Cineole

Endpoint summary

Description of key information

Acute oral:  A key study was not available on the target substance therefore data was presented on the read across substance, Clarycet.  The acute median lethal oral dose for males and females combined were 4.5 g/kg body weight; for males only it was estimated to be 4.7 g/kg body weight (and for females only was 4.3 g/kg body weight 
Acute dermal: A key study was not available on the target substance therefore data was presented on the read across substance, Clarycet. The LD50 of Clarycet was > 2.0 g/kg bodyweight; a supporting study on the target substance itself had an LD50 of 5.0 g/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute - Oral

A key study was not available on the target substance therefore data was presented on the read across substance, Clarycet. Clarycet was assessed for acute oral toxicity in the rat according to OECD guideline 401. The acute median lethal oral dose and the 95 % confidence limit for males and females combined were 4.5 g/kg body weight (3.3 - 5.8 g/kg confidence limits); for males only it was estimated to be 4.7 g/kg body weight (3.2 - 7.0 g/kg confidence limits) and for females only was 4.3 g/kg body weight (2.8 - 6.1 g/kg confidence limits).

In a supporting study, the target substance itself was assessed for acute oral toxicity. The oral administration of Cineole to rats for 14 days produced no toxicologically significant effects in the parameters measured. The study determined that the acute oral LD₅₀ of the test material to rats was 2480 mg/kg bw.

Acute - Dermal

Key study for acute dermal in vivo (Huntingdon, 1991, OECD Guideline 402).

The dermal administration of a single exposure to the read-across substance, Clarycet, at 2 g/kg bodyweight produced no toxicologically significant results. The acute dermal LD50 was therefore > 2 g/kg bodyweight.

To address toxicological endpoints as part of the REACH registration of Cineole (Target Substance) it is proposed to read-across to Clarycet (Source Substance).

The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible.

The Target Substance and Source Substance have been characterised in using the categories and databases present in the OECD (Q)SAR Toolbox. From the profiling in this table, it can be seen that the two substances share structural similarities and also "mechanistic action" similarities which are both general and endpoint specific.

Therefore read-across is justified.

Justification for selection of acute toxicity – inhalation endpoint
The oral and dermal LD50 levels for the test substance have been determined and both demonstrate relatively harmless levels of acute toxicity >2000 mg/kg bw, with the acute oral LD50 of > 4500 mg/kg and therefore do not require labelling under CLP. Testing by the inhalation route in accordance with column 2 of Annex VIII of 1907/2006/EC, is therefore considered to be inappropriate as exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance (122 Pa at 25°C) and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

Based on the oral LD50 values of >2480 mg/kg bodyweight and dermal LD50 values of > 2000 mg/kg bodyweight, there is no need to classify Cineole for acute to toxicity in accordance with the criteria outlined in Annex VI of 67/548/EEC (DSD) and Annex I of 1272/2008/EC (CLP).