Propane-1,2-diol, propoxylated

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No data on skin sensitizing 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.

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

Sensitizing potential of monopropylene glycol has been extensively studied in both experimental animals and humans. The most recent animal study of Basketter et al., 1998 involved Local Lymph Node Assay (LLNA) in CBA mice (4/dose) using monopropylene glycol as 50% aqueous solution and as a neat substance. The stimulation indices were 1.2 and 1.6, respectively, indicating that monopropylene glycol is not sensitizing to skin. Also numerous reports on the investigation of sensitizing potential of monopropylene glycol in humans appeared in the literature, out of which those considered to be most reliable are briefly summarized here. Two repeated insult patch tests using human volunteers under occlusive (Consumer Product Testing Co., 1999a) and semi-occlusive (Consumer Product Testing Co., 1999b) conditions were available for assessment. Approximately 0.2 ml of the test material was applied as a either occluded or semi-occluded patch to the upper back of 113 volunteers (as a neat substance for subjects 1-47 only, and as a 50% aqueous solution for the rest of the panel). Patches were applied three times per week (Monday, Wednesday, Friday) for a total of nine applications and were removed 24 hours after application. Approximately 2 weeks after the final induction patch application, a challenge patch was applied to a virgin test site adjacent to the original induction patch site, following the same procedure described for induction. The patch was removed and the site scored 24- and 72-hr post-application. One hundred and four subjects completed the study. With the exception of one subject, observations remained within normal limits throughout the test interval. One subject was observed to be hypersensitive in an irritant manner, throughout the induction and challenge phases of the study. Under the conditions of the study, monopropylene glycol did not cause allergic contact dermatitis.

Lessmann et al., 2005, reported the analysis of patch test data of 45138 patients with suspected allergic contact eczema, who have been tested with 20% aqueous solution of monopropylene glycol between 1992 and 2002. Out of these, 1044 patients (2.3%) tested positive, 1083 showed a doubtful, follicular or erythematous reaction (2.4%) and 271 explicit irritant reactions (0.6%). This profile of patch test reactions is indicative of a slightly irritant preparation, and thus, many of the "weak positive" reactions must probably be interpreted as false positive. No private or occupational exposures associated with an increased risk of monopropylene glycol sensitization were identified, except for lower leg dermatitis. The authors concluded that monopropylene glycol exhibits very low sensitization potential, and the risk for sensitization to monopropylene glycol on uncompromized skin appears to be very low.

Very similar findings have been reported by Warshaw et al., 2009, who performed a retrospective analysis of cross-sectional data compiled by the North American Contact Dermatitis Group (MACDG) from 1996 to 2006 to characterize the prevalence of positive patch-test reactions to monopropylene glycol and the epidemiology of affected patients. Out of a total of 23359 patients tested by NACDG between 1996 and 2006, 810 patients (3.5%) had an allergic patch-test reaction to 30% aqueous solution of monopropylene glycol. Of these allergic reactions, 12.8% were of definite clinical relevance (positive reaction to a personal product containing monopropylene glycol), 88.3% were considered to be currently relevant (definite, probably or possible relevance) and 4.2% were occupation related. Overall, the results concur with the conclusions of the study of Lessmann et al., 2005, suggesting that monopropylene glycol is a weak sensitizer.

For dipropylene glycol, one animal and one human studies were available for assessment. In the Buehler test with guinea pigs (Cosmopolitan Safety Evaluation, Inc., 1995f), performed under GLP and in accordance with EPA OPP 81-6 (Skin Sensitization) guideline, a dose of 0.5 ml of the freshly prepared test solution was applied to a shaved surface of 10 animals under occlusion and kept for six hours. This induction procedure was repeated at the same site during the next 2 weeks for a total of three 6-hour exposures, with 5-9 days interval between induction exposures. Two weeks after the last induction, the animals and a naive group were challenged at a virgin site (left side) with 0.5 ml at the non-irritating concentration at each site. The test substance was applied as for induction. Reactions were scored at approximately 24, 48 and 72 hours after challenge. No irritation was observed except for transient slight patchy erythema at one site in 1 of the 5 animals. Based on these results, dipropylene glycol is considered not to have a skin sensitizing potential.

Also one human study in an eczema population (Johansen et al., 1995) was available for assessment. 503 eczema patients were patch tested with 10% aqueous solution of dipropylene glycol of two different grades (cosmetic and synthesis, purity 96% and 97%, respectively. Patches were applied for 2 days and reactions were scored at days 2, 3 and 5-7. There was only 1 positive patch test to synthesis grade of dipropylene glycol, the remaining reactions being either equivocal (26 in total; 4 patients having equivocal reactions to both grades of dipropylene glycol) or irritating (7). Overall, the results suggest that dipropylene glycol has a very weak sensitizing potential, if any.

For tetrapropylene glycol, one Buehler test with guinea pigs is reported (Dow Chemical Company, 1996). A group of 10 male animals was induced topically, applying 0.4 ml of the test substance for 6 hours weekly for 3 consecutive weeks to the animals left side under occlusion. Approximately 2 weeks after the last induction animals were challenged with 0.4 ml of the neat test substance at the right side in the same exposure manner. Also 14 native animals were dosed either with the same aliquot of the test substance, or with two positive controls (dinitrobenzene or DER 331epoxy resin). The test sites were scored for sensitization response approximately at 24 and 48 hours after the test patch removal. Challenge application of tetrapropylene glycol did not induce erythema in any of the 10 animals. Positive controls were valid. Therefore tetrapropylene glycol was considered to be not sensitizing under the conditions of the study.

In summary, there is conclusive evidence that neither of lower propylene glycol homologues have potential skin sensitizing properties. Based on these results, it is concluded that ‘propane-1,2-diol, propoxylated’ is also not a skin sensitizer.

Migrated from Short description of key information:
No data on skin sensitizing potential of ‘propane-1,2-diol, propoxylated’ are available. Experimental data is available for the source substances monopropylene glycol and dipropylene glycol and human clinical data is reported for the former Whilst there are rare cases of adverse reactions reported in humans, the Guidance on the Application of the classification, labelling and packaging (CLP) criteria states that it is necessary to take into account the size of the population exposure and the extent of exposure and frequency (which in the case of propylene glycols are extensive). Human data should be incorporated with the animal data. In this case, the data overall indicates these substances have very low skin sensitization potential. The other members of the propylene glycol series contain the same functional groups as the source substances. None of the glycols contain any structural alerts for skin sensitization. Since higher members of the homologous series are metabolized via the two source substances, it can be concluded that there are no metabolites of the propylene glycols that could be skin sensitisers. Based on these results, it is concluded that ‘propane-1,2-diol, propoxylated’ is not a skin sensitizer. Please also refer to the separate read across justification document attached to chapter 13 of the IUCLID dossier.

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 sensitisation 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 sensitisation in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.