

    Exp. 1
    Weight of lettuce head (g)         5.4-5.7      13.8-15.2     36.2-39.6   75.8-92.6

    Quintozen (ppm)                    2.3-2.7      1.7-2.2       1.7-3.5     2.0-2.7   

    Exp. 2

    Weight of lettuce head (g)         17.8-17.9    37.0-37.2     85.3-92.7   162.5-168.2

    Quintozene (ppm)                   2.2-2.7      2.5-3.2       1.0-2.9     1.2-2.2
                                                            
                                                                                          

    a Each figure represents average of four replicates.
      Data corrected for non-treated controls.

    

         A definite uptake of quintozene and derivatives by both potatoes
    and carrots grown in treated soils is demonstrated in the first year
    of a two-year study by Beck and Hansen (1973b), the results of which
    is summarized in Table 3. A second-year residual uptake is further
    evident in carrots (a total of 0.59 ppm), but not detectable in
    potatoes. The sum of impurities and metabolites constituted up towards
    507 of total residues in those studies with PCA and MPCPS as the major
    components.

        TABLE 3.  TWO-YEAR STUDY OF QUINTOZENE UPTAKE IN CARROTS AND POTATOES
              (from Beck & Hansen, 1973b)
                                                                                             
           Date of                                                    Residues in ppm
                                                                                             
    Treatment   Harvest            Quintozene   Tecnazene    PCB      HCB      PCA      MPCPS
                                                                                             

    Carrots (60 kg a.i./ha
     per treatment)

    May 1970    September 1970     1.00         n.d.         0.02     0.03     n.d.     n.d.

    May 1970    September 1971     0.45         0.02         0.09     0.03     0.06     0.04

    May 1970 +
    May 1971    September 1971     2.02         0.06         0.07     0.07     0.11     0.07
                                                                                             

    Potatoes (60 kg a.i./ha
     per treatment)

    May 1970    October 1970       0.20         0.01         0.02     0.03     0.03     0.04

    May 1970    September 1971     n.d.         n.d.         n.d.     n.d.     n.d.     n.d.

    May 1970 +
    May 1971    September 1971     0.20         0.01         0.03     0.04     0.05     0.05
                                                                                             
    
    In animals

         Results of experimental feeding of residual quintozene to rats,
    dogs and cows have been published (Borzelleca, 1971). No quintozene
    could be found in tissues in these studies; neither could quintozene
    be identified in milk from cows receiving 0.1-10 ppm in rations.
    Pentachloroaniline and methyl pentachlorophenyl sulfide were found in
    tissues as metabolites of quintozene. The studies confirmed an
    apparent lack of metabolism of hexachlorobenzene and
    pentachlorobenzene which were stored in tissues in concentrations

    reflecting the level of these impurities in the technical quintozene.
    Results from the feeding of cows at the 1 ppm and 10 ppm level are
    summarized in Table 4. Only HCB (and PCD at the 10 ppm level) residues
    was noticeable in the milk.

    In soil

         The apparent high persistence of quintozene in soils has been
    confirmed by Beck and Hansen (1973a) through laboratory experiments,
    supplemented by a soil sampling programme from potato fields which had
    been treated intermittently through the proceeding 5 to 11 years. An
    average half-life of 14 months was calculated from 22 field samples.

         Quintozene losses from three California soils (fine sandy loam,
    and clay soil and peaty mulch) are described by Wang and Broadbent
    (1972) as following first-order reactions with halflives from 4.7-9.6
    months. These authors further find evidence that volatilization is of
    major significance in accounting for the losses of the compound. The
    possibility of losses of quintozone to the atmosphere from soil under
    field conditions is also described by Caseley (1968).

         Degradation of quintozene in soils through microbial and/or
    chemical processes is further confirmed as important. Chako et al.
    (1966) found that eight soil fungi and eight actinomycetes, grown in
    nutrient media, degraded PCNB. Streptomyces aureofaciens reduced the
    largest quantity of PCNB, producing pentachloroaniline (PCA).
    Nakanishi and Oku (1969) and Kaufmann, (1970) also demonstrated in
    addition to PCA, methylthiopentachlorobenzene (MPCPS) as a microbially
    produced metabolite. In the laboratory experiments by Beck and Hansen
    (1973a) evidence was given that not only PCA and MPCPS, but also
    pentachlorobenzene (PCB) could be produced from quintozene in soils.

