Table 4: Summary of genotoxicity studies Test Test system Dose Metabolic Result Reference (species/strain) activation In Reverse 100 1000 With and Negative Zeiger et al., S. typhimurium – mutation without 1985* TA98, TA100, μg/plate TA1535, TA1537 Reverse Not reported Not Negative Seed, 1982* S. typhimurium mutation reported TA100 L5178Y TK+/- Mouse -S9: 2000- With and Negative Hazelton mouse lymphoma lymphoma 10000 nl/mL without Biotechnologi cells mutation assay +S9: 250- es Company, 10000 nl/mL 1986* L5178Y TK+/- Mouse -S9: 2-10 With and Negative Barber et al., mouse lymphoma lymphoma µl/mL without 2000 cells mutation assay +S9: 0.25-2 µl/mL In vivo Micronucleus CD-1 mice (bone Single oral N/A Negative Hazelton test marrow) (gavage) dose Washington, of 0, 1250, 1994* 2500 or 5000 mg/kg bw Carcinogenicity Previous evaluations Two in vitro mammalian cell transformation assays were noted. In the first assay, DIDP was tested on Balb/c-3T3 mouse cells (Barber et al., 2000). With an exposure period of 72 hours and incubation over 4 weeks, DIDP did not induce statistically significant increases in transforming activity with concentrations up to 20 In μL/mL. the second assay, Balb/3T3 Clone A31 mouse embryo cells were treated for 20-24 hours and incubated for 4-6 weeks. Transforming frequencies were statistically significantly increased at a dose level of 1 but not at 0.01 or 0.1 μL/mL μL/mL. No in vivo carcinogenicity studies were available for assessment. Data not reported in previous evaluations No data. Conclusion No in vivo carcinogenicity studies were available. Positive results were recorded in one of two in vitro transformation assays conducted under different conditions. Overall, data are insufficient to establish the carcinogenic potential of DIDP.
Table 4: Summary of genotoxicity studies Test Test system (species/strain) Dose Metabolic activation Result Reference In Reverse mutation S. typhimurium TA98, TA100, TA1535, TA1537 100 – 1000 μg/plate With and without Negative Zeiger et al., 1985* Reverse mutation S. typhimurium TA100 Not reported Not reported Negative Seed, 1982* Mouse lymphoma mutation assay L5178Y TK+/- mouse lymphoma cells -S9: 2000- 10000 nl/mL +S9: 250- 10000 nl/mL With and without Negative Hazelton Biotechnologi es Company, 1986* Mouse lymphoma mutation assay L5178Y TK+/- mouse lymphoma cells -S9: 2-10 µl/mL +S9: 0.25-2 µl/mL With and without Negative Barber et al., 2000 In vivo Micronucleus test CD-1 mice (bone marrow) Single oral (gavage) dose of 0, 1250, 2500 or 5000 N/A Negative Hazelton Washington, 1994* mg/kg bw Carcinogenicity Previous evaluations Two in vitro mammalian cell transformation assays were noted. In the first assay, DIDP was tested on Balb/c-3T3 mouse cells (Barber et al., 2000). With an exposure period of 72 hours and incubation over 4 weeks, DIDP did not induce statistically significant increases in transforming activity with concentrations up to 20 μL/mL. In the second assay, Balb/3T3 Clone A31 mouse embryo cells were treated for 20-24 hours and incubated for 4-6 weeks. Transforming frequencies were statistically significantly increased at a dose level of 1 μL/mL but not at 0.01 or 0.1 μL/mL. No in vivo carcinogenicity studies were available for assessment. Data not reported in previous evaluations No data. Conclusion No in vivo carcinogenicity studies were available. Positive results were recorded in one of two in vitro transformation assays conducted under different conditions. Overall, data are insufficient to establish the carcinogenic potential of DIDP.