- Email: [email protected]
2838. Mutagenic action of ethylene thiourea in bacteria
398
Processing and packaging contaminants
chlorinated hydrocarbon insecticides have tended to concentrate on the possible carcinogenicity of such compounds (Cited in F.C.7: 1974,12, 764)rather than on their possibleeffectson reproductiveperformance and the health of successive generations. The first papercited above describesa four-generation experiment.Rats were fed from weaning‘on a nutritionally adequatediet, 200/,of which (38% on a caloriebasis)consistedof cottonseedoil, lard, soyabeanoil or hydrogenatedvegetable-oilshortening,or heated samplesof one of the first two, and which contained in each case a mixture of DDT, DDE, DDD, BHC, lindane, dieldrin, heptachlor epoxide, methoxychlor and Perthane. Control groups were given the various dietary fats without addedinsecticide. Adults of the Fe, Fi and F2 generationswere killed after the weaningof the secondlitter and F3 rats 12 wk after weaning,and tissueswere taken for analysis.Representativeweanlingsfrom each group were also killed for tissueanalysis. In the control groups,the highestconcentrations of DDT, DDE and DDD were found in the body fat of adult rats (at levelsof 037, 0.48and 0.30 ppm, respectively),and other tissuesgenerally contained lessthan @10ppm of residues.Rats fed the insecticide mixture in unheatedor heated fats showed higher body-fat concentrationsof DDT, DDE and DDD in the F, than in the Fe generation,but in general generationdifferencesweresmalland showedno continuing increasewith succeedinggenerations.Increasedlevelsof DDT, DDE, DDD and dieldrin (but not BHC and lindane)were stored in the livers and carcasses of weanlingsin the insecticide-fedgroups and therewassomeincreasein the levelsof the DDTtype compoundsand dieldrin in the adult livers, but again there was no evidenceof persistentenhancement through successivegenerations. Detectable levelsof methoxychlor and Perthanewerenot found in these tissues,but measurablelevels of lindane, BHC and heptachlorepoxideswerefound in the body fat of sometreated rats. The tissueconcentrations of the compoundsappearedto be little affected by the type of fat used as the vehicle, except in the caseof dieldrin, highertissueconcentrationsof which occurredin the F, generationwith the cottonseed-ol diet than with the other fats. The secondpapercited concernsthe administration of 15 ppm p,p’-DDT in the diet to Japanesequail (Coturnix coturnix) over three generations.The first, F,,. generationwas fed the test or control diet from the ageof 60 days,from which time they were allowed to lay eggsfor a SO-dayperiod, those laid between days 37 and 50 being incubatedand hatched.The resultingFi generationwasfed the parental diet from birth, matedat day 60 and allowed to produce eggs for 110days, the Fz generationbeing hatched from
eggslaid near the end of this period. Between the first and third generations,eggproduction diminished slightly, fertility and percentagefertility declinedsubstantially, and the production of abnormal(shell-less and thin-shelled)eggs and eggs with an enhanced DDT content increased.By the Fz generation,abnormal eggsconstituted 23.3%of the total egg production. There was a build-up of both p,p’-DDT and DDD over successivequail-chick generations,the residuelevelsin the Fz-generationeggsbeing significantly higher than thosefrom the Fe generation. Thesetwo paperssuggestthe possibility of a successivebuild-up of insecticideresiduesin someanimal speciesthough not in others, differencesprobably beingdeterminedby metabolicconsiderations. 