Ethylenediamine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In three studies (with a total of 4 test labs) the Ames test was performed using strains TA 98, TA 100, TA 1535, and TA 1537; in two of these studies also strain TA 1538 was used. In the key study (Guzzie et al., 1987), there was a slight, but less than 2-fold increase, using strain TA 100 with S9 mix. In one supportive study (Willems, 1979), all strains tested negative. In the second supportive study (Haworth et al., 1983), with less details as 250 chemicals were tested, EDA was tested in two different laboratories. Slight increases but less than 2-fold (TA 100) or less than 3-fold (TA 1535), were obtained in one lab. In the other lab, non-consistent increases viz. higher than 3-fold in the first experiment with and without rat liver S9 mix were seen with strain TA 1535 but not in the repeat; in strain TA 100 a slightly more than 2-fold increase was seen with rat liver S9-mix in the first experiment, whereas a slightly more than 2-fold increase was seen without S9-mix in the repeat. The cause of the weakly positive response in the latter Ames test has been hypothesized to be due to an impurity (Hedenstedt, 1978; as cited in the SIDS Risk Assessment dossier for Ethylenediamine, 2001) because in the test with a higher purity sample no such effects were seen. With regard to QSAR analysis, EDA does not match any structural alerts or examples for (bacterial in vitro) mutagenicity in Derek. Additionally, EDA does not contain any unclassified or misclassified features and is consequently predicted to be inactive in the bacterial in vitro (Ames) mutagenicity test including the 5th strain E. coli WP2. In addition, other in vitro tests, viz. a chromosome aberration test in human lymphocytes, an SCE test in CHO cells, an UDS test in primary rat hepatocytes, and a gene mutation test in mammalian cells were all negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

A dominant lethal assay in rats and a mutagenicity test in Drosophila (diet and injection) were all negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

In three out of four test labs, the Ames test was negative; some weak positive results were reported in a 4th lab in strains TA 100 and TA 1535. However, the negative results were obtained with high purity samples, and negative results were noted in strains TA 98, TA 1537 and TA 1538. Regarding QSAR analysis, EDA is predicted to be inactive in the bacterial mutagenicity test (Ames) including the 5th strain E. coli WP2. All other in-vitro tests were negative showing no evidence of mutagenicity in mammalian cells and no clastogenicity in human lymphocytes and CHO cells. In-vivo data from a dominant lethal study in rats and SLRL tests in Drosophila were also negative. Reviews by regulatory bodies such as WHO (1999), OECD SIDS (2001) and US EPA (2006) concluded that the weight of evidence from both in vitro and in vivo tests indicates that EDA is unlikely to be genotoxic. As such classification for genotoxicity is not warranted.