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Mutagenicity study of 2 combinations in rats
230 place in vivo, (d) the endpoints have a place in the conventional toxicological evaluation of compounds for effects on male fertility. Sperm assays are a means of identifying agents that alter sperm production in men and assessing the extent of induced damage. The reproductive implications are relatively well established but the genetic consequences are not yet defined.
124 T6th, K., J. Sugfir, Zs. Somfai and L. Hegedtis, National Oncology Institute, Research Institute for Oncopathology, Budapest (Hungary)
Comparative mutagenicity study on dibromoduicitol (DBD), an aikylating anticancer drug and its 3 metabolites and cyclophosphamide by the Salmonella/microsome assay DBD and one of its most important metabolites, dianhydrogalactitol (DAG) with similar cytostatic effect, were tested on strains TA1535, 1537, 1538, 98 and 100, using the plate-incorporation method. Both compounds proved to be mutagenic on strains TA1535 and TA100 without and with $9 mix and non-mutagenic in the other strains. The other metabolites, i.e. 1-bromo-3,6-anhydrodulcitol (BAD) and 1,2-epoxi-3,6anhydrodulcitol (EAD) were also strongly mutagenic on strains TA 1535 and TA100. Conclusions drawn from dose-response curves are: (1) mutagenic potency of DBD is very similar to that of the well known cyclophosphamide, (2) DBD is more mutagenic and less toxic than DAD though they have almost identical antitumour activity, (3) BAD and EAD are the strongest mutagenic compounds despite having no anticancer effect. No close correlation or parallelism could be detected between the mutagenic potency and chemotherapeutic effects of the 4 hexitol derivatives. Mutagenic metabolites of DBD are excreted with urine and not through the bile.
125 Vachkova-Petrova, R., Institute of Gastroenterology and Nutrition, Sofia (Bulgaria)
Mutagenicity study of 2 combinations in rats 2 combinations were studied with the method of cytogenetic analysis of rat bone marrow: the dithiocarbamate fungicide basfungin (metiram) with sodium nitrite, and the organophosphorous fungicide pyrazophos with the organochlorine insecticide lindane. The rats were exposed orally to equitoxic doses administered simultaneously in subacute (5 days) experiments. 5-6 animals per group and concurrent controls were used, all animals being killed 6 h after the last administration. 100 cells in metaphase were scored from each animal and examined for aneuploidy and aberrations. In the study of the combined effect of basfungin/sodium nitrite at a dose of 1/10 LDs0 the significant increases of cells with aberrations were of the same order
231 in the group with basfungin and in the group with a combination of 2 compounds. A somewhat lower but still significant increase of cells with chromatid breaks was established in the nitrite group. In the study of the combination of pyrazophos/lindane at a dose of 1/10 LDs0 significant increases of cells with aberration were observed in the group with lindane and in the combined group, this finding being more pronounced in the latter.
126 Noordsij, A., M.A. Van der Gaag and C.L.M. Poels, Testing and Research Institute of the Netherlands Waterworks, P.O. Box 70, 2280 AB Rijswijk (The Netherlands) Integrated toxicological and analytical chemical method for the determination of water quality
The assessment of water quality criteria can be improved if a direct relation can be established between toxicological and analytical-chemical measurements. This implies the use of a single isolation and sample preparation procedure which is suited for both toxicological and analytical-chemical techniques. For this purpose a specially adapted XAD adsorption procedure has been developed. Organic pollutants from 30 to 3001 of water can be adsorbed on 30-300 ml of XAD-4 in 3 sequential steps at a neutral, an acidic and a basic pH level in 17h. After elution with ethanol and cyclohexane, the remaining water and cyclohexane are removed through azeotropic destillation, leaving a sample in ethanol. This sample can be analysed by GC-MS, HPLC and group parameter (organic C1, N, P and S) determinations as well as in the Ames test or other toxicological tests. Using this concentration technique, mutagenic substances have been demonstrated in the lipophilic (neutral) and more hydrophilic (acid) fraction of Rhine water in the Ames test. A larger amount of organic material is isolated in the acid isolation step than in the preceding neutral step. However, ca. 90% of the isolated material cannot be analysed by GC-MS.
