Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

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

Additional information

A screening study for reproductive/developmental toxicity is not available. Reliable data has been included to cover toxicity to reproduction, as set out in Column 2 of Annex VIII, Section 8.7.1, Regulation (EC) No 1907/2006. A pre-natal developmental toxicity study performed with a source substance according to OECD 414 is available (Azuka and Daston, 2004). No treatment-related effects were observed on any of the assessed reproductive and developmental parameters up to and including the highest dose level of 1000 mg/kg bw/day. Thus, providing a screening study for reproductive/developmental toxicity is not necessary as the data requirements are met according to Column 2 of Annex VIII, Section 8.7.1, Regulation (EC) No 1907/2006.

Short description of key information:
No study available.

Justification for selection of Effect on fertility via oral route:
No study required since no adverse effects on reproductive organs were seen in the available subchronic studies conducted with structural analogues substances via the oral, dermal and inhalation route (OECD 408, OECD 413 and OECD 411).

Justification for selection of Effect on fertility via inhalation route:
No study required since no adverse effects on reproductive organs were seen in the available subchronic studies conducted with structural analogues substances via the oral, dermal and inhalation route (OECD 408, OECD 413 and OECD 411).

Justification for selection of Effect on fertility via dermal route:
No study required since no adverse effects on reproductive organs were seen in the available subchronic studies conducted with structural analogues substances via the oral, dermal and inhalation route (OECD 408, OECD 413 and OECD 411).

Effects on developmental toxicity

Description of key information

Dermal: OECD 414, rat, NOAEL development ≥ 2000 mg/kg bw/day
Dermal: OECD 414, rat, NOAEL maternal systemic ≥ 2000 mg/kg bw/day
 Dermal: OECD 414, rat, NOAEL maternal local = 200 mg/kg bw/day 

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2) and consistent study 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, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are no data available for developmental toxicity of the substance Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers. In order to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across to structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests", which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substance Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) is selected as source substances for hazard assessment.

Discussion

CAS 11138-60-6

Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) were tested in a prenatal developmental toxicity study similar to OECD Guideline 414 (Azuka and Daston, 2004). The test substance was percutaneously applied to Sprague-Dawley rats for 6 h/day under occlusive conditions. 25 animals per sex per dose were treated with 200, 600 or 2000 mg/kg bw/day in corn oil on Days 6-15 of gestation. Control animals (25 per sex per dose) received the vehicle. The middle and the high dose levels caused some local irritation at the site of application, but no decreases in maternal weight gain or food consumption were observed. No differences between control and test animals were detected in any of the developmental parameters measured, including embryo/fetal viability, fetal weight, malformations, or variations. Therefore, a NOAEL of 2000 mg/kg bw/day was derived for prenatal development and for systemic maternal toxicity. Due to the irritation effects on skin, the local maternal NOAEL was found to be 200 mg/kg bw/day.

Conclusion for developmental toxicity

There is one study available on a structurally related substance which was used to assess the developmental toxicity/teratogenic potential of Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers.

The prenatal developmental toxicity study conducted with the structural related substance Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) did not show any developmental toxic effects and hence, a NOAEL of 2000 mg/kg bw/day was derived.

Therefore, following a weight-of-evidence approach, Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers is not considered as hazardous for in utero development.

Justification for selection of Effect on developmental toxicity: via oral route:
A dermal study addressing developmental toxicity is available.

Justification for selection of Effect on developmental toxicity: via inhalation route:
A dermal study addressing developmental toxicity is available.

Justification for selection of Effect on developmental toxicity: via dermal route:
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 source and target substance and overall assessment of quality, duration and dose (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 Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers 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, fertility and development/teratogenicity does not meet the classification criteria according to Regulation (EC) 1272/2008, and is therefore conclusive but not sufficient for classification.