Tetradecyl stearate

Endpoint summary

Description of key information

Oral: OECD 408, 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 an adequate and reliable study (Klimisch score 2 due to read-across) 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

Data on the repeated dose toxicity of tetradecyl stearate (CAS 17661-50-6) 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.

CAS 868839-23-0

A 90-day repeated dose toxicity study was performed in rats according to OECD 408, using propylheptyl octanoate (CAS 868839-23-0) (Leuschner, 2006). 10 Wistar rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day of the test substance in soybean oil by gavage, for 90 consecutive days. 1/10 females in each of the low-, mid- and high dose groups, respectively, died during the laboratory examinations on the last treatment day after blood withdrawal. These deaths are considered to be caused by the ether narcosis and are therefore not treatment-related. No treatment-related clinical signs were observed. No treatment-related effects were noted on body weight, body weight gain, food consumption and water consumption. The ophthalmoscopic examination did not shown treatment-related effects on the eyes. No treatment-related effects were observed during the neurobehavioral and observational tests. There were no statistically significant differences in the haematology parameters between the control group and the treatment groups. The albumin and blood urea nitrogen levels were significantly increased in the males in the high-dose group. As no effects were noted on these parameters in the females of the high-dose group, and in the absence of related histopathological findings, these effects are not considered to be toxicologically relevant. A statistically significant decrease in urinary pH value was noted in males in the mid-dose group and in males and females in the high-dose groups. This is considered to be a treatment-related, but not toxicologically relevant, effect as no other effects on urinary parameters or kidney histopathology was noted. The absolute and relative liver weight in high-dose males and females was significantly increased. This is probably an adaptive response to the increased metabolic load due to ingestion of the test substance. As no related effects were noted on liver enzyme levels or liver histopathology, this is not considered to be a toxicologically relevant effect. There were no statistically significant differences in the mean length of the oestrus cycles and the number of complete cycles between the females in the control group and the treatment groups. In males, there were no statistically significant differences between the control group and the treatment groups in the mean number and percentage of ultrasound-resistant spermatids, number of motile spermatozoa in the cauda epididymis, and in the percentage of spermatids with malformations. No treatment-related gross pathological or histopathological effects were observed in organs or tissues.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.

CAS 22393-85-7

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test, according to OECD 422 and GLP is available (Rossiello, 2014). 10 rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day of tetradecyl oleate, formulated in carboxymethylcellulose (0.5% in purified water), once daily for at least 28 to 29 days (males) and up to 54 days (females) via gavage. The application started two weeks before mating on test Day 1 and ended on the day or one day before sacrifice. Day of sacrifice was on test Day 28 to 29 for the male rats and on Day 4 post-partum for the female rats. No test item-related premature death was noted. No test item-related signs of toxicity were noted in parental animals during the observational and neurological screenings. No differences of toxicological significance were seen in terminal body weight, body weight gain and in food consumption. No relevant changes were recorded in parental animals on clinical pathology investigations (haematology and clinical chemistry). Macroscopic inspection at autopsy and histopathological examination revealed no test item related changes. No other effect was observed in any further group or any parameter. On the basis of the results obtained in the study, the NOAEL for systemic toxicity was determined to be ≥ 1000 mg/kg b w/day for both sexes.

Overall conclusion for repeated dose toxicity

The data on the read-across analogue substances showed that no effects were observed up to and including the recommended limit values. Therefore, as the available data did not identify any hazard for repeated dose toxicity, tetradecyl stearate 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 tetradecyl stearate (CAS 17661-50-6) 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.