Gianni Angelini

Nickel, chromium and cobalt in consumer products: revisiting safe levels in the new millennium.

The transition metals nickel (Ni), chromium (Cr) and cobalt (Co) are common causes of allergic contact dermatitis (ACD). Given the high frequency with which these allergens can be associated with hand eczema in those responsible for domestic work, it has been suggested that contamination of household consumer products with these metals may be of relevance to the causation/chronicity of hand dermatitis. Dose–response studies using 48 h occlusive patch test conditions in sensitized individuals show that ≥90% of sensitized patients fail to react below 1 p.p.m., even on irritated skin. Assessment under more realistic exposure conditions has shown that in the presence of irritants and/or following repeated exposures, such individuals rarely react to levels below 10 p.p.m. On the basis of this information, it was recommended a decade ago that household (and other consumer) products should not contain more than 5 p.p.m. of each of Ni, Cr or Co and that, for an even greater degree of protection, the ultimate target level should be 1 p.p.m. The data generated since the original recommendations were made serve to reinforce the validity of these recommendations. Indeed, it is our view that typically the level of each of these transition metals should not normally exceed 1 p.p.m. Then, where consumer products meet this guideline fully, modern quantitative risk assessment shows clearly that elicitation of ACD is highly improbable, and the chance of the induction of sensitization is even lower.

3-Dimethylaminopropylamine: a key substance in contact allergy to cocamidopropylbetaine?

In the past year, 1200 consecutive eczematous patients were tested with cocamidopropylbetaine 1% aq. Contact allergy was evinced in 46 subjects (3.8%), while irritant reactions (slight erythema only) were observed in 15 cases (1.25%). 30 out of 46 patients with allergic reactions were subsequently tested with the substances used in the synthesis of cocamidopropylbetaine, together with a sample of cocamidopropylbetaine declared by the supplier to possess a greater purity. In all 30 subjects, positive reactions were obtained to 3‐dimethylaminopropylamine (DMPA) 1% aq., while the cocamidopropylbetaine denned of purer grade, at 0.5% and 1% aq., gave positive reactions in 10% and 53% of cases, respectively. These results suggest that the DMPA present at various levels as an impurity in the commercial product is responsible for cocamidopropylbetaine allergy. Owing to the inconsistency of positive reactions to cocamidopropylbetaine of variable purity, and to the consistency of positive reactions to DMPA, it seems likely that these reactions may also be connected with the presence in the product, defined of purer grade, of unknown amounts of DMPA as impurity. Structural similarities between the 2 molecules cannot be considered in this case, because the DMPA structure is radically changed in its transformation to the betaine structure, Further experiments with other molecules related to the above structures are in hand.

Sulfite contact allergy

In the last 2 years, 2,894 consecutive eczematous patients were patch tested with sodium metabisulfite 1% pet. Positive reactions were elicited in 50 subjects (1.7%). All 50 patients were also positive to potassium metabisulfite 1% pet. and sodium bisulfite 1% and 5% pet., while only 2 of them were positive to sodium sulfite 1% pet. Prick tests and intradermal tests with a sodium metabisulfite solution (10 mg/ml) were negative. No flare‐ups of dermatitis or patch test were provoked by oral challenge with 30 mg and 50 mg of sodium metabisulfite. The dermatitis was taken to be occupational in 7 cases. In only 5 out of 43 non‐occupational cases was the positive reaction considered relevant.

Occupational sensitization to epoxy resin and reactive diluents in marble workers

10 out of 22 marble workers handling a bicomponent resin, based on epoxy resin and ortho‐cresyl glycidyl ether (CGE), developed Contact dermatitis and airborne contact dermatitis within 20 days to 2 months of exposure. All 22 subjects were patch tested with epoxy resin, bisphenol A, epichlorohydrin and a series of reactive diluents. The 10 symptomatic subjects were all positive to the reactive diluent CGE, and 4 of them also to epoxy resin. The other reactive diluents that gave positive reactions were phenyl glycidyl ether (7 cases), cyclohexanedimethanol glycidyl ether (2 cases), 1,6‐hexanediol diglycidyl ether (2 cases) and allyl glycidyl ether (1 case). The findings of our Study suggest that allergic potential is directly proportional to the electronic charge available, for all electron‐rich molecules (solvents, high and low polymers, reagents) that interact with the glycidyl ether group. Lesser, but still noticeable, effects are detected when activation of the glycidyl group is related to the possible formation of intramolecular hydrogen bonds. In practice, the occupational problem was partly solved by changing the type of glycidyl ether.

