Registration Dossier

Administrative data

Description of key information

Oral: similar to OECD 408, rat, NOAEL ≥ 5725 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2 due to read-across) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

Analogue justification

Data on the repeated dose toxicity of 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Repeated dose toxicity, oral, subchronic

CAS No. 8001-79-4

The subchronic oral toxicity of Castor oil was investigated in male and female Fischer 344 rats in a GLP-conform study similar to OECD guideline 408 (Irwin, 1992). The test substance was administered daily for a period of 13 weeks to groups of 20 animals/sex at dietary concentrations of 0.62, 1.25, 2.50, 5 and 10% (w/w), equivalent to doses of 404, 809, 1583, 3067 and 5835 mg/kg bw/day in males and 401, 797, 1569, 3045 and 5725 mg/kg bw/day in females, respectively. A control group received the plain diet. Ten of the 20 animals per sex and group were used to analyse haematological and clinical chemistry parameters on Days 5 and 21 and at the end of the study. During the study period, no mortalities and no clinical signs were observed. The body weights and food consumption in treated animals were comparable to those in control animals. The observed changes in haematological parameters in males administered 10% test substance (decreased mean corpuscular volume and mean corpuscular haemoglobin, increased platelet count) and in females administered 10% (reduced reticulocyte level) are not considered to be biologically relevant, as they were only observed in one sex, were not dose-dependent and no histopathological changes were observed. The significant increase in hepatic alkaline phosphatase levels observed consistently in the 5 and 10% groups, and incidentally in the 1.25 and 2.5% groups, is considered to be a consequence of the higher hepatic load by the castor oil, and therefore an adaptive effect. The absolute and relative liver weights were increased at a dose level of 5835 mg/kg bw/day. An increase in relative heart weight in males was noted at 404, 1583 and 5835 mg/kg bw/day. Furthermore, a slight decrease in epididymal weight (6-7%) was observed in male animals of the middle and high dose groups. However, these effects were not considered to be treatment-related, since they were not dose-dependent and no correlating histopathological changes were noted. Macroscopic and microscopic examinations did not reveal any substance-related effects in the animals of any dose group. Based on the overall effects of the study, the NOAEL is considered to be ≥ 10% (w/w) for both sexes, equivalent to ≥ 5835 mg/kg bw/day in males and ≥ 5725 mg/kg bw/day in females, respectively.

A subchronic oral toxicity study was performed with Castor oil according to a protocol similar to OECD guideline 408 and under GLP conditions (Irwin, 1992). The test substance was administered to B6C3F1 mice at dietary concentrations of 0.62, 1.25, 2.50, 5 and 10% (w/w), equivalent to doses of 917, 2022, 3800, 7823 and 15017 mg/kg bw/day in males, and 1153, 2282, 5009, 9627 and 16786 mg/kg bw/day in females, respectively. 20 animals per sex and group received the test substance in the diet or plain diet (controls) daily ad libitum for 13 weeks. Ten of the 20 animals per sex and per group were used to analyse haematological and clinical chemistry parameters on Days 5 and 21. At study termination, no mortalities, no clinical signs and no biologically relevant changes in body weights and food consumption were observed in all treated animals compared to controls. No effects on parameters of clinical chemistry and haematology were observed in treated all animals compared to controls. At 5 and 10% doses, the liver weights were increased in both sexes. This is considered to be a consequence of the higher hepatic load by the castor oil, and therefore an adaptive effect. The kidney weights were increased in females administered 10% only. Since the effects were marginal and no histopathological changes were observed in the liver and kidney, they were not considered to be toxicologically relevant. Gross pathology and histopathology did not reveal any substance-related findings in the animals of any dose groups. The NOAEL is considered to be ≥ 10% (w/w) for both sexes, equivalent to ≥ 15017 mg/kg bw/day in males and ≥ 16786 mg/kg bw/day in females, respectively.

Overall conclusion for repeated dose toxicity

 The data for the read-across analogue substance showed that no effects were observed up to and including the recommended limit value of 1000 mg/kg bw/day in the subchronic repeated dose toxicity studies. Therefore, as the available data did not identify any hazard for repeated dose toxicity, 1,2,3-propanetriyl triisooctadecanoate is not considered to be hazardous following repeated exposure.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between the source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.