FAO/PL:1969/M/17/1 WHO/FOOD ADD./70.38 1969 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD THE MONOGRAPHS Issued jointly by FAO and WHO The content of this document is the result of the deliberations of the Joint Meeting of the FAO Working Party of Experts and the WHO Expert Group on Pesticide Residues, which met in Rome, 8 - 15 December 1969. FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS WORLD HEALTH ORGANIZATION Rome, 1970 QUINTOZENE IDENTITY Chemical name pentachloronitrobenzene Synonyms PCNB, Brassicol(R), Terrachlor(R), Tritistan(R), Folosan(R), Botrilex(R). Structural formulaOther relevant chemical properties Colourless crystalline needles practically insoluble in water, soluble in benzene and chloroform. Technical quintozene is usually 97-99 percent pure. The main impurity, is hexachlorobenzene (1.5%) together with lesser amounts of pentachlorobenzene and tetrachloronitrobenzene. Vp 11.3 × 10-5mm Hg at 25°C. Quintozene shows high stability in the soil. Quintozene is converted to pentachloroaniline (PCA) in moist soil, the metabolite having somewhat lower fungicidal activity. In animals the metabolites are pentachloroaniline and mercapturic acid (Betts et al., 1955). EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Fat samples from groups of ten rats (five males and five females) fed diets containing 63.5, 635, 1250, or 2500 ppm of technical quintozene for three months were examined for storage of quintozene. The apparent storage ranged from an average of 43 ppm in the fat for the 63.5 ppm diet to 1234 ppm for the 2500 ppm diet, there being a relatively linear relationship between the levels of fat storage to the concentration of quintozene in the diet. However, the neutron activation method of analysis which was used would have shown the presence of other chlorinated compounds as well an quintozene (Finnegan et al., 1958). Tissues from an unspecified number of dogs fed 5 or 1,080 ppm of technical quintozene in their diet for 2 years were analysed by gas chromatography for residues of quintozene and its metabolites. No quintozene was found in fat, muscle, kidney, or liver tissues but two metabolic products identified as pentachloroaniline and methyl-pentachlorophenyl sulfide were found in these tissues. Pentachloroaniline was found only in the fat and liver and in amounts of less than 1 ppm for both dose-levels. Methyl-pentachlorophenyl sulfide was found in the fat and liver of rats fed both dose levels and was present as well in kidney and muscle in the 1080 ppm group, the largest amount being 2.5 ppm in the fat of animals fed that level. In another study on fat from an unspecified number of rats fed 50 or 500 ppm of technical quintozene in their diet for seven months, there was less than 1 ppm of either of the metabolites in the fat of the rats fed 50 ppm of quintozene, and approximately 1 ppm of pentachloroaniline and 5 ppm of methyl-pentachlorophenyl sulfide for the 500 ppm group (Kuchar et al., 1969). Pentachloroaniline and another metabolite, a mercapturic acid, have been isolated in urine from rabbits treated with quintozene. With a 2 g. dose an average of 62 percent of quintozene was unabsorbed and excreted in the faeces. The average percentages excreted in urine as pentachloroaniline and N-acetyl-S-pentachlorophenyl-L-cycteine were 12 and 14 percent respectively (Betts et al., 1955). TOXICOLOGICAL STUDIES Special studies on reproduction A three-generation reproduction study was conducted with rats receiving technical quintozene in their diet in concentrations of 0, 5, 50 and 500 ppm. Groups of 20 females were used and 2 litters were produced in each generation. No significant differences were found between the control- and quintozene-treated rats with respect to