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EC number: 222-824-1 | CAS number: 3623-51-6
No studies are available with (±)-neomenthol. Reliable data are available with the read across menthol (CAS 89 -78 -1).
No effects were observed in life-time (103 weeks) studies in rats and mice by using menthol up to the highest tested dose corresponding to 375 mg/kg bw/day for the rat and 667 mg/kg bw/day for the mouse. In a 90-day feeding study with menthol the NOAEL was 937 mg/kg bw/day for rats (highest dose tested). In a 90-day feeding study the NOAEL was 1250 mg/kg bw/day for mice based on slightly reduced body weight gain. As no sytemic effects were seen in both 103 weeks repeated dose toxicity studies applied by oral route, repeated dose studies via dermal or inhalative route do not appear to be scientifically justified.
A carcinogenicity study in mice and rats is available from structural analogue menthol (CAS 89-78-1). It is concluded that (±)-neomenthol is not toxic after chronic exposure. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in the repeated dose toxicity.
There is no reliable repeated dose study on (±)-neomenthol available.
Justification for Read-across:
Based on the identical profiles of the different menthols and supported by the Read-Across Justification for menthols (IUCLID chapter 13) all studies on stereoisomers of (±)-neomenthol are used for read across. These isomers are L-menthol (CAS 2216-51-5), (+)-menthol (CAS 15356-60-2), D/L-menthol (CAS 1490 -04 -6) and menthol (CAS 89-78-1).Moreover, a comparative physico-chemical profile of these isomers reinforces this similarity. As structural isomers, the members of the menthol category share the same molecular weight. Of particular importance to environmental effects and human effects are the values for partition coefficient (log Pow between 3.12 and 3.45 at 25°C), vapour pressure (from 3.6 to 21 Pa at 25°C) and water solubility (moderately soluble from 231 to 456 mg/L at 25°C). The read across is consistent based on these physico-chemical parameters.
Details on the repeated dose studies :
- Two tests were performed with menthol in rats for 13-weeks (males up to 998 mg/kg bw/day and females up to 937 mg/kg bw/day) and in mice (males up to 1956 mg/kg bw/d and females up to 2386 mg/kg bw/day) respectively. No toxicity was noted at the maximum dose tested in rat, while in mice a slight body weight effect was observed at the highest dose without any gross and microscopic pathological findings related to the treatment. The NOAELs derived from these studies were 937 mg/kg bw/day for rat and 1250 mg/kg bw/day for mouse.
- After 103 weeks oral administration of menthol the mean body weights of the dosed male and female rats were slightly lower than those of the corresponding controls throughout the bioassay. No other clinical signs related to administration of the menthol were noted. Clinical signs commonly observed among rats of this strain were noted at comparable rates in the control and dosed groups, particularly during the second year of the bioassay, and increased in incidence as the animals aged.
The NOAEL resulted from this study was 7500 ppm (i.e. 375 mg/kg bw/day).
- After 103 weeks oral administration of menthol the mean body weights of the dosed male and female mice were slightly lower than those of the corresponding controls throughout the bioassay. The appearance and behaviour of the dosed and control groups of animals were generally similar, and clinical signs usually associated with aging were noted at comparable rates in the control and dosed groups.
The NOAEL resulted from this study was 4000 ppm (i.e. 667 mg/kg bw/day).
(±)-neomenthol does not meet the criteria for classification and labeling for repeated dose toxicity (STOT), as set out in Regulation (EC) NO. 1272/2008 as indicated by study results on menthol used for read across.
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