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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a pre-natal developmental toxicity study is available

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Developmental toxicity/teratogenicity and maternal toxicity (read-across, OECD 414) NOAEL rat: ≥1000 mg/kg bw/day

Link to relevant study records

Reference

Endpoint:

developmental toxicity

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:

NOAEL

Remarks:

rat

Effect level:

>= 900 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: no adverse toxic effects

Remarks on result:

other: Source: CAS 91031-31-1

Key result

Dose descriptor:

NOAEL

Remarks:

rat

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: no adverse toxic effects

Remarks on result:

other: Source: CAS 853947-59-8

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Remarks:

rat

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse toxic effects

Remarks on result:

other:

Remarks:

Source: CAS 853947-59-8

Key result

Abnormalities:

no effects observed

Key result

Developmental 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 a developmental study is given for the source substance Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1). In this study, the developmental NOAEL in male and female rats was found to be ≥ 900 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. In a developmental toxicity oral gavage study (OECD 414) in rats with the analogue substance C8-10, 1,3-Butandiolester (CAS 853947-59-8) the NOAEL for developmental and maternal toxicity was found to be greater than 1000 mg/kg/day (highest dose tested). For the target substance Fatty acids, C12-18, esters with 1,3-butanediol (CAS 73138-39-3) no reproduction/developmental toxic effects are anticipated based on common predictable ester hydrolysis breakdown products (fatty acids and butylene glycol). Therefore, a NOAEL for developmental toxicity of 1000 mg/kg bw/day is considered for the target substance.
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The 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, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no data on developmental 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).

CAS 853947-59-8

A developmental toxicity study was performed according to OECD Guideline 414 under GLP conditions (key study, 2007). 24 female Sprague-Dawley rats were administered the limit dose of 1000 mg/kg bw/day C8-C10-fatty acid-1,3 -butandiolester (CAS 853947-59-8) once daily from day 6 up to day 19 post mating via oral gavage in corn oil as vehicle. No adverse effects on maternal toxicity, developmental toxicity/teratogenicity were observable at the limit dose of 1000 mg/kg/day. The NOAEL for developmental toxicity/teratogenicity and maternal toxicity was found to be ≥1000 mg/kg bw/day.

CAS 91031-31-1

A developmental toxicity study was performed according to OECD Guideline 414 under GLP conditions (supporting study, 1997). 24 female Sprague-Dawley rats per dose were administered 100, 300, or 900 mg/kg bw/day Fatty acids, C16-18; ester with ethylenglycol (CAS 91031-31-1) once daily from gestational day 6 to 15 via oral gavage in 0.5% sodium carboxymethylcellulose and 0.25% Cremophor in aqua dest. as vehicle. No adverse effects on maternal toxicity, developmental toxicity/teratogenicity were observable. The NOAEL for developmental toxicity/teratogenicity and maternal toxicity was found to be ≥900 mg/kg bw/day.

Overall conclusion for developmental toxicity/teratogenicity

Analogue read-across from source substances was applied for the developmental toxicity /teratogenicity endpoint. No effects on reproductive parameters/organs were observed in the available prenatal developmental toxicity studies. The NOAEL for developmental toxicity was found to be 900 mg/kg bw/day. Based on the available data and following the analogue approach, absence of adverse effects on developmental toxicity/teratogenicity is expected for the target substance Fatty acids, coco, esters with 1,3 -butanediol (CAS 73138 -39 -3).

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, coco, esters with 1,3 -butanediol (CAS 73138 -39 -3), 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. Based on the analogue read-across approach, the available data on toxicity to reproduction does not meet the classification criteria according to Regulation (EC) No. 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.

Therefore, based on the analogue read-across approach, the available data do not indicate a hazard for reproduction toxicity.