monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol

Endpoint summary

Description of key information

Oral (OECD 422, rat): NOAEL female rat = 300 mg/kg bw/day (read-across)

Oral (OECD 422, rat): NOAEL male rat = 1000 mg/kg bw/day (read-across)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No adverse and treatment-related effects observed up to the highest tested dose level.

Remarks on result:

other: Source: CAS 59231-34-4

Key result

Critical effects observed:

no

The repeated dose toxicity study following the oral route performed with the source substance isodecyl oleate (CAS 59231-34-4) was selected as key study for reasons of structural similarity and data availability. Besides this, a further repeated dose toxicity study with the source substance decyl oleate (CAS 3687-46-5) was taken into account as supporting information. In this study the NOAEL was > 1000 mg/kg bw/day after oral administration of the test substance for 28 days.

Conclusions:

In the repeated dose toxicity studies following the oral route with the source substances no adverse effects were observed in males, therefore the systemic NOAEL was set at 1000 mg/kg bw/day for males. In females of the high dose group (1000 mg/kg bw/day) a statistically significant reduction in food consumption during gestation and lactation period and a statistically significant decrease in body weight during lactation period were noted. Therefore, the NOAEL for systemic toxicity was set at 300 mg/kg bw/day for females. As explained in the analogue justification, this result is considered to be valid also for the target substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 1 and 2) 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, eco-toxicological 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 Monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol. 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 59231-34-4

A combined repeated dose toxicity and reproduction/developmental toxicity screening study was performed according to OECD guideline 422 and under GLP conditions (LPT, 2013) with isodecyl oleate (CAS 59231-34-4). 10 rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day once daily for 35 days (males) and up to 56 days (females) via oral gavage. The control group received the concurrent vehicle. The application started two weeks before mating and ended on the day of or one day before sacrifice. Day of sacrifice was on day 35 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. A statistically significant decrease in body weight (‑9.4%) and food consumption (‑21.7%) was noted in females at 1000 mg/kg bw/day during lactation. There were no toxicologically relevant effects on water consumption and organ weights. No treatment-related effects were noted on the ophthalmology -, haematology - and clinical biochemistry parameters. The macroscopic examination at autopsy and subsequent histopathological examination did not reveal any treatment-related changes. The NOAEL for systemic toxicity was considered to be 300 mg/kg bw/day for female rats and 1000 mg/kg bw/day for male rats.

CAS 3687-46-5

A 28-day oral repeated dose toxicity study was performed with decyl oleate (CAS 3687-46-5) similar to OECD guideline 407 (Institut für Toxikologie, 1987). Ten Wistar rats per sex and dose and 5 per sex and dose satellite rats were administered once daily (5 days a week) 100, 500 and 1000 mg/kg bw/day by gavage, for 28 consecutive days. The control group received the concurrent vehicle. There was no mortality and no toxicologically relevant clinical signs were observed during the study period. No significant differences in body weight, body weight gain, food consumption, water consumption and organ weight were noted between the control group and treatment groups. No treatment-related effects on the ophthalmology-, hematology- and clinical biochemistry parameters were observed. No treatment-related changes were noted during the gross pathology and histopathology examinations. Based on the absence of adverse toxic effects the NOAEL for systemic toxicity was 1000 mg/kg bw/day.

Overall conclusion for repeated dose toxicity

The data for the source substances showed no adverse effects up to and including the recommended limit values. Therefore, as the available data did not identify any hazard for repeated dose toxicity, Monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-oli s not considered to be hazardous following repeated exposure.

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 Monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol, 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) No. 1272/2008 and are therefore conclusive but not sufficient for classification.

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