Table 4.5 Genetic and related effects of DDT in non-human mammals in vitro
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1 Table 4.5 Genetic and related effects of DDT in non-human mammals in vitro Species Tissue, cell line End-point Test Results Dose out Rat Primary hepatocytes DNA Alkaline elution NT 106 μg/ml DDT Sina et al. Rat Primary hepatocytes DNA UDS assay NT 35 μg/ml DDT Probst et al. Rat Primary hepatocytes DNA UDS assay NT 35 μg/ml DDT Maslansky & Williams Mouse Primary hepatocytes DNA UDS assay NT 35 μg/ml DDT Maslansky & Williams Mouse, Balb/c Primary hepatocytes DNA UDS assay NT 35 μg/ml p,p -DDT Klaunig et al. (1984) Chinese hamster Primary hepatocytes DNA UDS assay NT 35 μg/ml DDT Maslansky & Williams Chinese hamster V79 cells DNA Alkaline elution 354 μg/ml DDT Swenberg et al. Chinese hamster V79 cells DNA Alkaline elution 1060 μg/ml DDT Swenberg Rat Liver epithelial cells ARL/HGPRT assay NT NR DDT Telang et al. Rat, Fisher Primary hepatocytes Host-mediated assay (in vitro) NT 10 4 M DDT Tong et al. Mouse Balb/c 3T3 fibroblasts Cell transformation assay μg/ml DDT Fitzgerald et al. (1989) Mouse Embryo cells Cell transformation assay NT 15 μg/ml p,p -DDT Langenbach & Gingell (1975) Chinese hamster V79 cells Hprt mutation assay NT 14.2 μg/ml p,p -DDT Tsushimoto et al. Chinese hamster V79 cells Hprt mutation assay NT 35 μg/ml p,p -DDT Kelly-Garvert & Legator (1973)
2 Table 4.5 Genetic and related effects of DDT in non-human mammals in vitro Species Tissue, cell line End-point Test Results Dose out Chinese hamster V79 cells 6-thioguanine (6-TO) resistance assay Rat, kangaroo Potorous tridactylis aplicalis Aneuploid established cell line Chinese hamster V79 cells Chinese hamster B14 F28 cells Rabbit, New Zealand White Artic beluga whale Delphinapterus leucas Lymphocytes Skin fibroblasts Diphtheria toxin (DT) resistance assay NT 14.2 μg/ml p,p -DDT Tsushimoto et al. NT 14.2 μg/ml p,p -DDT aberrations + NT 10 μg/ml p,p -DDT Palmer et al. (1972) + NT 10 μg/ml o,p -DDT aberrations NT 45 μg/ml p,p -DDT Kelly-Garvert & Legator (1973) aberrations + NT 49 μg/ml 4h p,p -DDT Mahr & Miltenburger aberrations NT 100 μg/ml p, p -DDT Hart et al. (1972) Micronucleus formation + 10 μg/ml p, p -DDT Gauthier et al. (1999) +, positive;, negative; DDT, dichlorodiphenyltrichloroethane; HIC, highest ineffective concentration; LEC, lowest effective concentration, NT, not tested; UDS, unscheduled DNA synthesis
3 Table 4.6 Genetic and related effects of metabolites of DDT in non-human mammalian cells in vitro Species Tissue, cell line End-point Test Results Concentration out Rat Rat Rat Mouse Primary hepatocytes Primary hepatocytes Primary hepatocytes Primary hepatocytes DNA Alkaline elution + NT 95 μg/ml p,p -DDE Sina et al. DNA UDS assay NT 31 μg/ml DDE Maslansky & Williams DNA UDS assay NT 2000 μg/ml p,p -DDE Williams et al. (1982) DNA UDS assay NT 31 μg/ml DDE Maslansky & Williams Mouse Embryo cells Cell transformation assay Mouse Mouse Mouse Chinese hamster L5178Y mouse lymphoma cells L5178Y mouse lymphoma cells L5178Y mouse lymphoma cells Wild-type V79 cells (6TG s ) and a 6TG-resistant clone, T2 14 cells (6TG r ) NT 15 μg/ml p,p -DDE Langenbach & Gingell (1975) TK mutation assay μg/ml p,p -DDE Clive et al. (1979) TK mutation assay + NT 25 μg/ml p,p -DDE McGregor et al. (1988) Hprt mutation assay + NT 16 μg/ml p,p -DDE Amacher & Zelljadt (1984) Inhibition of cooperation assay + NT 10 μg/ml DDE Kurata et al. (1982) + NT 2.5 μg/ml TDE
