Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Studies in animals

In vivo studies

Cited from SIAR for SIAM 18 (Paris, April 2004):

"In a micronucleus assay with NMRI mice according to OECD TG 474, 5 male/female animals per group were orally administered single doses of 50, 150, or 500 mg/kg bw 3-aminomethyl-3,5,5- trimethylcyclohexylamine. The highest dose was considered the maximum tolerable dose (MTD) based on the induction of toxic effects without major effects on survival within 72 hours of test substance administration. Sampling times were 24, 48, and 72 hrs after test substance administration. 3-Aminomethyl-3,5,5-trimethylcyclohexylamine treatment did not result in an increase in the number of micronucleated polychromatic erythrocytes (PCE), nor did it negatively affect the PCE/NCE ratio (Cytotest Cell Research, 1990). This result was confirmed in another study with a slightly different design (Hüls AG, 1988a). Here a single dose of 100 mg/kg bw was administered, which – based on the absence of cytotoxic effects – was determined as the MTD. Sampling times were 24, 48, and 72 hrs after test substance administration."

In vitro studies

Cited from SIAR for SIAM 18 (Paris, April 2004):

"In an Ames test performed according to Directive 84/449/EEC B.14 (1984) with Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100, test substance concentrations of up to 5,000 μg/plate were employed in the presence and absence of Aroclor 1254-induced rat liver S9 mix. At non-toxic test substance concentrations, a significant increase in mutant frequency was not observed (Hüls AG, 1990). The same result was obtained in another test with comparable design (Hüls AG, 1988b; method according to the original publication by B. Ames, 1975).

In a HPRT test with Chinese Hamster ovary (CHO) cells according to OECD TG 476 (1984), 3- aminomethyl-3,5,5-trimethylcyclohexylamine concentrations of 20 - 2,000 mg/l (+/- S9 mix from Aroclor 1254 induced rat livers) did not significantly increase the mutant frequency of treated cells. Cytotoxicity was not observed at any of the concentrations tested (Hüls AG, 1992c). In a cytogenetic assay with Chinese Hamster Ovary (CHO) cells (according to OECD TG 473), concentrations of 156.25 – 1,375 mg/l (+/-S9 mix from Aroclor 1254-induced rat livers) were employed. A significant, test compound related increase in chromosomal aberrations was not observed (Safepharm, 1992)."

Short description of key information:
Cited from SIAR for SIAM 18 (Paris, April 2004):
"3-Aminomethyl-3,5,5-trimethylcyclohexylamine was not mutagenic in bacteria and mammalian cell systems in vitro (Ames test according to Directive 84/449/EEC B.14 (1984) and HPRT test according to OECD TG 476 (1984)). It did not induce chromosomal aberrations in CHO cells in
vitro in a test performed in accordance with OECD TG 473 (1981).
In vivo mouse micronucleus tests (one performed according to OECD TG 474 (1983) for the induction of micronucleated
polychromatic erythrocytes were clearly negative. From all in vitro and in vivo tests performed there is no evidence that 3-aminomethyl-3,5,5-trimethylcyclohexylamine has a mutagenic or clastogenic potential."

Endpoint Conclusion:

Justification for classification or non-classification

Because of the results of the mutagenicity studies the substance isophorone diamine is not classified according to 67/548/EEC and CLP regulation (1272/2008). Based on the data described here the substance isophorone diamine shows no genotoxic effects. Therefore, it seems unlikely that isophorone diamine induces carcinogenicity via an genotoxic mechanism.