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Frequent use of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI in cosmetic products has been the main cause of widespread sensitization and allergic contact dermatitis to these preservatives (biocides). Their use in non-cosmetic products is also an important source of sensitization. Less is known about sensitization rates and use of benzisothiazolinone (BIT), octylisothiazolinone (OIT), and dichlorooctylisothiazolinone (DCOIT), which have never been permitted in cosmetic products in Europe. BIT and OIT have occasionally been routinely patch-tested. These preservatives are often used together in chemical products and articles. In this study, we review the occurrence of contact allergy to MI, BIT, OIT, and DCOIT over time, based on concomitant patch testing in large studies, and case reports. We review EU legislations, and we discuss the role of industry, regulators, and dermatology in prevention of sensitization and protection of health. The frequency of contact allergy to MI, BIT, and OIT has increased. The frequency of contact allergy to DCOIT is not known because it has seldom been patch-tested. Label information on isothiazolinones in chemical products and articles, irrespective of concentration, is required for assessment of relevance, information to patients, and avoidance of exposure and allergic contact dermatitis., (© 2024 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cobalt (Co) causes allergic contact dermatitis (ACD) and the emerging use of Co nanoparticles (CoNPs) warrants gaining further insight into its potential to elicit ACD in sensitized individuals., Objectives: The aims of the study were to clarify to what extent CoNPs may elicit ACD responses in participants with Co contact allergy, and to evaluate whether the nanoparticles cause a distinct immune response compared with cobalt chloride (CoCl2) in the skin reactions., Methods: Fourteen individuals with Co contact allergy were exposed to CoNPs, CoCl2, a Co-containing hard-metal disc (positive control), and an empty test chamber (negative control) by patch testing. Allergic responses were evaluated clinically by a dermatologist at Days 2, 4 and 7. At Day 2, patch-test chambers were removed, and remaining test-substance and skin-wipe samples were collected for inductive-coupled plasma mass spectrometry (ICP-MS) analysis. Additionally, skin biopsies were taken from patch-test reactions at Day 4 for quantitative real-time polymerase chain reaction analysis, histopathology and ICP-MS analysis of Co skin penetration., Results: Patch testing with CoNPs elicited allergic reactions in Co-sensitized individuals. At all timepoints, clinical assessment revealed significantly lower frequencies of positive patch-test reactions to CoNPs compared with CoCl2 or to the positive control. CoNPs elicited comparable immune responses to CoCl2. Chemical analysis of Co residues in patch-test filters, and on skin, shows lower doses for CoNPs compared with CoCl2., Conclusions: CoNPs potently elicit immune responses in Co-sensitized individuals. Even though patch testing with CoNPs resulted in a lower skin dose than CoCl2, identical immunological profiles were present. Further research is needed to identify the potential harm of CoNPs to human health., Competing Interests: Conflict of interests: The authors have no conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

The widespread use of skin sensitizing preservatives is well-known. Contact allergy to preservatives is often caused by their presence in cosmetic products. Preservative use in non-cosmetic products is less well-known. We have reviewed European Union (EU) legislations on classification and labelling, biocides and cosmetics, concerning conditions for use of the most used sensitizing preservatives (including formaldehyde-releasing substances, isothiazolinones and parabens). We have analysed temporal trends in their use in non-cosmetic products (tonnes, number of products, concentrations), based on annual reports to the Swedish Products Register 1995-2018; and we discuss implications for stakeholders. Major changes over time are that the use of most of the preservatives has increased by tonnes and/or by number of products, and that several use concentrations have declined following harmonized classification as a skin sensitizer with low concentration limits for this classification. We conclude that the massive increase in use of preservatives is alarming, and that urgent action is needed for protection of health. Their use in non-cosmetic products is broad, increasing and often undisclosed. In the EU, legislations concerning chemicals can provide relevant restrictions to reduce their use and associated health risks, monitored by efficient surveillance. Prevention would be benefited by better coordination between legislations., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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/cm 2 ) 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., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Sensitization to a contact allergen brings