4 Table 4.6 Genetic and related effects of metabolites of DDT in non-human mammalian cells in vitro Species Tissue, cell line End-point Test Results Concentration out Chinese hamster Rat, kangaroo Potorous tridactylis aplicalis Chinese hamster Chinese hamster V79 cells Hprt mutation assay + NT 25 μg/ml p,p -DDE Kelly-Garvert & Legator (1973) Aneuploid established cell line V79 cells CHO cells aberrations aberrations aberrations Sister-chromatid exchanges + NT 10 μg/ml p,p - DDE Palmer et al. (1972) + NT 10 μg/ml o,p -DDE + NT 10 μg/ml p,p -DDD + NT 10 μg/ml o,p -DDD NT 100 μg/ml p,p - DDA + NT 35 μg/ml p,p -DDE Kelly-Garvert & Legator (1973) 60 μg/ml DDE Galloway et al. (+) 5 μg/ml DDE Chinese B14 F28 cells + NT 44 μg/ml 4 h p,p -DDE Mahr & hamster aberrations Miltenburger + NT 41 μg/ml 4 h p,p -DDA NT 75 μg/ml 4 h p,p -DDD +, positive;, negative; DDA, 2,2-bis(4-chlorophenyl)-acetic acid; DDD, dichlorodiphenyldichloroethane; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; HIC, highest ineffective concentration; LEC, lowest effective concentration, NT, not tested; TDE, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane; UDS, unscheduled DNA synthesis
5 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out Invertebrates Insects Zebra mussel, Dreissena polymorpha Shrimp, Litopenaeus stylirostris Shrimp, Litopenaeus stylirostris Drosophila melanogaster y/r(1)2,vf/b 5 Yy +, male, germ-line cells Drosophila melanogaster y/r(1)2,vf/b 5 Yy +, male, germ-line cells Drosophila melanogaster, male, somatic cells Drosophila melanogaster Canton-S, male, germ-line cells Drosophila melanogaster, male, germ-line cells Drosophila melanogaster, male, germ-line cells, germline cells Micronucleus formation + NA 0.1 μg/l for 168 h p,p -DDT Binelli et al. (2008b) DNA DNA adducts + NA Sublethal concentration NR DNA DNA strand breaks + NA Sublethal concentration NR aberrations aberrations + NA 1 μg, in feeding media NA 25 ppm, in feeding media Exposed to DDT for 4 days; DDT replaced daily and dead larvae removed Exposed to DDT for 4 days; DDT replaced daily and dead larvae removed Formulation (p,p -DDT, 80%; o,p -DDT, 18%; p,p -DDE, 2%) Formulated product of DDT not specified Galindo Reyes et al. (2002) Galindo Reyes et al. (2002) Clark (1974) Woodruff et al. Accord insertion + NA NT DDT Catania et al. (2004) Dominant lethal + NA 1 μg, in feeding media Sex linked recessive lethal Sex linked recessive lethal ± NA 0.14 mm,, in feeding media NA 20 μg, in feeding media Formulation (p,p -DDT, 80%; o,p -DDT, 18%; p,p -DDE, 2%) Clark (1974) DDT Vogel (1972) p,p -DDT Pielou (1952)
6 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out Lower eukaryote (yeast, mould, fungi) Drosophila melanogaster Canton-S, male, germ-line cells Sex linked recessive lethal Saccharomyces cerevisiae Mitotic gene conversion Saccharomyces cerevisiae D61.M Saccharomyces cerevisiae D61.M Aspergillus nidulans haploid strain 35 Aspergillus nidulans diploid strain P1 Neurospora crassa heterokaryon 12 Neurospora crassa heterokaryon 12 Tetrahymena thermophila Cu428 Colony formation assay loss assay NA 20 μg/week, in feeding media up to 8 mo Formulation (p,p -DDT, 80%; o,p -DDT, 18%; p,p -DDE, 2%) Clark (1974) NT NR DDT Fahrig (1974) mm p,p -DDT Albertini et al. (1988) mm p,p -DDT Albertini et al. (1988) Forward mutation NT 2.8 mm p,p -DDT Crebelli et al. (1986) Aneuploidy NT 2.8 mm p,p -DDT Crebelli et al. (1986) Host-mediated assay (in vivo) Host-mediated assay (in vitro) NT 75 mg/ml Formulation (p,p -DDT, 80% ; o,p -DDT, 18%; p,p -DDE, 2%) ± NT 75 mg/ml Formulation (p,p -DDT, 80% ; o,p -DDT, 18%; p,p -DDE, 2%) Toxicogenomics Gene expression + NA mol/l per 24 h Inconclusive results DDT Clark (1974) Clark (1974) Chang et al. (2011)
