Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters

Endpoint summary

Description of key information

Oral (OECD 422, OECD 407, read across): subacute NOAEL m/f rat ≥ 1000 mg/kg bw/day

Oral (OECD 408, read across): sub-chronic NOAEL m/f rat ≥ 1000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral, other

Remarks:

short term and subchronic

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Justification for type of information:

refer to the analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Remarks:

rat

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

Remarks on result:

other:

Remarks:

Source: CAS 22393-85-7

Key result

Critical effects observed:

no

The in vivo repeated dose toxicity data from the source substance tetradecyl oleate (CAS 22393-85-7) were selected as key results for reasons of data reliability and structural similarity.

Additional in vivo data was available for the two source substances.

In a 28-day oral repeated dose toxicity study with decyl octadec-9-enoate (CAS 3687-46-5) rats were administered oral doses up to 1000 mg/kg bw/day by gavage. No mortality and no toxicologically relevant adverse effects were observed during the study period. The NOAEL for systemic toxicity was ≥ 1000 mg/kg bw/day.

In a sub-chronic oral toxicity study with Octanoic acid, 2-propylheptylester (CAS 868839-23-0) rats were administered doses up to 1000 mg/kg bw/day by gavage. No treatment-related mortality and no toxicologically relevant adverse effects were observed during the study period. The NOAEL for systemic toxicity was ≥ 1000 mg/kg bw/day.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their repeated dose toxicity potential. The oral repeated dose toxicity of the target substance is estimated based on adequate and reliable short-term and subchronic toxicity studies with structural analogue source substances. The systemic NOAEL in male and female rats was found to be ≥1000 mg/kg bw/day for all three source substances, tetradecyl oleate (CAS 22393-85-7), decyl oleate (CAS 3687-46-5), and Octanoic acid, 2-propylheptylester (CAS 868839-23-0). Therefore, a NOAEL for repeated dose toxicity after oral exposure of 1000 mg/kg bw is considered for the target substance Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score ≤2) 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 studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII-X, 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

Mode of Action Analysis / Human Relevance Framework

Not applicable

Additional information

Read across justification

There are no data on the repeated dose toxicity of Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS). 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 is 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

CAS 22393-85-7

A combined repeated dose toxicity and reproduction/developmental toxicity screening GLP study was performed according to OECD Guideline 422 (key study, 2014) with Tetradecyl oleate (CAS 22393-85-7). Ten rats per sex and per dose were administered 0, 100, 300 and 1000 mg/kg bw/day once daily for 28-29 days (males) and up to 54 days (females) via oral 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%) 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 considered to be ≥ 1000 mg/kg bw/day.

 

CAS 3687-46-5

A short-term repeated dose oral toxicity study was performed with the source substance decyl oleate (CAS 3687-46-5) equivalent to OECD guideline 407 (WoE, 1987). No toxicologically relevant effects on clinical signs, mortality, body weight and weight gain, food consumption, water consumption, haematology, clinical biochemistry, organ weights, gross pathology, and histopathology were found at doses up to 1000 mg/kg bw/day administered by gavage on 5 days per week over an administration period of 28 days. The NOAEL in rats was found to be 1000 mg/kg bw/day.

 

CAS 868839-23-0

A sub-chronic oral toxicity study was performed with the source substance Octanoic acid, 2-propylheptylester (CAS 868839-23-0) according to OECD guideline 408 under GLP conditions (WoE, 2006). No toxicologically relevant effects on clinical signs, mortality, body weight and weight gain, food consumption, water consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis, neurobehaviour, organ weights, gross pathology, histopathology were found at doses up to 1000 mg/kg bw/day administered by gavage on 7 days per week to 10 male and female rats per dose over an administration period of 90 days. Moreover, no effects on the mean length of the oestrus cycles and the number of complete cycles was found in females and no effects on the mean number and percentage of ultrasound-resistant spermatids, number of motile spermatozoa in the cauda epididymis, and the percentage of spermatids with malformations was seen. The NOAEL in rats was found 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 values. Therefore, as the available data did not identify any hazard for repeated dose toxicity via oral route, Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) is 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 Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) 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.