127 Van der Gaag, M.A., A. Noordsij and C.L.M. Poels, Testing and Research Institute of the Netherlands Waterworks, P.O. Box 70, 2280 AB Rijswijk (The Netherlands) Mutagenicity of Rhine water in The Netherlands and influence of several watertreatment processes on the mutagenic effect
After isolation of organic material by adsorption on the macroreticular resin XAD-4 sequentially at pH 7 and pH 2, both neutral and acid XAD fractions of Rhine water induced mutations in the Salmonella strain TA98, without metabolic activation. More promutagens have been detected in the neutral fraction than in the acid fraction. A large fluctuation of the mutagenic effect of Rhine water in TA98
124 T6th, K., J. Sugfir, Zs. Somfai and L. Hegedtis, National Oncology Institute, Research Institute for Oncopathology, Budapest (Hungary)
Comparative mutagenicity study on dibromoduicitol (DBD), an aikylating anticancer drug and its 3 metabolites and cyclophosphamide by the Salmonella/microsome assay DBD and one of its most important metabolites, dianhydrogalactitol (DAG) with similar cytostatic effect, were tested on strains TA1535, 1537, 1538, 98 and 100, using the plate-incorporation method. Both compounds proved to be mutagenic on strains TA1535 and TA100 without and with $9 mix and non-mutagenic in the other strains. The other metabolites, i.e. 1-bromo-3,6-anhydrodulcitol (BAD) and 1,2-epoxi-3,6anhydrodulcitol (EAD) were also strongly mutagenic on strains TA 1535 and TA100. Conclusions drawn from dose-response curves are: (1) mutagenic potency of DBD is very similar to that of the well known cyclophosphamide, (2) DBD is more mutagenic and less toxic than DAD though they have almost identical antitumour activity, (3) BAD and EAD are the strongest mutagenic compounds despite having no anticancer effect. No close correlation or parallelism could be detected between the mutagenic potency and chemotherapeutic effects of the 4 hexitol derivatives. Mutagenic metabolites of DBD are excreted with urine and not through the bile.
125 Vachkova-Petrova, R., Institute of Gastroenterology and Nutrition, Sofia (Bulgaria)
Mutagenicity study of 2 combinations in rats 2 combinations were studied with the method of cytogenetic analysis of rat bone marrow: the dithiocarbamate fungicide basfungin (metiram) with sodium nitrite, and the organophosphorous fungicide pyrazophos with the organochlorine insecticide lindane. The rats were exposed orally to equitoxic doses administered simultaneously in subacute (5 days) experiments. 5-6 animals per group and concurrent controls were used, all animals being killed 6 h after the last administration. 100 cells in metaphase were scored from each animal and examined for aneuploidy and aberrations. In the study of the combined effect of basfungin/sodium nitrite at a dose of 1/10 LDs0 the significant increases of cells with aberrations were of the same order
231 in the group with basfungin and in the group with a combination of 2 compounds. A somewhat lower but still significant increase of cells with chromatid breaks was established in the nitrite group. In the study of the combination of pyrazophos/lindane at a dose of 1/10 LDs0 significant increases of cells with aberration were observed in the group with lindane and in the combined group, this finding being more pronounced in the latter.
126 Noordsij, A., M.A. Van der Gaag and C.L.M. Poels, Testing and Research Institute of the Netherlands Waterworks, P.O. Box 70, 2280 AB Rijswijk (The Netherlands) Integrated toxicological and analytical chemical method for the determination of water quality
The assessment of water quality criteria can be improved if a direct relation can be established between toxicological and analytical-chemical measurements. This implies the use of a single isolation and sample preparation procedure which is suited for both toxicological and analytical-chemical techniques. For this purpose a specially adapted XAD adsorption procedure has been developed. Organic pollutants from 30 to 3001 of water can be adsorbed on 30-300 ml of XAD-4 in 3 sequential steps at a neutral, an acidic and a basic pH level in 17h. After elution with ethanol and cyclohexane, the remaining water and cyclohexane are removed through azeotropic destillation, leaving a sample in ethanol. This sample can be analysed by GC-MS, HPLC and group parameter (organic C1, N, P and S) determinations as well as in the Ames test or other toxicological tests. Using this concentration technique, mutagenic substances have been demonstrated in the lipophilic (neutral) and more hydrophilic (acid) fraction of Rhine water in the Ames test. A larger amount of organic material is isolated in the acid isolation step than in the preceding neutral step. However, ca. 90% of the isolated material cannot be analysed by GC-MS.
127 Van der Gaag, M.A., A. Noordsij and C.L.M. Poels, Testing and Research Institute of the Netherlands Waterworks, P.O. Box 70, 2280 AB Rijswijk (The Netherlands) Mutagenicity of Rhine water in The Netherlands and influence of several watertreatment processes on the mutagenic effect
After isolation of organic material by adsorption on the macroreticular resin XAD-4 sequentially at pH 7 and pH 2, both neutral and acid XAD fractions of Rhine water induced mutations in the Salmonella strain TA98, without metabolic activation. More promutagens have been detected in the neutral fraction than in the acid fraction. A large fluctuation of the mutagenic effect of Rhine water in TA98