2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

Endpoint summary

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

Additional information

Short description of key information:
No screening for reproductive/developmental study was performed. The REACH Annex VIII data requirements are adapted according to column II of the Annex stating that such a study does not need to be conducted if a pre-natal developmental toxicity study is available.

Effects on developmental toxicity

Description of key information

No studies are available that address the toxicity to reproduction of menthon glycerin ketal. In the available 28d repeated dose study on menthon glycerin ketal, no adverse effects were observed in the reproductive organs examined at any of the dose levels.
The two-generation reproductive toxicity study that is available on read-across substance L-menthol did not show any embryotoxic or teratogenic effects at the highest administered dose of 218 mg/kg bw/d.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

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

No studies are available in which reproductive toxicity of the test substance is examined. In stead, a study is available on the read-across substance menthol. The hypothesis supporting the read-across justification is based on the fact that the source chemical, menthol, is formed upon the metabolisation of the target substance, menthon 1,2 -glycerin ketal. This hypothesis is substantiated by the ADME information available on the target and the source chemicals. A complete description of the read-across justification is attached as background material in IUCLID and can be found in the CSR.

A teratologic evaluation of FDA 71-57 (menthol natural, Brazilian) was performed according to unspecified guideline. Twenty-five female Wistar rats per group were assigned to five dosage groups. Virgin adult females were mated with young adult males. Suspensions of the test substance or the vehicle, corn oil, were administered orally via gavage to 0, 2.18, 10.15, 47.05 and 218.0 mg/kg bw/day at a volume of 10 mL/kg on days 6 through 15 of gestation. Detailed clinical observations were performed daily. Body weight was examined on days 0, 6, 11, 15 and 20. The animals were scarified on gestation day 20 and urogenital tract, number of implantations and resorptions were examined. Foetus was weighted per litter. In addition external, soft tissue and skeletal examinations were performed.

There was no cleary discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.

Therefore the NOEL for maternal toxicity and teratogenicity/fetotoxicity is considered to be at 218 mg/kg bw/day of L-Menthol, i.e. the highest applied dose. The NOEL for maternal toxicity and teratogenicity/fetotoxicity extrapolated to menthonglycerin ketal is 318 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:
The study available on the read-across substance menthol did not show any adverse effects.

Justification for classification or non-classification

As no toxic effects are observed in the 2 -generation reproductive toxicity study that is available on read-across substance methanol, classification for reproductive toxicity under EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) or Directive 67/548/EEC (Dangerous Substances Directive) is not required.