fertility, gestation, viability or lactation indices, or in weaning-weights. Histopathologic examination of the tissues of 10 pups of each sex from the F2b generation showed no effect from the treatment (Borzelloca and Larson, 1968b). Special studies on carcinogenicity Groups of 18 mice of each sex from two hybrid strains of mice were given quintozene (the specifications not given) from 7 days of age for 18 months. The dose of 464 mg/kg was given to the mice by stomach tube from the seventh day of age to the time weaning at four weeks of age and thereafter the chemical was added to the diet in a corresponding amount of 1,206 ppm. This level was a maximum tolerated dose for the mice. There was a significantly elevated incidence of tumours, mostly hepatomas, in both strains of mice (Innes. et al., 1969). Acute toxicity LD50 Animal Route mg/kg body-weight References Rat (M) oral 1710* Finnegan, et al., 1958 (oil solution) Rat (F) oral 1650* Finnegan, et al., 1958 (oil solution) Rat oral >30,000 Wit, et al., 1957 (aqueous suspension) Rat i.p. 5,000 Wit et al., 1957 (aqueous suspension) * technical grade; defined as: pentachloronitrobenzene ... 98.2 percent hexachlorobenzene ... 1.4 percent traces of tetrachloro- nitrobenzene and pentachlorobenzene Short-term studies Dog Groups, each of three mongrel dogs, of unspecified sex were placed on diets containing 25, 200 or 1,000 ppm of technical quintozene for one year. No adverse effect was noted on body-weight or survival. No haematologic changes were seen. Histopathologic changes were confined to liver-cell enlargement with pale-staining cytoplasm at all dose-levels, but there was no increasing severity of the lesions with increasing exposure to quintozene (Finnegan et al., 1958). Groups of four dogs of each sex were placed on diets containing 0, 5, 30, 180, or 1,080 ppm of technical quintozene for two years. No adverse effect was noted on body-weight or survival. Increased liver-weights, elevated serum-alkaline phosphatase and a moderate degree of cholestatic hepatosis with secondary bile nephrosis occurred in the dogs on the 1,080 ppm level. A minimum degree of cholestatic hepatosis with secondary bile necrosis occurred at 180 ppm. No effect was noted in the dogs fed 5 and 30 ppm of quintozene (Borzelloca and Larson, 1968a). Groups of six dogs, each comprising three male and three female animals, were fed diets containing 0, 500, 1,000 or 5,000 ppm of quintozene (the specification not given) for two years. Liver changes occurred in all groups with the degree of damage related to the dose. The 5,000 ppm level produced severe liver damage including fibrosis, narrowing of hepatic cell cords, increased size of the periportal areas and thick leucocyte infiltration. At the 1,000 and 500 ppm dose-levels the changes were similar to those at the 5,000 ppm level but to a lesser degree. The highest dose-level produced atrophy of bone-marrow and reduced haematopoiesis (Hoechst, 1968). Rat Groups of 35 rats of each sex were fed diets containing 0, 63.5, 635, 1,250, 2,500 or 5,000 ppm of technical quintozene for three months. Growth and survival were adversely affected in both sexes at the dose-level of 5,000 ppm and in males growth was suppressed at 2,500 ppm. Liver to body-weight ratios were elevated at all dietary levels except in the females fed 63.5 ppm. No haematologic changes were seen, and histopathologic changes were limited to fine vacuolization of liver-cell cytoplasm at 5000 ppm (Finnegan et al., 1958). An unspecified number of young rats were fed diets containing 0 or 2,000 ppm of quintozene for 10 weeks. No gross effects, other than a decreased growth rate in the males, were noted (Wit, et al., 1957). Groups of 20 rats each comprising 10 male and 10 female animals were fed diets