Registration Dossier

Administrative data

Description of key information

Skin irritation (WoE): not irritating
Eye irritation (WoE): 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)

Additional information

Skin Irritation

To characterise the skin irritancy properties of Fatty acids, vegetable-oil, esters with dipropylene glycol, an in vitro skin irritation test was performed according to OECD 439 (Colas, 2014). 16 µL undiluted test substance were topically applied to intact reconstructed human epidermis (SkinEthic Laboratories, Lyon, France) for 42 minutes prior washing with phosphate buffered saline. Concurrent negative control tissues were treated with an equal volume of phosphate buffered saline. Further, 5% sodium dodecyl sulfate (SDS) was included as positive control substance. After a post-incubation period of 41.5 h, MTT measurements revealed a relative cell viability of 84.2 ± 14.9% compared to the negative control. SDS reduced the relative cell viability to 1.1 ± 0% thereby validating the study. According to the evaluation criteria given in OECD 439, Fatty acids, vegetable-oil, esters with dipropylene glycol is considered to be non-irritating to skin.

 

To sufficiently cover the data requirements according to Annex VIII, the in vitro skin irritation test is combined with an in vivo skin irritation test available for the analogue substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) following a weight-of-evidence approach. Both substances represent UVCB substances comprised of short chain fatty acids (C8 – C10) bound to 1,2 propylene glycol units (for further information, please refer to the Analogue Justification provided in the dossier).

 

CAS 68583-51-7

The skin irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were 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 was observed which was fully reversible within 48 h (mean erythema score 0.3 after 24-72 h). The remaining animals revealed no erythema formation. No edema formation (mean over 24, 48 and 72 h) or further local or systemic effects were apparent in any animal during the study period.

 

Conclusion of skin irritation properties

The test substance Fatty acids, vegetable-oil, esters with dipropylene glycol did not exhibit irritating properties in the in vitro skin irritation test. Moreover, the in vivo study available for the structural analogue substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol does not indicate skin irritating properties. Therefore, following a weight-of-evidence approach, Fatty acids, vegetable-oil, esters with dipropylene glycol is not considered as skin irritant. This conclusion is justified based on the presence of common functional groups and similar intrinsic properties present in the target and analogue substance.

 

Eye Irritation

To evaluate the eye irritancy potential of Fatty acids, vegetable-oil, esters with dipropylene glycol, an isolated chicken eye test (ICE) was performed according to OECD 438 under GLP-compliance. 30 µL undiluted test substance was applied to 3 freshly prepared corneas and corneal opacity, fluorescein retention and corneal swelling were evaluated. Benzalkonium chloride (5%), applied to 3 corneas, was used as positive control substance and physiological saline applied to 1 cornea served as negative control. Eyes treated with the test substance showed no alteration in corneal opacity or fluorescein retention to any reading time point leading to ICE classes of “I” for each of these endpoints. In contrast, the test substance induced corneal swelling with the highest increase of 14% at 75 min post-dose corresponding to an ICE class of III. Therefore, a combination of the categories derived for the 3 endpoints results in 2 x ICE class I and 1x ICE class III for the test substance. Treatment with physiological saline did not induce any effects on the corneas leading to combined ICE classes of 3 x I which results in “No Category”, thereby validating the study. The positive control substance Benzalkonium chloride (5%) induced alterations in corneal opacity, fluorescein retention and corneal swelling thereby validating the study. Based on the results of the conducted study, the test item did not reveal corrosive/severe irritant properties. However, according to the in vitro classification criteria defined in OED GL 438 (§52, Table 6), no prediction can be made for the test result in regard to eye hazard potency. 

 

Therefore, based on the common metabolic fate of glycol esters and the presence of common functional groups, available data on the structural analogue substances Decanoic acid, mixed diesters with octanic acid and propylene glycol (CAS 68583-51-7) and Octanoic acid ester with 1,2-propanediol, mono- and di-(CAS 31565-12-5) are included in the dossier to allow a definitive conclusion for the eye hazardous potential of Fatty acids, vegetable-oil, esters with dipropylene glycol following a weight-of-evidence approach. The test substance and both structural analogue substances represent UVCB substances comprised of short chain fatty acids (C8 – C10) bound to 1,2 propylene glycol units.

 

CAS 68583-51-7

The eye irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were tested in a study according to OECD guideline 405 in compliance with GLP (Kästner, 1988). In a group of 4 male rabbits (Kleinrusse), 0.1 mL of the undiluted test substance was applied into one eye, in a single application without washing. The eyes were observed and reactions were evaluated 1, 6, 24, 48 and 72 h after application. No effects on corneal opacity and iris were noted at any time point in any animal. However, mild conjunctival redness was observed in 2/4 animals at the 1 h reading time point. In one of these animals the effect was fully reversible within 6 h; in the second animal mild redness was apparent until 6 h after application being fully reversible after 24 h as well (mean score over 24, 48 and 72 h out of all 4 animals = 0). No chemosis or exudation were observed during the study period in any animal. No further local or systemic effects were observed in any animal during the study period. Therefore, Decanoic acid, mixed diesters with octanoic acid and propylene glycol is considered as not irritating to eyes.

 

CAS 31565-12-5

Octanoic acid ester with 1,2-propanediol, mono- and di- was tested in 3 male rabbits (Kleinrusse) according to OECD 405 and GLP (Mürmann, 1992). Instillation of 0.1 mL undiluted test substance induced small erythema at the conjunctivae in all treated animals 1 hour after test substance application (scored with Grade 1) which were fully reversible within 24 h. Furthermore, 2/3 animals revealed weak chemosis visible only 1 h after substance application. No adverse effects on the cornea or iris were observed at this time point. At later reading time points, no other signs of irritation were noted in the test animals. In addition, no further local or systemic effects were reported. Thus, Octanoic acid ester with 1,2-propanediol, mono- and di- did not exhibit eye irritating properties.

Conclusion of eye irritation properties

Fatty acids, vegetable-oil, esters with dipropylene glycol were shown to be not corrosive to eyes in the ICE test. However, in regard to irritating properties, the available data for Fatty acids, vegetable-oil, esters with dipropylene glycol do not allow a definitive conclusion on eye irritation. Thus, the available in vitro data for Fatty acids, vegetable-oil, esters with dipropylene glycol on eye irritation are complemented by in vivo results obtained for the analogue substances Decanoic acid, mixed diesters with octanoic acid and propylene glycol and Octanoic acid ester with 1,2-propanediol, mono- and di-, which revealed no irritating properties for both analogue substances. The weight-of-evidence approach based on the combination of available in vitro and in vivo data allows the definitive conclusion that Fatty acids, vegetable-oil, esters with dipropylene glycol is not considered as eye irritant. This conclusion is justified based on the presence of common functional groups and similar intrinsic properties present in the target and analogue substances.

 

Justification for selection of skin irritation / corrosion endpoint:
No study was selected as hazard assessment is conducted by a weight-of-evidence approach based on data of the test substance combined with data from a structural analogue substance. The available studies are adequate and reliable. The read-across is based on identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
No study was selected as hazard assessment is conducted by a weight-of-evidence approach based on data of the test substance combined with data from structural analogue substances. The available studies are adequate and reliable. The read-across is based on identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance and the structural analogue substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 and Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.