Contact allergy in Swedish professional ice hockey players.

BACKGROUND: Professional ice hockey players may contract irritant and allergic contact dermatitis. AIMS: To investigate the presence of contact allergy (CA) in professional ice hockey players in Sweden. METHODS: Ten teams from the two top leagues were assessed for potential occupational exposure to sensitizers. Exactly 107 players were patch tested with an extended baseline series and a working series, in total 74 test preparations. The CA rates were compared between the ice hockey players and controls from the general population and dermatitis patients. RESULTS: One out of 4 players had at least one contact allergy. The most common sensitizers were Amerchol L 101, nickel and oxidized limonene. CA was as common in the ice hockey players as in dermatitis patients and significantly more common than in the general population. Fragrances and combined sensitizers in cosmetic products (fragrances + preservatives + emulsifier) were significantly more common in ice hockey players compared with the general population. CONCLUSION: The possible relationship between CA to fragrances and cosmetic products on the one hand and the presence of dermatitis on the other should be explored further.

Hexavalent chromium still a concern in Sweden - Evidence from a cross-sectional study within the SafeChrom project.

OBJECTIVES: Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown. METHODS: This cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance. RESULTS: The exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 µg/m3 (95% confidence interval: 0.11-0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 µg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 µg/L, 5th-95th percentile 0.10-3.20) and RBC concentrations (0.73 µg/L, 0.51-2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 µg/L, 0.06-0.56 and RBC 0.53 µg/L, 0.42-0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today. CONCLUSIONS: Our study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.

Inflammation-related proteins in blood after dermal exposure to some common chemicals depend on the skin barrier gene filaggrin - a human experimental study.

Filaggrin (FLG), a skin barrier protein, is associated with higher dermal uptake of some chemicals in carriers of loss-of-function (null) mutations. This study investigates FLG mutations and systemic effects following dermal exposure to chemicals. Individuals (n = 23 FLG null, n = 31 FLG wt) were simultaneously exposed to pyrimethanil, pyrene, oxybenzone, and nickel ions for 4 h. Pre- and post-exposure, 25-hydroxyvitamin D3 (25(OH)D3, LC-MS/MS) and 92 inflammation-related proteins (proximity-extension assay) were measured. FLG null carriers exhibited significantly higher 25(OH)D3 concentrations than wt carriers, both pre- and post-exposure. Eleven proteins differed in abundance post- vs pre-exposure among FLG null carriers, and 22 proteins among wt carriers (three proteins overlapped). Twelve proteins showed median differences (post- vs pre-exposure) between FLG null and wt carriers. Overall, FLG null carriers showed an increase, while FLG wt carriers showed a decrease in inflammation-related proteins. These findings suggest FLG-dependent differences in susceptibility to systemic effects following simultaneous dermal chemical exposure.

Cohort profile: The Swedish Tattoo and Body Modifications Cohort (TABOO).

PURPOSE: The Swedish Tattoo and Body Modifications Cohort (TABOO) cohort was established to provide an infrastructure for epidemiological studies researching the role of tattoos and other body modifications as risk factors for adverse health outcomes. It is the first population-based cohort with detailed exposure assessment of decorative, cosmetic, and medical tattoos, piercing, scarification, henna tattoos, cosmetic laser treatments, hair dyeing, and sun habits. The level of detail in the exposure assessment of tattoos allows for investigation of crude dose-response relationships. PARTICIPANTS: The TABOO cohort includes 13 049 individuals that participated in a questionnaire survey conducted in 2021 (response rate 49%). Outcome data are retrieved from the National Patient Register, the National Prescribed Drug Register and the National Cause of Death Register. Participation in the registers is regulated by Swedish law, which eliminates the risk of loss to follow-up and associated selection bias. FINDINGS TO DATE: The tattoo prevalence in TABOO is 21%. The cohort is currently used to clarify the incidence of acute and long-lasting health complaints after tattooing based on self-reported data. Using register-based outcome data, we are investigating the role of tattoos as a risk factor for immune-mediated disease, including hypersensitisation, foreign body reactions and autoimmune conditions. FUTURE PLANS: The register linkage will be renewed every third year to update the outcome data, and we have ethical approval to reapproach the responders with additional questionnaires.