         From the above-mentioned soil sampling programme (Beck and Hansen
    (1973a)) average content of quintozene plus impurities and metabolites
    was found as shown in Table 5.  The highest individual level was a
    total of 28.8 ppm found in a field which had been treated three times
    within five years with 30-60 kg a.i./ha, the last time one year before
    sampling.

    TABLE 4.  RESIDUES IN COW TISSUES AND MILK AFTER FEEDING QUINTOZENEa
              AT THE RATE OF 1 ppm AND 10 ppm IN THE RATION
                                                                            
                      For 12 weeks                                   8 weeks
                                                                             
                      Fat (abdom.)   Sk. Muse.   Liver     Kidney    Milk
                                                                            

    PCNB    1 ppm     n.d.           n.d.        n.d.      n.d.      n.d.

            10 ppm    n.d.           n.d.        0.031     n.d.      n.d.


    TABLE 4. (cont'd)
                                                                            
                                   For 12 weeks                      8 weeks
                                                                             
                      Fat (abdom.)   Sk. Muse.   Liver     Kidney    Milk
                                                                            

    PCA     1 ppm     0.005          n.d.        n.d.      n.d.      n.d.

            10 ppm    0.499          0.018       n.d.      0.043     0.006

    MPCPS   1 ppm     0.017          n.d.        n.d.      n.d.      n.d.

            10 ppm    n.d.           n.d.        n.d.      0.020     n.d.

    PCB     1 ppm     n.d.           n.d.        n.d.      n.d.      n.d.

            10 ppm    0.001          n.d.        n.d.      n.d.      n.d.

    HCB     1 ppm     0.046          0.008       n.d.      0.001     0.003

            10 ppm    0.618          0.015       n.d.      0.005     0.015
                                                                            

    a Composition of technical Qintozene: PCNB: 97.8%, HCB: 1.8%,
      PCB: <0.1% and TCNB: 0.4%

    TABLE 5.  RESIDUES OF QUINTOZENE AND RELATED COMPOUNDS
              IN SOIL PROM 22 PREVIOUSLY TREATED FIELDS
                                                                            

                             Treated 1-5 times         Treated 1-4 times
                             until 3 years before      until 1 or 2 years
                             sampling                  before sampling
                             Average (range) -ppm      Average (range) - ppm
                                                                            

    Quintozene (PCNB)        5.44 ppm (0.01-12.8)      8,41 ppm (1.47-25.3)

    Tecnazene (TCNB)         0.09 ppm (n.d-0.18)       0.12 ppm (0.03-0.28)

    PCB                      0.37 ppm (0.003-0.84)     0.32 ppm (0.16-0.77)
    HCB                      0.35 ppm (n.d.-0.53)      0.41 ppm (0.17-0.94)
    PCA                      2.11 ppm (0.01-4.10)      1.28 pp. (0.28-3.31)
    MPCPS                    0.38 ppm (n.d.-1.07)      0.29 ppm (0.03-0.73)
                                                                            

    (From Beck and Hansen, 1973a)

    Residues in food commodities in commerce

         Quintozene analyses have been included in regular market sample
    programmes for pesticide residues in two Scandinavian countries
    (Voldum-Clausen, 1973; Westöö and Norén, 1973). In the one country
    during the years 1969 to 1972 quintozene was found in 48% of carrots,
    49% of potatoes and 43% of lettuce in a total of 454 samples. In the
    other country 34%, 46% and 14% of the samples of lettuce, parsley and
    carrots were found positive respectively.

         These programmes comprised food items of both domestic and
    foreign origin. In the case of the domestic products, quintozene
    residues in potatoes, parsley and lettuce are the result of
    intentional applications, whereas residues in carrots are presumed to
    be unintentional, resulting from uptakes from previously treated soils
    (Beck and Hansen, 1973a and 1973b).

