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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.

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.

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.To elucidate the association between FLG status and nickel penetration into stratum corneum (SC) in individuals without self-reported history of nickel allergy.Forty participants (23 FLG wt and 17 FLG null) were exposed to a nickel solution (80 μg/cmThe 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.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.

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

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

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. (Less)

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.

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.

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.

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.

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.

SummaryBackground 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.

SummaryBackground 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. As initial steps 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.

SummaryBackground 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.

SummaryBackground 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 cm2) were sampled with 1% HNO3, 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% HNO3 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/cm2, from 0.00014 to −0.0020 µg/cm2 and from 0.00048 to −0.027 µg/cm2 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.

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.

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.

SummaryBackground 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/cm2), and Cr (0.00051–0.011 µg/cm2) and Ni (0.0062–0.15 µg/cm2) 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/m3), Cr in nine (0.43–71 µg/m3), and Ni in four (0.48–3.7 µg/m3). 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.

Background. Chromium ( Cr) release from Cr-tanned leather articles is amajor cause of Cr contact dermatitis. It has been suggested that Cr( VI) release from leather is not necessarily an intrinsic ...

SummaryBackground 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.

SummaryBackground Cobalt allergy is frequent, but knowledge about exposure is limited. The patch test concentration and relevance of positive reactions are sometimes questioned. Objectives To assess the suitability of cobalt 1% versus 0.5% for patch testing, and to analyse the co-occurrence of allergy to cobalt, chromium, and nickel. Materials and methods Consecutive dermatitis patients (n = 656) were patch tested with cobalt chloride 0.5% and 1%, potassium dichromate 0.5%, and nickel sulfate 5%, all in petrolatum. Reactions were assessed on day (D)3, and on D6 or D7, and the reactivity and development of reactions were analysed. Results Allergy to any metal was shown in 31% of patients, allergy to cobalt in 14%, allergy to chromium in 7%, and allergy to nickel in 20%. A significant proportion (37%) of cobalt allergy cases were missed by cobalt 0.5% versus 1%, whereas the reactivity profiles were similar. Cobalt allergy was solitary, without concomitant allergy to chromium or nickel, in 50% of patients. Conclusions Cobalt chloride 1% pet. is more suitable for patch testing than 0.5%. Solitary cobalt allergy is as frequent as concomitant allergy to cobalt and nickel or chromium. Sources of skin exposure to metals need to be identified for prevention of contact allergy. This is, owing to large knowledge gaps, particularly demanding for cobalt.

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.

Working as hairdressers has been associated with increased risk for cancer, particularly bladder cancer. To evaluate if current hairdressers have elevated risks of adverse health effects, we measured several biomarkers related to cancer-related DNA alterations. We enrolled 295 hairdressers and 92 non-hairdressers (all female non-smokers) from Stockholm and southern Sweden. Questionnaire data were collected for each participant, including work tasks for the hairdressers. We measured telomere length in peripheral blood leucocytes using quantitative PCR and DNA methylation status of genes relevant for bladder cancer using methylation sensitive high resolution melting analysis. The hairdressers had shorter telomeres (β = -0.069, P = 0.019) compared with non-hairdressers. Shorter telomeres were found in hairdressers up to 32 years old performing hair waving more than once per week as compared with hairdressers in the same age group performing hair waving less often (β = -0.12, P = 0.037). Hair waving was associated with less frequent CDKN2A methylation (odds ratio, OR = 0.19, P = 0.033). Shorter telomeres in hairdressers may indicate a genotoxic effect. Performing hair waving was associated with short telomere length, although the effect was only observed in young hairdressers. No clear patterns were discerned with regard to DNA methylation of bladder cancer-related genes. The observed changes of methylation were not all in the expected direction and warrant further investigation.