Nickel penetration into stratum corneum in FLG null carriers-A human experimental study.

BACKGROUND: The filaggrin gene (FLG) plays a role in skin diseases, with the skin barrier function being impaired in FLG null carriers. The role of FLG status in relation to nickel penetration into the skin remains unclear. OBJECTIVES: To elucidate the association between FLG status and nickel penetration into stratum corneum (SC) in individuals without self-reported history of nickel allergy. METHODS: Forty participants (23 FLG wt and 17 FLG null) were exposed to a nickel solution (80 µg/cm2 ) which was applied onto 2 × 2 cm on their left forearm. After 4 h, the area was tape-stripped with 10 consecutive tapes. Nickel in each tape was quantified using inductively coupled plasma mass spectrometry. RESULTS: The average recovered nickel dose was 35%-48%. A tendency towards lower recovery was seen in FLG null carriers compared to FLG wt carriers, and lower recovery in those with history of skin and/or respiratory symptoms compared to those without such history. This was however not statistically significant. CONCLUSION: FLG null carriers had less nickel recovered by tape strips compared with FLG wt carriers and, compared with individuals without a history of skin and/or respiratory symptoms, indicating higher nickel penetration into SC for FLG null carriers, but further studies are needed.

Underground emissions and miners' personal exposure to diesel and renewable diesel exhaust in a Swedish iron ore mine.

PURPOSE: Underground diesel exhaust exposure is an occupational health risk. It is not known how recent intensified emission legislation and use of renewable fuels have reduced or altered occupational exposures. We characterized these effects on multipollutant personal exposure to diesel exhaust and underground ambient air concentrations in an underground iron ore mine. METHODS: Full-shift personal sampling (12 workers) of elemental carbon (EC), nitrogen dioxide (NO2), polycyclic aromatic hydrocarbons (PAHs), and equivalent black carbon (eBC) was performed. The study used and validated eBC as an online proxy for occupational exposure to EC. Ambient air sampling of these pollutants and particle number size distribution and concentration were performed in the vicinity of the workers. Urine samples (27 workers) were collected after 8 h exposure and analyzed for PAH metabolites and effect biomarkers (8-oxodG for DNA oxidative damage, 4-HNE-MA for lipid peroxidation, 3-HPMA for acrolein). RESULTS: The personal exposures (geometric mean; GM) of the participating miners were 7 µg EC m-3 and 153 µg NO2 m-3, which are below the EU occupational exposure limits. However, exposures up to 94 µg EC m-3 and 1200 µg NO2 m-3 were observed. There was a tendency that the operators of vehicles complying with sharpened emission legislation had lower exposure of EC. eBC and NO2 correlated with EC, R = 0.94 and R = 0.66, respectively. No correlation was found between EC and the sum of 16 priority PAHs (GM 1790 ng m-3). Ratios between personal exposures and ambient concentrations were similar and close to 1 for EC and NO2, but significantly higher for PAHs. Semi-volatile PAHs may not be effectively reduced by the aftertreatment systems, and ambient area sampling did not predict the personal airborne PAHs exposure well, neither did the slightly elevated concentration of urinary PAH metabolites correlate with airborne PAH exposure. CONCLUSION: Miners' exposures to EC and NO2 were lower than those in older studies indicating the effect of sharpened emission legislation and new technologies. Using modern vehicles with diesel particulate filter (DPF) may have contributed to the lower ambient underground PM concentration and exposures. The semi-volatile behavior of the PAHs might have led to inefficient removal in the engines aftertreatment systems and delayed removal by the workplace ventilation system due to partitioning to indoor surfaces. The results indicate that secondary emissions can be an important source of gaseous PAH exposure in the mine.

Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin-A Human Experimental Study.

BACKGROUND: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. OBJECTIVE: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. METHOD: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects' urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. RESULTS: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20-22 repeats) and high FLG CNV (23-24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0-40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0-40h)) for pyrimethanil than wt carriers with low and high CNV, respectively. CONCLUSION: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.

Clinical relevance of positive patch test reactions to lanolin: A ROAT study.

