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Key value for chemical safety assessment

Additional information

Ames test

The substance was tested for mutagenicity using a preincubation modification of the Salmonella/microsome test with and without metabolic activation (tester strains: TA 98, TA 100, TA 1535, TA 1537). The test did not reveal indication for mutagenicity (Zeiger, 1987). This test result is supported by an AMES Assay without metabolic activation after reaction with nitrite in seven tester strains (TA 1537, TA 1538, TA 1950, TA 1952, TS24, G46, GW 19), also with negative test results in all strains (Murphey-Corb, 1983).

Mammalian chromosome aberration test (BASF SE, 2012)

The test item 1,3-Diaminopropane, dissolved in deionised water, was assessed for its potential to induce structural chromosome aberrations in V79 cells of the Chinese hamster in vitro in two independent experiments. The following study design was performed:

 

Without S9 mix

With S9 mix

Exp. I

Exp. II

Exp. I

Exp. II

Exposure period

4h

18 h

18 h

4 h

4 h

Recovery

14 h

-

-

14 h

24 h

Preparation interval

18 h

18 h

18 h

18 h

28 h

In each experimental group two parallel cultures were set up. At least 100 metaphases per culture were evaluated for structural chromosome aberrations, except for the positive control in Experiment II after 28 hours continuous treatment without metabolic activation, where only 50 metaphases were evaluated. The highest applied concentration (741.0 µg/mL; approx. 10 mM) was chosen with regard to the molecular weight of the test item and with respect to the current OECD Guideline 473. Dose selection for the cytogenetic experiments was performed considering the toxicity data. In both experiments in the absence and presence of S9 mix no cytotoxicity was observed up to the highest applied concentration. No clastogenicity was observed at the concentrations evaluated either with or without metabolic activation. One single statistically significant increase was observed in Experiment II after treatment with 370.5 µg/mL in the presence of S9 mix (2.8 % aberrant cells, excluding gaps), but the value was in the range of the laboratory historical control data (0.0 - 4.0 % aberrant cells, excluding gaps) and considered biologically irrelevant. No relevant increase in polyploid and endomitotic metaphases was found after treatment with the test item as compared to the frequencies of the control cultures. Appropriate mutagens (EMS and CPA) were used as positive controls. They induced statistically significant increases in cells with structural chromosome aberrations.

In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosome aberrations in V79 cells (Chinese hamster cell line) in vitro. Therefore, 1,3-Diaminopropane is considered to be non-clastogenic in this chromosome aberration test in the absence and presence of metabolic activation, when tested up to the highest required concentration.

Mammalian cell gene mutation test (BASF SE, 2012)

The study was performed to investigate the potential of 1,3-Diaminopropane to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The test was performed according to OECD guideline 476. The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The maximum concentration of the pre-experiment and the main experiments (741.0 µg/mL) was equal to a molar concentration of about 10 mM. The test item was dissolved in deionised water. The tested concentrations of the main experiments were as follows:

Experiment I, 4 h treatment:

11.6, 23.2, 46.3, 92.6, 138.9, 185.3 µg/mL (without S9 mix)

23.2, 46.3, 92.6, 138.9, 185.3, 370.5, 741.0 µg/mL (with S9 mix)

Experiment II, 24 h treatment (without S9 mix), 4 h treatment with S9 mix):

23.2, 46.3, 92.6, 185.3, 370.5, 741.0 µg/mL (with and without S9 mix).

No substantial and reproducible dose dependent increase of the mutation frequency was observed up to the maximum concentration with and without metabolic activation. Appropriate reference mutagens (EMS and DMBA), used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test system and the activity of the metabolic activation system.

In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, 1,3-Diaminopropane is considered to be non-mutagenic in this HPRT assay.


Justification for selection of genetic toxicity endpoint
No mutagenic effects in the in vitro tests (AMES tests, Chromosome aberration test, In vitro Mammalian Cell Gene Mutation Test).

Short description of key information:
Trimethylenediamine did not reveal mutagenicity in two bacterial reverse mutation assays (Ames test). No mutagenic potential was seen in the chromosome aberration assay and the mamalian cell gene mutation test.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the in vitro genetic toxicity studies, the test susbtance was neither found genotoxic nor mutagenic and is not subjected to classification and labelling according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).