Propane-1,2-diol, propoxylated

Endpoint summary

Description of key information

No data on skin and eye irritating properties of ‘propane-1,2-diol, propoxylated’ are available. Measured data is available for all the components except pentapropylene glycol. None the components for which data are available shows any indications of skin or eye irritation potential. Based on these results, ‘propane-1,2-diol, propoxylated’ is considered to be non-irritating.  Please also refer to separate read across justification document attached to chapter 13 of the IUCLID dossier.

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

No data on skin and eye irritating properties of ‘propane-1,2-diol, propoxylated’ are available. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

Data are available on skin and eye irritating properties of structural analogues of ‘propane-1,2-diol, propoxylated’, mono-, di-, tri- and tetrapropylene glycols. All four substances are also the constituents of polypropylene glycol (a multi-constituent substance), usually present in the commercial product at following concentrations: 0-2% monopropylene glycol, 0 -50% dipropylene glycol, 10 -80% tripropylene glycol and 0 -90% tetrapropylene glycol. Therefore it is considered acceptable to derive the data on skin and eye irritating properties of ‘propane-1,2-diol, propoxylated’ by read-across from its constituents.

Skin irritation

Skin irritating potentials of mono-, di- and tripropylene glycol have been studied in both animal studies and the studies with human volunteers. The animal studies with mono- and dipropylene glycol were performed according to modern guidelines (OECD Guideline 404 and EPA GuidelineOPP 81-5) (Hüls, 1984; Cosmopolitan Safety Evaluation, Inc.,1995d). At most, very minor, if any, signs of irritation (e. g. very slight erythema) were noted shortly after the removal of the test patch; these were usually resolved by 24 hours examination. Based on these results, all substances were found to be not irritating to rabbit skin.

Several skin irritation studies with human volunteers with all three substances were available for assessment. The first one, a 24-h semi-occluded patch study, was conducted to compare the skin irritancy potential of several test articles, including mono-, di- and tripropylene glycols (Hill Top Research, Inc., 1995). The test substance was prepared as a 25% solution in distilled water and 0.2 ml of the solution was placed on the patch pad and applied on the paraspinal region of the back of 33 subjects. The results were compared with 2 negative controls (water and USP oil) and a positive control (0.5% sodium lauryl sulfate). All skin sites were scored prior to the application, 30 min after the removal of the 24 h application and again 24 h following patch removal. Only minor signs of irritation, manifested as mild erythema, were observed in several subjects (13 for mono-, 9- for di- and 2 for tripropylene glycol). Some of these were resolved at 24 hours post-administration. As average Draize scores would be below 2 in all cases, the test substances were concluded to be not irritating to human skin in the study.

In the second type of studies (Consumer Product Testing Co., 1997a,b,c), a 14-day cumulative irritation test, also performed on all 3 substances, approximately 0.2 ml of the test material was applied neat and as 50% solution under occlusive dressing to the upper back of 26 human volunteers. The test material was applied Monday through Friday. Patches applied on Friday remained in place until the following Monday for a total of 14 days of skin contact. As in the first study, most of the subjects did not exhibit any signs of skin irritation during the whole duration of the test. In the test with monopropylene glycol, upon application of the neat substance, one out of 26 subjects exhibited a marked (3+) response and the applications were discontinued by the second observation day. This type of immediate reaction is indicative of a dose dependant pre-sensitization to the test material. Five more subjects exhibited mild erythema (grade 1, similar to Draize score 1) one day after the application, which was resolved on the second observation day in 4 subjects and on the third day in the last subject. For dipropylene glycol, only one of the subjects showed mild erythema upon treatment with neat dipropylene glycol during the first 4 days of the study, which was resolved for the rest of the test period, while for tripropylene glycol no skin reactions were observed at all in any of the subjects.

Three animal skin irritation studies with tetrapropylene glycol were available for the assessment, all performed according to non-standard protocols. Out of these studies, the most recent one were chosen as a key study. In this study (Dow Chemical Company, 1996), 0.5 ml of neat tetrapropylene glycol were applied to intact and abraded skin on the abdomen and 0.1 ml to the inside of one ear of one male rabbit. The animal was bandaged for 24 hours after application to provide occlusion. Twenty-four hours after application the bandage was removed and the application sites were graded. Five consecutive daily doses were applied to intact skin and the inside of the ear, and three consecutive daily applications were made to the abraded abdominal skin. Body weights were recorded. It should be noted that the applied testing regime was much more severe in comparison to the test procedure recommended by modern guidelines, which recommends the single 4 hours application of the test substance to the intact rabbit skin under semi-occlusion. No signs of irritation were noted throughout the study on the intact or abraded abdominal sites. There was slight erythema on test days 3, 4 and 5 at the ear test site, which was resolved by test day 8.