BACKGROUND: Lanolin is often included when patch testing for common contact allergens. The clinical relevance of a positive patch test reaction to lanolin markers is, however, still a subject for debate. OBJECTIVES: To evaluate Amerchol L101 as a marker of lanolin allergy and investigate the clinical impact of lanolin-containing moisturizers on healthy and damaged skin using the repeated open application test (ROAT). METHODS: Twelve test subjects and 14 controls were patch tested with Amerchol L 101 and additional lanolin markers. Subsequently, a blinded ROAT was performed on the arms of the study participants for 4 weeks. Each participant applied a lanolin-free cream base and two different lanolin-containing test creams twice daily on one arm with intact skin and on the other arm with irritant dermatitis, induced by sodium lauryl sulfate (SLS). RESULTS: Eleven test subjects (92%) had positive patch test reactions to Amerchol L 101 when retested and one test subject (8%) had a doubtful reaction. None of the study participants had any skin reactions to the ROAT on intact skin and all participants healed during the ROAT on damaged skin. CONCLUSIONS: Lanolin-containing emollients do not cause or worsen existing dermatitis when performing ROAT in volunteers patch test positive to Amerchol L101.

A comparative study between the two patch test systems Finn chambers and Finn chambers AQUA.

BACKGROUND: Finn Chambers AQUA (FCA) is a development of the Finn Chambers (FC) test system in which the test chambers are mounted on a moisture-resistant adhesive patch. FCA has pre-fixed filter papers. Because the use of FCA does not require any extra taping or use of separate filter papers, a change from FC to FCA chambers may be beneficial for both patients and patch test technicians. OBJECTIVES: To investigate whether there are any differences regarding detection of contact allergy when simultaneous patch testing is performed with FC and FCA. MATERIALS AND METHODS: Results from 434 dermatitis patients simultaneously tested with 10 allergens in both FC and FCA were evaluated. RESULTS: There were no significant differences regarding detection of positive reactions between the two test systems. There were significantly more doubtful reactions to methylisothiazolinone, fragrance mix I and hydroperoxides of linalool when testing with FCA. We only observed significantly more doubtful reactions in FC regarding nickel(II)sulfate. Irritant reactions to formaldehyde were also significantly more common when using FCA. CONCLUSION: The FC and FCA had good agreement in detection of positive reactions. However, the results including doubtful and irritant reactions justify further research regarding optimization of the dose.

Can patch testing with methylchloroisothiazolinone/methylisothiazolinone be optimized using a new diagnostic mix? - A multicenter study from the Swedish Contact Dermatitis Research Group.

BACKGROUND: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI) are tested to detect contact allergy to these isothiazolinones. OBJECTIVES: To study if an aqueous patch test preparation with MCI and MI in a mix of 0.015% and 0.2%, respectively, detects more contact allergies than the commonly used preparations of MCI/MI in 0.02% aq. and MI in 0.2% aq. METHODS: A total of 1555 patients with dermatitis in five Swedish dermatology departments were tested consecutively with MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. RESULTS: The share of contact allergy to MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. varied in the test centers between 7.9% and 25.9%, 3.2% and 10.3%, and 5.8% and 12.3%, respectively. MCI/MI 0.215% aq. detected significantly more patch-test positive individuals than both MCI/MI 0.02% aq. (P < .001) and MI 0.2% aq. (P < .001), as well as either one of MCI/MI and MI (P < .001). In the patients only reacting to MCI/MI 0.215% aq., 57.7% were recorded as having a dermatitis that was explained or aggravated by exposure to either MCI/MI or MI. CONCLUSION: The results speak in favor of replacing the preparations MCI/MI 0.02% aq. and MI 0.2% aq. with MCI/MI 0.215% aq. as the screening substance in the Swedish baseline series, which has been implemented in 2020.

Contact allergy to citral and its constituents geranial and neral, coupled with reactions to the prehapten and prohapten geraniol.

