Nine years of patch testing with isocyanates in a clinic of occupational dermatology.

BACKGROUND: Isocyanates are used as starting materials of polyurethane (PU) products. They are relatively important occupational skin sensitizers. OBJECTIVES: To analyse results of a large isocyanate patch test series of 19 isocyanate test substances and 4,4'-diaminodiphenylmethane (MDA), a marker of 4,4'-diphenylmethane diisocyanate (MDI) hypersensitivity. METHODS: Test files were screened for positive reactions in the isocyanate series. Patients with positive reactions were analysed for occupation, exposure and diagnosis. RESULTS: In 2010-2019, 53 patients had positive reactions in the series (16% of 338 patients tested). MDA, the well-established screening substance for MDI allergy, was positive in 30 patients, an in-house monomeric MDI test substance in 23 patients and 3 different polymeric MDI test substances in 19-21 patients. We diagnosed 16 cases of occupational allergic contact dermatitis (OACD) from MDI including 3 pipe reliners. Hexamethylene-1,6-diisocyanate (HDI) oligomers in paint hardeners caused 5 cases of OACD, more cases than 2,4-toluene diisocyanate (TDI; n = 3) and isophorone diisocyanate (IPDI; n = 1) put together. CONCLUSIONS: In contrast to previous studies, polymeric MDI test substances were not superior to a monomeric MDI. Pipe reliners may get sensitised not only by epoxy products and acrylates but also by MDI in hardeners of PU pipe coatings. HDI oligomers were the second most important causes of OACD after MDI.

2-Cyanoethyl dimethyldithiocarbamate, a new contact allergen found in accelerator-free nitrile gloves.

BACKGROUND: Allergic contact dermatitis (ACD) from rubber glove usage is usually caused by rubber additives such as the accelerators. However, in analyses of the suspected gloves, ordinary rubber allergens are not always found. Accelerator-free rubber gloves are available, but some patients with accelerator allergy do not tolerate them and might also be patch test positive to them. OBJECTIVES: To identify and chemically characterize a new allergen, 2-cyanoethyl dimethyldithiocarbamate (CEDMC), in rubber gloves. We describe two patient cases: patient 1 that led us to the identification of CEDMC and patient 2 with occupational ACD caused by CEDMC. METHODS: The patients were examined with patch testing including baseline and rubber series, and their own rubber gloves. High-performance liquid chromatography (HPLC) was used for chemical analysis of rubber gloves. The allergen was synthesized and identified by nuclear magnetic resonance, mass spectrometry and infrared spectrometry, and tested on patient 2. RESULTS: CEDMC was identified by HPLC in a nitrile glove associated with hand eczema in patient 1. Patient 2 whose nitrile gloves contained CEDMC was patch test positive to CEDMC. CONCLUSIONS: CEDMC is a new contact allergen in nitrile gloves and probably forms during vulcanization from residual monomer acrylonitrile and rubber additives.

Acrylates in artificial nails-Results of product analyses and glove penetration studies.

BACKGROUND: Artificial nail materials are mixtures that are prone to contain several sensitizing (meth)acrylates. It is not known whether the listing of (meth)acrylates is correct in these products' packages. Protective gloves suited for nail work are needed. OBJECTIVES: To analyse (meth)acrylates in gel nail and acrylic nail products chemically and to compare the results with the information in the product labels, and to study penetration of artificial nail materials through selected disposable gloves. METHODS: We analysed 31 gel nail products and 6 acrylic nail products for their (meth)acrylate content by gas chromatography-mass spectrometry (GC-MS). We tested the penetration of two nail products through three disposable gloves: nitrile rubber, neoprene rubber and polyvinyl chloride (PVC). RESULTS: Altogether 32/37 products contained (meth)acrylates. In all of them, there was discrepancy between the listed (meth)acrylates and those discovered in the analysis. The commonest (meth)acrylates were hydroxyethyl methacrylate (HEMA, 20/37 samples) and hydroxypropyl methacrylate (HPMA, 9/37 samples), but many of the product packages failed to declare them. Isobornyl acrylate (IBA) was discovered in nine gel nail products. The neoprene glove could withstand nail gel for 20 min and thin nitrile glove and PVC glove for 5 min. Acrylic nail liquid penetrated through disposable gloves quickly. CONCLUSIONS: Labelling of artificial nail products was notably incorrect on most products. Requirements for product labelling must be updated so that the risk of sensitization associated with artificial nail products is clearly indicated. Disposable gloves can probably be used short-term in gel nail work, whereas disposable gloves do not protect the user from acrylic nail liquids.

