Isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester

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

Reproductive toxicity (fertility) - Data waiving

According to Regulation (EC) No 1907/2006, Annex VIII, 8.7.1., column 2, a Reproduction/Developmental Toxicity Screening Test is not required as a test for prenatal developmental toxicity (Annex IX, 8.7.2) is available for the structural related substance TMP ester of C8/C10 fatty acids (CAS 11138-60-6), which will be used for read-across. On the basis of this dermal prenatal developmental toxicity study performed equivalent or similar to OECD guideline 414 no systemic test item related toxicological findings in dams or fetuses were revealed resulting in a NOAEL (systemic) of 2000 mg/kg bw/day. Necropsy findings on maternal animals were limited to skin flaking and scabbing first identified in life end observations related to wearing the Elizabethan collar (local alopecia, chromorhinorrhea, and neck lesions), thus a local NOAEL (maternal) of 200 mg/kg bw/day was derived. There were no significant differences in any of the developmental parameters examined including embryo/fetal viability, fetal weight, malformations, or variations when compared to the control, thus a NOAEL (developmental) of 2000 mg/kg bw/day was derived.

Effects on developmental toxicity

Description of key information

Dermal: OECD 414, rat, NOAEL (development, maternal systemic) ≥2000 mg/kg bw/day, 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

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 read-across

There is no data available addressing toxicity to reproduction of isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester (CAS 109884-54-0).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 the read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a comparable pattern as a result of structural similarity, the substance TMP ester of C8/C10 fatty acids (CAS 11138-60-6) is selected as source substance.

 

Developmental toxicity/teratogenicity

CAS 11138-60-6

Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) was tested in a prenatal developmental toxicity study comparable 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. There were no differences from control 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

The reliable data available for the source substance TMP ester of C8/C10 fatty acids indicate no hazard to development in the prenatal developmental toxicity study performed similar to OECD TG 414 via the dermal route in rats. Based on the available data, isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester is not expected to be hazardous for intrauterine 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 isooctadecanoic acid, 1,1'-(2,2-dimethyl-1,3-propanediyl) ester, 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.