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 acute oral toxicity studies within this category resulted in an acute oral Lethal Dose 50 (LD50) value higher than 2000 mg/kg bw (oral exposure) and LC50 was defined at higher than 5.7 mg/L (inhalation exposure). Hence, according to the CLP criteria, the test item Isostearate Ethyl Hexyl was not classified for acute oral hazard (or Category 5 according to GHS criteria)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute 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 Specific Report

Test type:

standard acute method

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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

ID#	CAS	Acute oralToxicity
Fatty acids, C8-16, 2- ethylhexylesters	135800-37-2	Experimental result: LD50 > 2000 mg/kgbw
Fatty acids, coco, 2-ethylhexyl esters	92044-87-6	Experimental result: LD50 > 2000 mg/kgbw
2-Ethylhexyl palmitate	29806-73-3	No data
Fatty acids, C16-18 and C18-unsatd., 2- ethylhexylesters	85049-37-2	Experimental result: LD50 > 17,200 mg/kgbw Reliability 4
Fatty acids, C16-18, 2-ethylhexyl esters	91031-48-0	LD50 > 4300 mg/kgbw
2-Ethylhexyloleate	26399-02-0	Experimental result: LD50 > 5000 mg/kgbw
2-Ethylhexylstearate	22047-49-0	Experimental result: LD50 > 4300 mg/kgbw

 

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.

 

Several studies were performed in members of the category for acute oral toxicity. For acute oral toxicity studies, results showed an LD50 value greater than 2000 mg/kgbw.

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results from experimental study performed on the substances of the LCAE Category, the LD50 value for the Isostearate Ethyl Hexyl was defined higher than 2000 mg/kg bw. Hence, according to the CLP criteria and the category approach, the registered substance was not classified for Acute Oral Hazard (or Category 5 according to GHS criteria).

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.

Several reliable studies were available (GLP, accordingly to OECD 401 guideline method). The experimental studies were performed in rodents (rat and mouse) which were treated orally (gavage) by single dose. Lethal Dose 50 (LD50 ) values were found to be greater than 2000 mg/kg bw, or 4300 mg/kg bw and 10 0000 mg/kg bw in the differents test performed.

According to the results from experimental study performed on the substances of the LCAE Category, the LD50 value for the Isostearate Ethyl Hexyl was defined higher than 2000 mg/kg bw. Hence, according to the CLP criteria and the category approach, the registered substance was not classified for Acute Oral Hazard (or Category 5 according to GHS criteria).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.7 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Table 1: Results from key studies on source chemicals of the category for acute inhalation toxicity tests

ID#	CAS	Acute inhalation Toxicity
Fatty acids, C8-16, 2- ethylhexyl esters	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	No data
2-Ethylhexyl oleate	26399-02-0	Experimental result: LC50 > 5.7 mg/L
2-Ethylhexyl stearate	22047-49-0	No data

 

Similar toxicokinetic behavior and toxicity profile

 

All the category substance are fatty acid esters. After inhalation, it is expected that substances are hydrolyzed by lipases. Substances that are absorbed through the pulmonary alveolar membrane could enter the systemic circulation directly before joining the liver where hydrolysis basically takes place. They are expected to be metabolized in common energetic pathways or excreted.

 

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.

 

One key study was performed in a member of the category for acute inhalation toxicity. Results showed an LD50 value greater than 5.7 mg/L (analytical).

 

 

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

One key study was performed in a member of the category for acute inhalation toxicity. Results showed an LD50 value greater than 5.7 mg/L (analytical).
 

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.

This category 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, not volatile and have high adsorption potential. They are not expected to be found in air or water compartments.  If released in surface water, the substances would probably partition from the water phase to the sediment. However these substances being readily biodegradability as measured in different screening tests, and highly sorptive as demonstrated with calculated estimations, so they will be eliminated in sewage treatment plants to a high extent. Release to surface waters and thereby exposure of sediment is therefore considered as negligible due to the elimination in sewage treatment plant. Moreover the fatty acids esters are expected to be metabolized by living organisms using common pathways, as dietary fats.

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.