In summary, there is conclusive evidence that mono-, di-, tri- and tetrapropylene glycols are not irritating to skin. Based on these results, it is concluded that ‘propane-1,2-diol, propoxylated’ is also not a skin irritant.

Eye irritation

Eye irritating potential of mono-, di- and tripropylene glycol was studied in guideline studies with rabbits (OECD Guideline 405 and/or EPA GuidelineEPA OPP 81-4), as well as in vitro using the SkinEthic Reconstituted Human Corneal Epithelium model for tripropylene glycol. For monopropylene glycol, mean scores at 24 + 48 + 72 hr examination points for cornea and chemosis were 0; mean score for conjunctivae was 0.4 and for iris 0.1 according to Draize scoring system. All reactions were fully reversible within 96 hours (Jacobs GA, 1988). For dipropylene glycol, in the study with 6 rabbits, at one hour there was very slight irritation characterized by conjunctival redness (grade 1) in all eyes with two out of 6 also showing chemosis (Grade 1). At 24 hours all eyes appeared normal and remained normal through 72 hours. At no time was there any corneal involvement and there was no corrosive effect on the eye (Cosmopolitan Safety Evaluation, Inc., 1995e).

For tripropylene glycol, both in vitro and in vivo studies were available. In thein vitrostudy (Harlan Laboratories Ltd., 2010c), using the SkinEthic Reconstituted Human Corneal model, triplicate SkinEthic tissues were treated with 30 µl of the test material for 10 minutes. Triplicate tissues treated with 30 µl of 1% w/v sodium dodecyl sulphate served as the positive control. The test is based on the hypothesis that irritant chemicals are able to penetrate the corneal epithelial tissue and are sufficiently cytotoxic to cause cell death. If the percentage relative mean tissue viability was >=60% the test material was considered to be non-irritant; if the percentage relative mean tissue viability was <60% the test material was considered to be an irritant. The relative mean viability of the test material treated tissues after a 10 minute exposure was 85.9%. Based on these results, tripropylene glycol was considered to be non-irritating to eyes. In the in vivo study with two rabbits (Harlan Laboratories Ltd., 2010d), no corneal or iridial effects were noted. Moderate conjunctival irritation was noted in both treated eyes one hour after treatment (score 1). Both treated eyes appeared normal at the 24-hour observation. Initial pain response upon substance instillation into the eye of the first animal was 3 by 6-point scale. Therefore one drop of local anaesthetic was instilled into both eyes of the second animal 1 to 2 minutes before treatment. Based on the results of the study, tripropylene glycol is considered to be not an eye irritant.

Two eye irritation studies with tetrapropylene glycol were available for the assessment, all performed according to non-standard protocols. Out of these studies, the most recent one was chosen as a key study. In this study (Dow Chemical Company, 1996), 0.1 ml of neat substance was instilled in to each conjunctival sac of one female rabbit. One eye was washed 30 seconds after exposure, another after 1 hour. The eyes were observed for 4 days. Moderate discomfort and very slight redness were noted in the right eye of the rabbit immediately after dosing. Opthaine anesthetic was administered to both eyes. Very slight conjunctival inflammation was present in both eyes of the rabbit 1, 24 and 48 hours after dosing. The occular irritation was resolved by 78 hours post-instillation of the test material. Based on these results, it was concluded that tetrapropylene glycol does not possess eye irritating properties.

In summary, the available evidence indicates that none of the constituents of ‘propane-1,2-diol, propoxylated’ possess a skin or eye irritating potential. Based on this, it is concluded that ‘propane-1,2-diol, propoxylated’ is not irritating to skin and eyes.

Justification for classification or non-classification

None of the components of ‘propane-1,2-diol, propoxylated’ for which data is available show any evidence of skin or eye irritation properties. Data on the components can be considered representative of the substance itself, which would lead to the conclusion that the multi-constituent substance of di, tri, tetra and pentapropylene glycol does not need to be classified for skin or eye irritancy in accordance with and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.