with it a lifelong risk to develop allergic contact dermatitis. Inflammation is an important part of the skin sensitizing mechanism, and understanding how different haptens stimulate the immune system, as well as the role played by different cell types present in skin, may be helpful for developing optimized in vitro models for risk assessment of new chemicals or mixtures. The aim of this study was to compare the cytokine profile following exposure of cells representing keratinocytes (HaCaT), monocytes (THP-1) and a co-culture of these cells to three clinically important skin sensitizers: cobalt (II) chloride (CoCl 2 ), methylisothiazolinone (MI) and p-phenylenediamine (PPD). Secretion of ten pro-inflammatory cytokines was measured using multiplexing. The results showed that the cytokine response differed substantially between the three cell assays. CoCl 2 caused an increase of IL-8 in HaCaT cells, while the induction of also IL-13 and IL-1β was observed in THP-1 cells and co-cultures. MI induced six cytokines in HaCaT cells but only IL-1β in the THP-1 cells and four cytokines in the co-culture. Interestingly, the IL-1β response was massive in the co-culture. PPD caused release of IL-1β in all three models as well as IL-8 in the co-culture. Control experiments with two non-sensitizers and irritants (lactic acid and sodium dodecyl sulfate) showed no effect on IL-8 or IL-1β in the co-culture. Taken together, results from this exploratory analysis show unique cytokine profiles dependent on the type of hapten and cell model. Importantly, all three haptens triggered secretion of IL-1β and IL-8 in a co-culture of HaCaT cells and THP-1 cells, representing the most robust test system.

Background: In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid-1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world., Objectives: To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co-occurrence of allergy to cobalt, chromium, and nickel., Results: Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty-seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt-positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males., Conclusion: The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 - 40 h ) ) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC ( 0 - 40 h ) ) 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.

Background: Filaggrin is an important protein for structure and function of the skin barrier. Filaggrin gene (FLG) mutations are known to result in dry skin, impaired skin barrier, and increased risk for atopic dermatitis. However, it is not clear whether these mutations are associated with contact allergy or hand eczema in adolescence., Objectives: The purpose of this study was to investigate whether FLG mutations are associated with contact allergy, self-reported hand eczema, or dry skin in adolescence., Methods: We used data from the 16-year follow-up in the BAMSE cohort, information obtained from a Web-based questionnaire including questions on hand eczema and dry skin, from FLG mutation analysis (R501X, R2447X, 2282del4), and patch testing (n = 1822)., Results: Logistic regression analyses showed no statistically significant associations between FLG mutations and contact allergy (any contact allergy, nickel allergy, or fragrance allergy) according to patch test, or self-reported hand eczema at 16 years, or hand eczema ever. However, FLG mutations were associated with self-reported dry skin at 16 years., Conclusions: FLG mutations are associated with self-reported dry skin at 16 years. However, in this study no consistent associations were found between FLG mutations and contact allergy or hand eczema at 16., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is characterized by an impaired skin barrier, which can allow enhanced penetration of allergens. It is not clear whether AD influences the risk of developing contact allergy., Objectives: To examine the association between AD at preschool age and contact allergy at 16 years of age., Methods: At 16 years of age, 2215 adolescents from the population-based cohort BAMSE were included. These adolescents had been followed with repeated questionnaires regarding AD throughout childhood, and contact allergy was assessed by skin patch test at 16 years., Results: AD at preschool age was associated with contact allergy to at least one of the tested substances at 16 years of age among boys [adjusted odds ratio (OR) 1·51, 95% confidence interval (CI) 1·03-2·20] but not among girls (adjusted OR 0·77, 95% CI 0·54-1·10). AD at preschool age was not associated with contact allergy to nickel in either boys or girls. In contrast, AD at preschool age was associated with contact allergy to fragrance mix I (adjusted OR 3·10, 95% CI 1·66-5·80). This association was observed especially for AD at preschool age in combination with IgE sensitization to airborne or food allergens (adjusted OR 3·80, 95% CI 1·67-8·61)., Conclusions: The results suggest that AD in early childhood may be associated with contact allergy to fragrances, but not to nickel, in adolescence., (© 2018 British Association of Dermatologists.)

