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

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Justification for read-across

There are no data available for the skin sensitisation potential of the target 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 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 toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substances Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5), Fatty acids, C8-18 and C18-unsatd., esters with Neopentylglycol (CAS 85186-86-3) and Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) are selected as source substances.

CAS 68855-18-5

The skin sensitisation potential of Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) was evaluated in guinea pigs with a Buehler test for skin sensitisation performed according to OECD guideline 406 under GLP conditions (Doyle, 1996). 20 male Dunkin-Hartley guinea pigs were treated with the test substance and compared to 10 male control animals. Three epidermal inductions were performed with 100% test substance at weekly intervals for 6 h under occlusive conditions. 14 days after the last induction treatment, all animals were challenged for 6 h epicutaneously with 100% (left top flank) and 30% (right top flank) test substance (diluted in corn oil) under occlusive conditions. The animals were evaluated for skin reactions 24 and 48 h after the challenge. 1/20 animals (5%) of the test group responded to the challenge treatment with 100% test substance formulation. Scattered mild redness was observed 24 h after challenge; the effect had cleared by the second reading (48 h). No further signs of irritation or sensitisation were observed during induction and challenge of the animals. The test item is considered not to be sensitising to guinea pigs under the conditions of the test.

CAS 85186-86-3

The skin sensitisation potential of Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS 85186-86-3) was evaluated in mice in a Local Lymph Node Assay performed according to OECD guideline 429 under GLP conditions (Pooles, 2012). The test substance was applied in concentrations of 25, 50, and 100% on three consecutive days to the dorsal surface of each ear of 4 female CBA/Ca (CBA/CaOlaHsd) mice each. Hexyl cinnamic aldehyde , 25% (v/v) in aceton/olive oil 4:1 served as positive control. On Day 6 the animals received 250 µL phosphate buffered saline (PBS) containing ³H-methyl thymidine and were sacrificed 5 h later for measurement of radioactivity. The disintegrations per minute were slightly increased by the test item. However, no dose-dependent increase was seen. The stimulation indices calculated for 25, 50 and 100% test item were 2.45, 1.49 and 1.68, respectively. These results indicate that the test substance could not elicit an SI of 3. Therefore, the test item is considered to be not sensitising to the skin under the conditions of the test.

CAS 147256-33-5

To assess the skin sensitising potential of Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5), a Local Lymph Node Assay (LLNA) in female CBA/Ca (CBA/CaOlaHsd) mice was performed according to OECD guideline 429 and in compliance with GLP (Pooles, 2012). Based on a preliminary range-finder study, the neat test substance (100%) and concentrations of 50 and 25% in acetone/olive oil (4:1 v/v) were selected for treatment of 5 females per dose group in the main experiment. Two further groups of 5 animals each were treated with the vehicle alone or with the positive control substance 25% hexyl cinnamic aldehyde. The test substance formulations, the positive control substance or the vehicle were applied once daily to the entire dorsal surface of each ear (25 µL/ear) for three consecutive days. Five days after the first topical application, the draining auricular lymph nodes were excised and the cell proliferation of pooled lymph nodes from individual animals was measured by incorporation of ³H-methyl thymidine and expressed as the amount of radioactive disintegration per minute (DPM). The mean DPM/animal for each test group was 2790.56, 2557.70 and 3011.09 at concentrations of 25, 50 and 100% of the test substance, respectively. For the control group, a DPM/animal of 1657.10 was obtained. Based on these results, stimulation indices (SI) of 1.68, 1.54 and 1.82 were calculated for the treatment concentrations of 25, 50 and 100%, respectively. The EC3 value could not be calculated as the stimulation indices of all concentrations were below 3. No signs of systemic toxicity and no effects on body weights were observed. The positive control hexyl cinnamic aldehyde at concentrations of 25% produced a SI of 9.91, and thus confirmed the sensitivity and reliability of the experimental technique. The test substance was not found to be a sensitiser in the LLNA.

Conclusion for skin sensitisation

Following a weight-of-evidence approach based on animal data (LLNA and Buehler studies) obtained for the structural analogue substances Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5), Fatty acids, C8-18 and C18-unsatd., esters with Neopentylglycol (CAS 85186-86-3) and Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) the target substance, 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 expected to have skin sensitising properties.

Migrated from Short description of key information:
Skin sensitisation (LLNA, Buehler; WoE): not sensitising

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

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.

Therefore, based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.