2838.Mutagenic action of ethylene thiourea in bacteria Seiler,J. P. (1974).Ethylenethiourea(ETU), a carcinogenicand mutagenicmetaboliteof ethylenebis-dithiocarbamate.Mutation Res. 26, 189. Ethylenebis(dithiocarbamate) fungicidesgive rise to ethylenethiourea(ETU) asa metabolitein mammals (Lyman, in Pesticide Terminal Residues, edited by A. S. Tahori, Butterworths, London, 1971)and as a decompositionproduct of certain cooking procedures (Cited in F.C.T. 1974,12, 779).ETU has beenshown to produce hepatomasin mice and thyroid hyperplasiaand thyroid cancer in rats, and to be teratogeniein rats (ibid 1973,11, 702; ibid 1974,12, 282). Evidenceof its mutagenicityis thereforenot particularly surprising. Seiler(cited above)hascomparedthe mutagenicity of ETU with that of relatedureaand thiourea derivatives in the ‘hisG-46’ strain of Salmonellatyphimurium grown in agar-tryptone culture. Aminopurine, used asa positivecontrol, hada relative mutagenicactivity of > 30(the incidenceof spontaneous reversionsbeing representedas 1.0).Comparedwith this, the indices for comparableconcentrationsof ETU (25), N-ethylthiourea (2.0), thiourea (1.0) propyleneurea(l.O), Nethylurea(1.0)and ethyleneurea(@9)showETU, with a fairly weak-but significant-level of mutagenic activity, clearly in the lead in relation to the other compoundstested. Investigationof the dose-response relationshipfor ETU indicated that whereasETU in concentrations of lO&lOOOppm exhibited significantmutagenicactivity in S. typhimurium, higherconcentrations(suchas 25,000ppm) killed otherwise viable bateria and so maskedany mutageniceffect. The overt mutagenic effect of 10,000ppm ETU was still significant but wasweakerthan that of 1000ppm, the relative mutagenic activity being only 1.6 insteadof 2.5.
PROCESSING AND PACKAGING CONTAMINANTS 2839.The biochemicaleffectsof phthalateesters
Influenceof dietary fat and di-2-ethylhexyl phthalate on tissuelipids in rats. J. Nutr. 104, 187. Daniel, J. W. & Bratt, H. (1974).The absorption, Much interest has centred recently on phthalate metabolismand tissuedistribution of di(2ethylhexyl) esters,particularly those usedwidely as plasticizers, phthalate in rats. Toxicology 2, 51. and this has beenreflectedin the numberof papers Stein,M. S., C’aasi,Priscilla I. & Nair, P. P. (1974). concerned with their toxicity and environmental
Processing and packaging contaminants
chlorinated hydrocarbon insecticides have tended to concentrate on the possible carcinogenicity of such compounds (Cited in F.C.7: 1974,12, 764)rather than on their possibleeffectson reproductiveperformance and the health of successive generations. The first papercited above describesa four-generation experiment.Rats were fed from weaning‘on a nutritionally adequatediet, 200/,of which (38% on a caloriebasis)consistedof cottonseedoil, lard, soyabeanoil or hydrogenatedvegetable-oilshortening,or heated samplesof one of the first two, and which contained in each case a mixture of DDT, DDE, DDD, BHC, lindane, dieldrin, heptachlor epoxide, methoxychlor and Perthane. Control groups were given the various dietary fats without addedinsecticide. Adults of the Fe, Fi and F2 generationswere killed after the weaningof the secondlitter and F3 rats 12 wk after weaning,and tissueswere taken for analysis.Representativeweanlingsfrom each group were also killed for tissueanalysis. In the control groups,the highestconcentrations of DDT, DDE and DDD were found in the body fat of adult rats (at levelsof 037, 0.48and 0.30 ppm, respectively),and other tissuesgenerally contained lessthan @10ppm of residues.Rats fed the insecticide mixture in unheatedor heated fats showed higher body-fat concentrationsof DDT, DDE and DDD in the F, than in the Fe generation,but in general generationdifferencesweresmalland showedno continuing increasewith succeedinggenerations.Increasedlevelsof DDT, DDE, DDD and dieldrin (but not BHC and lindane)were stored in the livers and carcasses of weanlingsin the insecticide-fedgroups and therewassomeincreasein the levelsof the DDTtype compoundsand dieldrin in the adult livers, but again there was no evidenceof persistentenhancement through successivegenerations. Detectable levelsof methoxychlor and Perthanewerenot found in these tissues,but measurablelevels