containing 0, 1,000, 5,000 or 10,000 ppm of quintozene (the specification not given) for 90 days. The animals grew slightly less than controls at the 5,000 ppm dose-level and markedly less at the 10,000 ppm level (Hoechst, 1964). Long-term studies Rat Groups of 10 rats of each sex were fed dicta containing 0, 25, 100, 300, 1,000 or 2,500 ppm of technical quintozene for two years. Growth suppression occurred in the females at dose-levels of 100 ppm and above; however, in the males growth depression occurred only at 2,500 ppm level. Haematologic and histopathologic observations in the test animals were similar to the control group (Finnegan, et al., 1958). OBSERVATIONS IN MAN Quintozene (75 percent wettable powder) did not cause primary irritation when applied to the skin of 50 human subjects; in 13 of them sensitization was produced (Finnegan et al., 1958). COMMENT The acute and short-term studies and the reproduction studies in rats are considered adequate. A preliminary report of studies in mice indicates a potential for carcinogenicity in animals given a high dose and further work is needed in other species. In the two-year study in dogs severe morphologic changes were observed in the liver and bone-marrow in the high dose-level groups. Furthermore, the apparent erratic effect on growth an indicated in the studies with rats is not explained. Additional studies should be done to delineate the exact cause of these effects. Insufficient information in available on the biological fate of the compound. For these reasons only a temporary acceptable daily intake is established based on the two-year study in the rats. TOXICOLOGICAL EVALUATION Level causing no significant toxicological effect Rat: 25 ppm in the diet, equivalent to 1.25 mg/kg body-weight/day ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN 0-0.001 mg/kg body-weight RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Pre-harvest treatments Quintozene is a fungicide mainly used for soil treatment or for treatment of seeds and transplants but some crop applications are recommended. The following table gives a review of application rates of quintozene and recommended pre-harvest intervals. TABLE I Pre-harvest Crop Rate Limitations interval days Bananas 1.63% paste Apply to stems only - not to fruit Beans 5.0 kg/ha Apply to foliage 21 0.5 g/kg seed Seed treatment 70 50g/100m of row Spray base of plants 21 40g/100m of row Soil treatment only 70 Cruciferous vegetables 60 kg/ha Pre-planting 70 470g/100m row Row application prior to transplanting 70 Corn 0.5g/kg seed Seed treatment 70 Garlic 150g/100m row Soil treatment at planting 90 Lettuce (head) 150g/100m row When plants 5-7.5 cm tall 30 30g/100m row 2 treatments at 10 day intervals 20 Onions 40 kg/ha Pre-planting TABLE I (cont'd) Pre-harvest Crop Rate Limitations interval days Peanuts 250g/100m row Pre-planting 90 200g/100m row At pegging time 60 Peas 1g/kg Seed treatment Peppers 70g/100m row At planting time 70 Potatoes 22 kg/ha Prior to planting 70 140g/100m row At planting time 70 Safflower, Sorghum, Soybeans, Sugarbeet 1.5 g/kg Seed treatment only 70 Tomatoes 160g/100m row Prior to transplanting 70 Wheat 0.5g/kg seed Seed treatment 150 Post-harvest treatments No post-harvest treatments with quintozene are known. Other uses Quintozene is used for control of fungi in alfalfa, clover, cotton, ornamentals, bulbs, lawns, mushrooms and coffee crops. RESIDUES RESULTING FROM SUPERVISED TRIALS Detailed residue data are available from United States trials with quintozene on important crops and have been deposited with FAO. Rates of application are similar to those given below. The typical data presented below are representative: TABLE II Post- Number treatment Residues (ppm) Rate of interval Crop kg/ha treatments