Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters

Endpoint summary

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): > 2.916 mg/L air (OECD 403, 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 environmental fate, ecotoxicological and toxicological profile (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 origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and 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 environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details).

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute toxicity of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7). In order 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, read-across from structurally related substances is 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.

Overview of Acute toxicity

CAS#	91031-45-7	111-60-4	627-83-8	151661-88-0	31565-12-5	68583-51-7	853947-59-8
Chemical name	Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO)	2-hydroxyethyl stearate	Ethylene distearate	Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol	Octanoic acid ester with 1,2-propanediol, mono- and di-	Decanoic acid, mixed diesters with octanoic acid and propylene glycol	Butylene glycol dicaprylate / dicaprate
Molecular weight	388.58; 416.63; 626.99; 683.1	328.53	563.00	328.54-622.97	202.29-328.49	328.49-384.59	342.52-398.63
Acute toxicity oral	RA: CAS 111-60-4 RA: CAS 627-83-8	LD50 > 2000 mg/kg bw	LD50 > 5000 mg/kg bw	--	--	--	--
Acute toxicity inhalation	WoE RA: CAS 68583-51-7	--	--	--	--	LC50 > 200 ppm (2.916 mg/L air)	--
Acute toxicity dermal	WoE RA: CAS 151661-88-0 RA: CAS 31565-12-5 RA: CAS 853947-59-8	--	--	LD50 > 2000 mg/kg bw	LD50 > 2000 mg/kg bw	--	LD50 > 2000 mg/kg bw

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7).

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

Discussion

Acute oral toxicity

No studies are available investigating the acute toxicity via the oral route of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7). In order to fulfil the standard information requirements set out in Annex VII, 8.5.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related analogue substances ethylene distearate (CAS 627-83-8) and Glycol Monostearate (CAS 111-60-4) is conducted.

The acute oral toxicity studies with ethylene distearate and Glycol Monostearate were performed in accordance or similarly to OECD guideline 401 (Wnorowski, 1991; Gloxhuber, 1982). Groups of 10 or 5 Wistar rats per sex were treated with the limit dose of 5000 mg/kg bw ethylene distearate or 2000 mg/kg bw Glycol Monostearate by gavage, respectively. The observation period following administration was 14 days. During both studies, no mortality and no clinical signs of toxicity were observed in any animal. All test animals showed normal body weight gain. No substance-related findings were observed.

Therefore, the oral LD50 in male and female rats was greater than 2000 mg/kg bw for Glycol Monostearate and greater than 5000 mg/kg bw for ethylene distearate, respectively. For the purpose of hazard assessment, the oral LD50 of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) is considered to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

No studies are available investigating the acute toxicity via the inhalation route of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7). In order to fulfil the standard information requirements set out in Annex VIII, 8.5.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related analogue substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) is conducted.

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 (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 in a limit test. The animals were observed for a period of 7 days following administration. No mortality occurred and no clinical signs of toxicity were apparent and 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

Since no studies are available investigating the acute dermal toxicity of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7), in order to fulfil the standard information requirements set out in Annex VIII, 8.5.3, in accordance with Regulation (EC) No 1907/2006 Annex XI, 1.5 read-across to the structurally related analogue substances Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5) is conducted.

The acute dermal toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol, Butylene glycol dicaprylate / dicaprate and Octanoic acid ester with 1,2-propanediol, mono- and di were evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Potokar, 1989; Mürmann, 1992a,b).

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 or 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 signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted. No substance-related findings during necropsy were observed in any animal (Mürmann, 1992a,b). In the study withOctanoic acid ester with 1,2-propanediol, mono- and di3 animals showed scaling after 48 h, being no longer apparent at the 72 h observation time point (Mürmann, 1992b).

The results of the three studies of the analogue substances 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.

Conclusion for acute toxicity

In summary, studies from the structurally related substances ethylene distearate (CAS 627-83-8) and Glycol Monostearate (CAS 111-60-4) investigating the acute oral toxicity resulted in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available for Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7). From these studies a LC50 value for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L) was obtained. Acute dermal toxicity studies conducted withFatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5)consistently showed no effects at the limit dose 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the analogue substances and thus no hazard for acute oral, inhalative and dermal toxicity was identified.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within 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 means of read-across based on 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 based on a category approach. 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 analogue substances following an analogue and weight of evidence approach, the available data on acute, dermal and inhalation toxicity of Fatty acids, C16-18, 1,2-ethanediylbis(oxy-2,1-ethanediyl) esters (3EO) (CAS 91031-45-7) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.