Characterization of patients with occupational allergy to two new epoxy hardener compounds.

BACKGROUND: The practical importance of two recently described epoxy hardener allergens-1,3-benzenedimethanamine, N-(2-phenylethyl) derivatives (1,3-BDMA-D) and hydrogenated formaldehyde benzenamine polymer (FBAP)-as occupational allergens remains to be defined. OBJECTIVES: To describe patients diagnosed at the Finnish Institute of Occupational Health (FIOH) with positive reactions to 1,3-BDMA-D or FBAP. METHODS: We searched FIOH's patch-test files from January 2017 to December 2020 for patients examined due to suspected occupational contact allergy to epoxy compounds. We analyzed the patch-test results and sources of exposure to various epoxy hardeners and focused on occupations, symptoms, and the sources of exposure to 1,3-BDMA-D and FBAP. RESULTS: During the study period, 102 patients were examined at FIOH for suspected occupational contact allergy to epoxy compounds. Of these, 19 (19%) were diagnosed with contact allergy to 1,3-BDMA-D (n = 10) or FBAP (n = 12). The largest occupational group was sewage pipe reliners (n = 8). Seven different hardener products contained FBAP, whereas 1,3-BDMA-D was present in only one hardener used by spray painters. CONCLUSIONS: A substantial number of patients with suspected occupational epoxy resin system allergy tested positive to in-house test substances of 1,3-BDMA-D and/or FBAP.

Occupations and exposure events in acute and subacute irritant-induced asthma.

BACKGROUND: Exposures leading to irritant-induced asthma (IIA) are poorly documented. METHODS: We retrospectively screened the medical records of patients with IIA diagnosed in an occupational medicine clinic during 2000-2018. We classified the cases into acute (onset after single exposure) and subacute (onset after multiple exposures) IIA. We analysed in detail, occupations, causative agents and their air levels in the workplace, exposure events and the root causes of high exposure. RESULTS: Altogether 69 patients were diagnosed with IIA, 30 with acute and 39 with subacute IIA. The most common occupational groups were industrial operators (n=23, 33%), metal and machinery workers (n=16, 11%) and construction workers (n=12, 8%). Among industrial operators significantly more cases had subacute IIA than acute IIA (p=0.002). Forty cases (57%) were attributable to some type of corrosive acidic or alkaline chemical. Acute IIA followed accidents at work in different types of occupation, while subacute IIA was typical among industrial operators performing their normal work tasks under poor work hygiene conditions. The most common root cause was lack of information or false guidance in acute IIA (n=11, 36%) and neglect of workplace hygiene measures in subacute IIA (n=29, 74%). CONCLUSIONS: Accidents are the main causes of acute IIA, whereas subacute IIA can develop in normal work in risk trades with poor work hygiene. Airborne strong acids or bases seem to be the most important causative agents of acute and subacute IIA. The different risk profiles of acute and subacute IIA should be considered in the prevention and identification of the cases.

Ten years of contact allergy from acrylic compounds in an occupational dermatology clinic.

