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Background: Cobalt allergy is prevalent in dermatitis patients. Very little documentation exists about current sources of cobalt exposure., Objectives: To investigate and discuss putative sources of cobalt exposure and to present selected epidemiological data on cobalt allergy from patch-tested dermatitis patients in an attempt to better understand cobalt allergy., Materials and Methods: 19,780 dermatitis patients aged 4-99 years were patch tested with nickel, chromium or cobalt between 1985 and 2010. The cobalt spot test was used to test for cobalt ion release from mobile phones as well as cobalt-containing dental alloys and revised hip implant components., Results: Six of eight dental alloys and 10 of 98 revised hip implant components released cobalt in the cobalt spot test, whereas none of 50 mobile phones gave positive reactions. The clinical relevance of positive cobalt test reactions was difficult to determine in the majority of patients. Isolated patch test reactivity to cobalt was less associated with occupational dermatitis and hand eczema than patch test reactivity to cobalt in combination with other contact allergies., Conclusions: It is often difficult to interpret the relevance of a positive patch test reaction to cobalt, and there is a need for further studies to determine sources of cobalt exposure., (© 2011 John Wiley & Sons A/S.)

Background: Oxidative hair dyes are important skin sensitizers, causing contact allergy and dermatitis in hairdressers and consumers., Objectives: To study the prevalence of hair dye substances, categorized as potent skin sensitizers, in consumer-available oxidative hair dye products on the market of a southern European country and to compare it with that in Sweden., Methods: Ingredient labels of 105 oxidative hair dye products from 19 brands were studied, and the prevalence and use pattern of hair dye substances, categorized as potent skin sensitizers, was assessed. Network diagrams were used to display results., Results: According to the labelling, all 105 products contained hair dye substances categorized as potent skin sensitizers. A total of 25 different hair dye substances categorized as potent skin sensitizers were identified. Eighty-seven per cent of the products contained at least four such substances. Either p-phenylenediamine, toluene-2,5-diamine or toluene-2,5-diamine sulfate was present in 103 products., Conclusions: Hair dye substances categorized as potent skin sensitizers were used in all studied hair dye products on the Spanish market. The prevalence of p-phenylenediamine was higher in the present study than in a similar study in Sweden. More than 20 potent sensitizers were identified in each country. Not only p-phenylenediamine should be used to diagnose allergy to hair dyes., (© 2011 John Wiley & Sons A/S.)

Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic algorithm to guide the selection of screening allergen series for patch testing is provided. At a minimum, an extended baseline screening series and metal screening is necessary. Static and dynamic orthopaedic implants, intravascular stent devices, implanted defibrillators and dental and gynaecological devices are considered. Basic management suggestions are provided. Our goal is to provide a comprehensive reference for use by those evaluating suspected cutaneous and systemic metal hypersensitivity reactions., (© 2011 John Wiley & Sons A/S.)

Introduction: Nickel and cobalt allergy remain frequent in dermatitis patients. It is important to determine possible nickel and cobalt exposures at work as these may offer important information to regulators and physicians who perform patch testing. Clinical relevance of metal exposure is usually assessed by the treating physician via the medical history and by presentation of allergic contact dermatitis., Objectives: To screen unused non-powered hand-held work tools for nickel and cobalt release by using colorimetric spot tests., Materials & Methods: A random selection of 200 non-powered hand-held work tools for sale in 2 retailers of home improvement and construction products were analyzed qualitatively for metal release using the colorimetric nickel and cobalt spot tests., Results: Nickel release was identified from 5% of 200 work tools using the dimethylglyoxime (DMG) test. In 8 of 10, positive results were located to the metal ring that acts like a cuff and is located at the end of the grip. The positive DMG test results were not related to specific categories of work tools. The cobalt spot test gave no positive test reactions., Conclusions: It appears that the proportion of work tools that release nickel, in amounts that may result in allergic nickel dermatitis, has decreased markedly, when results were compared with a Swedish study performed more than a decade ago. No cobalt release was detected but it should be underscored that hard-metal tools were not examined. Other sources of cobalt may explain the relatively high levels of cobalt allergy in dermatitis patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Nickel allergy is frequent and cause morbidity and increased health care costs., Objective: The aim of this study was to determine the proportion of inexpensive earrings randomly purchased from stores and street markets in two capitals that gave positive dimethylglyoxime (DMG) test reactions and to determine whether the degree of nickel release was related to shop category., Methods: Random inexpensive metallic earrings were purchased from stores and vendors in London and Warsaw. A qualitative investigation of nickel release by using the DMG test was performed., Results: DMG testing revealed that respectively 15.1% (n=205) and 18.4% (n=206) of earrings purchased in London and Warsaw released nickel as indicated by positive test outcomes. Stratification by store category showed that DMG test-positive jewellery were mainly purchased from street markets and from stores that were not part of national or international chains., Conclusions: Despite the EU Nickel Directive having resulted in decreasing prevalence of nickel allergy, a large proportion of inexpensive earrings still release nickel in concentrations that may result in nickel allergy and dermatitis. Authorities should prioritize information campaigns and random inspections as a legislation that is not followed is of limited value., (© 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.)

