Registration Dossier

Administrative data

Description of key information

skin irritation (OECD 404): not irritating
eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

There are no data for skin and eye irritation 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, 8.1 and 8.2.

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 the common metabolic fate of glycol esters, 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 are available on skin and eye irritation 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, C16-18, esters with ethylene glycol (CAS 91030-31-1) and Fatty acids, C14-18 and C16-18 unsaturated, ester with propylene glycol (CAS 84988-75-0) was conducted.

 

CAS 627-83-8

The skin irritation properties of Ethylene distearate was tested in a study equivalent to OECD guideline 404 (Wnorowski, 1991b). In the study, 3 male and 3 female New Zealand White rabbits were exposed to 0.5 g of the unchanged test substance, applied to the shaved and abraded skin for 25 h using an occlusive dressing. The treated skin was observed and evaluated at 25 and 72 h post-application. No erythema or edema was observed in any animal during the study period on intact shaved skin. On abraded skin, slight erythema in 2 animals was observed at 25 h, being fully reversible within 72 h. No further local or systemic effects were apparent in any animal during the study period.

Thus, Ethylene distearate is not irritating to the skin.

 

CAS 68583-51-7

The skin irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was tested in a study according to OECD guideline 404 in compliance with GLP (Guest, 1989). In the study, 3 New Zealand White rabbits were exposed to 0.5 mL of the undiluted test substance, applied to the shaved skin for 4 h using a semiocclusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h post-application. In 1/3 animals 24 h after removal of the test substance, slight erythema (score 1) was observed which was fully reversible within 48 h (mean erythema score 0.3 over 24, 48 and 72 h). The remaining two animals revealed no erythema formation. No edema formation or further local or systemic effects were apparent in any animal during the study period.

In summary, Decanoic acid, mixed diesters with octanoic acid and propylene glycol is not irritating to the skin.

 

CAS 91031-31-1

Fatty acids, C16-18, esters with ethylene glycol was tested in a study according to OECD guideline 404 in compliance with GLP (Coguet, 1976). 6 New Zealand White male rabbits were exposed to 0.5 mL of the test substance (40%) in olive oil, applied to the shaved and abraded skin for 24 h using an occlusive dressing. The treated skin was observed and evaluated at 24 and 72 h post-application. On intact skin, 2/6 animals showed slight erythema (on abraded skin 5/6 showed slight irritating effects) after 24 h which were fully reversible within 72 h (mean erythema score over 24 and 72 h out of all 6 animals = 0.22 (for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h)). No edema formation or further local or systemic effects were apparent in any animal during the study period. Thus, Fatty acids, C16-18, esters with ethylene glycol is not irritating to the skin at a concentration of 40%.

 

Conclusion on skin irritation properties

In conclusion, skin irritation potential of the read-across analogue substances has been investigated in vivo indicating no skin irritating properties. Therefore, Propyleneglycol dioleate is not considered as skin irritant.

 

Eye irritation

 

CAS 84988-75-0

The eye irritation properties of Fatty acids, C14-18 and C16-18 unsaturated, ester with propylene glycol were tested in a study performed according to OECD guideline 405 and in compliance with GLP (Steiling 1991). 0.1 mL of the unchanged test substance was applied into the eye of 3 male rabbits (Kleinrussen, Chbb:HM). The untreated eye served as control. After 24 hours, the treated eye was rinsed with tepid tap water. Observation of the eyes was performed 1, 24, 48 and 72 h after application. No effects on cornea and iris were noted in any animal during the study period. However, slight erythema (score 1) being fully reversible within 48 h (mean score 0.33 over 24, 48 and 72 h) were observed in 2/3 animals. In 1/3 animals, slight chemosis (score 1) was observed after 1 h being fully reversible within 24 h. No further edema formation was observed during the study period in any animal. No further systemic effects were observed in any animal during the study period and hence, Fatty acids, C14-18 and C16-18 unsaturated, ester with propylene glycol are considered as not eye irritating.

 

Conclusion on eye irritation properties

In conclusion, the eye irritation potential of the read-across analogue substance has been investigated in vivo indicating no eye irritating properties. Based on these data, Propyleneglycol dioleate is not considered as eye irritant.

 

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.

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.


Justification for selection of skin irritation / corrosion 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 eye irritation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is represents an adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance 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 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.