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Description of key information

Low acute toxicity for oral route (LD50  >2000 mg/kg bw).
Low acute toxicity dermal (LD50 >5000 mg/kg bw)
Low acute toxicity inhalative (LC50 (aerosol, 4h) 5289 mg/m3)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 615 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
5 289 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Justification for Read-across:

Based on the identical profiles of the different Menthols and supported by the Read-Across Justification for Menthols (see file MentholsReadAcrossFinal.pdf in section 13) we use all studies on stereoisomers of L Menthol for read across . These isomers are L Menthol (CAS 2216-51-5), D Menthol (CAS 15356-60-2) and DL 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 Kow around 3), vapour pressure (from 17 Pa at 25°C for the DL Menthol to 21 Pa 25°C for the natural L Menthol ) and water solubility ( moderately soluble from 410 mg/l at 25°C for the natural L Menthol to 470 mg/l at 25°C for the DL Menthol). The read across is consistent based on these physico-chemical parameters.

Details on the Acute toxicity studies :

ORAL:

A LD50 value of 3.4 g/kg for L-Menthol was determined in mice. An oral LD50 value in rat was found to be

2,6 g/kg bw for L Menthol, 2,6 g/kg bw for DL Menthol, and 2.05 g/kg bw for D Menthol .

Two studies, one with racemic menthol (Menthol RC composed of DL Menthol 77%, Iso Menthol 10%, NeoIso Menthol 5%, Para Menthol 4%, and Neo Menthol 1%) and one with DL Menthol administered to NMRI mice by gavage resulted in a LD50 value of 1.47 g/kg bw and 9 ml/kg bw, respectively. The studies are not regarded to be relevant for classification. Because only 2 animals per dose were used, the influence of the non DL, D and L Menthol isomeres on the potency is not clear and in case of the of 9 ml/kg bw dose no information was found to translate the result into a mg/kg bw value.

It can be assumed that L-Menthol has a low acute oral toxic potential.

 

INHALATIVE:

The acute inhalative toxicity testing was determined in an OECD 403 study using rats, administering DL Menthol as aerosol. The LC50 in this study (4 hours exposure) was determined to be 5289 mg/m3 and therefore Menthols are considered to have a low acute inhalative toxic potential.

 

DERMAL:

The acute dermal LD50 of L Menthol in rabbits was determined to be greater than 5 g/kg bw.

It can be assumed that L Menthol has a low acute dermal toxic potential.

 

Other routes:

In a study performed by intraperitoneal application a LD50 of 1.5g/kg bw was determined. Since intraperitoneal application is not seen to be a relevant exposure route, this study will not be further considered.

Taken all information and application ways together L Menthol is considered as having a low acute toxic potential

Justification for classification or non-classification

Studies performed by oral and dermal exposure indicate LD50 values beyond the limits for classification and hence L Menthol does not meet the criteria for classification and labelling for these endpoints, as set out in Regulation (EC) No 1272/2008 or in Directive 67/548/EEC respectively. Inhalative exposure to DL Menthol aerosol resulted in an LC50 of 5289 mg/m3 and therefore was found also to be not indicative for classification under CLP (Regulation (EC) No 1272/2008).

Specific target organ toxicity: According to CLP classification criteria, the substance does not meet the criteria for classification and labelling for this endpoint (STOT single exposure) as set out in Regulation (EC) No. 1272/2008 as no indications were observed in acute animal studies.