Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Bacterial mutation assays

 

Several reports were identified using reverse bacterial mutation assays to determine the mutagenicity of diethylene triamine, only three gave positive results where one of the strains tested had an increase number of revertants. In the key guidelines study by BASF. DETA led to an increased number of revertants using E. coli WP2 uvrA with and without S9 using the criteria of 2 times the background for a positive result. Negative reponses were achieved for each of the other strains (TA98, TA100, TA1535, and TA1537). Another, Ames test was conducted by Haskell laboratories where DETA was added to the plate at 3,000 ug/plate. Negative results were recorded for TA100, TA1535, TA1537 and TA1538, but were positive for strain TA98. The test was re-ran after the preparation of DETA used for the analysis was further purified. The purified DETA preparation lacked any mutagenic activity in the TA 98 strain. 

 

Another Ames test was conducted using a sample of 99.5%. In this case, the Ames test was negative in TA1535 and TA1538, but positive in TA98, TA100, and TA1537.  The results were not reproducible on a retest for strains TA98 and TA100.  Only TA1537 showed a reproducible positive effect. 

 

The other four reports using bacterial reverse mutation assays were negative in the following strains: TA98, TA100, TA1535, TA1537, and TA1538. 

 

In vitro Chromosome aberration test   

 

Diethylenetriamine (DETA) was evaluated in an in vitro chromosomal aberration assay using Chinese hamster ovary (CHO) cells. The concentrations of the test material were up to and including 2500 ul/plate. There were no statistical significant increases in the frequencies of chromosomal aberrations in cultures treated with any of the grades of DETA with or without metabolic activation.

 

In vitro Mammalian cell mutation assays

 

All grades of DETA were negative in the CHO HPGRT, CHO Mutation, Sister Chormatoid Exchange (SCE) , and Unscheduled DNA Synthesis assays with and without metabolic activation. The UDS data indicated that none of the grades of DETA over a 1000 fold conscentration range induced DNA synthesis in this test. Moreover, none of the grades of DETA produced dose-related increased in the frequency of SCE in tests both with and without the incorporation of an S9 metabolic activation system. Another report investigated a 98.9% purified grade of DETA for genotxoic protential in mammalian cells using SCE in CHO cells. This study indicated that DETA statistically increased the incidence of SCE without metabolic activation. A marginal increase was observed when DETA was tested in the presence of S9 mix.

 

In vivo: Drosophila Sex-Linked Recessive Lethal Test

 

The mutagenic potential of diethylenetriamine (DETA) was evaluated in the Drosophila sex-linked recessive lethal (SLRL) assay. The test chemical was administered to Drosophila melanogaster males by adult feeding at an exposure concentration of 60 mM. DETA was considered negative in the Drosophila SLRL assay.

 

In vivo: Micronucleus test

DETA was evaluated in the mouse micronucleus tests (OECD 474).  It was concluded that DETA did not significantly increase the frequency of micronucleated polychromatic erythrocytes in the treated groups. 

In vivo: Transgenic Rodent Asssay

A higher tier Transgenic Rodent Mutation assay was performed as a definitive test to determine the mutagenic potential of DETA. Big Blue C57B/6 mice were dosed at 50, 150, and 400 mg/kg/day via gavage for 28 days. Bone marrow, liver, and stomach tissues were taken post-exposure and were processed for DNA isolation. The evaluation of mutation frequencies at the Cll gene in liver, bone marrow, and stomach were comparable to the controls. Under the conditions of the test DETA did not demostrate any mutagenic activity.

Evidence from in vitro studies and the three in vivo tests indicate that DETA is a non-mutagenic substance. 

 

 

 

 


Short description of key information:
In vitro: Diethylene triamine was studied for its mutagenic potential in 7 different Ames tests. Other studies include one CHO Sister Chromatid Exchange assay, one chromosomal aberration test with CHO, three CHO HPGRT forward mutation assays (CHO Mutation test, the Sister Chromatid Exchange (SCE ) test and Unscheduled DNA systhesis (UDS), and three studies examined the effects of DETA on unscheduled DNA synthesis. Four studies were found using chinese hamster ovary cells to determine the potential of DETA to cause chromosomal aberration.

In vivo: Two key in vivo studies were identified for determining the mutagenic potential of diethylene triamine: a mouse micronucleus assay and a Drosophila sex-linked recessive lethal test.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Evidence from in vitro and in vivo studies indicate that DETA in not genotoxic and not classifiable under GHS.