Oleic acid, monoester with oxybis(propanediol)

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, analogue approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 5.0 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 due to read across) 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).
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 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 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.

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6). 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 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 of acute toxicity

CAS	Acute toxicity oral	Acute toxicity inhalation	Acute toxicity dermal
CAS 49553-8-76-6 (a) Target substance	RA: CAS 111-03-5 RA: CAS 90431-24-7	RA: CAS 68424-31-7 RA: CAS 85536-35-2 RA: CAS 73398-61-5	RA: CAS 63705-03-3 RA: CAS 555-43-1
CAS 111-03-5 (b)	LD50 > 2000 mg/kg bw	--	--
CAS 90431-24-7	LD50 > 2000 mg/kg bw	--	--
CAS 68424-31-7	LD50 > 2000 mg/kg bw	LC50 > 5.1 mg/L	--
CAS 85536-35-2	--	LC50 > 5.0 mg/L	--
CAS 73398-61-5	LD50 > 34020 mg/kg bw	LC50 > 1.86 mg/L	--
CAS 63705-03-3	LD50 > 5000 mg/kg bw	--	LD50 > 5000 mg/kg bw
CAS 555-43-1	LD50 > 20000 mg/kg bw	--	LD50 > 2000 mg/kg bw

 (a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

 (b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

The above mentioned substances are 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 Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6).

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

 

Discussion

 

Acute toxicology: oral

Since no studies investigating the acute oral toxicity of Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6) are available, in accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance 2,3-dihydroxypropyl oleate (CAS# 111-03-5) and isooctadecanoic acid, mono-, di and triesters with triglycerol (CAS# 90431-25-7) was conducted.

CAS 111-03-5

For 2,3-dihydroxypropyl oleate (CAS# 111-03-5), an acute oral toxicity study (limit test) according to OECD TG 423 (Ishida, 2005) and GLP compliant is available. Groups of 3 female Sprague-Dawley rats received doses of 2000 mg/kg bw of test substance in corn oil by gavage. The animals were observed for 14 days. No mortality, signs of systemic toxicity no abnormalities during gross necropsy and no change in body weight gain were observed. Thus, the acute oral LD50 in rats was determined to be greater than 2000 mg/kg bw.

CAS 90431-25-7

For Isooctadecanoic acid, mono-, di and triesters with triglycerol (CAS# 90431-25-7), an acute oral toxicity study (limit test) according to OECD TG 401 (Dufour, 1997, 2005) is available. Groups of 5 female NMRI mice received doses of 2000 mg/kg bw of test substance by gavage. The animals were observed for 6 days. No mortality, signs of systemic toxicity and no abnormalities in body weight gain and during gross necropsy were seen. Thus, the acute oral LD50 in rats was determined to be greater than 2000 mg/kg bw.

Acute toxicology: inhalation

Since no studies investigating the acute inhalation toxicity of Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6) are available, in accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance Fatty acids, C5-10 esters with pentaerythritol (CAS# 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) and Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) was conducted.

CAS 68424-31-7

An acute inhalation toxicity study (limit test) was performed with Fatty acids, C5-10, mixed esters with pentaerythritol (CAS# 68424-31-7) according to OECD Guideline 403 (Parr-Dobrzanski, 1994). Five rats per sex were exposed (nose only) to an aerosol of the test material at an analytical concentration of 5.10 mg/L air (nominal concentration was 5.0 mg/L air) for an exposure duration of four hours. No mortality occurred during the 14 day study period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhoea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. No effect on body weight was noted. Finally necropsy and histopathological examination revealed no substance-related findings. Thus, the LC50 after acute inhalation of fatty acids, C5-10, mixed esters with pentaerythritol in male and female rats was found to be greater than 5.1 mg/L air.