SummaryBackground Cobalt is a strong skin sensitizer (grade 5 of 5 in the guinea-pig maximization test) that is used in various industrial and consumer applications. To prevent sensitization to cobalt and elicitation of allergic cobalt dermatitis, information about the elicitation threshold level of cobalt is important. Objective To identify the dermatitis elicitation threshold levels in cobalt-allergic individuals. Materials and methods Published patch test dose–response studies were reviewed to determine the elicitation dose (ED) levels in dermatitis patients with a previous positive patch test reaction to cobalt. A logistic dose–response model was applied to data collected from the published literature to estimate ED values. The 95% confidence interval (CI) for the ratio of mean doses that can elicit a reaction in 10% (ED10) of a population was calculated with Fieller's method. Results On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 µg cobalt/cm2, corresponding to 30.8–259 ppm. Conclusions Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contact dermatitis in sensitized individuals, and thereby the basis for future prevention of cobalt allergy.

Summary Background Contact allergy is common among adults. However, little is known about the prevalence in adolescents. Objectives To assess the prevalence of allergy to common contact allergens in Swedish adolescents in the general population. Participants and methods The BAMSE cohort is a population-based birth cohort with the main aim of studying the risk factors for asthma, rhinitis, and atopic dermatitis. Patch testing was performed at the 16-year follow-up. The test (TRUE Test®) was applied at home, and removed 2 days later by nurses, who recorded and photographed the results. Dermatologists made final assessments on the basis of photographs and protocols. Results Two thousand two hundred and eighty-five participants (88% of all 16-year follow-up participants) were patch tested; 15.3% had at least one positive reaction. Contact allergy was more common in girls than in boys (17.0% versus 13.4%, p = 0.018). Sensitization to nickel was most common (7.5%), followed by sensitization to fragrance mix I (2.1%) and p-tert-butylphenol formaldehyde resin (1.9%). Nickel allergy was more frequent in girls (9.8% versus 4.9%, p < 0.001). Solitary sensitization to cobalt was more common than co-sensitization to nickel and cobalt. Conclusions The prevalence of contact allergy in adolescents is of almost the same high magnitude as in adults. The applied method was feasible in the population-based setting.

Summary Background There is a well-known association between atopic dermatitis (AD) and hand eczema but less is known about how age at onset, persistence and severity of AD influence the risk of developing hand eczema. Objectives To examine the role of AD in the occurrence of hand eczema in adolescence. In addition, associations between asthma and rhinoconjunctivitis, sensitization to common airborne and food allergens, and hand eczema were studied. Methods From the population-based birth cohort BAMSE, 2927 adolescents who had been followed up repeatedly concerning allergy-related disease were included. Questionnaires identified adolescents with hand eczema at 16 years, and their blood was analysed for specific IgE. Results A total of 152 (5·2%) adolescents had hand eczema at the age of 16 years. Many of these adolescents had a history of AD (n = 111; 73·0%) and asthma and/or rhinitis (n = 83; 54·6%), respectively. Children with AD (aged 0–16 years) had more than threefold increased odds ratios (OR) for having hand eczema; those with persistent or severe AD had a crude OR of 6·1 [95% confidence interval (CI) 4·0–9·1] and 5·3 (95% CI 2·9–9·6), respectively. Conclusions We confirm a strong association between AD during childhood and hand eczema in adolescence. Children with persistent or more severe AD are at greater risk of developing hand eczema. Asthma and/or rhinoconjunctivitis, positive specific IgE or age at onset of AD are not associated with hand eczema in adolescence.

Summary Background Several studies have shown nickel and cobalt release from jewellery by using spot tests, but the metal composition of jewellery is largely unknown. Objectives To evaluate the metal composition of a large worldwide sample of mainly inexpensive jewellery items, and investigate the release of nickel, cobalt and lead from a subsample by using EN 1811:1998-required methods. Methods A total of 956 metallic jewellery components were examined with X-ray fluorescence spectroscopy. A subsample of 96 jewellery items purchased in the United States were investigated for nickel, cobalt and lead release by the use of artificial sweat immersion and plasma optical emission spectroscopy. Results Eighteen elements were detected. The 10 most frequently occurring were, in order of frequency, copper, iron, zinc, nickel, silver, chromium, tin, manganese, lead, and cobalt. Release of nickel was noted from 79 of the 96 US samples (0.01–98 µg/cm2/week), release of cobalt from 35 samples (0.02–0.5 µg/cm2/week), and release of lead from 37 samples (0.03–2718 µg/cm2/week). Conclusions We present here a comprehensive list of the most frequently encountered metals in jewellery and fashion accessories. Different allergenic and non-allergenic metals are utilized. We also report the frequent release of nickel, cobalt and lead from these objects, despite legislative restrictions.