One key study was performed in a member of the category for acute inhalation toxicity. Results showed an LD50 value greater than 5.7 mg/L (analytical). Hence, the target substance was not classified for acute inhalation toxicity according to CLP criteria.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 700 mg/m³

Additional information

Justification and rationale of the category approach for the isostearate 2-ethylhexyl :

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:

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

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

- 2-Ethyl hexyl palmitate (29806-73-3)

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

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

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

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

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 for acute oral toxicity

2-Ethylhexyl palmitate CAS 29806-73-3

Three reliable studies investigating the acute toxicity via the oral route of 2-ethylhexyl palmitate are available (CAS No. 29806-73-3). This key study was performed equivalently to OECD Guideline 401 (Sugar, 1980). Single oral gavage dosing of 2000 mg test substance /kg bodyweight in vegetable oil to three fasted male and female CD-1 rats caused no mortality or clinical signs of toxicity. Thus, the acute oral LD50 in rats was found to be greater than 2000 mg/kg bw.

In another oral gavage supporting study with the same substance, 2-ethylhexyl palmitate an acute oral LD50 > 5 mL/kg body weight for male and female NMRI mice was reported (Planchette, 1985).

In the third study (suporting study, Green, 1972), 5 male and female Albino rats were orally treated with undiluted 2-ethylhexyl palmitate at 2000, 4000, 8000, 16,000, 32,000 and 64,000 mg/kg bw. No mortality occurred during the 14 day observation period. Animals dosed at 16,000 mg/kg bw and below did not exhibit any toxic effects. At 32,000 mg/kg bw wet, unkempt coat and mild diarrhoea were noted. These effects were reversible within 48 hours. At 64,000 mg/kg bw slight ocular haemorrhage accompanied with moderate diarrhoea were noted. The coat of the animals appeared wet and unkempt for 5 days following treatment.

Fatty acids, coco, 2-ethylhexyl esters CAS 92044-87-6

Two studies investigating the acute toxicity via the oral route of fatty acids, coco, 2-ethylhexyl esters are available (CAS No. 92044-87-6):

An acute oral toxicity study (limit test) was performed as key study with fatty acids, coco, 2-ethylhexyl esters according to OECD Guideline 401 under GLP conditions (Reijnders, 1987). Groups of 5 male and female fasted Wistar rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days after administration. No mortalities and no signs of clinical toxicity were reported. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

Another supporting study in which the acute oral toxicity of fatty acids, coco, 2-ethylhexyl esters was studied in NMRI mice similarly to OECD guideline 401 is available (Masson, 1985). The test material was administered at a single dose of 4300 mg/kg bw (equivalent to 5 mL/kg bw, based on a density of 0.87 g/mL). No mortalities and no clinical signs were observed during the observation period. Therefore, under the conditions of this study, the oral LD50 in male and female mice was greater than 4300 mg/kg bw.

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

The acute oral toxicity of fatty acids, C16-18, 2-ethylhexyl esters (CAS No. 91031-48-0) was tested in male and female NMRI EOPS mice according to OECD Guideline 401 (Key study, Masson, 1985). Administration of 4300 mg/kg bodyweight as single oral gavage dose caused no mortality, abnormal clinical reactions or changes in bodyweight gain. Therefore, the acute oral LD50 in mice was found to be greater than 4300 mg/kg bodyweight.

In a second study (supporting study, Potokar, 1978), 10 male CF-1 mice were orally treated with 10,000 mg/kg bw. No mortality occurred and no only clinical signs were noted during the 8 day observation period. Thus, the acute oral LD50 was found to be greater than 10,000 mg/kg bw in mice.

Acute Inhalation Toxicity study summary

An acute inhalation study was performed with 2-ethylhexyl oleate (CAS No. 26399-02-0) according to OECD guideline 436 as acute toxic class method in 3 male and 3 female Crl:WI(Han) rats (van Huygevoort, 2010). The animals were exposed to an analytical concentration of 5.7 mg/L of the test substance for 4 hours nose only in an exposure chamber based on the flow past nose-only inhalation chamber. No mortalities were reported during the exposure or within the 14 days observation period. Hunched posture was shown by all animals on Day 2 after exposure. No clinical signs were noted during exposure. Additionally body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post-mortem examination of the animals. The inhalatory 4 hour LC50 value of 2-ethylhexyl oleate aerosol in Wistar rats was found to exceed 5.7 mg/L.

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 acute oral toxicity studies within this category resulted in an acute oral Lethal Dose 50 (LD50) value higher than 2000 mg/kg bw (oral exposure) and LC50 was defined at higher than 5.7 mg/L (inhalation exposure). Hence, according to the CLP criteria, the test item Isostearate 2-Ethyl Hexyl was not classified for acute oral hazard (or Category 5 according to GHS criteria)