Cyclohexylamine

Endpoint summary

Additional information

In general negative results were obtained in the gene mutation tests using bacteria or mammalian cells. There are many in vitro studies available; most of these studies have no or only limited value for risk assessment due to limitations in study design or documentation.

Bacterial reverse mutations were investigated in a study conduced according OECD TG 471. No mutagenic effects were reported in Salmonella typhimurium TA 98, TA 97, TA 100, TA 1535 and TA 1537 in the presence and in the absence of metabolic activator S9 at different concentrations, 0, 33, 100, 333,1000, 3333, 10000 µg/plate. The highest dose tested was defined based on cytotoxic effects observed in a pilot study. Vehicel controls, negative controls and positive controls were included into the experiment and gave the expected results. Generally, negative results were obtained in gene mutation tests in bacteria (Mortelmans 1986).

In another study 4 Salmonella typhimurium strains (TA 98, TA 100, TA 1535, TA 1537) were investigated at concentrations up to 2500 µg/plate. Positive and negative controls were included in the experiment and gave the expected results. No mutagenic activity was reported with or without S9 mix (Herbold 1980).

Gene mutations were investigated in a mammalian cell mutation assay using the HGPRT forward mutation study design and Chinese hamster ovary cells. The study was conducted in compliance with all international guidelines and EPA GeneTox. Two trials were reported with concentrations in the rage of 172- 1720 µg/ml (first trial) and 344-1376 µg/ml (second trial). Cytotoxicity was observed in the presence and in the absence of an activation system. No evidence of mutagenic activity was reported by the authors (Brusik 1989).

Unscheduled DNA synthesis was investigated in hepatocytes obtained from adult male Fischer 344 rats. UDS was measured by counting nuclear grains for 150 randomly selected cells. In order to confirm the assay, an independent repeat was performed. In both experiments no increase in unscheduled DNA synthesis was observed. The negative and positive controls were functional (Brusik 1989).

There are no guideline in vitro cytogenetic test reported with cyclohexylamine. In some early in vitro cytogenetic tests small increases in frequency of chromosome gaps and/or breaks were observed. According to the actual guideline for “in vitro mammalian chromosome aberration test” OECD TG 473 gaps should be recorded separately and reported but not included in the total aberration frequency. Because no exchange figures, translocations, or other chromosome aberrations were found it is concluded that these early studies are not reliable and cyclohexylamine is not clastogenic in vitro (Bopp et al., 1986, NL Health Council 2010, MAK 2006).

There are more than 30 in vivo studies reported in the literature mainly conducted in the 1970 years with sometimes contradictory results. In most studies no genetic damage from cyclohexylamine could be detected (Bopp et al., 1986, NL Health Council 2010, MAK 2006). Bopp et al. (1986) concluded: “When the entire battery of mutagenicity tests with cyclamate and cyclohexylamine is evaluated, the evidence suggests that neither compound represents a significant mutagenic hazard.” The NL Health Council concluded: “From these data, the committee does not consider cyclohexylamine to be a mutagenic / genotoxic compound.” Most recently the German MAK comission reevaluated the data and came to the conclusion: “On the whole, no genotoxic potential worth mentioning can be attributed to cyclohexylamine”.

Short description of key information:
Cyclohexylamine is not nutagen and not clastogen

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the EU classification criteria 67/548/EWG Annex 1 and EU regulation no. 790/2009 (GHS) Annex 1 the compound is not classified. No further classificatio is proposed.