         Quintozene residues in lettuce were similarly reported by the
    Netherland delegation to the sixth session of the Codex Comittee on
    Pesticide Residues, 1972. Surveys in that country had indicated that
    the frequency of positive samples was significantly higher during the
    season of glasshouse growing (61% positive from January to April) than
    during summer months (32.5% positive from May to June) (CCPR, 1972).

         Residue levels in these three surveys were generally below 3 ppm
    with the exception of only a few individual lettuce samples.

    Methods of residue analysis

         Gas-chromatographic methods which allow the determination of
    quintozene and its individual impurities and metabolites have been
    described by several authors (Kilgore and White, 1970; Collins et al.,
    1972; Beck and Hansen, 1973 and Kuchar et al., 1969). The method
    described by the latter authors determine PCNB, PCB, HCB and PCA in
    animal tissues, blood, bile and urine with a determination limit of
    0.005 ppm for each of the compounds and with average recoveries
    ranging from 84 to 1077. For MPCPS it was established that recoveries
    of 87-105% were obtained at the 0.1 ppm level. Their method uses
    extraction with acetonitrile and partitioning into hexane followed by
    GLC with electron capture detector.

         Baker and Flaherty (1972) have adapted an earlier multiresidue
    method for chlorinated pesticides (de Faubert Maunder et al. (1964))
    for the determination of quintozene in tomatoes, lettuces and bananas,
    as representative products on which quintozene may be used. It
    consists of extraction with hexane, partitioning with
    dimethylformamide and column chromatographic clean-up on alumina.
    Quantitative determination using electron capture gas-chromatography
    may be supplemented by a confirmatory chemical test for quintozene
    based on reduction to PCA, which is then determined by GLC. This

    method shows recoveries of 83-94% at the 0.005-0.1 ppm level in
    tomatoes, 75-103% for 0.01-5.0 ppm in bananas and 90-108% for 0.01-5.0
    ppm in lettuce.

    National tolerances

         Some national tolerances reported in 1969 (FAO/WHO, 1970) have
    been changed and new tolerances have been established. The following
    is a list of national tolerances available to the Meeting.

    Federal Republic    Lettuce                     0.3 ppm
    of Germany
                        Oil Seeds                   0.03 ppm

                        Cabbage                     0.02 ppm

                        Bananas, without peel)
                        Other vegetable foods)      0.01 ppm

    Netherlands and     Fruits and vegetables,
    Belgium             except potatoes             1.0 ppm

                        Leafy Vegetables            3.0 ppm

    United States of    Cotton-seed                 0.1 ppm as negl.
    America                                         residue

                        Others                      Originally on "no
                                                    residue basic".
                                                    At present under
                                                    review

    German Democratic   Potatoes                    5.0 ppm
    Republic
                        Potatoes, peeled            0.5 ppm

                        Cabbage                     0.3 ppm

    Switzerland         Lettuce, wheat              1.0 ppm

                        Cereal products,            0.1 ppm
                        flour, bakery
                        products, etc.

    Appraisal

         Since the evaluation of quintozene in 1969 further information
    has become available on several of the questions which were raised.

         More detailed information has been received on technical
    quintozene and its impurities. Depending on the production procedure
    varying amounts of impurities may be formed. Dominant are

    hexachlorobenzene (levels ranging from (< 0.1 to 10.8%),
    pentachlorobenzene (from (< 0.1 to 3.6%) and tetrachloronitrobenzenes
    (from 0.3 to 3.8%).

         Additional data on quintozene residues (including metabolites and
    impurities) derived from supervised trials indicate that residue
    levels largely conform to the temporary tolerance levels recommended
    by the 1969 Joint Meeting, the exception being peanut kernels on which
    the composite residues of parent compound, metabolites and impurities
    following recommended use patterns are such as to require a limit of 2
    ppm.

