Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

In the chosen key study for skin sensitization, i.e. the mouse Local Lymph Node Assay according to the OECD TG 429 (Research Institute for Fragrance Materials Inc, 2007), 4 -methoxybenzaldehyde was applied as 0 (vehicle alone), 1, 2.5, 5, 10 or 25 % (w/v) preparations in 1:3 Ethanol/Diethylphthalate (1:3 EtOH:DEP). None of the evaluated test substance concentrations induced a 3 fold increase in lymphocyte proliferation (SI values of 1.4, 1.0, 1.1, 1.5 and 1.5 respectively at 1, 2.5, 5, 10 and 25 % test substance concentrations). Mild skin irritation on or around the ear area was observed on study days 3 and 6 for all animals of the 10 and 25 % w/v dose groups, respectively, indicating confounding skin irritation effects at putative higher test substance concentrations. SI values observed for the positive control compound, hexylcinnamaldehyde, confirmed the validity of the protocol used for this study.

Further published data with limited information, indicate the absence of a skin sensitizing potential of 4-methoxybenzaldehyde in guinea pigs (Ishihara 1986, Klecak 1979/1985).

Skin reactions in guinea pigs have been reported in a publication after 7 daily repeated intradermal injections of 1% 4-methoxybenzaldehyde (in saline containing 1% Tween 80) followed by an intradermal challenge with 0.25, 0.5 and 1% 4-methoxybenzaldehyde in the same vehicle (Watanabe 2001). However, testing has not been performed under current standard protocols (e.g. intracutaneous injection for induction and challenge, low animal number, scoring system).

A human repeated insult patch tests have been reported in literature with limited documentation. No sensitization reactions were reported in 25 volunteers after repeated dermal application of 10% 4-methoxybenzaldehyde (Kligman 1973).

In human repeated insult patch tests, 4-methoxybenzaldehyde has been applied dermally for 9 induction patches at concentrations of 2, 4 or 5.5% (2363, 4724, 6496 µg/cm2) in EtOH:DEP  (Harrison 2008, 2009). After a rest period of approx. 14 days, subjects have been challenged with the respective test substance concentration.

The test material at 5.5% (6496 µg/cm2) did induce an edemateous reaction indicative of skin sensitization in 1 of 109 subjects. This subject also showed edemateous reactions at two rechallenge patch tests.

The test material at 4% (4724 µg/cm2) did induce an edematous reaction in 1 of 111 subjects indicative of dermal sensitization. However these findings could not be confirmed in a rechallenge patch test.

The test material at 2% (2363 µg/cm2) did not induce any skin sensitization reactions in 109 subjects under the chosen testing conditions.

Overall in the light of the other data available, the observed single skin findings are not to be considered as evidence for a skin sensitization potential of p-methoxybenzaldehyde.

Several patch tests in patients with dermatoses or perfume sensitive patients from literature with limited documentation have been reported no or single sporadic dermal responses after dermal application of 4-methoxybenzaldehyde (Larsen 1975, Larsen 1977, Hjorth 1961, Takenaka 1968, Fujii 1972, Rudzki 1976).

Taken together, the 4-methoxybenzaldehyde is not to be considered a skin sensitizer.


Migrated from Short description of key information:
LLNA (OECD 429, GLP): negative (Research Institute for Fragrance Materials Inc., 2007)

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
No data available

Justification for classification or non-classification

The present data on dermal sensitization do not fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and therefore, a non-classification is warranted.