The role of 3-dimethylaminopropylamine and amidoamine in contact allergy to cocamidopropylbetaine

Since it has been found that all subjects with contact allergy to cocamidopropylbetaine (CAPB) have positive reactions to 3‐dimethylaminopropylamine (DMAPA), and reports have appeared in literature of the sensitizing action of amidoamine in products containing CAPB, we aimed to verify the possibility that pure amidoamine may have a sensitizing role in subjects with positive reactions to CAPB. To this end, in 10 patients with contact allergy to a commercial CAPB, we tested DMAPA 1% aq. and a pure amidoamine in concentrations ranging from 0·5% aq. to 0·1% aq. The study showed that all patients with positive reactions to DMAPA reacted to amidoamine at 0·5% and 0·25% aq., while 4 of the 10 also had positive reactions to amidoamine at 0·1% aq. We consider that simultaneous allergic reaction to DMAPA and amidoamine represents cross‐reactivity and hypothesize that DMAPA is in fact the true sensitizing substance, while amidoamine, which may in any case release DMAPA in vivo as a result of enzymatic hydrolysis, may favour the transepidermal penetration of the sensitizing agent. In addition, we advise that testing of CAPB be suspended, because, as suggested by chemico‐structural analyses and demonstrated in vivo, when thoroughly purified, it no longer has a sensitizing action.

Occupational contact allergy to cephalosporins

Patients, Methods and Results 18 nurses (4 male and 14 female), ages ranging between 24 and 52 years (mean 35.5 years), were studied. They all had contact dermatitis and reported frequent contact with various cephalosporins; their eczema had lasted between 8 months and 15 years (mean 5.2 years). Lesions were localized on the hands (18 cases), forearms (3 cases) and face (2 cases). 2 patients had a history of allergic rhinitis, 1 of allergic asthma and 1 of atopic dermatitis. All were patch tested with the European standard series, penicillin and the cephalosporins listed in Table 1. The patch tests were applied in double series on the back with Finn Chambers. 1 series was removed and read after 20 min and the other after 2 days, with further readings at D3 and D4. In 4 subjects with positive reactions to cephalosporins, intradermal (i.d.) tests were made with 0.01 ml of the same substances in water ( 1: I 0), and with 0.01 ml of the main penicillin antigenic determinant, penicilloyl polylysine (PPL) (Sigina Chemical, St. Louis, Missouri, USA) at a concentration of 6X 10 M. 30 control subjects were tested with the same cephalosporins at 20% pet., with negative results. Negative results were obtained to the 20-min patch tests, for both cephalosporins and penicillin. The results of the D2 patch tests are reported in Table 1. 7 patients

Contact allergy to impurities in surfactants : amount, chemical structure and carrier effect in reactions to 3-dimethylaminopropylamine

Since finding that all Subject with contact allergy to cocamidopropylbetaine give positive reactions to 3‐dimethylaminopropylamine (DMPA), we wished to verify whether sensitization to other industrially‐used tensioactives might also be due to contact of DMPA as an impurity. We also investigated the possible “carrier action” that tensioactives might exert on minimal quantities of DMPA. Finally, we analyzed the relationship between the structure of DMPA and other chemically‐correlated molecules and their sensitizing potential, with particular reference to the structure of alkylam‐idopropylbetaines. For this purpose, in 34 patients with contact allergy to DMPA, we tested: (i) DMPA in concentrations below the threshold limit in water and in different tensioactives: (ii) substances that employ DMPA as a reagent in their synthesis: (iii) substances similar to DMPA as regards chemically reactive groups. The study showed that: (i) DMPA remains as a quantitatively detectable impurity in all tensioactives employing it in their synthesis: (ii) some common anionic (SLES) and non‐ionic (polysorbate 20) tensioactives enhance the risk of sensitization from very low doses of DMPA, presumably due to a “carrier effect:” (iii) the sensitizing chemical structures in DMPA and related molecules are the primary amine and the tertiary (dimethyl‐substituted) amine groups, when separated by either 2 or 3 carbon atoms:(iv) no sensitizing action can be attributed to the functional groups present in alkylamidopropylbetaine molecules.

Photoallergic contact dermatitis to 8-methoxypsoralen in Ficus carica

Background: Photocontact dermatitis to Ficus carica is induced by furocoumarins present in sap. These substances are generally considered to cause phototoxic reactions.

Pure cocamidopropylbetaine is not the allergen in patients with positive reactions to commercial cocamidopropylbetaine

Discussion Allergic contact dermatitis from antimycotic imidazoles is uncommon when compared to their widespread use. The high concentration of tioconazole (28%) in the nail solution, the presence of undecylenic acid and of ethyl acetate in the vehicle, as well as its application to periungual folds, are all factors favouring sensitization. Cross-reactions between phenethyl imidazoles and phenmethyl imidazoles have previously been described (1, 2, 5, 6), the common structure, 2-(2,4-dichlorophenyl)ethyl imidazole, appearing to be the antigenic determinant.

Purpuric clothing dermatitis due to Disperse Yellow 27

Comment Contact sensitization to bufexamac is not rare, though often unknown or forgotten by the patient, but seems to be less frequent in our series than in previous reports (2, 3). Bufexamac (4-butoxy-N-hydroxy-benzeneacetamide) and diclofenac (2[(2,6-dichlorophenyl)amino]-benzeneacetic acid) both have a benzene ring, with an acetamide (bufexamac) or an acetic acid group (diclofenac) on the alkyl chain. This difference might explain the absence