BACKGROUND: Contact allergy from acrylic compounds is a "hot topic". Knowledge on the exact chemical composition of acrylic products is superficial. AIMS: To retrospectively describe patients with allergic reactions to acrylic compounds. METHODS: We included patients who had been tested with acrylate patch test series and displayed allergic reactions to at least one acrylic compound. Chemical analyses were often performed when safety data sheets of implicated products failed to reveal acrylic compounds to which the patient tested positive. RESULTS: In 2010-2019 a total of 55 patients met the inclusion criteria. Eight cases of allergic contact dermatitis were due to anaerobic sealants, seven to dental products, three to windscreen glues, seven to eyelash glues and/or nail products in the beauty sector, three to UV-cured printing inks, two to paints/lacquers, and one to polyester resin system. The origin of these contact allergies was occupational with the exception of four beauty sector workers who had developed eyelid symptoms from eyelash extensions glued onto their own eyelashes. We invariably detected methacrylate monomers in 15 chemical analyses of 12 different anaerobic sealants. CONCLUSIONS: Safety data sheets of anaerobic sealants often lack warnings for skin sensitization, although these products regularly contain sensitizing methacrylates.

Asthma onset after exposure to fluorinated hydrocarbons in the presence of combustion.

Fluorinated hydrocarbons, which can thermally degrade into toxic hydrofluoric acid, are widely used as, for example, cooling agents in refrigerators and air conditioning systems and as medical aerosol propellants. Hydrofluoric acid is a known causative agent of irritant-induced asthma. We report on two patients with asthma initiation shortly after exposure to fluorinated hydrocarbon-based cooling agents while welding or smoking cigarettes in a confined space. Both cases developed respiratory symptoms and headache and later demonstrated nonspecific bronchial hyperresponsiveness. In follow-up, asthma was persistent and responded poorly to asthma medication. Exposure to the fluorinated hydrocarbons themselves is unlikely to have caused asthma due to their low toxicity. Instead, exposure to small amounts of hydrofluoric acid via the thermal degradation of the fluorinated hydrocarbons was considered the most likely cause of asthma onset. This is supported by the typical clinical picture of irritant-induced asthma and acute symptoms resembling hydrofluoric acid poisoning. When fluorinated hydrocarbons are used in the presence of combustion, thermal degradation may lead to the formation of hydrofluoric acid. In confined spaces, this exposure may induce asthma via irritation. Welding, smoking, and other sources of combustion in confined spaces may be a risk in workplaces and other places in which fluorinated hydrocarbons are used.

Occupational allergic contact dermatitis caused by colophonium.

BACKGROUND: Colophonium is a common contact allergen that is present not only in household products but also in occupational settings. OBJECTIVES: To describe the sources of occupational exposure to colophonium and the occupations at risk of colophonium allergy. METHODS: We reviewed patch test files from the years 2002 to 2017 at the Finnish Institute of Occupational Health for patients with allergic reactions to colophonium and abietic acid. We analysed the patch test, occupation and exposure data of 39 patients diagnosed with occupational allergic contact dermatitis (OACD) caused by colophonium. RESULTS: Of the patients examined for suspected occupational dermatitis, 4.6% (n = 118) reacted positively to colophonium. The majority of the OACD patients worked in the wood industry, as machinists, or were involved in soldering or agriculture. The most common occupational sources of exposure were coniferous wood and wood-derived materials, followed by glues, metalworking fluids, and soldering materials. Colophonium is not always mentioned in safety data sheets (SDSs), and the sources of colophonium exposure are often materials for which there are no SDSs. CONCLUSION: OACD caused by colophonium is quite common and occurs in a variety of occupations. SDSs provide poor information for exposure assessment. Patch testing with the patient's own materials was often useful in establishing the diagnosis.

Skin exposure to epoxy chemicals in construction coating, assessed by observation, interviews, and measurements.