of lindane, BHC and heptachlorepoxideswerefound in the body fat of sometreated rats. The tissueconcentrations of the compoundsappearedto be little affected by the type of fat used as the vehicle, except in the caseof dieldrin, highertissueconcentrationsof which occurredin the F, generationwith the cottonseed-ol diet than with the other fats. The secondpapercited concernsthe administration of 15 ppm p,p’-DDT in the diet to Japanesequail (Coturnix coturnix) over three generations.The first, F,,. generationwas fed the test or control diet from the ageof 60 days,from which time they were allowed to lay eggsfor a SO-dayperiod, those laid between days 37 and 50 being incubatedand hatched.The resultingFi generationwasfed the parental diet from birth, matedat day 60 and allowed to produce eggs for 110days, the Fz generationbeing hatched from
eggslaid near the end of this period. Between the first and third generations,eggproduction diminished slightly, fertility and percentagefertility declinedsubstantially, and the production of abnormal(shell-less and thin-shelled)eggs and eggs with an enhanced DDT content increased.By the Fz generation,abnormal eggsconstituted 23.3%of the total egg production. There was a build-up of both p,p’-DDT and DDD over successivequail-chick generations,the residuelevelsin the Fz-generationeggsbeing significantly higher than thosefrom the Fe generation. Thesetwo paperssuggestthe possibility of a successivebuild-up of insecticideresiduesin someanimal speciesthough not in others, differencesprobably beingdeterminedby metabolicconsiderations. 2838.Mutagenic action of ethylene thiourea in bacteria Seiler,J. P. (1974).Ethylenethiourea(ETU), a carcinogenicand mutagenicmetaboliteof ethylenebis-dithiocarbamate.Mutation Res. 26, 189. Ethylenebis(dithiocarbamate) fungicidesgive rise to ethylenethiourea(ETU) asa metabolitein mammals (Lyman, in Pesticide Terminal Residues, edited by A. S. Tahori, Butterworths, London, 1971)and as a decompositionproduct of certain cooking procedures (Cited in F.C.T. 1974,12, 779).ETU has beenshown to produce hepatomasin mice and thyroid hyperplasiaand thyroid cancer in rats, and to be teratogeniein rats (ibid 1973,11, 702; ibid 1974,12, 282). Evidenceof its mutagenicityis thereforenot particularly surprising. Seiler(cited above)hascomparedthe mutagenicity of ETU with that of relatedureaand thiourea derivatives in the ‘hisG-46’ strain of Salmonellatyphimurium grown in agar-tryptone culture. Aminopurine, used asa positivecontrol, hada relative mutagenicactivity of > 30(the incidenceof spontaneous reversionsbeing representedas 1.0).Comparedwith this, the indices for comparableconcentrationsof ETU (25), N-ethylthiourea (2.0), thiourea (1.0) propyleneurea(l.O), Nethylurea(1.0)and ethyleneurea(@9)showETU, with a fairly weak-but significant-level of mutagenic activity, clearly in the lead in relation to the other compoundstested. Investigationof the dose-response relationshipfor ETU indicated that whereasETU in concentrations of lO&lOOOppm exhibited significantmutagenicactivity in S. typhimurium, higherconcentrations(suchas 25,000ppm) killed otherwise viable bateria and so maskedany mutageniceffect. The overt mutagenic effect of 10,000ppm ETU was still significant but wasweakerthan that of 1000ppm, the relative mutagenic activity being only 1.6 insteadof 2.5.
PROCESSING AND PACKAGING CONTAMINANTS 2839.The biochemicaleffectsof phthalateesters
Influenceof dietary fat and di-2-ethylhexyl phthalate on tissuelipids in rats. J. Nutr. 104, 187. Daniel, J. W. & Bratt, H. (1974).The absorption, Much interest has centred recently on phthalate metabolismand tissuedistribution of di(2ethylhexyl) esters,particularly those usedwidely as plasticizers, phthalate in rats. Toxicology 2, 51. and this has beenreflectedin the numberof papers Stein,M. S., C’aasi,Priscilla I. & Nair, P. P. (1974). concerned with their toxicity and environmental