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Carcinogenicity

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Description of key information

There is no evidence of carcinogenity of Ethylenediamine via the oral route (dietary) in rats or dermal exposure in mice for lifetime.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
159 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Klimisch 2 study from published literature carried out in well recognized industry laboratory

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
8.3 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
Klimisch 2 study from published literature carried out in well recognized industry laboratory

Justification for classification or non-classification

Ethylenediamine (as the dihydrochloride salt) was administered in the diet to Fischer 344 rats up to a dose level that can be seen as a maximum tolerated dose of 159 mg EDA base/kg bw/day and there were no indications of any carcinogenicity. Also in a lifetime dermal dosing study in C3H/HeJ mice, in which the mice were shown to be sensitive to the skin carcinogen 3-methylcholanthrene, there were no skin tumours observed in the ethylenediamine treated mice at a maximum non-irritant dose equivalent to 8.3 mg/kg bw/day, confirming the lack of carcinogenicity seen in the rats. This lack of carcinogenicity in rats and mice is consistent with the lack of genotoxicty seen in the in-vitro and in-vivo tests. Overall it is concluded that Ethylenediamine is not carcinogenic.


 

Additional information

Ethylenediamine dihydrochloride was fed to Fischer 344 rats in the diet for 2 years with a top dose of ca. 350 mg/kg equivalent to 159 mg/kg of the Ethylenediamine base. There was an increased number of mortalities at the top dose but no increase in tumour incidence at any dose level. There was a decreased incidence of pituitary adenomas and interstitial cell adenomas of the testis in males; this may have been influenced by the increased mortalities resulting in fewer rats surviving sufficiently long for these tumours to develop spontaneously.

 

In the dermal carcinogenicity study in C3H/HeJ mice, the maximum level of ethylene diamine that could be applied to the skin of the mice without causing significant skin irritation was 25 µL of a 1% solution equivalent to 8 mg/kg bw. Mice were dosed three times a week for their lifetime with separate groups of 50 mice for each of two samples of Ethylenediamine from two different suppliers; both samples were high purity but had different impurities. The study also included a positive control group dosed with the dermal carcinogen 3 -methylcholanthrene at 0.1% in acetone. Negative controls were dosed with water only.

No skin tumours were observed in the EDA treated animals. The positive control group confirmed the sensitivity of the mice to skin carcinogens with 98% of the animal developing skin tumours.