Fatty acids, C8-12, isopentyl esters

Endpoint summary

Description of key information

Oral: All available acute oral toxicity studies of the structural analogues resulted in an acute oral LD50 > 2000 mg/kg bw. 
Inhalation: LC50 > 5.3 mg/L
Dermal: All available acute dermal toxicity studies of the structural analogues resulted in an acute 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 (changing of reliability from Klimisch score 1 to Klimisch score 2 due to read-across when necessary) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on a common functional group, common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to 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

Dose descriptor:

LC50

Value:

5 300 mg/m³

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on a common functional group, common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus 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 adequate, reliable (changing of reliability from Klimisch score 1 to Klimisch score 2 due to read-across when necessary) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on a common functional group, common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to 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.

Additional information

Acute toxicity

Justification for read-across

There are no data regarding acute toxicity available for Fatty acids, C8-12, isopentyl ester. In order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5, read-across from appropriate substances is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5.

According to 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) “to avoid the need to test every substance for every endpoint”.

Fatty acids, C8-12, isopentyl ester is a multi-constituent substance specified by C8, C10 and C12 linear saturated fatty acids esterified with isopentanol resulting in monoesters which meets the definition of an UVCB substance. Thus, the test substance represents fatty acid esters which undergo to a high extent hydrolysis by ubiquitous enzymes into the free fatty acid components and the respective alcohol (Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common functional groups, common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals, common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

As no data on acute toxicity are available for Fatty acids, C8-12, isopentyl ester, read-across to reliable data on the analogue substances Isopropyl Myristate (CAS 110-27-0), Octyl Octanoate (CAS 2306-88-9) and Isopropyl Laurate (CAS 10233-13-3) was conducted for acute oral toxicity. Data on Isopropyl Laurate (CAS 10233-13-3) were read across to the target substance to cover acute inhalation toxicity endpoint. In addition, data on acute der mal toxicity for Ethyl Linoleate (CAS 544-35-4) and Fatty acids, C16-18 and C18-unsatd., branched and linear, Bu esters (CAS 163961-32-8) were read across to the target substance. The substances were chosen based on their structural similarities regarding the branched alcohol component (Isopropyl Myristate (CAS 110-27-0) and Isopropyl Laurate (CAS 10233-13-3)) and / or the linear fatty acid component (Octyl Octanoate (C8; CAS 2306-88-9), Isopropyl Laurate (C12; CAS 10233-13-3) and Isopropyl Myristate (C14; CAS 110-27-0)). Furthermore, data of the structural analogue substances Fatty acids, C16-18 and C18-unsatd., branched and linear, Bu esters (CAS 163961-32-8) and Ethyl Linoleate (CAS 544-35-4) were considered to allow a weight-of-evidence approach covering short and long chain fatty acids and saturated/unsaturated fatty acids.

Acute oral toxicity

CAS 110-27-0

An acute oral toxicity study (limit test) was performed with Isopropyl Myristate (CAS 110-27-0) according to OECD guideline 401 and GLP conditions (Reijnders, 1988). 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 occurred. No signs of clinical toxicity were reported. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

CAS 2306-88-9

Octyl Octanoate (CAS 2306-88-9) was tested for acute oral toxicity similarly to OECD guideline 401 (Potokar, 1981). Ten male Wistar rats received single oral gavage doses of the test substance at dose levels of 1000 and 5000 mg/kg bw. No mortality, abnormal clinical signs or body weight changes occurred within the observation period of 14 days. Thus, the acute oral LD50 was found to be greater than 5000 mg/kg bw in rats.

CAS 10233-13-3

An acute oral toxicity study (limit test) with Isopropyl Laurate (CAS 10233-13-3) similar to OECD guideline 401 was performed (Dufour, 1991). A group of 5 female NMRI EOPS mice received single oral doses of 5000 mg/kg bw. The animals were observed for 6 days after administration. No mortalities were observed during the study period. No signs of clinical toxicity were reported. All animals showed the expected gain in bodyweight. The acute oral LD50 in mice was found to be greater than 5000 mg/kg bw.

Acute toxicity following inhalation

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 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 (actual concentration). 

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 and GLP conditions (Otterdijk, 2010). 5 male and 5 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. The application site did not display any signs of skin irritation. 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 and GLP conditins (Sanders, 2004). 5 male and 5 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. No signs of dermal irritation were observed up to the end of the observation period. Based on the study results the acute dermal LD50 in rats was found to be greater than 2000 mg/kg bodyweight.

Overall conclusion

In summary, reliable data available for the read-across analogue substances indicate a very low level of acute toxicity following exposure via the oral, dermal and inhalation route. Oral and dermal LD50 values and also the LC50 value were greater than the currently applied limit values. Thus, as the available data did not identify any hazard for acute oral and dermal toxicity as well as for acute toxicity following inhalation Fatty acids, C8-12, isopentyl ester is not considered to be hazardous after acute exposure.

 

References

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.

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, C8-12, isopentyl ester, data will be generated from information on 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 target substance information and analogue read-across approach, the available data on acute oral, dermal and inhalation 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.