The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

Summary Background The existing EU nickel restriction does not sufficiently protect the population from skin exposure to nickel. Better understanding is needed of the extent to which short and frequent contact with nickel-releasing items contributes to nickel deposition on skin. Objectives To quantify nickel skin exposure from short and frequent contact with nickel-releasing materials. Materials/methods Sequences of short contact events were assessed in (i) touch tests for measurement of nickel skin dose, (ii) wipe tests to similarly quantify the nickel release during a touch, and (iii) immersion tests in artificial sweat, for nickel-containing alloys and pure nickel. Results Nickel skin doses from a single touch were 0.024–4.7 µg/cm2 for all materials. Touching or wiping five untouched surfaces resulted in more accumulated nickel than five repeated touches of the same surface. The released amounts of nickel were generally lower at immersion, but increased with the number of repeated immersion periods. Conclusions Nickel skin doses were quantified after one single touch for all study materials. Touch tests, and potentially wipe tests as a proxy for skin dose measurements, are preferred to immersion tests for the assessment of short and frequent skin contact with nickel.

Summary Many key ingredients of hair cosmetics (in particular, dyes, bleaches, and hair-styling agents) are potent (strong to extreme) contact allergens. Some heterogeneity is apparent from published results concerning the range of allergens for which patch testing is important. The objective of the present review was to collect information on the current practice of using ‘hair cosmetic series’, and discuss this against the background of evidence concerning consumer/professional exposure and regulatory aspects to finally derive a recommendation for a ‘European hair cosmetic series’. The methods involved (i) a survey targeting all members of the COST action ‘StanDerm’ (TD1206) consortium, (ii) analysis of data in the database of the European Surveillance System on Contact Allergies (ESSCA), and (iii) literature review. Information from 19 European countries was available, partly from national networks, and partly from one or several departments of dermatology or, occasionally, occupational medicine. Apart from some substances being tested only in single departments, a broad overlap regarding ‘important’ allergens was evident. Some of the substances are no longer permitted for use in cosmetics (Annex II of the Cosmetics Regulation). An up-to-date ‘European hair cosmetics series’, as recommended in the present article, should (i) include broadly used and/or potent contact allergens, (ii) eliminate substances of only historical concern, and (iii) be continually updated as new evidence emerges.

ObjectivesCobalt (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.MethodsCo 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.ResultsQuantile 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% (pConclusionsThe 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.

BackgroundIrritant 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.ObjectivesTo examine the feasibility and usefulness of a form with different items addressing both occupational and non-occupational irritant exposures in a semiquantitative way.MethodsBetween 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.ResultsAltogether, 193 patients were included; 114 females and 79 males, with a mean age of 40years (range 18-68years). The most common occupational group comprised healthcare workers (n =35); occupational exposure of the hands to gloves, dusts and water without detergents of >2hours/day was seen in 54.5%, 24.4% and 24.3% of patients, respectively. Non-occupational exposures rarely exceeded 2hours/day.ConclusionsIt 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.

Nickel is the most common skin sensitizer, affecting large proportions of the population. Nickel allergy is more prevalent among girls and women than boys and men, owing to differences in exposure patterns. There are large differences in prevalence between age groups, countries and occupations, over time. Skin exposure to nickel in various consumer articles results in nickel allergy and dermatitis on exposed body parts, including the hands. Occupational exposure to nickel is an important cause of occupational skin disease, particularly hand eczema. Nickel allergy has started to decline in some countries owing to the EU restriction of nickel.