days Range Average Beans 1 1 60 0.003-0.004 0.003 10 1 60 0.005-0.006 0.005 Beans 1 1 60 <0.01 <0.01 Beans 1.5 1 60 <0.01 <0.01 Beans (small white dry) 1 1 150 <0.01 <0.01 Beans (string) 0.5 1 70 <0.01 <0.01 Beans (navy) 8 4 120 0.003-0.152 0.07 Beans (Lima) 1.5 1 90 <0.01 Broccoli 20 1 0.003-0.018 0.012 40 1 140 0.002-0.021 0.013 Cabbage 20 1 140 0.000-0.014 0.007 40 1 140 0.000-0.020 0.007 Cottonseed 0.3 1 70 0.000-0.017 <0.017 Cottonseed 5.0 1 150 <0.012 <0.012 Cottonseed 2.5 1 150 <0.012 <0.012 5.0 1 180 0.004-0.032 0.014 Lettuce heads 100 1 180 0.00 -0.01 0.00 Lettuce outer leaves 100 1 180 0.02 -0.11 0.06 Lettuce heads 2 8 0.00 0.00 2 16 0.00 0.00 Lettuce 18G 1 60 0.03 -0.05 0.03 (Greenhouse) 18WP 1 60 0.20 -0.30 0.26 18WP 1 70 0.09 -0.139 0.104 18G 1 70 0.048-0.093 0.058 TABLE II Post- Number treatment Residues (ppm) Rate of interval Crop kg/ha treatments days Range Average Mushrooms 1.5 1 1 9.57 -9.68 9.6 1.5 1 3 2.75 -2.97 2.8 1.5 1 7 1.30 -1.36 1.34 Peanuts,kernels 10 1 130 0.063-0.154 0.104 kernels 100 1 130 0.208-0.212 0.210 Peanut shells 100 1 130 4.60 -5.21 4.96 Peppers 50 1 75 0.0 -0.008 0.002 50 2 35 0.0 -0.009 0.003 Potatoes 10 1 130 0.01 -0.066 0.027 10 1 130 0.066-0.125 0.088 10 1 130 0.00 -0.002 0.001 20 1 130 0.001-0.005 0.002 Tomatoes 3 2 50 0.00 -0.08 0.02 10 1 70 0.00 -0.01 0.01 50 1 100 0.00 -0.02 0.01 FATE OF RESIDUES In animals No data was available to show the residues in animal tissues or animal products from the feeding of forage grown in soil treated with quintozene. In view of the stability of the compound, its solubility in lipids and its resistance to metabolism it seems highly likely that significant residues of quintozene or pentachlor - derivatives do occur in animal fats, milk and eggs. Quintozene was reported in trace amounts in dairy produce and in oils, fats and shortening in the U.S. total diet studies. A paper by Kuchar et al. (1969) not available for consideration at the time the original data was reviewed reports analytical studies of metabolism of quintozene in beagle dogs, rats and plants. Tissues from beagle dogs fed food containing 1,080 ppm quintozene in their rations for 2 years were examined by GLC methods. Pentachloroaniline (PCA) was identified in blood. Fat, liver, urine and faeces yielded pentachloronitrobenzene (quintozene); pentachlorobenzene (PCB); hexachlorobenzene (HCB) and pentachloroaniline (PCA) and methyl pentachlorophenyl sulphide. Quintozene was not detected in muscle, kidney, fat or liver of dogs receiving 1,080 ppm in their diet over 2 years (234 gms quintozene in all). HCB was the most prominent residue yielding 194 ppm in fatty tissue. PCB occurred in a significant amounts only in fat (5.15 ppm) and PCA only in faeces. A small amount of the quintozene fed is excreted in the faeces (14 ppm). No metabolites, only HCB, were found in tissues of rats fed quintozene for 7 months at 500 ppm. In plants There is evidence of a slight systemic uptake by plants revealed by analysis by spectrophotometric methods following application of quintozene to soil. The following table gives typical examples from the extensive data available (Olin Mathieson, 1969). TABLE III Residues Seeds or Applied Soil Roots Leaves fruit Crop kg/acre ppm ppm ppm ppm Beans 1 1.2 0.59 0.034 0.003 1.5 0.68 1.12 0.017 0.013 1.5 0.59 2.27 N.D. 0.004 Snap beans 1.0 9.2 9.0 0.004 - 1.5 3.4 7.0 0.09 - String beans 0.75 - 0.94 0.288 - 1.0 - 3.62 0.221 - 1.5 - 2.37 0.461 - Field beans 1.5 7.77 19.33 0.12 - Lettuce 4.0 - - 0.0 - (field) 15.0 - - 0.02 - 50.0 - - 0.00 - 100.0 - - 0.00 - 100 - - 0.06 outer - leaves TABLE III Residues Seeds or Applied Soil Roots Leaves fruit Crop kg/acre ppm ppm ppm ppm Lettuce 18 dust - - 0.05 - (greenhouse) 0.4 Spray - - 0.03 - 18 Granule - - 0.02 - Cabbage 