Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, analogue approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 5.3 mg/L air (OECD 436, analogue approach)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile (refer to endpoint discussion for further details).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile (refer to endpoint discussion for further details).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile (refer to endpoint discussion for further details).

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of Fatty acids, soya, 2-ethylhexyl esters (CAS 93572-14-6). In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, a read-across from structurally related substances was conducted.

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, 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).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity,

the substance listed below are selected as reference substances for hazard assessment.

Overview for acute toxicity

CAS

Acute Oral

Acute Inhalation

Acute Dermal

93572-14-6 Target substance

RA: 29806-73-3

RA: 22047-49-0

 

RA: 10233-13-3

RA: 26399-02-0

RA: 67762-63-4

RA: 544-35-4

RA: 163961-32-8

544-35-4

--

--

LD50 (rat) > 2000 mg/kg bw

10233-13-3

--

LC50 (rat) > 5 mg/L

--

67762-63-4

--

LC50 (rat) > 5 mg/L

--

163961-32-8

--

--

LD50 (rat) > 2000 mg/kg bw

29806-73-3

LD50 (rat) > 5000 mg/kg bw

--

--

26399-02-0

--

LC50 (rat) > 5 mg/L

--

22047-49-0

 

LD50 (rat) > 4300 mg/kg bw

--

--

The above mentioned substance is considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, soya, 2-ethylhexyl esters (CAS 93572-14-6).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity:

CAS 29806-73-3 

One reliable study investigating the acute toxicity via the oral route of 2-ethylhexyl palmitate are available (CAS 29806-73-3). The acute oral toxicity of 2-ethylhexyl palmitate was assessed in study 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. 

CAS 22047-49-0

2-ethylhexyl stearate (CAS 22047-49-0) was tested for acute oral toxicity similarly to OECD guideline 401 (Masson, 1985). Five male and female NMRI mice received single oral gavage doses of the test substance at a dose level of 4300 mg/kg bw. No mortality, and abnormal clinical signs occurred within the observation period. Thus, the acute oral LD50 was found to be greater than 4300 mg/kg bw in mice.

Acute inhalation toxicity:

CAS 10233-13-3

An acute inhalation study was performed with isopropyl laurate (CAS 10233-13-3) 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 5.3 mg/L of the test substance for 4 hours nose only in an exposure chamber based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950, Hospitak Inc.). No mortalities were reported during the exposure or within the 14 days observation period. Hunched posture was shown by all animals at 1 and 3 hours 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 h LC50 value of isopropyl laurate in Wistar rats was found to exceed 5.3 mg/L.

 

CAS 67762-63-4

An acute inhalation study was performed with Fatty acids, tall-oil, Bu esters (CAS 67762-63-4) 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 5.3 mg/L of the test substance for 4 hours nose only in an exposure chamber based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950, Hospitak Inc.). No mortalities or any abnormal clinical signs were reported during the exposure or within the 14 days observation period. 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. Macroscopic post-mortem examination of the animals revealed pale discolouration of the lungs of one female. No other abnormalities were noted in any of the animals. The inhalatory 4 h LC50-value of Fatty acids, tall-oil, Bu esters in Wistar rats was found to exceed 5.3 mg/L.

 

CAS 26399-02-0 

An acute inhalation study was performed with 2-ethylhexyl oleate (CAS 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 (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950, Hospitak Inc.). 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.

Acute dermal toxicity:

CAS 544-35-4

An acute dermal toxicity (limit test) was performed on ethyl linoleate (CAS 544-35-4) according to OECD Guideline 402 (Otterdijk, 2010). 5 male and female Wistar rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on the back skin under occlusive conditions. The observation period was 14 days. Besides chromodacryorrhoea shown by two animals on Day 1, no other clinical signs of systemic toxicity were noted in any animal. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for ethyl linoleate was found to be greater than 2000 mg/kg bw.

 

CAS 163961-32-8 

An acute dermal toxicity (limit test) was performed with fatty acids, C16-18 and C18-unsatd., branched and linear, Bu esters (CAS 163961-32-8) according to OECD Guideline 402 (Sanders, 2004). 5 male and female Sprague-Dawley rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on back and flank skin under semiocclusive conditions. The observation period was 14 days. No deaths, clinical signs of systemic toxicity, changes in bodyweight gain or abnormalities in gross pathology were observed. Based on the study results the acute dermal LD50 in rats was found to be greater than 2000 mg/kg bodyweight. 

Conclusion for acute toxicity

In summary, based on a weight of evidence approach from structurally similar substances two studies are available investigating the acute oral toxicity of 2-ethylhexyl palmitat (CAS 29806-73-3) and 2-ethylhexyl stearate (CAS 22047-49-0) resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity three studies are available from 2-Ethylhexyl oleate (CAS 26399 -02 -0), Fatty acids, tall-oil, butyl esters (CAS 67762 -63 -4) and isopropyl laurate (CAS 10233 -13 -3). From these studies a LC50 value of > 5 mg/L was determined. Acute dermal toxicity data from ethyl linoleate (CAS 544 -35 -4) and Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961 -32 -8) consistently showed no effects at the limit dose of 2000 mg/kg bw.

Thus, the available data indicate no hazard for acute toxicity for Fatty acids, soya, 2-ethylhexyl esters and thus no hazard for acute oral, inhalative and dermal toxicity was identified.


Justification for selection of acute toxicity – oral 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 acute toxicity – inhalation 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 acute toxicity – dermal 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 classification or non-classification

Based on read-across from structurally similar substances, the available data on oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.