Cineole

Endpoint summary

Description of key information

The test substance was assessed for repeated dose oral toxicity according to OECD 407.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

600 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The test substance was assessed for repeated dose oral toxicity according to OECD 407. The No Observed Adverse Effect Level (NOAEL) for the female rat was considered to be 600 mg/kg bw/day but for the male rat was only 30 mg/kg bw/day. However, the adverse findings observed for males were characterised by renal changes specific to the male rat and of no toxicological relevance to man. Excluding these renal changes, the NOAEL was 600 mg/kg bw/day and this represents the most appropriate dosage for any assessment of the risk to human health.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The test substance was assessed for repeated dose oral toxicity according to OECD 407.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
In line with Column 2, point 8.6.1, Annex VIII of Regulation 1907/2006, a repeat-dose inhalation study does not need to be performed as the substance has low vapour pressure and high melting point, so the potential for the generation of inhalable forms is low. The use of this substance should not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and a repeat-dose inhalation study is not required. As an objective of Regulation EC No. 1907/2006 is to reduce, replace or refine animal testing, based on the above information and information in this dossier, it can be reasonably expected that inhalation exposure is not expected and as such, further investigation using vertebrate animals is therefore considered unnecessary.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
The physicochemical and toxicological properties suggest low potential for significant rate of absorption through the skin. Furthermore the results of laboratory animal studies show low acute dermal toxicity. In the 28 - days repeated dose study via dietary administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can be extrapolated to repeated dermal route administration. Furthermore, contact with neat substance will be prevented by risk mitigation measures in the modern industrial setting. Further investigation using vertebrate animals is therefore considered unnecessary.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The results of laboratory animal studies show low acute dermal toxicity. In the 28 - days repeated dose study via dietary administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can be extrapolated to repeated dermal route administration. Also, dermal absorption is not considered likely to be greater than absorption via the oral route. Furthermore, contact with neat substance will be prevented by risk mitigation measures in the modern industrial setting.
Therefore, further investigation using vertebrate animals is considered unnecessary.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The results of laboratory animal studies show low acute dermal toxicity. In the 28 - days repeated dose study via dietary administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can be extrapolated to repeated dermal route administration. Also, dermal absorption is not considered likely to be greater than absorption via the oral route. Furthermore, contact with neat substance will be prevented by risk mitigation measures in the modern industrial setting.
Therefore, further investigation using vertebrate animals is considered unnecessary.