Fatty acids, C14-18 and C18-unsatd., branched and linear, 2-ethylhexyl esters

Endpoint summary

Description of key information

Using a Read Across Category approach with Long Chain Acid Esters substances (C8 to C18) according to the Annex XI Item 1.5, of Regulation (EC) No 1907/2006, all available skin sensitisation studies within this category resulted in not sensitising after the treatment of the animals. Hence, according to the CLP criteria, the test item Isostearate 2-Ethyl Hexyl was not classified for skin sensitisation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read Across Category Target Substance Endpoint Record

Remarks on result:

no indication of skin sensitisation

Table 1: Results from key studies on source chemicals of the category for Repeated oral dose toxicity tests

ID#	CAS	Skinsensitisation
Fatty acids, C8-16, 2- ethylhexylesters	135800-37-2	Experimental result: Not sensitising
Fatty acids, coco, 2-ethylhexyl esters	92044-87-6	No data
2-Ethylhexyl palmitate	29806-73-3	No data
Fatty acids, C16-18 and C18-unsatd., 2- ethylhexylesters	85049-37-2	No data
Fatty acids, C16-18, 2-ethylhexyl esters	91031-48-0	Experimental result: Not sensitising
2-Ethylhexyloleate	26399-02-0	No data
2-Ethylhexylstearate	22047-49-0	No data

 

Similar toxicokinetic behavior and toxicity profile

 

All category members are subject to enzymatic hydrolysis by pancreatic lipases resulting in free acids and alcohol. Based on current literature, when absorbed from intestines and carried through blood stream, fatty acids are oxidized by beta-oxydationpathway in order to provide energy for cell and stored as glycerides esters in fat deposit. The alcohols are primarily metabolized in the liver.

 

Hence, it can be stated that the members of the category have the same toxicity due to the same metabolic pathways when absorbed in the organisms.

 

Based on the available key studies, the members of the category were considered as not sensitizing. Hence, based on the structural similarity between source chemicals and target chemical of the category and their similar toxicokineti cbehavior, the target substance was considered as not sensitizing.

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results from experimental study performed on the substances of the LCAE Category, the category substances did not led to sensisation when treated on animals. Hence, according to the CLP criteria and the category approach, the registered substance was not classified for skin sensitisation.

Executive summary:

This category approach is based on similar chemical properties as long fatty chain (C8 to C18) linked to 2-ethylhexyl esters.  The members of the category are poorly soluble in water. They are not expected to be found in water compartiments.  If released in surfaces water, the substances would probably partition from the water phase to the sediment. These substances in water are readily biodregadable. Due to the fatty acids property, they are expected to be metabolized by common pathways, as dietary fats. Members of the category are readily biodegradable and are expected to be rapidly eliminated from the environment.

This fatty acids linked with 2-ethylhexyl esters have a common metabolic fate in organisms as glycolytic and fatty acid pathways after first hydrolysis step which led in breakdown products. The possible common toxicokinetic properties and behavior are expected due to the constant pattern (ethylhexyl esters and the fatty acid chain). The toxicological profiles between the members of the category are expected to be the same.

According to the close structural similarities in physico-chemical, toxicological, ecotoxicological properties, the substances can be considered as a category group according to Regulation (EC) NO. 1907/2006, Annex XI, 1.5.

Several experimental studies were available as Guinea pigs maximization tests which were performed on Fatty acids, C16-18, 2-ethylhexyl esters and Fatty acids, C8-16, 2-ethylhexyl esters. In the GPMT studies, induction and challenge application with each test substance did not led to skin irritation and hypersensitivity. According to the negative response to these tests, no hypersensitivity after dermal exposure was observed. Hence, the members of the category were considered as not sensitizing.

According to the results from experimental study performed on the substances of the LCAE Category, the category substances did not led to sensitisation when treated on animals. Hence, according to the CLP criteria and the category approach, the registered substance was not classified for skin sensitisation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Justification and rationale of the category approach for the Isostearate 2-ethyl hexyl :

This category group covers 2-ethyl hexyl esters linked with fatty acid chains (C8 to C18) unsatured and satured. This category includes monoconstituent substances and UVCB substances varying fatty acid chain length. This category was made in order to provide sufficient information for physicochemical, ecotoxicological and toxicological caracterisation of the Fatty acids, C14-18 and C18-unsatd., branched and linear, 2-ethylhexyl esters (CAS No 85186-76-1)

The category group includes:

- 2-Ethyl hexyl stearate (CAS No 22047-49-0)

- Fatty acids, C8-16, 2-ethylhexyl esters (CAS No 135800-37-2)

- Fatty acids, C16-18 and C18-unsatd., 2-ethylhexyl esters (CAS No 85049-37-2)

- Fatty acids, coco, 2-ethylhexyl esters (CAS No 92044-87-6)

- Fatty acids, C16-18, 2-ethylhexyl esters (CAS No 91031-48-0)

- Fatty acids, C8-16, 2-ethylhexyl esters (CAS No 135800-37-2)

- 2-Ethylhexyl oleate (CAS No 26399-02-0)

Target substance for Category Approach : Fatty acids, C14-18 and C18-unsatd., branched and linear, 2-ethylhexyl esters (CAS No 85186-76-1)

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, environmental fate and ecotoxicity, 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)”. Therefore, the available experimental data were collected and evaluated according to Annex XI requirements.

2-ethylhexyl palmitate CAS 29806-73-3

The skin sensitising potential of 2-ethylhexyl palmitate (CAS 29806-73-3) was assessed by a Landsteiner and Jacobs Guinea Pigs sensitization procedure (Bio-Tox Lab, 1972). Groups of male guinea pigs were exposed 10x via intradermal injection (3x a week) to the test substance (no data on purity) at a concentration of 0.1% in physiol. saline. The first injection was done with 0.05 mL, the following injection volume was 0.1 mL each. After two weeks resting time, challenge exposure was also done by intradermal injection of 0.05 mL of 0.1% of the test material. Scoring was done 24 hours following every injection. No reaction was observed in any animal. No control groups were included in the study. Based on the study results no indication for a skin sensitising potential was seen.

 

Fatty acids, C16 -18, 2 -ethylhexyl esters CAS 91031-48-0

Fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was tested for its skin sensitisation potential in a Guinea pig maximization test according to OECD Guideline 406 (Clouzeau, 1991). 20 test and 10 control animals (Dunkin-Hartley guinea pigs) were induced intradermally with the test substance diluted to 25% in paraffin oil. 7 days later the epidermal induction was performed with the undiluted test substance, as this concentration (100%) was found to be slightly irritating in the range finding test. 12 days after the last induction treatment the animals were challenged with a 50 % test substance solution in paraffin oil. 24 and 48 hours after termination of challenge exposure skin readings revealed no indications for a skin sensitising potential of the test substance.

According to the results from experimental study performed on the substances of the LCAE Category, the category substances did not led to sensisation when treated on animals. Hence, according to the CLP criteria and the category approach, the registered substance was not classified for skin sensitisation.

Justification for classification or non-classification

Using a Read Across Category approach with Long Chain Acid Esters substances (C8 to C18) according to the Annex XI Item 1.5, of Regulation (EC) No 1907/2006, all available skin sensitisation studies within this category resulted in not sensitising after the treatment of the animals. Hence, according to the CLP criteria, the test item Isostearate 2-Ethyl Hexyl was not classified for skin sensitisation.