2-pentylcinnamaldehyde and Dermatitis--Contact

Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals (<500 g/mol). For sensitizing chemicals that are not protein reactive, it is hypothesised that metabolic activation can convert such chemicals into protein reactive toxins within the skin. trans-Cinnamaldehyde, alpha-amyl cinnamaldehyde, and trans-cinnamic alcohol are known sensitizers with differing potencies in man, where the former two are protein reactive and the latter is not. Here, we have used immunochemical methods to investigate the extent of protein-cinnamaldehyde binding in rat and human skin homogenates that have been incubated (for either 5, 15, 30, or 60 min) at 37 degrees C with cinnamaldehyde, alpha-amyl cinnamaldehyde (at concentrations of between 1 and 40 mM), and cinnamic alcohol (at higher concentrations of 200 or 400 mM). Cinnamaldehyde specific antiserum was raised specially. A broad range (in terms of molecular mass) of protein-cinnamaldehyde adducts was detected (as formed in a time- and concentration-dependent manner) in skin treated with cinnamaldehyde and cinnamic alcohol but not with alpha-amyl cinnamaldehyde. Mechanistic observations have been related to relative skin sensitization potential, as determined using the local lymph node assay (LLNA) as a biological read-out. The work presented here suggests that there is a common hapten involved in cinnamaldehyde and cinnamic alcohol sensitization and that metabolic activation (to cinnamaldehyde) is involved in the latter. Conversely, there does not appear to be a common hapten for cinnamaldehyde and alpha-amyl cinnamaldehyde. Such mechanistic work on protein modification is important in understanding the early mechanisms of skin sensitization. Such knowledge can then be used in order that effective and appropriate in vitro/in silico tools for predicting sensitization potential, with a high confidence, can be developed.

Topics: Acrolein; Aldehydes; Animals; Dermatitis, Contact; Dose-Response Relationship, Drug; Female; Humans; Immunoenzyme Techniques; Local Lymph Node Assay; Propanols; Protein Binding; Rabbits; Rats; Rats, Inbred F344; Skin

Deodorants are one of the most frequently used types of cosmetics and side-effects from them are common. Recent studies relate perfume allergy to this type of product. 73 deodorants were analyzed by gas chromatography--mass spectrometry for the determination of the contents of 7 wellknown fragrance allergens from the fragrance mix and 14 other commonly used fragrance materials. The deodorants were purchased at retail outlets in 5 European countries. It was found that in general, fragrance mix ingredients were more frequently present in vapo- and aerosol sprays than in roll-on products. The levels of the fragrance mix substances ranged from 0.0001-0.2355%. The products investigated contained cinnamic aldehyde and isoeugenol less frequently (17% and 29% respectively), and eugenol and geraniol most frequently (57% and 76% respectively). The 14 other fragrance materials were found in 40-97% of the deodorants, with hedione and benzyl acetate the most frequently found substances. The concentration of these 14 substances ranged from 0.0001-2.7%. It is concluded that the levels of cinnamic aldehyde and isoeugenol found in the deodorants could prove to be relevant for elicitation of contact dermatitis. No conclusions could be drawn about the other fragrance mix constituents, as threshold levels in sensitized individuals have not been investigated. Furthermore, all of the fragrance materials investigated were frequently found in deodorants and, apart from the fragrance mix ingredients, the extent of problems with sensitization to these fragrance materials is largely unknown.

Topics: Acrolein; Acyclic Monoterpenes; Aldehydes; Allergens; Deodorants; Dermatitis, Contact; Eugenol; Europe; Gas Chromatography-Mass Spectrometry; Humans; Perfume; Propanols; Terpenes

Sensitivity to alpha-amylcinnamic aldehyde (alpha-AcAld) is apparently uncommon, but, like allergy to alpha-amylcinnamic alcohol (alpha-AcAlc), it often accompanies allergy to the perfume in Mycolog cream. Although alpha-AcAlc is a known ingredient, alpha-AcAld is not. However, gas-liquid chromatographic analysis shows alpha-AcAld to be present. Of fourteen persons sensitive to either chemical, ten reacted to both. Of these, one man and three women were markedly sensitive, and all three women had chronic recalcitrant vulvar eczema. That condition might have been the cause as well as the result of sensitization, but reexposure to a suspected product reproduced the eruption in both persons tested. Its use with other potent sensitizers, e.g., ethylenediamine, to treat irritations and chronic eczemas in an area of high absorption may partly explain development of allergy to a relatively weak sensitizer.

Topics: Alcohols; Aldehydes; Dermatitis, Contact; Drug Combinations; Female; Gramicidin; Humans; Male; Neomycin; Nystatin; Patch Tests; Perfume; Triamcinolone Acetonide