2.0 - - 0.007 - 2.0 - - 0.008 - Tomatoes 6.0 - - - 0.02 50.0 - - - 0.01 Potatoes 10.0 - - - 0.03 10.0 - - - 0.008 Alfalfa 10 - - 0.02 - 20 - - 0.05 - Peanut 10 - - 0.235 - 1.0 - 0.44 0.003 - Gorbach and Wagner (1967) showed, by using highly sensitive GLC techniques capable of detecting both quintozene and PCA that potatoes growing in soil treated with quintozene at rates from 25 to 800 kg/ha showed significant residues of quintozene in the skin (up to 3 ppm at 800 kg/ha) but only insignificant traces of PCA (up to 0.4 ppm) in the skin. The flesh of these potatoes contained no detectable residues of quintozene (less than 0.01 ppm) and less than 0.1 ppm of PCA and unidentified metabolites. Gorbach (1969) reports that the most recent studies reveal no evidence of translocation from soil into green parts of leafy plants. A carefully controlled experiment, where all possible contamination by splash or vapour was eliminated, revealed no uptake by parsley growing in quintozene treated soil. Kuchar et al. (1969) reports that the metabolic pathway in plants appears to be the same mechanism as in animals. Studies using cotton seed planted in soil containing 300 ppm quintozene yielded the following residues in the young cotton plants two weeks later: (1) pentachloranitrobenzene (quintozene) 155 ppm; (2) pentachlorobenzene 4 ppm; (3) methyl pentachlorophenyl sulphide 3 ppm; (4) hexachlorobenzene 5 ppm; (5) pentachloroaniline 1.1 ppm; and (6) 2, 3, 4, 5 - tetrachloronitrobenzene 0.018 ppm. Residues (2), (4) and (6) may have originated partly from impurities in the technical grade quintozene (97.8% PCNB; 1.8% HCB; 0.1% PCB and 0.4% TCNB). These authors were able to show that the two unidentified materials reported by Gorbach and Wagner (1967) were in fact hexachlorobenzene (HCB) and the metabolite methyl pentachlorphenyl sulphide. In soils Quintozene appears to persist for long periods in the soil as disease control may be as long an 12 months (Hertzfield, 1967). Ko and Farley (1969) show that in moist soil quintozene is gradually converted to pentachloroaniline (PCA) and the conversion was greatly enhanced by submergence of the soil in water. PCA was stable in both moist and submerged soil and was inhibitory to micro-organisms but to a lesser extent than quintozene. The long term action of quintozene is partly due to its conversion to PCA. Quintozene remains unchanged in sterilized, moist soil but disappears from submerged sterilized soil with a half life of three weeks. No PCA was detected in sterilized submerged soil. Studies by Ko and Farley (1969) showed that soil micro-organisms are responsible for the conversion of quintozene to PCA. Evidence of residues in food in commerce or at consumption The only data available on quintozene residues in food moving in commerce was gathered in the U.S.A. The U.S.D.A./H.E.W. 1968 reports that of 9,789 samples of leaf and stem vegetables produced in the U.S.A. and examined for a wide range of pesticides, 89 samples (0.89%) contained quintozene at levels ranging from trace quantities to greater than 2.0 ppm. The following shows the range: ppm % Trace - 0.03 0.42 0.04 - 0.5 0.19 0.51 - 1.0 0.1 1.01 - 2.0 0.04 Above - 2.0 0.14 0.89% Quintozene was reported to occur in trace amounts in the fat of dairy produce and at a level of 0.021 ppm in a composite sample of oils, fats and shortening in the total diet studies conducted in the U.S.A. in 1963-68 (Duggan 1968, Corneliussen 1969). The total intake in the diet was calculated to be no more than trace amounts (less than 0.001 mg). METHODS OF RESIDUE ANALYSIS A review of analytical methods is given in the book by Zweig (1964). Klein and Gajan (1961) have carefully compared a colorimetric, a polarographic and a gas chromatographic - colometric