Hairdressers are exposed to high levels of chemicals, including possible carcinogens. For dermal exposure, the skin protects against the uptake of chemicals and the protein filaggrin (encoded by FLG) has a key role in skin barrier function. This study investigated if variants of FLG previously linked to impaired skin barrier function, i.e. null mutations and copy number variation (CNV) alleles (CNV10), are associated with cancer-related DNA changes. Blood and questionnaire data were collected from hairdressers (n = 295) and controls (n = 92). Exposure to aromatic amines was measured as hemoglobin adducts by gas chromatography tandem mass spectrometry. DNA from peripheral blood was used to test for FLG null mutations and CNV (10, 11, or 12 repeats), telomere length, and methylation of selected cancer-related genes. Hairdressers had a lower frequency of FLG null mutations (4.1 vs. 7.6%, P = 0.18) and CNV10 (43.2 vs. 56%, P = 0.0032) than controls. In hairdressers, CNV10 carriers had a decreased risk of high ortho-toluidine adducts in blood compared with non-carriers (odds ratio, OR = 0.49, 95% CI = 0.30-0.81). Further, telomere length was shorter for carriers of any FLG null allele (β = -0.18, 95% CI = -0.31 to -0.044) and CNV10 carriers (β = -0.054, 95% CI = -0.11 to -0.00051, linear regression adjusted for age, passive smoking, residence, and education) compared to non-carriers. Carriers of any FLG null allele showed higher methylation of the cyclin-dependent kinase inhibitor 2A gene CDKN2A (OR = 6.26, CI = 1.13-34.7), but not of the other genes analyzed. These associations were not found among the controls. Our study showed that the frequency of FLG CNV10 was lower among hairdressers than controls, which may indicate a healthy worker selection. Moreover, FLG null and CNV10 were associated with cancer-related DNA changes in hairdressers, which may influence their risk of cancer., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Knowledge about the skin deposition and penetration of nickel into the stratum corneum (SC) after short contact with metallic items is limited., Objective: To quantify nickel skin deposition and penetration into the SC after short contact with metallic nickel., Methods: Sixteen nickel-allergic participants and 10 controls were exposed to 3 pure nickel discs and 1 aluminium disc on each volar forearm for 3 × 10 minutes. Before exposure, 1 forearm was irritated with 0.5% sodium lauryl sulfate under 24-hour occlusion. Immediately, as well as 24 and 72 hours after metallic disc exposure, outer SC layers were removed with adhesive tapes and the nickel content was measured., Results: Nickel deposition and SC penetration capable of eliciting allergic nickel dermatitis were found immediately and after 24 hours. Significantly higher nickel amounts were found on normal skin and in the SC of nickel-allergic participants than in controls both immediately and after 24 hours, and on irritated skin immediately after exposure., Conclusions: Nickel deposition and SC penetration is considerable after nickel skin exposure of 3 × 10 minutes. Combined with the allergic responses resulting from the same exposures reported previously, this study highlights that short skin exposure to nickel-releasing items may cause allergic nickel dermatitis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Knowledge about the required duration of exposure for elicitation of allergic nickel dermatitis in nickel-allergic individuals is limited. However, it often has been proposed that short skin contact is safe., Objectives: To examine whether repeated skin contact with nickel over short time periods (3 × 10 min) can elicit allergic nickel dermatitis., Methods: Sixteen nickel-allergic adults and 10 controls were exposed to, respectively, nickel- and aluminium-containing discs on each volar forearm and on each earlobe for 3 × 10 min. One arm was pretreated for 24 h with sodium lauryl sulfate (SLS) 0·5% under occlusion before exposure. One aluminium and one nickel exposure site were clinically evaluated, and blood flow was measured with laser Doppler flowmetry at day 2 and day 4., Results: Ten of 16 (63%) nickel-allergic participants developed allergic nickel dermatitis on SLS-pretreated arm skin and three of 16 (19%) developed it on normal skin on the earlobe. On the SLS-pretreated arms of nickel-allergic participants, blood flow increased significantly more on the nickel-exposed skin than on the aluminium-exposed skin on days 2 and 4. No change in clinical reactivity or blood flow was found on normal forearm skin in nickel-allergic participants or on any skin in controls., Conclusions: This experimental study showed that relatively short repeated skin contact (3 × 10 min) with metallic nickel elicits allergic nickel dermatitis in irritated skin and at sites with previous dermatitis. The results support the restrictions in current nickel regulation., (© 2018 British Association of Dermatologists.)