BACKGROUND: Epoxy resin systems (ERSs) are among the leading causes of occupational allergic contact dermatitis. OBJECTIVES: To identify riskful exposures and sources of skin exposure, and to quantify skin exposure to diglycidyl ether of bisphenol A (DGEBA) epoxy monomer, in construction coating work. METHODS: Skin exposure to epoxy chemicals was studied in 5 coating companies through (a) interviews and visual observation, (b) quantifying DGEBA on 12 workers' skin by tape-stripping, (c) measuring DGEBA on 23 surfaces by wipe-sampling, and (d) quantifying DGEBA in new sewage pipe. Acetone extracts of the tapes, wipes and sawdust from a newly hardened sewage pipe were analysed by gas chromatography/mass spectrometry. RESULTS: Identified riskful exposures were, for example, mixing ERSs, handling coating pots, and working above shoulder level. Epoxy stains on, for example, tools, equipment and clothing were seen in all workplaces. Protective gloves were of varying quality, and were not always suitable for chemicals. The amount of DGEBA on the workers' skin varied considerably. All screened tool handles were contaminated. Two-day-old epoxy sewage pipe contained 3.2% DGEBA. CONCLUSIONS: Construction coating entails skin contact with ERSs directly and via contaminated surfaces, personal protective equipment, and recently hardened epoxy materials. Observation is a useful method for assessing skin exposure in coating work.

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- benzoic acid: a new cause of sensitiser induced occupational asthma, rhinitis and urticaria.

OBJECTIVES: 3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)-benzoic acid (BCMBA) has not previously been identified as a respiratory sensitiser. We detected two cases who presented respiratory and urticaria symptoms related to BCMBA and had positive skin prick tests to the agent. Subsequently, we conducted outbreak investigations at the BCMBA-producing factory and performed clinical examinations to confirm occupational diseases. METHODS: The outbreak investigations included observations of work processes, assessment of exposure, a medical survey with a questionnaire and skin prick tests with 0.5% BCMBA water solution on 85 exposed workers and 9 unexposed workers. We used specific inhalation or nasal challenge and open skin application test to investigate BCMBA-related occupational asthma, rhinitis and contact urticaria. RESULTS: We identified nine workers with respiratory and/or skin symptoms and positive skin prick tests to BCMBA in a chemical factory. A survey among chemical factory workers indicated a BCMBA-related sensitisation rate of 8% among all exposed workers; the rate was highest (25%) among production workers in the production hall. Sensitisation was detected only in workers with the estimated highest exposure levels. Six cases of occupational asthma, rhinitis and/or contact urticaria caused by BCMBA were confirmed with challenge tests. Asthma-provoking doses in specific inhalation challenges were very low (0.03% or 0.3% BCMBA in lactose). CONCLUSIONS: We identified a new low molecular weight agent causing occupational asthma, rhinitis and contact urticaria. A typical clinical picture of allergic diseases and positive skin prick tests suggest underlying IgE-mediated disease mechanisms. Stringent exposure control measures are needed in order to prevent BCMBA-related diseases.

Patterns of concomitant allergic reactions in patients suggest cross-sensitization between octylisothiazolinone and methylisothiazolinone.

BACKGROUND: Recent animal tests have indicated cross-reactivity between methylisothiazolinone (MI), octylisothiazolinone (OIT), and benzisothiazolinone (BIT). OBJECTIVES: To retrospectively analyse concomitant reactions to different isothiazolinones in patients in an occupational dermatology clinic during the ongoing MI contact allergy epidemic. METHODS: We searched patch test files (January 2012 to February 2017) for patients with allergic reactions to OIT, BIT, and MI, and analysed their patch test results, occupations, exposure, and diagnoses. RESULTS: We found 61 (9.4%) allergic reactions to MI, 19 (2.9%) reactions to OIT and 9 (1.4%) reactions to BIT in a total of 647 consecutively tested patients. Seventeen (89%) of the OIT-positive patients had concomitant reactions to MI, whereas only 3 (33%) BIT-positive patients had allergic reactions to MI. The MI reactions in OIT-positive patients were almost exclusively extreme reactions (+++). Exposure to OIT was identified in 26% of the OIT-positive patients, and 56% of the BIT-positive patients had been exposed to BIT. CONCLUSIONS: Allergic reactions to OIT were strongly associated with extreme reactions to MI, which suggests cross-sensitization. In contrast, BIT reactions were mostly independent.

