Assessment of dermal uptake of diphenylmethane-4,4'-diisocyanate using tape stripping and biological monitoring.

Very little is known about the dermal uptake of isocyanates, and dermal exposure to isocyanates has been discussed as a factor involved in the induction of respiratory diseases. To investigate the dermal uptake of diphenylmethane-4,4'-diisocyanate (4,4'-MDI). Four volunteers were dermally exposed to 10, 25, 49 and 50 mg 4,4'-MDI, respectively, for eight hours. The exposed areas were tape stripped. Urine and blood were biologically monitored for 48 hours. Tape strips, plasma, and urine were analysed by liquid chromatography-mass spectrometry. In total, 35-70% of the applied dose of 4,4'-MDI was absorbed by the skin. Very low fractions of applied dose were found in the tape strips. The 4,4'-MDA concentration in plasma and urine was low, but peaked in urine at 10-14 hours and plasma at 8-32 hours after exposure. 4,4'-MDI is readily absorbed by human skin. Only small fractions of 4,4'-MDI remain as such in the superficial skin layers. The amounts found in blood and urine were only small fractions of the total applied doses which indicates that very small amounts of 4,4'-MDI penetrate the skin and reach the blood stream. The dermal uptake and distribution of 4,4'-MDI is much slower compared to that associated with airway uptake. Our data strongly indicate that formation of 4,4'-MDA from 4,4'-MDI upon reacting with water in the skin can only occur to a very limited extent.

Sensitization and cross-reactivity patterns of contact allergy to diisocyanates and corresponding amines: investigation of diphenylmethane-4,4'-diisocyanate, diphenylmethane-4,4'-diamine, dicyclohexylmethane-4,4'-diisocyanate, and dicylohexylmethane-4,4'-diamine.

BACKGROUND: Isocyanates are used in polyurethane production. Dermal exposure to isocyanates can induce contact allergy. The most common isocyanate is diphenylmethane diisocyanate used for industrial purposes. The isomer diphenylmethane-4,4'-diisocyanate (4,4'-MDI) is used in patch testing. Diphenylmethane-4,4'-diamine (4,4'-MDA) is its corresponding amine. Concurrent reactions to 4,4'-MDI and 4,4'-MDA have been reported, as have concurrent reactions to 4,4'-MDI and dicyclohexylmethane-4,4'-diisocyanate (4,4'-DMDI). OBJECTIVES: To investigate the sensitization capacities and the cross-reactivity of 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and dicyclohexylmethane-4,4'-diamine (4,4'-DMDA). METHODS: The guinea-pig maximization test (GPMT) was used. RESULTS: The GPMT showed sensitizing capacities for all investigated substances: 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and 4,4'-DMDA (all p < 0.001). 4,4'-MDI-sensitized animals showed cross-reactivity to 4,4'-MDA (p < 0.001) and 4,4'-DMDI (all p < 0.05). 4,4'-MDA-sensitized animals showed cross-reactivity to 4,4'-DMDA (p = 0.008). CONCLUSION: All of the investigated substances were shown to be strong sensitizers. Animals sensitized to 4,4'-MDI showed cross-reactivity to 4,4'-MDA and 4,4'-DMDI, supporting previous findings in the literature. The aromatic amine 4,4'-MDA showed cross-reactivity to the aliphatic amine 4,4'-DMDA.

Formaldehyde in cosmetics in patch tested dermatitis patients with and without contact allergy to formaldehyde.

BACKGROUND: Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in cosmetics. OBJECTIVES: To survey the release of formaldehyde in cosmetics brought by patients investigated because of suspected allergic contact dermatitis, to compare it with information given by the manufacturers on the packages, and to investigate whether formaldehyde-allergic patients are potentially exposed to more cosmetics releasing formaldehyde than dermatitis patients without contact allergy to formaldehyde. PATIENTS/METHODS: Cosmetics from 10 formaldehyde-allergic and 30 non-allergic patients (controls) matched for age and sex were investigated with the chromotropic acid spot test, which is a semiquantitative method measuring the release of formaldehyde. RESULTS: Formaldehyde was found in 58 of 245 (23.7%) products. Twenty-six of 126 (20.6%) leave-on products released formaldehyde, and 17 of 26 (65.4%) of these were not declared to contain formaldehyde or formaldehyde releasers. Among the rinse-off products, there were 32 of 119 (26.8%) formaldehyde-releasing products, and nine of 32 (28.0%) of these were not labelled as containing formaldehyde or formaldehyde releasers. Five of 10 formaldehyde-allergic patients brought leave-on products with ≥ 40 ppm formaldehyde, as compared with 4 of 30 in the control group (p = 0.029). CONCLUSIONS: Cosmetic products used by formaldehyde-allergic patients that are not declared to contain formaldehyde or formaldehyde-releasing preservatives should be analysed.

A positive cobalt spot test falsely indicating an occupational allergic contact dermatitis caused by cobalt.

BACKGROUND: For investigation of chemical exposure in allergic individuals, spot tests are invaluable. A reagent may react with a specific compound to give a specific typical colour, and thus indicate the presence of the specific substance. Spot tests can give both false-negative and false-positive reactions. To confirm the presence of the substance and quantify it, more sophisticated methods are required. On the basis of a positive cobalt spot test result, a woman was initially diagnosed with an occupational allergic contact dermatitis caused by cobalt. OBJECTIVES: To investigate cobalt release from three different metal weaves to which our patient was occupationally exposed. METHODS: The cobalt gel test and atomic absorption spectroscopy (AAS) were used to investigate the metal weaves. Two types of extract based on artificial sweat and nitric acid, respectively, were investigated with AAS. RESULTS: No cobalt release was demonstrated with AAS. CONCLUSIONS: When a diagnosis of allergic contact dermatitis caused by a sensitizer based on a positive spot test result will have far-reaching consequences, such as change of work, retraining, and claim on and payment of worker's compensation, conformational analysis must be performed.

Dermal uptake study with 4,4'-diphenylmethane diisocyanate led to active sensitization.

BACKGROUND: To investigate the dermal uptake of 4,4'-diphenylmethane diisocyanate (4,4'-MDI), a study was performed in which 2 female volunteers were exposed to 10 and 25 mg, respectively, of 4,4'-MDI by applying 2.0% 4,4'-MDI in petrolatum over areas where the surface concentration corresponded to 800 µg/cm(2) . Ten days later, they developed eczematous dermatitis at the area of application. OBJECTIVES: To investigate whether the dermal application caused active sensitization to 4,4'-MDI. METHODS: Chemical analysis of the 4,4'-MDI preparation used in the application and the amount of 4,4'-MDI not absorbed by the skin was performed with liquid chromatography-mass spectrometry. The volunteers were tested with serial dilutions of 4,4'-MDI and the potentially cross-reacting substances 4,4'-diaminodiphenylmethane (4,4'-MDA), p-phenylenediamine (PPD), and dicyclohexylmethane-4,4'-diisocyanate (DMDI). RESULTS: Patch test results suggested that the volunteers were actively sensitized to 4,4'-MDI following the dermal uptake study, as they reacted positively to 4,4'-MDA, a marker for 4,4'-MDI allergy. No positive reactions were seen to PPD or DMDI. Chemical investigation confirmed that the correct concentration had been used for the dermal uptake study, and showed that about 70% of the applied 4,4'-MDI was not absorbed. CONCLUSIONS: A dermal uptake study with 4,4'-MDI in 2.0% pet. with an occlusion time of 8 hr induced active sensitization to 4,4'-MDI and subsequently to 4,4'-MDA.