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

Description of key information

Skin, in vitro (WoE): not irritating
Eye, rabbit (WoE): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no data available for 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 on skin and eye irritation/corrosion. 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 substances 2,2-dimethyl-1,4-propanediyl dioleate (CAS 42222-50-4), and Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5), are selected as source substances.

Skin irritation

CAS 42222-50-4
The skin irritation potential of 2,2-dimethyl-1,4-propanediyl dioleate (CAS 42222-50-4) was determined in the Human Skin Model Test following EU-Method B.46 and OECD guideline 439, respectively, under GLP conditions (Andres, 2012). Three tissues of the human skin model EpiDerm TM were treated with the test item for 1 h. 30 µL of the liquid test item were applied to each tissue. DPBS-Buffer and 5% SDS-solution were used as negative and positive controls, respectively. At the end of the treatment, no irritation potential of the test substance was observed, since the mean relative cell viability of tissue after 1 h treatment followed by a 42-h post-treatment incubation period was 100.3. This value is well above the threshold for irritation potential (50%) compared with the negative control. The positive and negative controls were shown to be valid; the mean values of relative cell viability of positive and negative control were 7.8 and 100 respectively. On the basis of these findings, 2,2,-dimethyl-1,4-propanediyl dioleate is considered to be not irritant in the Human Skin Model Test.

CAS 147256-33-5
The skin corrosion potential of Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) was investigated in an in vitro skin corrosion/irritation test using a human skin model according to OECD guideline 431 (Remmele, 2012). In the study, two replicates of intact reconstructed human epidermis (EpiDerm™) were topically treated with the undiluted test substance for 3 min or 1 h to assess the skin corrosion potential. Cells treated with de-ionized water served as negative controls. The cell viability after 3 min exposure was greater than 50% (mean: 92%) and the cell viability after 1 h exposure was greater than 15% (mean: 100%). The positive controls 8 N KOH showed the expected decrease in cell viability. Under the conditions of this in vitro study, the test material was non-corrosive to reconstructed human epidermis in vitro.

The skin irritation potential of Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) was investigated in an in vitro skin irritation tests using a human skin model according to OECD guideline 439 (Remmele, 2012). Three replicates of intact reconstructed human epidermis (EpiDerm™) were topically treated with the undiluted test substance for 1 h followed by a 42-h post-incubation period. Cells treated with PBS served as negative controls. After the 1-h treatment and 42-h post-exposure in the skin irritation test, cell viability was greater than 50% (mean: 112%). The positive control 5% SDS in de-ionized water showed the expected decrease in cell viability. Under the conditions of this in vitro study, the test material was non-irritating to reconstructed human epidermis in vitro.

Eye irritation

Since no studies investigating the eye irritating properties of Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related analogue substances 2,2-dimethyl-1,4-propanediyl dioleate (CAS 42222-50-4), and Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) was conducted.

CAS 42222-50-4
The acute eye irritation potential of 2,2-dimethyl-1,4-propanediyl dioleate (CAS 42222-50-4) was assessed in an in vivo study carried out according to OECD guideline 405 and under GLP conditions (Colas, 2013). 0.1 mL of the test material was applied as a single treatment to the eye of three New Zealand white rabbits. Eye irritation was scored using the Draize scoring system at the following reading time points: 1, 24, 48 and 72 h. At the 24-h reading time point, slight to moderate conjunctivae (score 1 - 2) was observed in 3/3 animals. The slight conjunctivae persisted in 3/3 anmals until the 48-h reading time point, and cleared completely within 72 h. In addition, slight chemosis was observed 1 hour after application in 2/3 animals. This effect had cleared completely within the 24-h reading time point. All scores for iris and cornea were 0 for 3/3 animals. The individual mean scores for conjunctivae after 24, 48 and 72 h were 1.0, 1.0 and 0.67. Based on these findings, the test material is not considered to be irritating to the eyes under the conditions of this study.

CAS 147256-33-5
The eye irritation potential of Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane was investigated according to OECD guideline 405 and in compliance with GLP (Pooles, 2012). The undiluted test material (0.1 mL) was placed into the conjunctival sac of the right eye of 3 male New Zealand White rabbits. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after instillation. Minimal conjunctival irritation (score 1) was noted in all treated eyes 1 and 24 h after test substance instillation. However, this effect were fully reversible within 48 h. No corneal or iridial effects were noted at any observation time point during the study. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals. The mean scores for conjunctivae after 24, 48 and 72 h were 0.33 for each individual animal. Based on these results, the test substance is not considered to be an eye irritant.

Conclusion for skin and eye irritation

In conclusion, three reliable skin and two eye irritation studies are available for structurally related substances. Following a weight-of-evidence approach, 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 be a skin irritant or an eye irritant.

Justification for selection of skin irritation / corrosion 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 the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation 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 the source and target substance and overall quality assessment (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.

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.