Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): 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 skin and eye irritation for Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7). In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VII and VIII, 8.1 and 8.2.

According to 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) “to avoid the need to test every substance for every endpoint”.

 

Fatty acids, C16-18, 2-hydroxyethyl esters is an UVCB substance comprised of mainly mono- and diesters of ethylene glycol conjugated with C16 and C18 fatty acids. Thus, the test substance represents a glycol ester, which in general is known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common precursors and the likelihood of common breakdown products via biological processes that result in structurally similar chemicals, and on common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

 

As no reliable data are available on irritation, read-across to the analogue substanceFatty acids,C16-18, esters with ethylene glycol (CAS 91031-31-1) and 2-hydroxyethyl stearate (CAS 111-60-4) was conducted for irritation to the skin. Furthermore, data of the analogue substance Ethylene distearate (CAS 627-83-8) was considered as read across to meet the requirements for the eye irritation endpoint.

 

Skin Irritation

CAS 91031-31-1

Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) was tested in a study according to OECD guideline 404 in compliance with GLP (Coguet, 1976). In the study, 6 New Zealand White male rabbits were exposed to 0.5 mL of the test substance (40%) in olive oil, applied to the shaved and abraded skin for 24 h using an occlusive dressing. The treated skin was observed and evaluated at 24 and 72 h post-application. On intact skin, 2/6 animals showed slight erythema (on abraded skin 5/6 showed slight irritating effects) after 24 h which were fully reversible within 72 h (mean erythema score over 24 and 72 h out of all 6 animals = 0.22). No edema formation or further local or systemic effects were apparent in any animal during the study period. Thus, Fatty acids, C16-18, esters with ethylene glycol is not irritating to the skin at a concentration of 40%.

CAS 111-60-4

No skin irritating properties were identified for 2-hydroxyethyl stearate (CAS 111-60-4), which was tested similar to OECD guideline 404 in 3 male New Zealand albino rabbits (Dufour, 1994). The results of the conducted study are reported in a summary with limited information. However, as the basic data provided were sufficient for hazard assessment, the study is considered as reliable (reliability 2). Slight local skin reactions characterised as erythema (score 1) were observed in all test animals 1 hour after patch removal. The erythema was fully reversible within 48 hrs in all animals. Oedema was not observed in any test animal. Based on the limited severity of local reactions and the reversibility of the skin reactions, the test substance 2-hydroxyethyl-stearate is not considered to exhibit skin irritating properties.

 

 

Eye irritation

CAS 627-83-8

The eye irritation properties of ethylene distearate were tested in a study similarly performed to OECD guideline 405 (Wnorowski, 1991). In a group of 6 New Zealand white rabbits, 0.1 g of the test substance was applied into the eye. Observation of the eyes was performed 24, 48 and 72 h after application. No effects on cornea and iris were noted in any animal during the study period. However, mild conjunctival redness was observed in 4/6 animals after 24 h and in 2/6 animals moderate redness was apparent. In 2 animals the mild redness was still persistent after 72 h ( mean score of 0.78 over 24, 48 and 72 h out of all 6 animals). Chemosis was observed in 1/6 animals after 24 h being fully reversible within 48 h. Chemosis was not observed in the remaining 5 animals during the study period. No further systemic effects or abnormal behaviour were observed in any animal during the study period.

 

An additional study of the same laboratory with ethylene distearate similarly to OECD guideline 405 was conducted (Wnorowski, 1991e). No effects on cornea and iris were apparent in any animal during the study period and no chemosis was observed in the test animals. Mild to moderate conjunctival redness was observed in all animals being fully reversible within 72 h post-instillation with a mean score of 0.61 over 24, 48 and 72 h out of all 6 animals. No further local or systemic signs of toxicity were apparent in the test animals.

 

 

Conclusion on skin and eye irritation properties

The irritation properties of the analogue substances were investigated in vivo; indicating no irritating properties towards the skin or eyes. Therefore, based on these data, Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7) is not considered to be a skin or an eye irritant.

 

References

 

Lehninger, A.L. (1970). Biochemistry. Worth Publishers, Inc.

 

Long, C.L. et al. (1958). Studies on absorption and metabolism of propylene glycol distearate.Arch Biochem Biophys, 77(2):428-439.

 

Mattson, F.H. and Nolen, G.A. (1972). Absorbability by rats of compounds containing from one to eight ester groups. J Nutrition, 102: 1171-1176.


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 source and target substances 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 a structural analogue. 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).

Justification for classification or non-classification

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