Reaction mass of octadecyl heptanoate and octadecyl octanoate

Endpoint summary

Description of key information

Oral: OECD 422, rat, NOAEL ≥ 1000 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 stuides 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

Justification for read-across

There are no data on the repeated dose toxicity of Reaction mass of octadecyl heptanoate and octadecyl octanoate (List No. 915-334-0). 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, subacute

CAS 22393-85-7

A 14-day dose range-finding study was performed with Tetradecyl oleate (CAS 22393-85-7) in order to find appropriate dose levels for a subsequent combined repeated dose toxicity and reproduction/developmental toxicity screening study according to OECD guideline 422 (Rossiello, 2013). In this study, 5 rats per sex and dose were administered the test substance once daily at 100, 300 and 1000 mg/kg bw/day via oral gavage for 14 days. No mortality occurred and no clinical signs were observed during the study period. The body weight and food consumption was comparable between the control and treatment groups. Minor changes were observed in organ weights as noted by decreases in the absolute and relative thymus weight (approximately -18%) in males receiving 1000 mg/kg bw/day and statistically significant decreases in absolute and relative kidneys weight (-12%, for absolute weights) in females receiving 1000 mg/kg bw/day. These effects were not considered to be adverse, as they were observed in one sex only and no corresponding histopathological changes were seen. Based on the results of this study, the subacute NOAEL for male and female rats was considered to be ≥ 1000 mg/kg bw/day.

A combined repeated dose toxicity and reproduction/developmental toxicity screening study (according to OECD guideline 422 and in compliance with GLP) was performed (Rossiello, 2014). 10 rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day Tetradecyl oleate once daily for 28-29 days (males) and up to 54 days (females) via gavage. The application started two weeks before mating on test day one and ended on the day of or one day before sacrifice. Day of sacrifice was on test day 29 or 30 for the male rats and on lactation day 3 or shortly thereafter for the female rats. There was no mortality during the study period. No toxicologically relevant clinical signs were observed. The body weight, body weight gain and food consumption was comparable between the control and treatment groups. There were no toxicologically relevant effects on organ weights. The statistically significant differences in haematological parameters between control and treated animals (erythrocytes, mean corpuscular haemoglobin and leucocytes in males, haemoglobin, haematocrit and platelets in females) were of low magnitude and/or not dose-related and therefore considered incidental. Statistically significant fluctuations of some biochemical parameters, compared with the control groups, were recorded in both sexes. An increase in glucose levels in males administered 100 and 1000 mg/kg bw/day (48% for both doses), and an increase in urea in males receiving 100 mg/kg bw/day (19%) was observed. In females in the 300 mg/kg bw/day group, an increase in aspartate aminotransferase level (35%) was noted, while for females administered 1000 mg/kg bw/day, a decrease in bilirubin levels (81%) and an increase in potassium levels (10%) was observed. Due to the lack of dose- and/or sex-consistency, and due to the absence of other relevant findings, these changes are not considered to be toxicologically relevant. There was no significant difference between control and treatment groups during the observational and neurological screenings. The macroscopic inspection at autopsy and subsequent histopathological examination did not reveal any treatment-related changes. The NOAEL for systemic toxicity was considered to be ≥ 1000 mg/kg bw/day.

 

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 in the conducted combined repeated dose toxicity and reproduction/developmental toxicity screening studies. Therefore, as the available data did not identify any hazard for repeated dose toxicity, Reaction mass of octadecyl heptanoate and octadecyl octanoate 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 Reaction mass of octadecyl heptanoate and octadecyl octanoate (List No. 915-334-0), 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.