Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw
Dermal : LD50 > 2000 mg/kg bw
Inhalation: no data available

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 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 study available

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 functional group(s), 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 VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

There are no data for acute toxicity available for Propyleneglycol dioleate. In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

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”. 

Propyleneglycol dioleate represents an UVCB substance comprised of diesters of 1,2-propyleneglycol chemically linked to mainly oleic acid (C18:1) and/or palmitic and/or stearic acid (C16, C16:1).Gylcol esters are in general known to bestepwise hydrolysed by gastrointestinal enzymes into the free fatty acid component and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972).

Based on thecommon metabolic fate of glycol esters, the read-across approach is based on the presence ofcommon 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 are available on acute toxicity following the oral, dermal or inhalation route of Propyleneglycol dioleate, read-across to reliable data on the analogue substances Ethylene distearate (CAS 627-83-8), Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7), Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5) was conducted.

 

Acute oral toxicity

CAS 627-83-8

A study for acute oral toxicity of Ethylene distearate was performed in rats in accordance with OECD guideline 401 (Wnorowski, 1991a). 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 value in male and female rats was greater than 5000 mg/kg bw.

 

CAS 68583-51-7

A study for acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was performed in rats in accordance with EU Method B.1 under GLP conditions (Potokar, 1988). A group of 10 Wistar rats (5 males and 5 females) was dosed with 2000 mg/kg bw of the test material in peanut oil by gavage. 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. No effect on body weight gain was noted. During necropsy, in 1/5 males a tightly filled urinary bladder and in 1/5 females a mild hydrometra was observed. These findings were not considered to be substance-related. Therefore, under the conditions of this study, the oral LD50 value in male and female rats was greater than 2000 mg/kg bw.

 

CAS 151661-88-0

Acute oral toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was tested equivalent to OECD guideline 401 under GLP conditions in a group of 10 Wistar rats (5 males and 5 female), treated with the limit dose 2000 mg/kg bw in peanut oil by gavage Potokar, 1989a). No mortality occurred and no clinical signs of toxicity were observed up to the end of the 14-day observation period in male animals. In one female a slightly coloured red nose was observed 4-24 h after treatment. No further clinical signs were observed. No effect on body weight was noted and pathology of male animals revealed no substance-related findings. In one female hydrometra was observed but was considered to be not substance-related.

Therefore, under the conditions of this study, the oral LD50 value in male and female rats was greater than 2000 mg/kg bw.

 

Conclusion on acute oral toxicity

In summary, based on the available data on acute oral toxicity of the read-across analogue substances, the oral LD50 value of Propyleneglycol dioleate is considered to be ≥ 2000 mg/kg bw.

 

Acute inhalation toxicity

No data on acute toxicity following inhalation are included in the dossier as exposure to humans via the inhalation route is considered negligible, especially as the test substance is a liquid with low vapour pressure (experimental result: < 1.1E-1 Pa at 20°C (Kintrup, 2015), calculated result <2.67E-10 (Werth, C. 2014)) thereby indicating a low volatility (ECHA, 2012). Therefore, testing for acute toxicity following inhalation is not appropriate and should be avoided for reasons of animal welfare.

Acute dermal toxicity

CAS 151661-88-0

Reliable data from the read-across analogue substances Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5) investigating the acute toxicity via the dermal route are available.

The acute dermal toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Potokar, 1989b). 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.

 

CAS 31565-12-5

Dermal toxicity of Octanoic acid ester with 1,2-propanediol, mono- and di was established according to OECD guideline 402 and GLP (Mürmann, 1992). 5 rats/sex were exposed to 2000 mg Octanoic acid ester with 1,2-propanediol, mono- and di /kg bw under occlusive or semiocclusive conditions for 24 h followed by an observation period of 14 days.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. In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point (Mürmann, 1992).

 

Conclusion on acute dermal toxicity

The results of the studies of the read-across analogue substances consistently showed no effects at the limit dose of 2000 mg/kg bw. Therefore, the dermal LD50 value of Propyleneglycol dioleate is considered to be ≥2000 mg/kg bw.

 

Overall conclusion for acute toxicity

In summary, reliable data available for the read-across analogue substances indicate a very low level of acute toxicity as oral and dermal LD50 values were greater than 2000 mg/kg bw.

Thus, as the available data did not identify hazards for acute oral and dermal route, Propyleneglycol dioleate is not considered as hazardous after acute exposure.

 

References

Agency for Toxic Substances and Disease Registry (ATSDR) (1997). Toxicological Profile for Propylene Glycol. US Department of Health and Human Services. Atlanta, US.

Agency for Toxic Substances and Disease Registry (ATSDR) (2010). Toxicological Profile for Ethylene Glycol. US Department of Health and Human Services. Atlanta, US.

ECHA (2014). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

Lehninger, A.L. (1970). Biochemistry. Worth Publishers, Inc.Long, C.L. et al. (1958). Studies on absorption and metabolism of propylene glycol distearate. Arch Biochem Biophys, 77(2):428-439.

Mattson, F.H. and Volpenhein, R.A. (1972). Hydrolysis of fully esterified alcohols containing from one to eight hydroxyl groups by the lipolytic enzymes of the rat pancreatic juice. Journal of Lipid Research 13: 325-328..

Miller, O.N., Bazzano, G. (1965). Propanediol metabolism and its relation to lactic acid -metabolism. Annals of the New York Academy of Sciences 119: 957-973.

Ritchie, A.D. (1927). Lactic acid in fish and crustacean muscle. Journal of Experimental Biology 4:327-332.

Werth, C. 2014. Propyleneglycol dioleate (CAS 105-62-4). EPIsuite 4.11 calculation with 9-Octadecenoic acid (Z)-, 1-methyl-1,2-ethanediyl ester.Dr. Knoell Consult GmbH, Report No. 20140626-Wer-1. 2014-06-26

 



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
No study required as inhalation is not considered as a relevant route of human exposure. In regard to the nature of the test substance and its uses, data on the oral and dermal route are provided thus fulfilling the data requirements according to Regulation (EC) No 1907/2006, Annex VIII, Section 8.5.

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of a read-across based on a 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 classification or non-classification

Based on the analogue read-across approach, the available data on acute oral and dermal 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.