The Skin Allergenic Properties of Chemicals May Depend on Contaminants – Evidence from Studies on Coumarin

Abstract

Background/Aims: Positive patch tests are considered representative of a contact allergy to the tested chemical. However, contaminants and derivatives rather than the suspected chemical itself could be responsible for the allergic skin reactions. Here, we tested the importance of contaminants in the sensitizing and allergenic properties of coumarin in mice and humans. Coumarin, an ingredient in cosmetics and fragrances, was chosen as the reference chemical since conflicting results have been obtained regarding its ability to induce contact allergy. In some chemical preparations, this could be explained by the presence of coumarin derivatives endowed with allergenic properties. Methods: In mice, three different coumarin preparations were tested in the local lymph node assay. In humans, we assessed the irritant and allergenic properties of highly pure coumarin in nonallergic and fragrance-allergic patients. Results: Pure coumarin did not exhibit irritant or sensitizing properties in the local lymph node assay. In contrast, two other commercially available coumarins and three contaminants that were detected in these coumarin preparations were identified as weak and moderate sensitizers, respectively. In humans, pure coumarin was extremely well tolerated since only 1 out of 512 patients exhibited a positive patch test to the chemical. Conclusions: These results indicate that coumarin cannot be considered as a common contact allergen and further emphasize that purity of chemicals is mandatory for the assessment of their allergenicity.

Integrated decision strategies for skin sensitization hazard

“…protective of human health), our reference result was positive. While it was a weak sensitizer in the positive tests (EC3 = 29.6%), the response was attributed to contaminants in commercial products containing coumarin (Vocanson et al , ). For undecylenic acid, both DPRA and KeratinoSens produced correct positive results.…”

Rapid classification of perfumes by extractive electrospray ionization mass spectrometry (EESI‐MS)

“…In some cases, impurities derived from natural products could be allergenic or toxic compounds, which in turn could be the molecular basis of known side effects resulting from counterfeit perfumes. 19,20 The degree of these effects would depend on the 'quality' of a particular counterfeit sample.…”

Lack of evidence for allergenic properties of coumarin in a fragrance allergy mouse model

“…DHC, 98% pure and α‐hexylcinnaldehyde (HCA, 85% pure) were purchased from Sigma–Aldrich (Saint Quentin en Fallavier, France). Pure coumarin (Rhodiascent extra pure ® , >99.9% pure) was produced in Rhodia Organics (Lyon, France) (10). All the chemicals were prepared freshly before application, and dissolved in N , N ‐dimethylformamide (DMF; Sigma‐Aldrich, Saint Quentin en Fallavier, France) or in acetone/olive Oil (AOO, Carlos Erba and Lessieur) (4:1, v/v).…”

“…Because the chemical process of coumarin is critical for the purity of the molecule and because coumarin derivatives and contaminants are endowed with irritant and allergenic properties, we hypothesized that the reported allergenic properties of coumarin could in fact be attributed to contaminants. In a recent study combining murine experiments and human clinical studies, we showed that the coumarin chemical (pure coumarin preparation) was extremely well tolerated (10). In contrast, derivatives contaminating some coumarin preparations were endowed with sensitizing properties detected in the local lymph node assay (LLNA) suggesting that contaminants but not the pure chemical are responsible for both the irritant and sensitizing properties previously attributed to coumarin (10).…”