Objectives: Cobalt (Co) exposure is associated with adverse health effects including skin sensitisation, asthma and interstitial lung fibrosis. Exposure to Co in industrial settings is often assessed using air samples or biomonitoring in urine. Skin exposure is rarely measured. Aim of this study was to quantify and compare the importance of Co skin exposure and respiratory exposure in determining urinary Co concentrations., Methods: Co skin exposure was measured in 76 hard metal workers by acid wipe sampling before and at the end of work shifts. Spot urine was collected during a 24-hour period from the start of a shift. Respiratory exposure was measured by personal inhalable dust sampling during a shift in 30 workers. Co was analysed by inductively coupled plasma mass spectrometry., Results: Quantile regression modelling showed that a doubling of Co on skin before or at the end of shift increased the median urinary concentration of Co by 70% (p<0.001) or 32% (p<0.001), respectively. A doubling of Co in air increased median urinary Co by 38% (p<0.001). Co skin exposures were still significantly associated with urinary Co after excluding a group of workers with high respiratory exposure (33%, p=0.021 and 17%, p=0.002)., Conclusions: The results indicate an association between Co skin exposure and urinary Co concentrations. This should be considered when using urinary Co as a biomarker of exposure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hair dyeing is very common and may cause allergic contact dermatitis. Oxidative (often termed permanent or semi-permanent) hair dye products have constituted the focus of market surveys and toxicological risk assessments, while non-oxidative (semi-permanent, temporary or direct) products have not been assessed., Objectives: To identify the hair dye substances presently used in non-oxidative hair dye products in Europe., Methods: Ingredient label data on eligible products in 5 European countries were collected, and 289 different non-oxidative hair dye products were included in this study., Results: Up to 9 hair dye substances were present in each product. Sixty-eight individual hair dye substances were identified on the 289 product labels, and their occurrence ranged from 0.3% to 34%. There were differences concerning substances used and their number per product between products of different consistency and colour., Conclusions: The hair dye substances in non-oxidative hair dye products are different from those in oxidative hair dye products, and are currently not covered by patch test series. The toxicological and skin-sensitizing profile of the substances in non-oxidative hair dye products, as well as their concentrations, should be further investigated., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It is well known that hard metal workers have historically been affected by contact allergy to cobalt. Knowledge is sparse about occupational skin exposure to cobalt, in terms of skin doses and sources of exposure, which could be used to improve protection of workers., Objectives: To improve knowledge about skin doses and sources of skin exposure to cobalt within hard metal production, thereby facilitating better protection of workers., Methods: Forty workers were sampled on the index finger by acid wipe sampling after 2 hours of work. The samples were analysed with inductively coupled plasma mass spectrometry. Cobalt spot testing was performed in the work environment., Results: The highest skin doses were found among raw material workers. Skin doses among other production workers were also significant. Most office workers had low, but measurable, levels of cobalt on the skin. Glove use varied between workers. Cobalt was found on production equipment, on items in the canteen area, and on handles and buttons throughout the company., Conclusions: Cobalt skin doses were prominent, and originated from contact with raw materials, sintered materials, and contaminated surfaces. Cobalt was present on surfaces outside production areas. Companies need to identify and reduce skin exposure for protection of workers., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Irritant exposure may be a contributory cause or the sole cause of (occupational) hand dermatitis. However, the documentation of irritant exposures in clinical practice is not standardized., Objectives: To examine the feasibility and usefulness of a form with different items addressing both occupational and non-occupational irritant exposures in a semiquantitative way., Methods: Between May 2016 and May 2017, successive patients with work-related hand dermatitis, irrespective of aetiology, were examined in 9 specialized European departments. Department-specific investigation was supplemented with the above proforma. The results were recorded by use of an anonymized secured online documentation system in a pilot study., Results: Altogether, 193 patients were included; 114 females and 79 males, with a