Registration Dossier

Administrative data

Description of key information

Sub-acute toxicity: NOAEL - Males and females: 1000 mg/kg/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Single study available for evaluation

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

A combined repeat-dose toxicity reproduction/developmental toxicity screen has been undertaken on an analogue of the substance according to OECD TG 422 methods. Dose levels of 0, 100, 300 and 1000 mg/kg/day were investigated. No treatment-findings were noted during the in-vivo phase. Changes in clinical pathological investigations were considered of no toxicological significance. No treatment-related changes were observed at post mortem examinations. On the basis of these findings, the NOAEL (No Observed Adverse Effect Level) for general toxicity is considered to be 1000 mg/kg/day for both males and females.

The lack of toxicity is supported by a 13 -week subchronic toxicity study has been undertaken on castor oil. Dietary levels of 0.00, 0.62, 1.25, 2.50, 5.00 and 10.00% (equivalent to 0, 404, 809, 1583, 3067 and 5835 mg/kg/day in males and 0, 401, 797, 1569, 3045 and 5725 mg/kg/day in females).Exposure was associated with only minimal indications of toxicity with absolute and relative liver weights increased in male rats receiving diets that contained the higher concentrations. These increases were not accompanied by corresponding histopathologic lesions or alterations in clinical chemical endpoints that would indicate hepatotoxicity. Since castor oil is composed of triacylglycerols, the increased liver weights could be a reflection of elevated metabolic activity associated with increased lipid absorption, rather than a toxic response. This conclusion is consistent with the observed increases of total bile acids in serum of male rats and of alkaline phosphatase activity in the serum of both sexes of rats. Bile acids and alkaline phosphatase (intestinal form) are both involved with intestinal absorption and metabolism of lipids, and the serum concentrations are normally increased in association with ingestion of a lipid-rich diet. Although there was some variation in epididymal weights, their small magnitude and the absence of changes in other endpoints suggested that there was little or no evidence of any reproductive toxicity associated with exposure.

Justification for classification or non-classification

No significant toxicity was observed at a concentration of 1000 mg/kg/day in a repeated-dose subacute study of at least 28 days duration.

 

According to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification and labelling is not needed for repeated dose toxicity, as the effects seen in the repeated dose toxicity test do not indicate significant functional change or organ dysfunction occurring at levels below indicated cut-off values. Those effects that were observed are regarded as being of minimal toxicological significance insufficient to warrant classification.