Fatty acids, C12-18 (even-numbered), 3-methylbutyl esters

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw 
Inhalation: LC50 > 5.3 mg/L
Dermal: LD50 > 2000 mg/kg bw

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 precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2) study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

Data on the acute oral, inhalation and dermal toxicity of Fatty acids, C12-18, even numbered, 3-methylbutyl esters (CAS 1314963-50-2) are not available. The assessment of acute toxicity was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 163961-32-8 

The acute oral toxicity of Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8) was assessed in a study performed according to OECD guideline 423 (Sanders, 2002). Single oral gavage dosing of 2000 mg/kg bw to three fasted male and female Sprague-Dawley rats caused no mortality, clinical signs of toxicity, changes in bodyweight gain or gross pathology after a 14-day observation period. Thus, the acute oral LD 50 in rats was found to be greater than 2000 mg/kg bodyweight. 

 

CAS 34316-64-8

A study for acute oral toxicity of Hexyl laurate (CAS 34316-64-8) is available (Masson, 1987). The study was performed according to OECD guideline 401. 5 male NMRI mice were treated with the limit dose of 4300 mg/kg bw (converted from 5 mL/kg bw, based on a density of 0.87 g/mL) of the unchanged test substance by gavage. No mortality occurred and no clinical signs of toxicity were observed up to the end of the observation period in all animals. Therefore, under the conditions of this study, the oral LD50 in male NMRI mice was greater than 4300 mg/kg bw.

 

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 mortality was reported during the exposure or within the 14-day 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 (analytical concentration).

 

CAS 67762-63-4

An acute inhalation study was performed with Fatty acids, tall-oil, bu esters (CAS No. 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 (analytical concentration).

 

Acute dermal toxicity

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 semi-occlusive conditions. The observation period was 14-day. 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.

Overall conclusion for acute toxicity

The reliable data available for the read-across analogue substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Fatty acids, C12-18, even numbered, 3-methylbutyl esters (CAS 1314963-50-2) is not considered to be hazardous following acute exposure.

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 the 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 the 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 a structural analogue. The selected study is most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C12-18, even numbered, 3-methylbutyl esters (CAS 1314963-50-2), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute 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.