Trimethylenediamine

Carcinogenicity

Description of key information

There is no evidence of carcinogenicity by dermal or oral route exposure to triethylenediamine based on read across to test results generated in carcinogenicity studies with ethylenediamine and ethylene diammonium chloride.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

195 mg/kg bw/day

Carcinogenicity: via dermal route

Endpoint conclusion

Dose descriptor:

NOAEL

10.2 mg/kg bw/day

Justification for classification or non-classification

No carcinogenic effects have been observed in studies with ethylenediamine and ethylene diammonium chloride. A read across approach is justified as trimethylenediamine is structural very similar to ethylenediamine (difference: chain length / one CH2-group) or ethylenediammonium dichloride (applied doses of ammonium and chloride of no toxicological relevance), respectively. Thus, there is no evidence that trimethylenediamine has carcinogenic potential and is thus not classified in accordance to Directive 67/548/EEC (DSD) and Regulation (EC) No 1271/2008 (GHS).

Additional information

Oral route

In a 2 year combined chronic toxicity and carcinogenicity study, Fischer 344 rats were dosed with ethylene diammonium chloride via diet (Hermansky, 1999). There is no evidence, under the conditions of this study, that chronic feeding of ethylenediamine dihydrochloride - and based on a read across approach of triethylenediamine - exhibited a carcinogenic effect in the Fischer 344 rat up to the highest dose tested (350 mg/kg/day of EDA*2HCl, equivalent to 195 mg/kg/day triethylenediamine).

Dermal route

The dermal oncogenic potential of ethylenediamine (EDA) was assessed on male CH3 mice.The doses of EDA were selected in preliminary 2-week studies in which various concentrations, 1 to 10%, were applied daily. The skin was closely observed for signs of irritation, and the mice were weighed several times to assess any effects on weight gain. Application of a 5% solution resulted in open sores on the skin of 80% of the treated mice. The 1% solution was the highest EDA concentration which resulted in neither gross skin irritation nor reduced weight gain and was, therefore, chosen for the lifetime dermal carcinogenicity study in 50 male mice (application of 25 µL three times a week). Two EDA samples (purity 99.91% and 99.1%) from different producers were tested. A negative control group was treated with water only and a positive control group received 0,1% 3 -methylcholanthrene in acetone. No skin tumours were observed in the EDA treated animals. In the positive control group 98% of the animals had skin tumours (DePass, 1984).

Based on this study the dermal carcinogenic NOAEL was calculated to be 10.2 mg/kg bw/day trimethylenediamine (actually received dose).