method for residue analysis on lettuce, cabbage and beans. The colorimetric method of Ackermann et al. (1958) is reported to be the most accurate in the range below 5 ppm with a recovery of 94%. The latter method was improved by Ackermann et al. (1963). This method is however the slowest of the three methods and does not differentiate quintozene from tetrachlorobenzene. The polarographic method (Bache and Lisk, 1960; Klein and Gajan, 1961 and Gorbach, 1961) is the most rapid because of less stringent cleanup requirements. Gorbach (1961) used a sublimation step in the cleanup before the polarographic determination and thus eliminated many of the interfering substances. With the polarographic method, recoveries averaged 81%. with a standard deviation of 12%. The gas chromatographic-colometric method (Klein and Gajan, 1961) yielded average recoveries of 90% with average deviation of 15%. For proper identification, extracts should be checked for quintozene by paper chromatography (Mitchell, 1957, 1958) or by thin layer chromatography (Gorbach, 1967). In the latter paper, methods are given to separate and identify the metabolite pentachloroaniline. All three methods can be recommended and can be selected according to equipment available. (a) The colorimetric method (Ackermann et al., 1963). The quintozene residue in fat-free extract is hydrolized to nitrite with alcoholic potassium hydroxide, the nitrite is used to diazotize procaine hydrochloride and the diazonium salt coupled with l-naphthylamine to give a magenta solution having absorption maximum at 525 mu. (b) Polarographic method (Bache and Lisk, 1960; Klein and Gajan, 1961; Gorbach, 1961). The crop material is extracted with hexane. The extract is filtered and dried and a part of the co-extractives are removed by freezing and adsorption on Attaclay. Chromatography of the concentrated extract using Florisil removes the remainder of the interfering substances. The solvent is then evaporated and the residue dissolved in isopropyl alcohol. After adding sodium acetate and acetic acid for supporting electrolyte and deoxygenating the solution, the polarogram in recorded from 0.00 to 1.15 volts against saturated calomel electrode. The half-wave potential for quintozene in -0.47 volts. The later papers recommend a number of modifications to the polarographic procedure. (c) Gas Chromatographic - Microcolometric Method (Klein and Gajan, 1961; Gorbach, 1961). The extraction is carried out as described for the polarographic method. The concentrated extract is evaporated to dryness and the residue dissolved in hexane is injected into the instrument. The multi-detection procedure for determining chlorinated residues in non-fatty foods based on JAOAC, 49 222 (1966) paragraph 24.213 which in official for a number of pesticides is satisfactory for the determination of quintozene residues. A method using electron capture gas chromatography (Methratta T.P. et al., 1967) suitable for determining quintozene residues in plants, seeds and soil has a sensitivity of 0.01 ppm and is relatively free of interference from plant extracts. The method is probably suitable for development towards greater sensitivity. NATIONAL TOLERANCES Country Crop Tolerance (ppm) Germany (Fed.Rep.) Cabbage, lettuce 1.0 onions, cucumber 1.0 horse radish 1.0 leaf vegetables 3.0 bananas (peeled) 0.1 Netherlands Fruit and vegetables 5.0 United States of America Bananas, beans, broccoli, Originally on "no brussels sprouts, cabbage, residue basis". At cauliflower, cotton, present under review. garlic, lettuce, peanuts, peas, peppers, potatoes, tomatoes, wheat. APPRAISAL Quintozene or pentachloronitrobenzene (PCNB) is a versatile fungicide used chiefly against soil fungi in agriculture and horticulture. It was first