Screening allergic reactions to resol resin based on phenol and formaldehyde in a clinic of occupational dermatology.

BACKGROUND: Allergic reactions to resol-type phenol formaldehyde resin [phenol formaldehyde resin 2 (PFR2)] are relatively common. It has been suggested that PFR2 should be included in baseline series. However, a recent international study found clinical relevance in only 25% of patients. OBJECTIVES: To report the results of screening with PFR2 over a 5-year period (2012-2016), and to study the clinical relevance of allergic reactions to PFR2 over a 15-year period (2002-2016). METHODS: At the Finnish Institute of Occupational Health, PFR2 was added to the baseline series in 2012. We had previously tested PFR2 in the plastic and glue series. We searched the patch test files for patients with allergic reactions to PFR2, and analysed their patch test results, occupation, exposure, and diagnosis. RESULTS: During the screening period of 5 years, a total of 10 (1.6%) patients reacted positively to PFR2. Seven of these had occupational allergic contact dermatitis caused by phenol formaldehyde resin (PFR). In 3 patients, we found no exposure to PFR. Over the preceding 10 years, the clinical relevance of 10 additional allergic reactions to PFR2 was similarly high. CONCLUSIONS: In an occupational dermatology clinic, 70% of PFR2 reactions were clinically relevant. Further studies in general dermatology clinics are needed.

Occupational contact allergy to components of polyester resin systems.

BACKGROUND: Allergic contact dermatitis caused by polyester resin is considered to be rare. OBJECTIVES: To describe 11 new patients diagnosed with occupational contact allergy to components of polyester resin systems in 1994-2009. METHODS: Data on occupations, patch test results, symptoms and exposure to polyester products were retrieved from patient files, covering 1994 to February 2015. RESULTS: Five patients reacted to unsaturated polyester resin putties. In 3 of these cases, putties were considered to be the main cause of the dermatitis. Four patients had cobalt allergy resulting from cobalt salts that were used as accelerators in polyester resins. Three patients were sensitized to triglycidyl isocyanurate (TGIC), a cross-linker in polyester powder paints. CONCLUSIONS: Two product types are of particular importance in contact allergy to polyester resin: powder paints cured by heat with TGIC as the cross-linker, and car putties. Car putties are used not only in repair car painting, but also in some industrial trades to smoothen surfaces before painting. As commercial patch test substances of polyester resin putties are lacking, patients' own products need to be tested. Cobalt salts are used in several types of polyester resin product as accelerators, and these must be considered as a possible cause of cobalt sensitization.

Testing Penetration of Epoxy Resin and Diamine Hardeners through Protective Glove and Clothing Materials.

Efficient, comfortable, yet affordable personal protective equipment (PPE) is needed to decrease the high incidence of allergic contact dermatitis arising from epoxy resin systems (ERSs) in industrial countries. The aim of this study was to find affordable, user-friendly glove and clothing materials that provide adequate skin protection against splashes and during the short contact with ERS that often occurs before full cure. We studied the penetration of epoxy resin and diamine hardeners through 12 glove or clothing materials using a newly developed test method. The tests were carried out with two ERS test mixtures that had a high content of epoxy resin and frequently used diamine hardeners of different molar masses. A drop (50 µl) of test mixture was placed on the outer surface of the glove/clothing material, which had a piece of Fixomull tape or Harmony protection sheet attached to the inner surface as the collection medium. The test times were 10 and 30 min. The collecting material was removed after the test was finished and immersed into acetone. The amounts of diglycidyl ether of bisphenol A (DGEBA), isophorone diamine (IPDA), and m-xylylenediamine (XDA) in the acetone solution were determined by gas chromatography with mass spectrometric detection. The limit for acceptable penetration of XDA, IPDA, and DGEBA through glove materials was set at 2 µg cm(-2). Penetration through the glove materials was 1.4 µg cm(-2) or less. The three tested chemical protective gloves showed no detectable penetration (<0.5 µg cm(-2)). Several affordable glove and clothing materials were found to provide adequate protection during short contact with ERS, in the form of, for example, disposable gloves or clothing materials suitable for aprons and as additional protective layers on the most exposed parts of clothing, such as the front of the legs and thighs and under the forearms. Every ERS combination in use should be tested separately to find the best skin protection material, and this can be done by using this simple test method.

