Fatty acids, coco, esters with 1,3-butanediol

Endpoint summary

Description of key information

Oral (Read-across, equivalent to OECD 408, rat) NOAEL: 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:

sub-chronic toxicity: oral

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:

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:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of any adverse toxic effects

Remarks on result:

other: CAS 853947-59-8

Key result

Critical effects observed:

no

Data from the source substance C8-10, 1,3-Butandiolester (CAS 853947-59-8) was selected as key results for reasons of structural similarity and data reliability.

Additional data from sub-chronic (90-day) oral toxicity testing is given for the source substance stearic acid, monoester with propane-1,2-diol / 2-hydroxypropyl stearate (CAS 1323-39-3). In this study, the systemic NOAEL in male and female rats was found to be ≥ 5000 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 repeated dose toxicity studies with source substances. In a sub-chronic (90-day) oral gavage study (OECD guideline 408) in male and female rats with the source substance C8-10, 1,3-Butandiolester (CAS 853947-59-8) the NOAEL was found to be greater than 1000 mg/kg/day (highest dose tested). Therefore, a NOAEL for repeated dose toxicity after oral exposure of > 1000 mg/kg bw/day is considered for the target substance Fatty acids, C12-18, esters with 1,3-butanediol (CAS 73138-39-3).
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

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:

TThe available information comprises adequate and reliable (Klimisch score 2) studies from reference substances with a common mode of action. Read-across is justified based on different compounds having the same type of effect(s) as described in scenario 2 of the Read-Across Assessment Framework (Read-Across Assessment Framework (RAAF), European Chemicals Agency, Helsinki, Finland, 2017), (please refer to the Analogue Justification for further details provided in IUCLID section 13).The selected studies are 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

Mode of Action Analysis / Human Relevance Framework

Not applicable

Additional information

There are no data on the repeated dose toxicity of Fatty acids, coco, esters with 1,3-butanediol (CAS 73138-39-3). 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. Read-across is justified based on different compounds having the same type of effect(s) as described in scenario 2 of the Read-Across Assessment Framework (Read-Across Assessment Framework (RAAF), European Chemicals Agency, Helsinki, Finland, 2017. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Repeated dose toxicity, oral, subchronic

CAS 853947-59-8

A 90-day oral gavage repeated dose toxicity study equivalent to OECD guideline 408 (key study, 2001) was performed with C8-10, 1,3-Butandiolester (CAS 853947-59-8). Ten Sprague-Dawley rats/sex/dose were administered 250, 500 and 1000 mg/kg bw/day, once daily for 13 weeks. There was no mortality. Except for slight salivation no clinical signs were observed during the study. No treatment related effects on body weight, ophthalmology, haematology, clinical biochemistry, urine analysis, behaviour, gross pathology, neuropathology and histopathology were found. Based on the lack of toxicologically relevant effects up to and including the highest dose level, the NOAEL was considered to be 1000 mg/kg bw/day.

CAS 1323-39-3

A 90-day oral feeding repeated dose toxicity study equivalent to OECD guideline 408 (supporting study, 1967) was performed with Stearic acid, monoester with propane-1,2-diol / 2-hydroxypropyl stearate (CAS 1323-39-3). Twenty-four Sprague-Dawley rats/sex/dose were administered 1.5, 3.36 or 7.52 %(w/w) in diet for 13 weeks. There was no mortality. No clinical signs were observed during the study. Based on the lack of toxicologically relevant effects up to and including the highest dose level, the NOAEL was considered to be greater than 5000 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, Fatty acids, coco, esters with 1,3-butanediol (CAS 73138-39-3) 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, data will be generated from data of 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.