         Results of studies carried out on the use of quintozene for the
    control of fungal complexes of Botrytis and Selerotinia in lettuce
    grown in glasshouses were evaluated. A yearly proplanting soil
    treatment of 3 g a.i./m2 as registered in some countries was found in
    extensive supervised trials to give rise to residues which only
    occasionally exceed 3 ppm. This established use pattern is reflected
    in published data on residues found in lettuce moving in commerce
    indicating that up to 43% of samples of commercial lettuce may carry
    quintozene residues, the frequency being considerably higher in the
    winter season than during summer when lettuce is mainly grown in the
    open air.

         Market sample surveys in European countries further show that
    residues of quintozene (including impurities and metabolites) may be
    present in up to 50% of root vegetables (carrots and potatoes)
    examined. The residues in potatoes result from deliberate soil
    applications during the growth of the crop whereas residues in carrots
    originate from growing the crop in soils previously treated for
    another crop.

         Further studies of the persistence of quintozene in soils were
    presented to the Meeting. Half-life values of from 4.7 to 9.6 months
    were found in three Californian soils, whereas an average of 14 months
    was required to give 50% degradation under more temperate Scandinavian
    conditions.

         Results of experiments where quintozene was fed to rats, dogs and
    cows have been published. These studies confirmed an apparent lack of
    metabolism of hexachlorobenzene and pentachlorobenzene which were
    stored in tissues in concentrations reflecting the level of these
    impurities in the technical quintozene. Excretion with the milk was
    noticeable in the case of HCB.

         Analytical methods for the determination of quintozene and
    individual impurities and metabolites based on GLC-technique and
    suitable for regulatory purposes are now available.

    RECOMMENDATIONS FOR TOLERANCES, TEMPORARY TOLERANCES OR PRACTICAL
    RESIDUE LIMITS

         Recognizing that the major problem resulting from the use of
    quintozene is the presence of persistent and intractable residues of
    impurities, especially hexachlorobenzene, in the technical product it
    is recommended that every effort should be made to encourage
    manufacturers to reduce the amount of these impurities to the minimum.

         The temporary tolerances recommended in 1969 have been confirmed.
    New data justifies revision of the tolerances for lettuce and peanuts
    and the following recommendations are made.

    Tolerance

         Lettuce             3 ppm
         Peanuts (kernels)   2 ppm

         It should be noted that the limits for quintozene residues in all
    commodities include not only quintozene but the following impurities
    and metabolites:

         hexachlorobenzene;
         pentachloroaniline;
         methyl pentachlorophenylsulfide
         pentachlorobenzene.

    FURTHER WORK OR INFORMATION

    Required before 1975

    1. Carcinogenicity studies in two species of animal.

    2. Short-term studies to elucidate the difference in the teratogenic
    activity in rats and mice.

    3. Studies to explain the effects on the liver and bone marrow of
    dogs.

    4. Comparison in rats and mice of the absorption, distribution, and
    excretion of quintozene, its metabolites and any contaminants present
    in significant concentrations in the technical product.

    5. Further studies on the toxicity of metabolites.

    6. Studies to show the nature and levels of residues in meat, milk,
    and eggs following the feeding of quintozene residues in animal feeds.

    REFERENCES

    Baker, P.B. and Flaherty, B. (1972) Fungicide residues. Part I.
    The detection, identification and determination of residues of
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    Beck, J. and Hansen, K.E. (1973a) The degradation of quintozene,
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    Beck, J. and Hansen, K.E. (1973b) Uptake in carrots and potatoes of
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    Borzelleca, J.F., Larson, P.B., Crawford, E.M. Honnigar, G.R., Kuchar,
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    CCPR. (1973) Reply from Netherland delegation to question B(11),
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    Chako, C.I, Lockwood, J.L. and Zabik, M. (1966) Chlorinated
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    St. John, L.E., Ammering, J.W., Wagner, D.G., Warner, R.G. and Lisk,
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    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 4)
       Quintozene (WHO Pesticide Residues Series 5)
       Quintozene (Pesticide residues in food: 1977 evaluations)
       Quintozene (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)