Evaluation of the genotoxic potential of alkyleneamines

A series of 6 alkyleneamines [ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), aminoethylethanolamine (AEEA), and aminoethylpiperazine (AEP)] were evaluated for potential genotoxic activity using a battery of in vitro and in vivo assays. Only TETA was considered mutagenic in the Salmonella typhimurium mutation assay. All 6 alkyleneamines tested except AEP were considered inactive in the Chinese hamster ovary (CHO) gene mutation assay. AEP was considered inconclusive in this assay. In 2 the sister-chromatid exchange (SCE) assay, EDA, DETA and AEEA were inactive with or without metabolic activation. TETA, TEPA and AEP were considered active in the induction of SCE in CHO cells. With hepatocytes, no positive effects of EDA, DETA AEEA and AEP upon unscheduled DNA syntheses (UDS) were noted. However, TETA and TEPA produced significant increases in the amount of UDS activity, and thus were considered positive in inducing primary DNA damage in this assay. In a micronucleus study with Swiss-Webster mice, no clastogenic activity was observed with TETA, TEPA and AEP. The overall weight of evidence from the in vitro and in vivo tests suggested that EDA, DETA and AEEA were not mutagenic, while TETA was mutagenic, and TEPA and AEP had a weak mutagenic potential.