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Key value for chemical safety assessment

Additional information

In vitro Studies:

TDA was tested negative in the Ames test with and without metabolic activation, both in the standard plate test and in the preincubation test (BASF AG, 1989; Val. 2). The study was conducted according to OECD TG 471. The substance was tested in the range 6 – 5000 μg/plate in the standard test and 1.25 – 50 μg/plate in the Preincubation test using the S. typhimurium test strains TA1535, TA100, TA1537, and TA98. Bacteriotoxic effects were seen in the standard plate test from about 25 – 50 μg/plate without metabolic activation and from 50 – 100 μg/plate with metabolic activation. In the preincubation test cytotoxicity was seen in all test strains at 20 μg/plate without metabolic, or with metabolic activation at 50 μg/plate only in TA 1535

 

In vivo Studies:

TDA was tested negative in a GLP Mouse Micronucleus test that was performed in accordance with OECD TG 474 (BASF AG, 2002; Val. 1). The mice received single doses of 200, 400, and 600 mg TDA dissolved in olive oil/kg bw by oral gavage which caused clinical signs of toxicity at the mid- and the high-dose level. Transient squatting posture was seen in animals receiving 400 mg/kg bw at 1 h after dosing. At 600 mg/kg bw, squatting posture and tremor were seen in all animals on the first and second day after treatment. Poor general state was seen at 1 h after treatment in all high dose animals. In the main test, 5/10 animals died at 800 mg/kg within 48 h. The highest dose was therefore lowered to 600 mg/kg bw in the course of the study.

 

The evaluation of 2000 polychromatic erythrocytes 24 and 48 hours after dosing revealed that the proportion of polychromatic erythrocytes containing micronuclei was 0.8, 0.9, and 2.2 ‰ in the groups at 200, 400, and 600 mg/kg bw, respectively, after 24 hours, and 1.1 ‰ after 48 hours in animals receiving the high dose. This was within the range of the historical control data for this vehicle (mean ± SD: 2.0±0.6 ‰; n=56). At the high dose, TDA slightly inhibited erythropoiesis, showing that the test material had reached the target. The positive control substances, cyclophosphamide and vincristine, gave significantly positive effects on the p< 0.01 level as expected. Overall, there was no indication of a clastogenic or aneugenic activity


Short description of key information:
In vitro studies:
Ames-Test: negative (OECD 471)

In vivo studies:
Mouse Micronucleus Test: negative (OECD 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

TDA was not mutagenic in an Ames test with 4 strains, both with and without metabolic activation. In vivo, TDA did not induce clastogenic or aneugenic effects in a micronucleus study.