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The sensitizing capacity of coumarins (III).

9 coumarins used as chemical reagents, laser dyes, in perfumery, cosmetics or occurring naturally, were investigated experimentally in guinea pigs to determine their contact sensitizing capacity. 5,7-dihydroxycoumarin, limettin and 5,7-dihydroxy-4-methylcoumarin were found to be moderate sensitizers, while scoparone, isoscopoletin and 4-hydroxycoumarin were weak. The 3 laser dyes were completely negative. The results indicate that substitution in the 6 and 7 or 5 and 7 positions with 2 hydroxy groups supports allergenic capability, while other substituents (e.g., methoxy groups) in the same positions, or an additional (third) substituent, diminish activity.

4-Hydroxycoumarins↗

Studies of the quenching phenomenon in delayed contact hypersensitivity reactions.

Studies in guinea pig and man have shown that eugenol can quench non-specifically contact urticarial responses, whereas limonene seems largely ineffective. In a comprehensive series of studies, there was little evidence of quenching of delayed contact hypersensitivity reactions to cinnamic aldehyde or citral, including in 'pre-quenched' material supplied by a perfume/flavour company, and in a similar mixture prepared in this laboratory, in the guinea pig model. In addition, there was no evidence of the quenching by eugenol of allergic reactions to cinnamic aldehyde in a panel of human subjects with a proven history of cinnamic-aldehyde-induced allergic contact dermatitis. Overall, the results lend little credibility to earlier literature reports of quenching phenomena in delayed contact hypersensitivity responses.

Acrolein↗

Frequency of false-negative reactions to the fragrance mix.

To estimate the frequency of false-negative reactions to the fragrance mix, the 8 constituents of the mix in concentrations of 5% (2% for cinnamic aldehyde) were added to the European standard series for routine testing. Patients with positive reactions to individual ingredients in the absence of a reaction to the mix were retested with serial dilutions. In a 4-month period, 677 patients were tested. 61 (9%) reacted to the mix and to 1 or more of the ingredients. 4 patients (0.6% of all patients tested and 6.2% of the patients allergic to fragrances) had false-negative reactions to the mix. They were allergic to cinnamic alcohol, geraniol, isoeugenol and oak moss (1 reaction each), in the absence of a reaction to the fragrance mix. It is concluded that the currently used concentration of the mix (8 x 1%) not infrequently results in false-negative reactions, and that further research should be done to overcome this problem.

Dermatitis, Allergic Contact↗

Allergic contact dermatitis from the synthetic fragrances Lyral and acetyl cedrene in separate underarm deodorant preparations.

The case is reported of a 28-year-old man who developed allergic contact dermatitis from 2 synthetic fragrance ingredients, Lyral (3- and 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene-1-aldehyde) and acetyl cedrene, in separate underarm deodorant preparations. The implications of the patient's negative patch test reactions to the European standard series (Trolab) and cosmetics and fragrance series (both Chemotechnique Diagnostics) are discussed. The importance is stressed of patch testing with the patient's own preparations when cosmetic dermatitis is suspected, and of identifying and reporting offending fragrance ingredients, with a view possibly to updating the European standard series and commercially available cosmetics and fragrance series.

Adult↗

Sensitization to thimerosal (Merthiolate) is still present today.

The results on thimerosal (Merthiolate) hypersensitivity of a retrospective study, together with the relevant data on thimerosal hypersensitivity referred to in the literature up to 1993, are presented. Positive patch test reactions to thimerosal (0.1% pet.) were observed in 32 (1.3%) of 2461 adult patients with suspected contact allergy examined in the period 1987-1992. 20 (0.8%) patients had a solitary positive patch test to thimerosal. The observed incidence is low. Clinical symptoms related to thimerosal hypersensitivity were observed in only 3 patients. The collected results are discussed with emphasis on the clinical implications of sensitization to thimerosal. It appears that a positive patch test to thimerosal is frequently clinically irrelevant.

Adult↗

The clinical effect of percutaneous histamine on allergic contact dermatitis elicited to fragrance mix.

Histamine (2-(4-imidazol)ethylamine) has been shown to downregulate cell-mediated reactions in vitro. However, the rôle of such downregulation in vivo has not yet extensively been studied in humans. In an attempt to gain more insight into this, we studied in vivo the effect of percutaneous histamine on an allergic contact reaction elicited to fragrance mix in 28 human volunteers with previously-known sensitization (patch tests) to this allergen. Histamine (0.1 mg/ml) was administered either via subcutaneous injections or by scratching at the site of patch tests to one concentration (8% pet.) of fragrance mix at different times. Histamine and control solution were administered immediately before patch testing (0 hours) or 2x at 0 and 24 h (after application). No significant differences were observed in the grade of delayed-type hypersensitivity reaction (DTHR) to fragrance mix (8% pet.) by visual reading when histamine or control solution was administered. This study did not exclude the possibility that histamine could inhibit DTHR to lower concentrations of the allergen used, and therefore additional in vivo studies are required.

Administration, Cutaneous↗

Testing with fragrance mix. Is the addition of sorbitan sesquioleate to the constituents useful?

In a multicentre study, the value of adding sorbitan sesquioleate (SSO) to the constituents of the 8% fragrance mix (FM) was investigated. In 7 centres, 709 consecutive patients were tested with 2 types of FM from different sources, its 8 constituents with 1% SSO, its 8 constituents without SSO, and 20% SSO. 5 patients (0.71%) reacted to the emulsifier SSO itself, read as definitely allergic on day 3/4. 53 patients reacted to either one of the mixes with an allergic type of reaction. When tested with the constituents without SSO, 41.5% showed an allergic reaction versus 54.7% with SSO. If both types of reactions were considered (allergic and irritant) 38.3% of 73 patients showed a positive "breakdown" result without SSO, versus 54.8% with SSO. The differences were statistically significant. Reactivity to FM constituents was changed in a specific pattern by addition of SSO--irritant reactions increased, particularly for cinnamic alcohol, eugenol, geraniol, oak moss and hydroxycitronellal, whereas others showed only a slight change. Allergic reactions were also increased by SSO, but the rank order of the top 3 sensitizers (isoeugenol, oak moss and eugenol) did not change. Cinnamic alcohol was the only constituent with decreased reactivity after addition of SSO. A positive history of fragrance sensitivity (HFS) was clearly associated with a positive allergic reaction to either the mix or 1 of its constituents (51% versus 28.6% with a negative HFS). Irritant reactions were linked to a negative HFS in a high proportion (64.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