mean age of 40 years (range 18-68 years). The most common occupational group comprised healthcare workers (n = 35); occupational exposure of the hands to gloves, dusts and water without detergents of >2 hours/day was seen in 54.5%, 24.4% and 24.3% of patients, respectively. Non-occupational exposures rarely exceeded 2 hours/day., Conclusions: It is hoped that the set of descriptors will offer a basis for (clinical) epidemiological studies assessing the role of irritant exposures in occupational hand dermatitis, and to support a high level of quality and consistency in daily patient care., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chromium (Cr) is a common skin sensitizer. The use of Cr(VI) in leather is restricted in the EU, but that of Cr(III) is not., Objectives: To assess whether prolonged exposure to Cr-tanned leather with mainly Cr(III) release may elicit allergic contact dermatitis in Cr-allergic individuals., Method: Ten Cr-allergic subjects and 22 controls were patch tested with serial dilutions of Cr(III) and Cr(VI), and with leather samples. They then conducted a use test with a Cr-tanned and a Cr-free leather bracelet over a period of 3 weeks, for 12 h per day. Cr deposited on the skin from the bracelets was measured in the controls, and the diphenylcarbazide test for Cr(VI) and extraction tests for Cr(III) and Cr(VI) were conducted for the different leathers., Results: Four of 10 Cr-allergic subjects developed positive reactions to the Cr-tanned bracelet within 7-21 days, whereas only 1 of 10 had a positive patch test reaction to this leather. Cr released from the Cr-tanned leather was most probably entirely Cr(III), with a quantifiable amount being deposited on the skin., Conclusions: This study strongly suggests that prolonged and repeated exposure to Cr-tanned leather with mainly Cr(III) release is capable of eliciting allergic contact dermatitis in Cr-allergic individuals., (© 2018 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: An increasing incidence of contact allergy to methylisothiazolinone (MI) has been seen, caused, in particular, by cosmetic products and paints. A study from 2015 showed that 93.0% of paints bought in five European countries contained MI. New regulations have been discussed for paints in the EU, which may have influenced this market., Objectives: To re-evaluate the use and concentrations of MI and four other isothiazolinones in water-based wall paints., Methods: Water-based white wall paints (n = 60) were purchased in retail stores in five European countries: Denmark, France, Germany, Sweden, and the United Kingdom. The paints were analysed for isothiazolione content by the use of high-performance liquid chromatography coupled to ultraviolet detection, and the results were confirmed with high-performance liquid chromatography-tandem mass spectrometry., Results: MI was identified in 55 (91.7%) of the paints, with concentrations ranging from 1.1 to 142.7 ppm. The other isothiazolinones were identified in 20.0% [methylchloroisothiazolinone (MCI)] to 88.3% [benzisothiazolinone (BIT)] of the paints. BIT concentrations varied significantly between countries, whereas MI and MCI concentrations did not. There were no statistically significant differences in MI, MCI and BIT concentrations between the current study and the 2015 study., Conclusions: MI and other isothiazolinones are widely used in paints available in Europe. Their use does not seem to be decreasing., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In 2011, a multicentre study was conducted in order to determine how hair dye manufacturers instructed consumers to perform a self-test prior to dyeing their hair, in order to identify individuals who are likely to react upon subsequent hair dyeing. A number of concerns were raised concerning the variability in instructions between products and producers, and the safety and validity of this tool., Objectives: To perform a 5-year follow-up study in order to determine whether manufacturers still recommend a self-test, and if so, whether the procedures have been changed., Methods: During March 2016, a total of 40 oxidative hair dye products from 21 different manufacturers were bought in retail stores in 8 European countries., Results: The consumers were instructed to perform a self-test prior to hair dyeing for 39 of the products; however, the procedures varied greatly regarding the method of application, the amount of hair dye applied, the location and size of the application area, the number of applications, whether or not rinsing was performed after application, the reading times, and how a positive reaction was defined., Conclusions: Self-testing is still recommended by almost all manufacturers of permanent hair dyes. There are major variations in the instructions, even in products from the same manufacturer. The previously raised concerns regarding safety and validity still remain., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The