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The genetic toxicity in vitro of Geraniol was analyzed in several tests. In one Ames test, bacteria strains S. typhimurium TA 1535, TA 1537, TA 98, TA 100, TA92, TA94 and TA2637 were tested with concentrations of geraniol up to 0.5 mg/ plate with and without metabolic activation by polychlorinated biphenyls induced rat liver microsome S9 mix (Ishidate, 1984). As a result, no mutagenic effects induced by geraniol were observed in this study.

In another Ames test, also no mutagenic effects were found, when S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 were incubated with 3 umol/plate (= 0.46 mg/plate) with and without metabolic activation (Florin, 1980).

Only one bacteria strain was tested in two studies, where S. typhimurium TA 100 was tested according the method by Ames with concentrations of 0.01 - 1 ul geraniol /2 ml medium with and without metabolic activation by Aroclor 1254 induced rat liver S9 mix (Eder, 1980, 1982). In both studies, geraniol was found to be negative.

The most recent Ames test used unspecified S. typhimurium and E coli strains and found geraniol to be not mutagenic.

Geraniol 60 (reaction mass of geraniol and nerol (E- and Z-isomers)) was tested in a HPRT test in CHO cells with and without metabolic activation (BASF SE, 2010). Cytotoxicity was found in the highest doses of 200 µg/ml for each condition. The test substance did not cause any relevant increase in the mutant frequencies in two independent experiments.

In a chromosome aberration test, concentrations of 0.0313, 0.0625, 0.125 mg/ml geraniol were tested in mammalian CHL cells 1-164 cells for clastogenic effects (Ishidate, 1984). After 48 h 8% of the cells were polyploid (slightly, but significant elevated compared to control), and 4% of the cells showed chromosomal aberrations (not elevated compared to control). Thus, the test results were regarded as ambiguous.

In another chromosome aberration assay, a significant increase in the number of cells with structural aberrations (deletions and exchanges) was seen in cultures exposed for 3 h to 78.1 - 156.3 ug/ml geraniol in 1 of 2 experiments with and without Aroclor 1254-induced rat liver metabolic activation (Rupa, 2003). On the other hand, no significant increase in polyploidy and endoreduplications was observed either with or without metabolic activation. Thus, the overall result of the study was inconclusive.

However, a third chromosome aberration test found geraniol to be nonclastogenic in Chinese hamster lung cells (Serra, 2003).

In a sister chromatid exchange assay in mammalian cells concentrations of 0, 33.3, 100, 333 and 1000 uM (5.14, 15.4, 51.4, 154 mg) were tested in CHO cells (Sasaki, 1989). Although cytotoxicity was noted at a concentration of 1000 uM (154 mg), no substance induced chromatid exchange was detected.

Also no genotoxic effect was observed, when concentrations of 16 ug/disk were tested with Bacillus subtilis H17 (rec+) and M45 (rec-) in a Bacillus subtilis recombination assay (Oda, 1978).

The genetic toxicity in vivo of geraniol was analyzed in a micronucleus test (MNT) and found to be not mutagenic (Rupa, 2003). However, this study could not be taken for assessment as only limited data were given.

The reaction mass of geraniol and nerol (E- and Z-isomers) was also tested in a MNT in NMRI mice (BASF SE, 2010). For this purpose, the test substance, dissolved in DMSO and emulsified in corn oil, was administered once orally to male animals at dose levels of 375 mg/kg, 750 mg/kg and 1 500 mg/kg body weight in a volume of 10 mL/kg body weight in each case. The animals were sacrificed and the bone marrow of the two femora was prepared 24 and 48 hours after administration in the highest dose group of 1 500 mg/kg body weight and in the vehicle controls. In the test groups of 750 mg/kg and 375 mg/kg body weight and in the positive control groups, the 24-hour sacrifice interval was investigated only. After staining of the preparations, 2 000 polychromatic erythrocytes were evaluated per animal and investigated for micronuclei. The normocytes with and without micronuclei occurring per 2 000 polychromatic erythrocytes were also recorded. As vehicle control, male mice were administered merely the vehicle, DMSO/corn oil (ratio 2:3), by the same route and in the same volume as the animals of the dose groups, which gave frequencies of micronucleated polychromatic erythrocytes within the historical vehicle control data range. Both positive control substances, cyclophosphamide for clastogenicity and vincristine sulfate for spindle poison effects, led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei. No inhibition of erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected.

According to the results of the study, the single oral administration of the reaction mass of geranion and nerol did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was within the range of the concurrent vehicle control in all dose groups and at all sacrifice intervals and within the range of the historical vehicle control data. Thus, under the experimental conditions of this study, the reaction mass of geraniol and nerol does not induce cytogenetic damage in bone marrow cells of NMRI mice in vivo.

All results taken together show that Geraniol can clearly be considered as not mutagenic.


Short description of key information:
Genetic toxicity:
in vitro in bacteria: negative with and without metabolic activation (Ames)
in vitro in mammalian cells: ambiguous (chromosome aberration)
in vitro in mammalian cells: negative (HPRT)
in vivo in mammalian cells: negative (micronucleus test)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Due to numerous negative results in bacteria and mammalian cells in vitro (mutagenicity and cytogenicity) as well as negative results in vivo, Geraniol does not need to be classified as mutagenic according to Regulation (EC) No 1272/2008.