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

Endpoint summary

Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information

Based on the read-across category approach and the available experimental result, the NOAEL value for embryo- and maternotoxicity was defined as 1000 mg/kg bw/day. Hence, the registered substance is not classified for teratogenicity.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: Available study for read across category

Abnormalities:

no effects observed

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: Basedon available study for read across category approach

Abnormalities:

no effects observed

Developmental effects observed:

no

Table 1: Results from key studies on source chemicals of the category for teratogenicity tests.

ID#	CAS	Toxicity to reproduction – Developmental Toxicity
Fatty acids, C8-16, 2- ethylhexylesters	135800-37-2	No data
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	NOAEL 1000 mg/kgbw/day
2-Ethylhexyl oleate	26399-02-0	No data
2-Ethylhexyl stearate	22047-49-0	NOAEL: 1000 mg/kgbw/day

 

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.

 

Two studies for the developmental toxicity were available within the LCAE C8 to C18, for the category members 2-ethylhexyl stearate and Fatty acids, C16-18 2-ethylhexyl esters. (OECD 414 method for Teratogenicity test performed in rat). They did not show treatment related effects up to the highest tested dose level. Thus, no hazard for developmental toxicity was identified. The NOAEL forembryotoxicityandmaternotoxicitywas defined at 1000 mg/kgbw/day.

 

According to the results of the available studies for LCAE Category members, the NOAEL for materno- and embryo- toxicity was defined at 1000 mg/kgbw/day. According to the CLP criteria and the Category Members results, the registered substance was not classified for teratogenicity.

 

Conclusions:

According to the results of the available studies for LCAE Category members, the NOAEL for materno and embryotoxicitywas defined at 1000 mg/kgbw/day. According to the CLP criteria and the Category Members results, the registered substance was not classified for teratogenicity.

Effect on developmental toxicity: via oral route

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 the available studies

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

A Prenatal Developmental Toxicity Study was performed with the fatty acids, C16-18, 2-ethylhexyl esters according to OECD Guideline 414 (Pittermann, 1994). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at concentrations of 0, 100, 300 and 1000 mg/kg bw/d during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and foetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/d. Examination of foetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, soft tissue and skeletal abnormalities and head examinations showed no abnormalities and no indication for teratogenic effects. Therefore, the NOAEL for embryo-foetotoxicity and teratogenicity in rats for fatty acids, C16-18, 2-ethylhexyl esters was found to be 1000 mg/kg bw/d.

2 -ethylhexyl stearate CAS 22047-49-0

The developmental toxicity of 2-Ethylhexyl Stearate was investigated according to OECD Guideline 414 and GLP conditions (Aulmann, 2000). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/d during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/d. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats for 2-Ethylhexyl Stearate was found to be 1000 mg/kg bw/day.

According to the results of the available studies for LCAE Category members, the NOAEL for materno and embryotoxicity 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 teratogenicity.