7 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out Prokaryote (bacteria) TA92 Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Reverse mutation 500 μg/plate DDT De Flora et al. (1989) Reverse mutation 2500 μg/plate DDT Byeon et al. Reverse mutation 170 μg/plate DDT Bartsch et al. (1980) Reverse mutation 177 μg/plate DDT Nishimura et al. (1982) Reverse mutation 370 μg/plate DDT Van Dijck & Van de Voorde Reverse mutation 500 μg/plate DDT Bruce & Heddle (1979) Reverse mutation 35 μg/plate DDT Probst et al. Reverse mutation NT 2500 μg/plate DDT Simmon et al. (1977) Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Reverse mutation 5000 μg/plate p,p -DDT Moriya et al. Reverse mutation 177 μg/plate p,p -DDT Planche et al. (1979)
8 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out Reverse mutation 35 μg/plate DDT Probst et al. Reverse mutation 370 μg/plate DDT Van Dijck & Van de Voorde Reverse mutation 177 μg/plate DDT Nishimura et al. (1982) Reverse mutation 170 μg/plate DDT Bartsch et al. (1980) Reverse mutation 500 μg/plate DDT De Flora et al. (1989) Reverse mutation 2500 μg/plate DDT Byeon et al. Reverse mutation 500 μg/plate DDT Bruce & Heddle (1979) Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Reverse mutation NT 2500 μg/plate DDT Simmon et al. (1977) Reverse mutation 5000 μg/plate p,p -DDT Moriya et al. Reverse mutation 177 μg/plate p,p -DDT Planche et al. (1979) Reverse mutation 35 μg/plate DDT Probst et al.
9 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out TA1536 Reverse mutation 2500 μg/plate DDT Byeon et al. Reverse mutation 2500 μg/plate DDT Marshall et al. Reverse mutation 500 μg/plate DDT Bruce & Heddle (1979) Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Reverse mutation NT 2500 μg/plate DDT Simmon et al. (1977) Reverse mutation 5000 μg/plate p,p -DDT Moriya et al. Reverse mutation 2500 μg/plate DDT Marshall et al. Reverse mutation 35 μg/plate DDT Probst et al. Reverse mutation 2500 μg/plate DDT Marshall et al. Reverse mutation 500 μg/plate DDT Bruce & Heddle (1979) Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Reverse mutation NT 2500 μg/plate DDT Simmon et al. (1977) Reverse mutation 5000 μg/plate p,p -DDT Moriya et al.
10 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out TA1978 C3076 D3052 Reverse mutation 2500 μg/plate DDT Byeon et al. Reverse mutation 35 μg/plate DDT Probst et al. Reverse mutation 2500 μg/plate DDT Marshall et al. Reverse mutation NT 2500 μg/plate DDT Simmon et al. (1977) Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Reverse mutation 5000 μg/plate p,p -DDT Moriya et al. Reverse mutation 370 μg/plate DDT Van Dijck & Van de Voorde Reverse mutation 35 μg/plate DDT Probst et al. Reverse mutation 35 μg/plate DDT Probst et al. G46 Reverse mutation 35 μg/plate DDT Probst et al. Escherichia coli Q-13 DNA DNA-cell-binding NT 150 μm DDT Kubinski et al. Escherichia coli PQ37 SOS chromotest 1000 μg/ml DDT Dayan et al.
