Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No skin sensitisation studies on phenylephrine hydrochloride were available. 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. Therefore, information from the structural analogue +(-)pseudoephedrine was used to determine the possible skin sensitising effects of phenylephrine hydrochloride.

In a GLP compliant skin sensitisation study, performed in accordance with OECD Guideline 442B, groups of five female mice were treated once daily with (+)-pseudoephedrine at concentrations of 0, 2.5, 5, and 10% (w/w) in propylene glycol by topical application to the dorsum of each ear for three consecutive days (BASF 2012). A positive control group of five mice was treated with 25 % (w/w) α-hexyl cinnamaldehyde dissolved in acetone: olive oil (4:1 v/v). Four days after the first topical application the mice were intraperitoneally injected with BrdU. Approximately 24 hours after intraperitoneally injection, the mice were sacrificed and the draining auricular lymph nodes excised, pooled per animal and immediately weighed. The proliferative capacity of pooled lymph node cells was determined by the incorporation of BrdU measured in a photometer. All treated animals survived the scheduled study period. At the test concentration of 5% and 10% (w/w) one animal of the 5% and 3 animals of the 10% test group showed scaling on day 5 only, in one animal with incrustation. No systemic findings were observed during the study period. A statistically significant increase in ear weights was observed for the low (2.5%) and the high (10%) doses groups, but was considered not to be biologically relevant and did not exceed the threshold value of 25% increase. A statistically significant increase in lymph node weights and lymph node cell count was observed for the mid (5%) and high (10%) dose group. The cut-off-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was exceeded in the high dose group (index of 2.4). A statistically significant increase in BrdU labeling was observed for the mid (5%) and high (10%) dose group. In this study stimulation indices (S.I.) of 1.2, 1.7 and 3.1 were determined with the test item at concentrations of 2.5, 5 and 10% (A test item is regarded as a sensitizer if the exposure to one or more test concentration resulted in 1.6-fold or greater increase in incorporation of BrdU compared with concurrent control). Based on the S.I.s obtained with 2.5 and 5% test item concentration, an EC1.6 value of 4.5% (w/w) was calculated. In conclusion, (+)-Pseudoephedrine was found to be a skin sensitizer under the test conditions of this study.


Migrated from Short description of key information:
The structural analogue of phenylephrine hydrochloride: +(-)pseudoephedrin, is considered to be a skin sensitiser in an OECD 422b study.

Justification for classification or non-classification

Based on the findings in the skin sensitisation study of (+)-pseudoephedrine (a structural analogue of phenylephrine hydrochloride), phenylephrine hydrochloride needs to be classified as sensitising to the skin Xi:R43 according to the Directive 67/548/EEC and Cat 1B: H317 according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.