high risk of occupational skin disease among hairdressers, caused by skin exposure to irritants and sensitizers, such as hair dye substances, is of great concern., Objectives: The aim of the present study was to assess how the various tasks involved in hair dyeing contribute to hairdressers' exposure to hair dye, in order to enable the formulation of well-founded recommendations on working routines that will reduce exposure and prevent occupational disease., Methods: Skin exposure to hair dye was measured for 20 hairdressers applying highlights and all-over hair colour with the hand rinsing technique. Resorcinol was used as a proxy for hair dye exposure., Results: Applying hair dye and cutting the newly dyed hair were the tasks that contributed most to exposure in treatments for highlights. After cutting all-over-coloured hair, all hairdressers had measurable amounts of hair dyes on both hands., Conclusions: Hairdressers are exposed to hair dye ingredients during all steps of the hair dyeing procedure. Cutting newly dyed hair contributes significantly to exposure. For the prevention of occupational disease resulting from hair dye exposure, we suggest cutting hair before dyeing it, and wearing gloves during all other work tasks., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Knowledge about the relations between skin exposures, skin symptoms and contact allergy in adolescents is limited., Objectives: To explore self-reported skin exposures and skin symptoms in girls and boys, and to assess the associations between exposures, symptoms and contact allergy at age 16 years., Participants and Methods: In all, 3115 adolescents from the population-based BAMSE birth cohort answered a questionnaire at age 16 concerning various skin exposures and related skin symptoms. Of these, 2285 were patch tested., Results: The prevalences of self-reported piercing (55.4%), hair dyeing (50.1%) and related skin symptoms were high, particularly in girls. Piercing and itchy rash after contact with metal items were associated with increased risks of nickel allergy [respectively: odds ratio (OR) 1.77, 95%CI: 1.04-3.03, and OR 2.25, 95%CI: 1.57-3.23]. An itchy rash resulting from the use of personal hygiene products or makeup was associated with a positive patch test reaction to fragrance mix I (OR 2.11, 95%CI: 1.02-4.35)., Conclusions: Adolescents are exposed to skin-sensitizing substances, for example because of piercing, hair dyeing, and tattooing. Such early-life skin exposure may lead to lifelong contact allergy and future allergic contact dermatitis and hand eczema., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nickel, cobalt and chromium are frequent skin sensitizers. Skin exposure results in eczema in sensitized individuals, the risk being related to the skin dose., Objectives: To develop a self-sampling method for quantification of skin exposure to metals, to validate the method, and to assess its feasibility., Methods: Defined metal doses (0.01-5 µg) were applied to the fingers of 5 participants. Skin areas (2 cm 2 ) were sampled with 1% HNO 3 , either as 0.1 ml on a swab, or as 0.5 ml on a wipe. Furthermore, 17 participants performed self-sampling by swab after 2 h of leisure activity. Samples were extracted in 1% HNO 3 and analysed by inductively coupled plasma mass spectrometry., Results: The sampling efficiency by swab was 46%, as compared with 93% for acid wipe sampling, for all tested doses. Most metal from the skin dose was detected in the first swab (33-43%). Despite lower sampling efficiency by swab, skin doses of metals following 2 h of leisure activity without hand washing were quantified in all participants, and ranged from 0.0016 to 0.15 µg/cm 2 , from 0.00014 to -0.0020 µg/cm 2 and from 0.00048 to -0.027 µg/cm 2 for nickel, cobalt, and chromium, respectively., Conclusions: The results indicate a future potential of skin sampling by swab to detect and monitor metals on skin by self-sampling. This will contribute to better knowledge of metal skin exposure among dermatitis patients, workers, and the general population., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Water exposure on the skin of the hands has previously been studied in adults. The aim of this study was to investigate self-reported water exposure in adolescents in the BAMSE cohort in Stockholm, Sweden. A questionnaire including a question on daily water exposure on the hands was answered by 3,091 adolescents at age 16 years. Exposure < 10 times/day was reported by 28.7% and < 20 times/day by 3.1%; boys had somewhat higher exposure than girls (p = 0.03). In a multivariate analysis, adolescents with dry skin reported higher exposure (adjusted odds ratio (ORadj) 1.4; 95% CI 1.2-1.7), while no statistically significant exposure differences were found in relation to hand eczema or atopic dermatitis. Reported exposure may be considered as baseline exposure during a period of life with limited occupational and domestic duties.