11 Table 4.7 Genetic and related effects of DDT in non-mammalian systems Phylogenetic class Species, strain, tissue End-point Test Results Concentration out Acellular systems Escherichia coli WP2 uvra Reverse mutation 35 μg/plate DDT Probst et al. Escherichia coli WP2 uvra Reverse mutation NT 1000 μg/plate DDT Glatt & Oesch Escherichia coli WP2 hcr Reverse mutation 5000 μg/plate p,p -DDT Moriya et al. Escherichia coli Reverse mutation Pol-A mutation 500 μg/plate p,p -DDT Fluck et al. Bacillus subtilis M 45 Rec, Rec assay NT NR DDT Shirasu et al. H17 Rec + Serratia marcescens Host-mediated assay (in vivo) Isolated DNA from ColE1 plasmid DNA DNA single-strand breaks/alkaline labile sites NT NR DDT Buselmaier et al. (1973) NT 100 μg/ml DDT Griffin & Hill (1978) +, positive;, negative; ±, equivocal (variable response in several experiments within an adequate study); DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; HIC, highest ineffective concentration; LEC, lowest effective concentration; NA, not applicable; NR, not reported; NT, not tested
12 Table 4.8 Genetic and related effects of metabolites of DDT in non-mammalian systems in vitro Phylogenetic class Species, strain End-point Test Results Concentration out Prokaryote (bacteria) TA92 Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation 500 μg/plate p,p -DDE Mortelmans et al. (1986) Reverse mutation 5000 μg/plate p,p -DDE De Flora Reverse mutation 860 μg/plate p,p -DDE Bartsch et al. (1980) Reverse mutation 500 μg/plate p,p -DDE De Flora et al. (1989) Reverse mutation 2500 μg/plate p,p -DDE Brams et al. Reverse mutation 5000 μg/plate p,p -DDE Moriya et al. Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation 500 μg/plate p,p -DDE Mortelmans et al. (1986) Reverse mutation 5000 μg/plate p,p -DDE De Flora
13 Table 4.8 Genetic and related effects of metabolites of DDT in non-mammalian systems in vitro Phylogenetic class Species, strain End-point Test Results Concentration out Reverse mutation 860 μg/plate p,p -DDE Bartsch et al. (1980) Reverse mutation 500 μg/plate p,p -DDE De Flora et al. (1989) Reverse mutation 2500 μg/plate p,p -DDE Brams et al. Reverse mutation 5000 μg/plate p,p -DDE Moriya et al. Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde Reverse mutation NT 2500 μg/plate p,p -DDE McCann et al. (1975) Reverse mutation 1000 μg/plate DDE Marshall et al. Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation 500 μg/plate p,p -DDE Mortelmans et al. (1986) Reverse mutation 5000 μg/plate p,p -DDE De Flora Reverse mutation 2500 μg/plate p,p -DDE Brams et al. Reverse mutation 5000 μg/plate p,p -DDE Moriya et al. Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde
14 Table 4.8 Genetic and related effects of metabolites of DDT in non-mammalian systems in vitro Phylogenetic class Species, strain End-point Test Results Concentration out TA1536 TA 1537 TA 1537 TA 1538 Reverse mutation 1000 μg/plate DDE Marshall et al. Reverse mutation 1000 μg/plate DDE Marshall et al. Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation 500 μg/plate p,p -DDE Mortelmans et al. (1986) Reverse mutation 5000 μg/plate p,p -DDE De Flora Reverse mutation 2500 μg/plate p,p -DDE Brams et al. Reverse mutation 5000 μg/plate p,p -DDE Moriya et al. Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde Reverse mutation NT 2500 μg/plate p,p -DDE McCann et al. (1975) Reverse mutation 1000 μg/plate DDE Marshall et al. Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation 5000 μg/plate p,p -DDE De Flora Reverse mutation 5000 μg/plate p,p -DDE Moriya et al.
