Fatty acids, C16-18, 2-hydroxyethyl esters

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw 
Inhalation: LC50 > 2.916 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 functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties 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

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 functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties 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 VIII, 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

Additional information

Justification for read-across

There are no data for acute toxicity available for Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7). In order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5, read-across from an appropriate substance 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, C16-18, 2-hydroxyethyl esters is an UVCB substance comprised of mainly mono- and diesters of ethylene glycol conjugated with C16 and C18 fatty acids. Thus, the test substance represents a glycol ester, which in general is known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common precursors and the likelihood of common breakdown products via biological processes that result in structurally similar chemicals, and on 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 are available on acute toxicity following the oral, dermal or inhalation route, read-across to reliable data on the analogue substances 2-hydroxyethyl stearate (CAS 111-60-4), Ethylene distearate (CAS 627-83-8, Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0), Octanoic acid ester with 1,2-propanediol, mono- and di- (CAS 31565-12-5) and Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) was conducted.

 

 

Acute oral toxicity

CAS 111-60-4

The acute toxicity via the oral route of ethylene glycol monostearate has been investigated in rats and mice.

An acute oral toxicity study was performed similar to OECD guideline 401 as a limit test (Gloxhuber, 1982). 5 male and 5 female Wistar rats were treated with a single dose of 2000 mg/kg bw of ethylene glycol monostearate. Animals were observed for 14 days and no clinical signs or mortalities reported. Body weights and gross necropsy revealed no abnormal findings as well. Therefore the LD50 for ethylene glycol monostearate in Wistar rats was set to be > 2000 mg/kg bw.

 

In an acute oral toxicity study similar to OECD guideline 402, 5 male NMRI mice were treated with a single dose of 2000 mg/kg bw of the read across substance 2-hydroxyethyl stearate in a limit test (Dufour, 1994). No mortalities or any clinical signs occurred. Body weight and necropsy revealed no abnormal findings. Therefore the LD50 mouse was set to be > 2000 mg/kg bw.

 

CAS 627-83-8

A study for acute oral toxicity of ethylene distearate was performed in rats in accordance with OECD guideline 401 (Wnorowski, 1991). A group of 10 Wistar rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance in carboxymethyl cellulose by gavage. The observation period following administration was 14 days. During the study period, no mortality and no clinical signs of toxicity were observed in any animal. All test animals showed normal body weight gain. Therefore, the oral LD50 in male and female rats was greater than 5000 mg/kg bw.

 

 

In summary, the oral LD50 values of the analogue substances are consistently > 2000 mg/kg bw.

 

Acute toxicity following inhalation

CAS 68583-51-7

 

The acute inhalation toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was evaluated in two studies similar to OECD guideline 403 in a limit test (Re, 1978 a,b). A group of 10 male Sprague-Dawley rats and a group of 10 male and female guinea pigs and 3 control animals, respectively, were exposed whole body to 200 ppm (equivalent to 2.916 mg/L air) for 6 h. The animals were observed for a period of 7 days following administration.

 

No mortality occurred and no clinical signs of toxicity were apparent during the study period in any animal. Necropsy revealed no substance-related findings in both studies.

 

Therefore, the LC50 for male rats and male and female guinea pigs was greater than 200 ppm (2.916 mg/L).

 

Acute dermal toxicity

CAS 151661-88-0

Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol was evaluated in rats equivalent to OECD guideline 402 under GLP conditions (Potokar, 1989). Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under occlusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal.Furthermore, no effects on body weight were noted.

 

CAS 31565-12-5

Octanoic acid ester with 1,2-propanediol, mono- and di- was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Mürmann, 1992). Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under semiocclusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signsof toxicity occurred in any animal. Furthermore, no effects on body weight were noted. In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point.

 

The results of the available studies consistently showed no effects at the limit dose 2000 mg/kg bw. Therefore, the dermal LD50 is considered to be greater than 2000 mg/kg bw.

 

 

Overall conclusion

In summary, reliable data available for the read-across analogue substances indicate a very low level of acute toxicity following the oral, dermal and inhalation route, as oral and dermal LD50 and the defined LC50 values were greater than the currently applied limit values. Thus, as the available data did not identify any hazard for acute oral, dermal and inhalation toxicity, Fatty acids, C16-18, 2-hydroxyethyl esters is not considered as 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 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
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 functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties 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 VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Based on the 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, and are therefore conclusive but not sufficient for classification.