developed in 1930 as a seed dressing for wheat. It is used in many countries as a soil fungicide against Sclerotinia, Rhizoctonia, Botrytis, Sclerotium, Fusrium and similar fungi of vegetable and forage crops. Application by means of wettable powder, emulsion concentrate or dust ranges from 10 to 55 kg/ha or 15 to 600g per 100m of row. Seed dressings applied in the form of dust range from 30g to 300 g per 100 kg of seed. Treatments other than those applied to the soil are usually aimed at the base of the plant but some foliage applications are made, particularly to lettuce, beans and mushrooms. Pre-harvest intervals are four to eight weeks. The data available to the meeting were obtained solely in the United States of America and did not include information about residues following use elsewhere. Some information is available about residues in foods in commerce. Quintozene has high stability in soil and under neutral conditions remains stable for exceptionally long periods. The literature includes a number of methods of residue analysis based on electron-capture gas chromatography and spectrophotometric methods. The sensitivity of the methods is reported to be 0.01 ppm but the spectrophotometric method does not determine the metabolite pentachloroaniline (PCA). Quintozene and PCA may be determined by multi residue methods for chlorinated compounds but no regulatory methods have been evaluated, and there is reason to believe that the recovery from many food commodities may be low unless special provision is made for extraction and cleanup. Further work on the development of an acceptable regulatory method is required. RECOMMENDATIONS FOR TOLERANCES, TEMPORARY TOLERANCES OR PRACTICAL RESIDUE LIMITS TEMPORARY TOLERANCES (effective to 1973) Residues of the metabolite pentachloroaniline to be included. Bananas (pulp) 0.01 ppm (whole) 1.0 Beans 0.01 Beans (navy) 0.2 Broccoli 0.02 Cabbage 0.02 Cottonseed 0.03 Lettuce 0.3 (cont'd) Mushrooms 10.0 Peanuts (kernels) 0.3 (whole) 5.0 Peppers 0.01 Potatoes 0.2 Tomatoes 0.1 FURTHER WORK OR INFORMATION REQUIRED (before June 1973) 1. Carcinogenicity studies in two species of animals. 2. Studies to explain the cause of growth depression in rats and the effect on liver and bone-marrow in dogs. 3. Further studies on the metabolism and on the metabolites, particularly pentachloroaniline. 4. Data from countries other than the United States of America on the required rates and frequencies of application, pre-harvest intervals and the resulting residues. 5. Information on residues in edible animal tissues and in animal products resulting from the feeding of plant products (including forage) treated with quintozene in accordance with normal agricultural practice. 6. Information on the frequency and level of quintozene residues in food commodities in commerce. 7. Information on the level of metabolites, particularly pentachloroaniline in plants and animals. DESIRABLE 1. Development of analytical methods for greater sensitivity and evaluation for regulatory purposes. 2. Information on the residue levels in root crops, especially carrots, grown in soil treated previously with quintozene in crop rotation. REFERENCES Ackermann, H.J. et al. (1958) Spectrophotometric determination of pentachloronitrobenzene on food and forage Crops. J. Agric. and Food Chem. 6:747-50 (Oct.) Ackermann, H.J. et al. (1963) Modifications to the spectrophotometric analysis of PCNB in Soil and Crops. J. Agric. and Food Chem. 11(4) 297 (July/Aug. 1963) Bache, C.A. and Lisk, D.I. (1960) Journal of Agriculture and Food Chemistry 8, 459 Betts, J.J., James, Sybil P. and Thorpe, W.V. (1955) The metabolism of pentachloronitrobenzene and tetrachloronitrobenzene and the formation of mercapturic acid in the rabbit Biochem. J. 61 (4) 611-7 Borzelloca, J.F. and Larson, P.S. (1968a) Toxicologic study on the effect of adding Terrachlor to the diet of beagle dogs for a period of two years. Unpub. Rept. from the Medical College of Virginia submitted by Olin Mathieson Chemical Corporation Borzelloca, J.F. and Larson, P.S. (1968b) Three generation reproduction study on rats receiving Terrachlor in their diet. Unpub. Rept. from the Medical College of Virginia submitted by Olin Mathieson Chemical Corporation Corneliussen, P.E. (1969) Residues in food and feed - pesticide residues in total diet samples (IV). Pesticides Monitoring Journal 2 (4) 140-52 Duggan, R.E. (1968) Residues in food and feed 1963-67. Pesticides Monitoring Journal 2 (1) 2-46 Gorbach, S. (1961) Acta Chemica (Academiae Scientarum Hungaricae) 28 (1-3), 199-206 Gorbach, S. and Wagner, U. (1967) Pentachloronitrobenzene residues in potatoes. J. Agric. and Food Chem. 15 (4) 654 Gorbach, S. (1969) Personal Communication to FAO Hertzfield, E.G. (1967) Terrachlor - a new Soil Fungicide Agricultural Chemicals 12 30-3 Hoechst. (1964) Toxikologische Prüfung von Pentachlornitrobenzol. 3. Auf chronische Toxizität (90-Tage-Test) an Ratten. Unpub. Rept. prepared and submitted by Farbwerke Hoechst, AG. Hoechst. (1968) Chronische orale Toxizatätsprüfung von Pentachlornitrobenzol. 2-Jahres-Versuch an Hunden. Unpub. Rept. prepared and submitted by Farbwerke Hoechst AG. Finnegan, J.K., Larson, P.S., Smith, R.B. Jr., Haag, H.B. and Hennigar, G.R. (1958) Acute and chronic toxicity studies on pentachloronitrobenzene. Arch. int. Pharmacodyn. 114:38-52 Innes, J.R.M., Ulland, B.M., Valerio, M.G., Petrucelli, L., Fishbein, L., Hart, E.R., Pallota, A.J., Bates, R.R., Falk, H.L., Gart, J.J., Klein, M., Mitchell, I. and Peters, J. (1969) Bioassay of pesticides and industrial chemicals for tumorigenicity in mice. A preliminary note. J. nat. Cancer Inst. 42:1101-14 Klein, A.K. and Gajan, R.J. (1961) Methods for the determination of PCNB Residues. JAOAC 44:712 Ko, W.H. and Farley, J.D. (1969) Conversion of pentachloronitrobenzene to pentachloroaniline in soil and the effect of these compounds on soil Micro-organisms. Phytopathology 59 (1) 64-7 Kuchar, E.J., Geenty, Frances, O, Griffith, William P. and Thomas, Raymond J. (1969) Analytical studies of metabolism of Terraclor in beagle dogs, rats and plants, J. Agric. and Food Chem. 17 (6) 1237-40 Methratta, T.P., Montagna, R.W. and Griffith, W.P. (1967) Determination of PCNB in crops and soil by electron-capture gas chromatography. J. Agric. and Food Chem. 15 (4) 648 (July/Aug. 1967) Mitchell, L.C. (1957) J. Assoc. Offic. Agric. Chemists 40, 294 Mitchell, L.C. (1958) J. Assoc. Offic. Agric, Chemists 41, 781 Olin Mathieson Chemical Corporation. (1969) Research reports on quintozene United States of America. (1969) Department of Agriculture Summary of Registered Agricultural Pesticide Chemical Uses United States of America. (1968) Department of Health, Education and Welfare FDA Pesticide Analytical Manual Volume 1 Section 212.1 Wit, S.L., van Esch, G.J. and van Genderen, H. (1957) Toxicity of some chloronitrobenzen compounds (trichlorodinitrobenzene, trichloronitrobenzene, tetrachloronitrobenzene and pentachloronitrobenzene) to laboratory rats and residues found in crops treated with these fungicides. Proceedings of the Fourth International Congress of Crop Protection, Hamburg, September 1957. Vol. 2 (Braunschweig 1960): pp. 1665-8 Zweig, Gunter. (1964) Analytical Methods for Pesticides and Plant Growth Regulators and Food Additives Vol. III Academic Press. New York
See Also: Toxicological Abbreviations Quintozene (EHC 41, 1984) Quintozene (HSG 23, 1989) Quintozene (ICSC) Quintozene (WHO Pesticide Residues Series 3) 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)