BACKGROUND: Citral is commonly used as a fragrance and flavor material and consists of the aldehydes geranial and neral. Citral is included in fragrance mix (FM) II. Geranial and neral have also been identified in autoxidation of geraniol, a fragrance compound present in FM I. OBJECTIVES: To study contact allergy to citral, geranial, and neral, and concomitant reactivity to oxidized geraniol and fragrance markers of the baseline series. METHODS: A total of 1476 dermatitis patients with suspected allergic contact dermatitis were patch tested using geranial, neral, and citral, all 3.5% petrolatum (pet.) as well as geraniol 6.0% and oxidized geraniol 11% pet. in addition to the Swedish baseline series. RESULTS: Frequencies of positive reactions to citral, geranial, and neral were 2.9%, 3.4% and 1.9%, respectively. Together, citral and geranial gave 4.2% positive patch test reactions in consecutive dermatitis patients. In patients with positive reactions to citral or its components, 25% to 34% reacted to FM II and 61% reacted to oxidized geraniol. CONCLUSIONS: Patch testing with citral, its components, or oxidized geraniol detects contact allergic reactions not detected using the baseline series. Patch testing with pure geraniol was shown to be of little value. Geranial and neral, although closely chemically related, are concluded to be separate haptens.

Skin application of glutathione and iron sulfate can inhibit elicitation of allergic contact dermatitis from hexavalent chromium.

BACKGROUND: Allergic contact dermatitis (ACD) caused by hexavalent chromium, Cr(VI), is often severe and difficult to treat. The most common source of exposure to Cr(VI) in Sweden used to be cement, and more recently leather. The contact allergy can be diminished or inhibited if the exposure is decreased or ceases. Barrier creams against different kinds of allergens have been investigated for their protective properties which may offer protection against Cr(VI) exposure. OBJECTIVES: To investigate the capacity of formulas containing glutathione (GSH) and iron sulfate to inhibit elicitation of ACD in Cr(VI)-allergic individuals when exposed to Cr(VI). METHODS: In 18 Cr(VI)-allergic volunteers the back was divided into eight patch test areas which were treated with preparations of possible barrier creams, prior to patch testing with a dilution series of potassium dichromate and a buffered extract of cement. RESULTS: A significant reduction in reactivity to Cr(VI) and cement extract on skin treated with formulas containing GSH or iron sulfate was noticed, compared with untreated skin. CONCLUSION: Formulas containing GSH or iron sulfate in barrier creams inhibit ACD in individuals allergic to Cr(VI) when applied before exposure to Cr(VI) and cement extract.

Can reducing cosmetic substances help prevent chromate contact allergy?

BACKGROUND: Allergic contact dermatitis caused by Cr(VI) is often severe and difficult to treat. Therefore, primary prevention is a main goal but, secondary prevention can be valuable to ease the symptoms or prevent relapse of Cr(VI) dermatitis when sensitization has occurred. Barrier creams have been tried for many chemical substances, but until now there is no successful barrier cream against Cr(VI). OBJECTIVES: To investigate the ability of reducing agents to transform Cr(VI) into Cr(III) in an experimental situation, in order to find suitable chemicals to investigate for possible use in a barrier cream. METHODS: The capacity to reduce the amount of Cr(VI) was analyzed in water solutions of acetylcysteine, cysteine, dihydroxyacetone, glutathione, and iron sulfate heptahydrate. Thereafter the reducing capacity of acetylcysteine, dihydroxyacetone, glutathione, and iron sulfate on the amount of Cr(VI) in cement extracts was investigated. The content of Cr(VI) in the test solutions and in the cement extracts was estimated by the diphenyl carbazide spot test. RESULTS: All of the chosen chemicals reduced the amount of Cr(VI) in the test solutions and in the cement extracts to some extent. The reducing capacity was most prominent for iron sulfate. CONCLUSION: A reducing capacity was found for all chosen chemicals.

Patch Testing with a New Composition of Mercapto Mix: A Multi-centre Study by the Swedish Contact Dermatitis Research Group.

This study investigated whether more patients with contact allergies were detected by patch testing with mercapto mix with a higher concentration of 2-mercaptobenzothiazolinone (MBT) than the commonly used mercapto mix. A total of 3,143 dermatitis patients in 5 Swedish dermatology departments were patch- tested with 3 mercapto test preparations: MBT 2.0% petrolatum (pet.); mercapto mix 2.0% pet.; and mercapto mix 3.5% pet. Positive reactions to these mercapto mixes varied between 0-0.50%, 0-0.93%, and 0-1.4%, respectively, in the 5 centres. Numerically, mercapto mix 3.5% pet. detected all positive patients and more patch-test positive patients than did the 2 other substances, but the difference was not statistically significant. The authors recommend replacing mercapto mix 2.0% pet. in the Swedish baseline series with mercapto mix 3.5% pet., since the latter also detected those patients who would have been missed because MBT 2.0% is not included in the Swedish baseline series.