CAS 85536-35-2

An acute inhalation toxicity study (limit test) was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) according to OECD Guideline 403 (Parr-Dobrzanski, 1994). Five rats per sex were exposed (nose only) to an aerosol of the test material at an analytical concentration of 5. 0 mg/L air for an exposure duration of four hours. No mortality occurred during the 14 day study period. Clinical signs were seen during and/or immediately after exposure including hunched posture, chromodacryorrhoea, piloerection, stains around the nose and wet fur. In general, animals showed a rapid recovery from these effects by Day 2, although, hunched posture and piloerection persisted in few animals up to Days 4 and 8, respectively. No effect on body weight was noted. Finally necropsy and histopathological examination revealed no substance-related findings. Thus, the LC50 after acute inhalation of Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol in male and female rats was found to be greater than 5.0 mg/L air.

 

CAS 73398-61-5

Another acute inhalation toxicity study was performed with Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) according to OECD Guideline 403 (Reminghaus, 1976). Ten male rats were exposed (nose only) to an aerosol of the test material at an analytical concentration of 1.86 mg/L air for an exposure duration of six hours. No mortality occurred during the 14 day study period. No clinical signs of toxicity were observed in any of the animals during the 14-day observation period. No effect on body weight was noted. Finally necropsy and histopathological examination revealed no abnormal findings in lungs or tracheae. Macroscopically no deposits of oily test substance could be detected in the respiratory tissues. Thus, the LC50 after acute inhalation of glycerides, mixed decanoyl and octanoyl in male rats was found to be greater than 1.86 mg/L air.

 

Acute toxicology: dermal

Since no studies investigating the acute dermal toxicity of Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) and Glycerol tristearate (CAS# 555-43-1) was conducted.

The acute dermal toxicity potential of 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) was investigated in a limit test performed according to OECD Guideline 402 (Cords, 2012) and GLP compliant. The dorsal and dorsolateral parts of the trunk of five male and female rats were treated semiocclusively with the test material at 5000 mg/kg bw. 24 hours after application, the treated area of skin was rinsed with warm water. No mortality occurred and no clinical signs of systemic toxicity were observed in any of the animals during the 14-day observation period. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. Finally no macroscopic pathologic abnormalities were noted at necropsy. Thus, the dermal LC50 after treatment with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate in male and female rats was found to be greater than 5000 mg/kg bw.

 

CAS 555-43-1

The acute dermal toxicity potential of Glycerol tristearate (CAS# 555-43-1) was investigated in a limit test performed according to OECD Guideline 402 (Krueger, 1988) and GLP compliant. The dorsolumbar region of five male and female rats was treated semiocclusively with the test material at 2000 mg/kg bw. 24 hours after dosing, the treated area of skin was cleaned with corn oil and absorbent paper. No mortality occurred and no clinical signs of toxicity were observed in any of the animals during the 14-day observation period. With regard to the body weight: male rats achieved satisfactory body weight gains throughout the study.

Four female rats showed minimal body weight gain after the first week. One female showed little body weight loss after the first week. At the end of the study, minimal body weight gain was recorded in two female animals and one animal showed no body weight gain while two female rats achieved satisfactory body weight gains throughout the study. Finally the macroscopical examination on day 14 after treatment revealed no abnormalities. Thus, the dermal LC50 after treatment with glycerol tristearate in male and female rats was found to be greater than 2000 mg/kg bw.

 

Conclusion for acute toxicity

In summary, acute oral toxicity studies from 2,3-dihydroxypropyl oleate (CAS# 111-03-5) and Isooctadecanoic acid, mono-, di and triesters with triglycerol (CAS# 90431-25-7), with fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) are available and resulted in oral LD50 values greater than 2000 mg/kg bw.

For acute inhalation toxicity, studies with Fatty acids, C5-10 esters with pentaerythritol (CAS# 68424-31-7), Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) and Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) are available. The studies conducted with Fatty acids, C5-10 esters with pentaerythritol (CAS# 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) resulted in no mortality and some clinical signs including hunched position, chromodacryorrhoea, piloerection, staining around nose and wet fur. In addition, the highest attainable concentration of Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) resulted in the LC50 value of > 1.86 mg/L air

Acute dermal toxicity studies conducted 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) and Glycerol tristearate (CAS# 555-43-1) showed no treatment related effects at the limit dose of the current valid guideline. Therefore, the dermal LD50 is considered to be greater than 5000 and 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the target and source substances 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 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 classification or non-classification

Based on read-across from structurally similar substances, the available data on skin and eye irritation 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.