Hexadecyl (R)-12-hydroxyoleate

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 studies from reference substances 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 available data on the repeated dose toxicity of Hexadecyl (R)-12 -hydroxyoleate (CAS 10401-55-5). 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).

Repeated dose toxicity, oral, subacute

CAS 22393-85-7

A combined repeated dose toxicity and reproduction/developmental toxicity screening study was performed according to OECD guideline 422 and in compliance with GLP (Rossiello, 2014). 10 rats/sex/dose were administered 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 were 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%) were 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 therefore considered to be ≥ 1000 mg/kg bw/day.

CAS 3687-46-5

A 28-day oral repeated dose toxicity study was performed according to a protocol similar to OECD guideline 407, using Decyl oleate (CAS 3687-46-5) (Potokar, 1987). 10 Wistar rats/sex/dose were administered 100, 500 and 1000 mg/kg bw/day by gavage, 5 days/week, over a period of 28 days. A satellite group of 5 rats/sex/dose was included for the control and all dose levels. No detailed clinical observations outside the home cage or neurobehavioural tests were performed. There was no mortality and no toxicologically relevant clinical signs were observed during the study period. No treatment-related differences in body weight, body weight gain and food consumption between the control group and treatment groups were observed. The ophthalmoscopic examination did not show treatment-related effects on the eyes. Significant decreases in haemoglobin levels were observed in all dose groups. As the changes were not dose-related and no other treatment- related effects were noted in histopathological parameters, this effect isnot considered to be a toxicologically relevant effect. The inorganic phosphorus level was increased significantly in the males of all dose groups and in the low- and mid-dose females. The effect was not dose-related in the males and not observed at the highest dose level in females, therefore it is not considered to be toxicologically relevant. The urinary parameter values were comparable between the control group and the treatment groups. In females administered the highest dose, the absolute kidney weight was increased. The relative weight was not affected and the change was seen only in one sex, leading to the conclusion that this effect does not have toxicological relevance. The relative heart weight in males in the mid- and high-dose groups was reduced slightly, but significantly, while the absolute heart weight was increased in the mid-dose group. The male high-dose group was not affected and no related effects were noted in the histopathological examination. Therefore, this effect is not considered to have toxicological relevance. No treatment-related gross pathological effects were observed in organs or tissues. The mucosa of the forestomach in control and treatment groups showed degenerative changes or signs of inflammation; 1/10 males and 3/10 females in the control group, and 2/10 females in the high-dose group had hyperplasia. 7/10 males and 7/10 females in the control group, and 5/10 males and 7/10 females in the high-dose group exhibited focal eosinophilic infiltration of the forestomach. These effects were possibly caused by the repeated use of a stomach tube for  gavage. As humans do not have a forestomach, this effect is not relevant to human exposure. No other treatment-related effects were observed on organs or tissues during the histopathological examination. No treatment-related changes were noted in the salivary gland, lungs, pancreas or stomach in the satellite animals. Based on the lack of toxicologically relevant effects up to and including the highest dose level, the NOAEL is considered to be ≥ 1000 mg/kg bw/day. For details on reproductive and developmental toxicity, please refer to the respective chapters included in the dossier.

 

Overall conclusion for repeated dose toxicity

Analogue read-across from subacute studies from 2 source substances was applied to assess the potential for the target substance to cause repeated dose toxicity. The NOAEL values for repeated dose toxicity were above the currently applied limit dose value of 1000 mg/kg bw/day. No hazard after repeated oral exposure was identified. Therefore, Hexadecyl (R)-12 -hydroxyoleate is not expected to cause long-term toxic effects via the oral route.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. 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 substances and overall assessment of quality, duration and dose (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 Hexadecyl (R)-12 -hydroxyoleate (CAS 10401-55-5), 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 and are therefore conclusive but not sufficient for classification.