Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

No data is available regarding developmental toxicity for (±)-neomenthol.

Reliable data is available for L-menthol. Developmental toxicity studies in rats, mice, rabbits and hamsters do not show any developmental toxicity potential of menthol. Thus, (±)-neomenthol is also not considered to be embryo-or fetotoxic or teratogenic.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to IUCLID section 13 for a detailed justification of the category approach.
Reason / purpose:
read-across source
Related information:
Composition 1
Reason / purpose:
read-across source
Related information:
Composition 1
Reason / purpose:
read-across source
Related information:
Composition 1
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Details on maternal toxic effects:
Maternal toxic effects: no effects

Details on maternal toxic effects:
No clinical signs of maternal toxicity
Dose descriptor:
NOEL
Remarks:
rat
Effect level:
> 218 mg/kg bw/day
Based on:
no data
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Remarks:
mouse
Effect level:
> 185 mg/kg bw/day
Based on:
not specified
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Remarks:
rabbit
Effect level:
> 425 mg/kg bw/day
Based on:
not specified
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Remarks:
hamster
Effect level:
> 405 mg/kg bw/day
Based on:
not specified
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects: no effects
Dose descriptor:
NOEL
Remarks:
rat
Effect level:
> 218 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: teratogenicity and fetotoxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Remarks:
mouse
Effect level:
> 185 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: teratogenicity and fetotoxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Remarks:
rabbit
Effect level:
> 425 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: teratogenicity and fetotoxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Remarks:
hamster
Effect level:
> 405 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: teratogenicity and fetotoxicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
L-menthol was not embryo- or fetotoxic and had no teratogenic properties in rat, mice, rabbit and hamster at non-maternally toxic doses (218, 185, 425 and 405 mg/kg bw/day, respectively).
Executive summary:

Developmental toxicity tests are available from structural analogue L-menthol (CAS 2216 -51 -5) in rats, mice, rabbits and hamsters. It is concluded that (±)-neomenthol does not have developmental toxicity effects. 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 developmental toxicity.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
185 mg/kg bw/day
Study duration:
subacute
Species:
mouse
Quality of whole database:
The available information comprises studies which each alone are regarded insufficient for assessment from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarities of the menthols and their similarities in PC/ECO/TOX properties (refer to read across justification for further details). However, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex X, 8.7, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are currently no experimental data available to assess developmental toxicity / teratogenicity for the test substance.

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 developmental toxicity studies:

For the structural similar substance L-menthol (CAS 2216 -51 -5) four studies are available which were done before guidelines were available (1973). These studies were conducted similar to OECD 414 in four different species - rats, mice, rabbits and hamster. Although the reports are not as detailed as required according to todays standards these four studies are considered reliable in order to assess the developmental toxicity of (±)-neomenthol. A reason for the dosage levels are not given which in fact are considered too low since no maternal toxicity is observed. But since the tests were conducted in four different species and in none of these studies developmental effects were observed these studies are considered as reliable on the basis of weight of evidence.

For Wistar rats the doses of 2.18, 10.15, 47.05 and 218.0 mg/kg bw/day were administered by gavage from gestation day 6 to 15. There was no maternal toxicity and fetotoxicity determined. Therefore the NOEL derived for maternal and fetal toxicity and teratogenicity in rats can be determined as 218.0 mg/kg bw/day. For CD-1 Mice the doses of 1.85, 8.59, 39.9 and 185.0 mg/kg bw/day were administered from gestation day 6 to 15. There was no maternal toxicity and fetotoxicity determined. The NOEL derived for maternal and fetal toxicity and teratogenicity was 185.0 mg/kg bw/day. For Dutch belted Rabbits the doses of 4.25, 19.75, 91.7 and 425.0 mg/kg bw/day were administered from gestation day 6 to 18. Few of the rabbits died or aborted before day 29 (at 4.25 mg/kg bw/day 2 animals died on day 13 , at 19.75 mg/kg bw/d 3 animals died on day 13, at 91.7 mg/kg bw/d 1 animals died on day 11, at 425.0 mg/kg bw/day 4 animals died on day 14), however, these effects were not dose related and are not considered to be a consequence of test substance toxicity, but due to administration errors. There was no maternal toxicity and fetotoxicity determined. The NOEL derived for maternal and fetal toxicity and teratogenicity was therefore 425.0 mg/kg bw/day. For Syrian hamsters the doses of 4.05, 21.15, 98.2 and 405.0 mg/kg bw/day were administered during gestation days 6-10. There was no maternal toxicity and fetotoxicity. The NOEL for maternal and fetal toxicity and teratogenicity was therefore 405.0 mg/kg bw/day.

Since all studies performed with the structural analogue menthol miss detailed description of effects a weight of evidence evaluation is performed. In all four studies no recurring effects were observed. Therefore, it is considered that (±)-neomenthol also does not have a teratogenic potential. It is not considered to be scientifically justified to further investigate the effects of (±)-neomenthol on developmental toxicity and as such no classification on developmental toxicity is proposed and no further studies are deemed necessary.

Justification for classification or non-classification

The available data indicate that (±)-neomenthol does not meet the classification criteria for developmental toxicity in accordance with Regulation (EC) No 1272/2008.