Background: It is not fully understood where and how people are exposed to sensitizing metals. Much can be learnt from studying occupational settings where metals are handled., Objectives: To quantify cobalt (Co), chromium (Cr) and nickel (Ni) exposure on the skin and in the air, and urine levels, in dental technicians working with tools and alloys that may result in skin and respiratory exposure., Methods: The metal skin dose was quantified with acid wipe sampling in dental technicians (n = 13). Air exposure was monitored by personal air sampling. Spot urine samples were collected for 24 h. Metals were analysed with inductively coupled plasma mass spectrometry., Results: Before work, Co was detected on the skin of 10 participants (0.00025-0.0039 µg/cm 2 ), and Cr (0.00051-0.011 µg/cm 2 ) and Ni (0.0062-0.15 µg/cm 2 ) on the skin of all participants. After a 2-h period without hand washing, CoCr-exposed participants had more Co on the skin (p = 0.004) than non-CoCr-exposed participants. Co was found in 10 air samples (0.22-155 µg/m 3 ), Cr in nine (0.43-71 µg/m 3 ), and Ni in four (0.48-3.7 µg/m 3 ). Metal urine concentrations were considered to be normal., Conclusions: Dental technicians were exposed to Co, Cr and Ni on the skin and through the air, which was not reflected in the urine concentrations in this study. Cobalt skin doses may potentially elicit allergic contact dermatitis and cause sensitization., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The local lymph node assay (LLNA) is used for assessing sensitizing potential in hazard identification and risk assessment for regulatory purposes. Sensitizing potency on the basis of the LLNA is categorized into extreme (EC3 value of ≤0.2%), strong (>0.2% to ≤2%), and moderate (>2%). To compare the sensitizing potencies of fragrance substances, preservatives, and hair dye substances, which are skin sensitizers that frequently come into contact with the skin of consumers and workers, LLNA results and EC3 values for 72 fragrance substances, 25 preservatives and 107 hair dye substances were obtained from two published compilations of LLNA data and opinions by the Scientific Committee on Consumer Safety and its predecessors. The median EC3 values of fragrances (n = 61), preservatives (n = 19) and hair dyes (n = 59) were 5.9%, 0.9%, and 1.3%, respectively. The majority of sensitizing preservatives and hair dyes are thus strong or extreme sensitizers (EC3 value of ≤2%), and fragrances are mostly moderate sensitizers. Although fragrances are typically moderate sensitizers, they are among the most frequent causes of contact allergy. This indicates that factors other than potency need to be addressed more rigorously in risk assessment and risk management., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Metal release from materials immersed in artificial sweat can function as a measure of potential skin exposure. Several artificial sweat models exist that, to various degree, mimic realistic conditions. Study objective was to evaluate metal release from previously examined and well characterized materials in two different artificial sweat solutions; a comprehensive sweat model intended for use within research, based on the composition of human sweat; and the artificial sweat, EN1811, intended for testing compliance with the nickel restriction in REACH. The aim was to better understand whether there are advantages using either of the sweat solutions in bio-elution testing of materials. Metal release in two different artificial sweat solutions was compared for discs of a white gold alloy and two hard metals, and a rock drilling insert of tungsten carbide at 1 h, 24 h, 1 week and 1 month. The released amount of metal was analysed by means of inductively coupled plasma mass spectrometry. Similar levels of released metals were measured from test materials in the two different artificial sweat solutions. For purposes in relation to legislations, it was concluded that a metal release test using a simple artificial sweat composition may provide results that sufficiently indicate the degree of metal release at skin contact., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In April 2014, the European Chemicals Agency defined the concept of 'prolonged contact with skin' as used in the EU nickel restriction., Objectives: To establish a baseline of nickel-releasing items on the Swedish market conforming with the EU nickel restriction according to the definition of 'prolonged contact' with the skin., Methods: We performed a limited market survey in Stockholm, Sweden. Items with metallic parts that come into contact with the skin, except those explicitly mentioned in the legal text, were chosen. The dimethylglyoxime (DMG) test was used to evaluate nickel release., Results: One hundred and forty-one items belonging to one of three categories - accessories, utensils for needlework, painting and writing (called utensils), and electronic devices - were tested in the study. Forty-four percent of all items were DMG test-positive (releasing nickel), and 9% gave a doubtful DMG test result., Conclusions: The large proportion of nickel-releasing items in the present study shows clearly that broader parts of industry need to take action to prevent nickel allergy. The high proportion of DMG test-positive items indicates that there is still much work to be done to reduce the nickel exposure of the population., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)