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

Endpoint summary

Description of key information

According to the results of the studies performed on differents substances which belong to LCAE category, a No Observed Adverse Effect Level can be derived for the registered substance, the 2-ethyl hexyl isostearate, at 1000 mg/kg bw/day for rats. No adverse effect or toxicity was observed on the studies, the substance was not classified for STOT-RE according to CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

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 Endpoint Target Substance Record

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: according to the results of available studies

Critical effects observed:

no

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

ID#	CAS	Repeated dose toxicity
Fatty acids, C8-16, 2- ethylhexylesters	135800-37-2	Experimental Result : NOAEL : 1000 mg/kgbw/day
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: NOAEL: 1000 mg/kgbw/day
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-oxydation pathway 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 irritating when applied on eye. Hence, the target substance was not classified for repeated oral toxicity according to CLP criteria.

 

 

Conclusions:

According to the results of the available studies for LCAE Category members, the NOAEL value was defined at 1000 mg/kg bw/day. According to the CLP criteria and the Category Members results, the registered substance was not classified for repeated dose toxicity.

Executive summary:

According to the Regulation (EC) NO. 1907/2006, Annex XI, 1.5, A Read-Across Category for Long Chain Fatty Acid was performed in order to provide informations on the Isostearate Ethyl Hexyl.

This category was based on common and shared physico-chemical and structural properties as:

-       common functional group,

-       common precursors and the likehood of common impurities as well as common breakdown products via biological processes, which are chemically structurally similar, and

-       constant pattern in the changing of the potency of the properties across the category.

The 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 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.

Two key studies were available dor repeated dose oral toxicity, and were performed on Fatty acids, C16-18, 2-ethylhexyl esters and fatty acids C8 -C16, 2 -ethylhexyl esters. On the two 28 days repeated toxicity study, rats were dosed once daily. The NOAEL was defined at 1000 mg/kg bw/day due to absence of systemic effects in this two studies.

According to the results of the available studies for LCAE Category members, the NOAEL value was defined at 1000 mg/kg bw/day. According to the CLP criteria and the Category Members results, the registered substance was not classified for STOT-RE.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Justification and rationale of the category approach for the isostearate 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.

Summary of available studies

Fatty Acids, C8-16, 2-Ethylhexyl Esters CAS 135800-37-2

The oral toxicity after daily oral administration for 28 consecutive days of Fatty Acids, C8-16, 2-Ethylhexyl Esters (CAS# 135800-37-2) was tested according to OECD Guideline 407 and GLP (Fitzgerald, 1991). Groups of 5 male and female Sprague-Dawley rats received daily oral gavage doses of the test substance in corn oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/d. Concurrent negative control animals received the vehicle alone. Based on clinical observations, neurological observations, examinations of various blood parameters (haematology and clinical chemistry), necropsy observations, organ weights, body weights, food consumption and histopathological findings, the 28d oral NOAEL for male and female rats was found to be 1000 mg/kg bw/d.

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

The chemical was tested for systemic toxicity at repeated doses of 0, 100, 500 and 1000 mg/kg body weight. The compound was administered to Sprague-Dawley rats daily by gavage over a period of 28 days. All doses applied were tolerated without lethality. No symptoms were noted as compound-related effects. The total body weight gain was comparable to control in all male and female test groups. The haematological examinations showed no compound-related effects. The clinical chemistry showed no compound-related effects. The examination of the eyes by slit lamp microscope showed no compound-related effects. The absolute and relative organ weights showed no compound-related effects. The macroscopical examination of the organs displayed no compound-related effects. Some observations like hydrometra, hydronephrosis, discolouration of the thymus and one suspicion of hydrocephalus internus were considered to be spontaneous. The histological examination of the organs of all groups displayed no compound-related effects.

According to the results of the available studies, the NOAEL value was defined at 1000 mg/kg bw/day. According to the CLP criteria and the Category Members results from this two key studies, the registered substance was not classified for repeated dose toxicity.

Justification for classification or non-classification

According to the results of the studies performed on differents substances which belong to LCAE category, a No Observed Adverse Effect Level can be derived for the registered substance, the 2-ethyl hexyl isostearate, at 1000 mg/kg bw/day. No adverse effect or toxicity was observed on the studies, the substance was not classified for STOT-RE according to CLP regulation.