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)