15 Table 4.8 Genetic and related effects of metabolites of DDT in non-mammalian systems in vitro Phylogenetic class Species, strain End-point Test Results Concentration out TA1950 TA1978 Escherichia coli WP2 uvra Escherichia coli WP2 uvra Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde Reverse mutation NT 2500 μg/plate p,p -DDE McCann et al. (1975) Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde Reverse mutation 370 μg/plate p,p -DDE Van Dijck & Van de Voorde Reverse mutation NT 0.10 μg/plate Metabolite 2,2- bis(p-chlorophenyl)- 2- chloroacetaldehyde (αc1-ddcho) Reverse mutation μg/plate Metabolite 1,1- bis(p-chlorophenyl)- 2,2-dichloroethane was mutagenic when norharman was added to the metabolizing system Reverse mutation + NT μg/plate Metabolite l-chloro- 2,2-bis(pchlorophenyl)ethene (DDMU)-epoxide Gold et al. Glatt & Oesch Gold et al. Reverse mutation NT 1000 μg/plate DDE Glatt & Oesch Reverse mutation NT 1000 μg/plate p,p -DDE Mamber et al. (1984)
16 Table 4.8 Genetic and related effects of metabolites of DDT in non-mammalian systems in vitro Phylogenetic class Species, strain End-point Test Results Concentration out Lower eukaryote (yeast, mould, fungi) Invertebrates Escherichia coli WP2 hcr Reverse mutation 5000 μg/plate p,p -DDE Moriya et al. Escherichia coli Pol-A Reverse mutation 500 μg/plate p,p -DDE Fluck et al. Escherichia coli Pol-A Reverse mutation 500 μg/plate p,p -DDD Fluck et al. Serratia marcescens a21 Reverse mutation + NT NR DDD Buselmaier et al. Leu - (1973) Serratia marcescens a31 Reverse mutation + NT NR DDD Buselmaier et al. His - (1973) Serratia marcescens Host-mediated assay (in vivo) Serratia marcescens Host-mediated assay (in vivo) Saccharomyces cerevisiae Saccharomyces cerevisiae Saccharomyces cerevisiae Saccharomyces cerevisiae RS112 Zebra mussel Dreissena polymorpha Mitotic gene conversion Mitotic gene conversion Mitotic gene conversion Intrachromosomal recombination assay NT NR DDE Buselmaier et al. (1973) NT NR DDA Buselmaier et al. (1973) NT NR DDE Fahrig (1974) NT NR DDD Fahrig (1974) NT NR DDA Fahrig (1974) μg/ml p,p -DDE Schiestl (1989); Schiestl et al. (1989) DNA Comet assay + NA 0.1 μg/l for 168 h p,p -DDE Binelli et al. (2008a)
17 Table 4.8 Genetic and related effects of metabolites of DDT in non-mammalian systems in vitro Phylogenetic class Species, strain End-point Test Results Concentration out Zebra mussel Dreissena polymorpha Micronucleus formation + NA 0.1 μg/l for 168 h p,p -DDE Binelli et al. (2008a, b) Zebra mussel Dreissena polymorpha Micronucleus formation + NA 0.1 μg/l for 168 hours p,p -DDD Binelli et al. (2008b) Insects Drosophila melanogaster Canton-S, male, germ-line cells Drosophila melanogaster, male, germ-line cells Drosophila melanogaster, male, germ-line cells Drosophila melanogaster, male, germ-line cells Drosophila melanogaster, male, germ-line cells Drosophila melanogaster Canton-S, male, germ-line cells Sex-linked recessive lethal Sex-linked recessive lethal Sex-linked recessive lethal Sex-linked recessive lethal Sex-linked recessive lethal Heritable translocation assay + NA μg/ml, in feeding media + NA 3.4 mm, in feeding media NA 3.1 mm, in feeding media NA 0.3 mm, in feeding media NA 3.7 mm, in feeding media NA μg/ml, in feeding media p,p -DDE Valencia et al. (1985) DDA Vogel (1972) DDE Vogel (1972) DDD Vogel (1972) DDOM Vogel (1972) p,p -DDE Valencia et al. (1985) +, positive;, negative; DDA, 2,2,-bis(4-chlorophenyl)-acetic acid; DDD, trichlorodiphenyldichloroethane; DDE, dichlorodiphenyldichloroethylene; DDOM, 2,2-bis(p-chlorophenyl-ethane); DDT, dichlorodiphenyltrichloroethane; HIC, highest ineffective concentration; LEC, lowest effective concentration; NA, not applicable; NR, not reported; NT, not tested
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