Occupational allergic contact dermatitis caused by epoxy chemicals: occupations, sensitizing products, and diagnosis.

BACKGROUND: Epoxy products are among the most common causes of occupational allergic contact dermatitis. Diglycidyl ether of bisphenol A resin (DGEBA-R) is the most important sensitizer in epoxy systems. OBJECTIVES: To describe patients with occupational allergic contact dermatitis caused by epoxy products. METHODS: Patients with allergic reactions to epoxy chemicals were chosen from test files (January 1991 to June 2014). Only patients with occupational contact allergy to some component of epoxy resin systems were included. We analysed patch test results, occupation, symptoms, and exposure data. RESULTS: We found a total of 209 cases with occupational contact allergy to epoxy chemicals. The largest occupational groups were painters (n = 41), floor layers (n = 19), electrical industry workers (n = 19), tile setters (n = 16), and aircraft industry workers (n = 15). A total of 82% of the patients reacted to DGEBA-R. Diagnosis of the DGEBA-R-negative patients required testing with m-xylylenediamine, N,N'-tetraglycidyl-4,4'-methylenedianiline, 1,4-butanediol diglycidyl ether, 2,4,6-tris-(dimethylaminomethyl)phenol, diglycidyl ether of bisphenol F resin, N,N'-diglycidyl-4-glycidyloxyaniline, isophoronediamine, 4,4'-diaminodiphenylmethane, diethylenetriamine, and cresyl glycidyl ether. The hands/upper extremities were most commonly affected (69%), but facial symptoms were also frequent (60%). CONCLUSIONS: Allergic contact dermatitis caused by to epoxy products cannot always be diagnosed by the use of commercial test substances. Workplace products need to be tested.

Contact allergy to reactive diluents and related aliphatic epoxy resins.

BACKGROUND: Diglycidyl ether of bisphenol A resin (DGEBA-R) is the most common sensitizer in epoxy systems, but a minority of patients also develop contact allergy to reactive diluents. OBJECTIVES: To analyse the frequency and clinical relevance of allergic reactions to different epoxy reactive diluents and related aliphatic epoxy resins. METHODS: Test files (January 1991 to June 2014) were screened, and the clinical records of patients with allergic reactions were analysed for occupation, concomitant allergic reactions, and exposure. RESULTS: A total of 67 patients reacted to at least one of the compounds. The largest numbers of allergic reactions were to phenyl glycidyl ether (PGE; n = 41), 1,4-butanediol diglycidyl ether (BDDGE; n = 34), and p-tert-butylphenyl glycidyl ether (PTBPGE; n = 19). Ten of the patients did not have contact allergy to DGEBA-R. The reactions of 5 of these were related to the use of BDDGE-containing products. We found no significant exposure to PGE or PTBPGE in patients sensitized to them, but some of the patients had used cresyl glycidyl ether-containing products. CONCLUSIONS: Allergic reactions to reactive diluents and related aliphatic epoxy resins usually occurred together with reactions to DGEBA-R. BDDGE was the clinically most significant compound, and was the sole cause of occupational allergic contact dermatitis in 3 patients.