Variation and covariation in patch test reactivity to palladium and nickel salts.

Concomitant reactions to palladium chloride (PdCl2), sodium tetrachloropalladate (Na2PdCl4), and nickel hexahydrate sulphate (NiSO4·6H2O) are very common during patch testing and have mainly been explained by cross-sensitisation. Whether there is variation in reactivity to palladium or covariation to nickel and palladium is not known. The aim of this study was to investigate the variation in patch test reactivity to PdCl2 and Na2PdCl4 over time and compare this to variation in patch test reactivity to NiSO4·6H2O. Fifteen females known to be sensitised to nickel and palladium were patch tested four times with 12-week intervals using a dilution series of NiSO4·6H2O, PdCl2 or Na2PdCl4. Patch test reactivity to Na2PdCl4 was less variable compared to that for NiSO4·6H2O or PdCl2. All test salts showed higher patch test reactivity during wintertime. No significant correlation was observed between the variation in patch test reactivity to Na2PdCl4 and PdCl2 and the variation in patch test reactivity to NiSO4·6H2O during the entire test period. Patch test reactivity to Na2PdCl4 is less variable over time compared to that for PdCl2 or NiSO4·6H2O. No clear covariation was identified between tests for palladium salts and NiSO4·6H2O. The variation in patch test reactivity found in this study could be due to seasonal changes.

Contact allergy to oxidized geraniol among Swedish dermatitis patients-A multicentre study by the Swedish Contact Dermatitis Research Group.

BACKGROUND: Geraniol is a widely used fragrance terpene, and is included in fragrance mix I. Geraniol is prone to autoxidation, forming the skin sensitizers geranial, neral, and geraniol-7-hydroperoxide. Oxidized geraniol has previously been patch tested in 1 clinic, giving 1% to 4.6% positive reactions in consecutive patients when tested at 2% to 11%. AIM: To compare test reactions to pure and oxidized geraniol, to compare 2 different test concentrations of oxidized geraniol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series in a multicentre setting. METHODS: One thousand four hundred and seventy-six consecutive patients referred for patch testing were patch tested with geraniol 6% pet. and oxidized geraniol 6% and 11% pet. RESULTS: Pure geraniol 6% pet., oxidized geraniol 6% pet. and oxidized geraniol 11% pet. gave 1%, 3% and 8% positive patch test reactions and 0.7%, 3% and 5% doubtful reactions, respectively. Approximately 50% of the patients with doubtful reactions to oxidized geraniol 6% pet. had positive reactions to oxidized geraniol 11% pet. CONCLUSIONS: Oxidized geraniol 11% pet. provides better detection than oxidized geraniol 6% pet. As most patients reacted only to oxidized geraniol, it is important to explore further whether oxidized geraniol should be included in a baseline patch test series.

Hand eczema and occupational contact allergies in healthcare workers with a focus on rubber additives.

BACKGROUND: Hand eczema (HE) in healthcare workers (HCWs) is common. Besides wet work, healthcare work also implies exposure to contact allergens. OBJECTIVES: To assess HE and contact allergy related to occupational exposures in HCWs. METHODS: In a cross-sectional study, 311 HCWs with HE within the preceding 12 months and a control group of 114 HCWs without HE were investigated with the baseline series and a special patch test series based on substances found in the gloves, soaps, alcoholic hand disinfectants and hand creams provided at the hospitals. RESULTS: Contact allergy to rubber additives was significantly more common in HCWs with HE (6%) than in HCWs without HE (1%, P = .02). The corresponding percentages for fragrances were 11% and 3%, respectively (P = .004). Occupational HE was found in 193 of 311 (62%) HCWs. Of these, 22 of 193 (11%) had occupational allergic contact dermatitis, including 17 with glove-related rubber contact allergy. Contact allergy to diphenylguanidine was as common as contact allergy to thiurams. Occupational contact allergy to rubber additives was significantly associated with sick-leave related to HE. CONCLUSION: Contact allergy to rubber additives in medical gloves is the most common cause of occupational allergic contact dermatitis in HCWs. Aimed patch testing with relevant rubber additives is mandatory when HE in HCWs is investigated.

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.