Background: Contact allergy to phenol-formaldehyde resins (PFRs) based on phenol and formaldehyde is not detected by a p-tertiary-butylphenol-formaldehyde resin (PTBP-FR) included in most baseline patch test series., Objectives: To investigate the rate of contact allergy to PFR-2 (a mixture of monomers and dimers from a resol resin based on phenol and formaldehyde) in a Swedish population, and to investigate associated simultaneous allergic reactions., Methods: Five centres representing the Swedish Contact Dermatitis Research Group included PFR-2 in their patch test baseline series for a period of 1.5 years., Results: Of 2504 patients tested, 27 (1.1%) reacted to PFR-2. Of those 27 individuals, 2 had a positive reaction to formaldehyde and 2 to PTBP-FR. Simultaneous allergic reactions were noted to colophonium in 6, to Myroxylon pereirae in 14, and to fragrance mix I in 15., Conclusions: The contact allergy frequency in the tested population (1.1%) merits its inclusion in the Swedish baseline series and possibly also in other baseline series. Simultaneous allergic reactions were noted to colophonium, M. pereirae, and fragrance mix I., (© 2011 John Wiley & Sons A/S.)

Sesquiterpene lactone mix detects contact allergy to these compounds present in the plant family Asteraceae. This marker is present in many baseline series. An additional marker is Compositae mix, which is not present in many baseline series. To investigate whether this allergen should be inserted into the Swedish baseline series, six dermatology centres representing the Swedish Contact Dermatitis Research Group included Compositae mix into their baseline series for 1.5 years. Of 2818 patients tested, 31 (1.1%) reacted to Compositae mix and 26 (0.9%) to Sesquiterpene lactone mix. Active sensitization to Compositae mix was noted in two cases. Only 0.4% of Asteraceae contact allergy cases would have been missed if Compositae mix had not been tested, a frequency too low to merit its inclusion in the baseline series. Due to obvious geographical differences in frequency in frequency of simultaneous allergic reactions to Compositae mix and Sesquiterpene lactone mix, the question as to whether specific baseline series (including Compositae mix or not as a "tail" substance) should be used in the different centres must be addressed. Another option could be to remove Sesquiterpene lactone mix from the baseline series and substitute it with Compositae mix.

Background: Preservatives and fragrances are important and frequent skin sensitizers, found in a wide range of products intended for personal and occupational use., Objectives: To examine the use of preservatives and fragrances in certain cosmetics and detergents on the market. The product types studied were shampoos, hair conditioners, liquid soaps, wet tissues, washing-up liquids, and multi-purpose cleaners., Materials/methods: Ingredient labels of 204 cosmetic products and ingredient data sheets of 97 detergents, available on company websites, were examined., Results: The preservatives most frequently identified were phenoxyethanol, methylparaben, sodium benzoate, propylparaben, and methylchloroisothiazolinone/methylisothiazolinone. Parabens were found in 44% of cosmetics and 9% of detergents; formaldehyde-releasers in 25% of cosmetics and 8% of detergents; and isothiazolinones in 23% of cosmetics and 28% of detergents. The fragrances most frequently identified were linalool, limonene, hexyl cinnamal, butylphenyl methylpropional, and citronellol. Eighty-eight per cent of the products contained fragrances, and any of the 26 fragrances requiring labelling were found in half of the cosmetics and one-third of the detergents., Conclusions: Several preservatives and fragrances with well-known skin-sensitizing potential were common in the examined product types. Such products may be used several times a day by consumers and workers., (© 2010 John Wiley & Sons A/S.)

In July 2001, the EU Nickel Directive came into full force to protect European citizens against nickel allergy and dermatitis. Prior to this intervention, Northern European governments had already begun to regulate consumer nickel exposure. According to part 2 of the EU Nickel Directive and the Danish nickel regulation, consumer items intended to be in direct and prolonged contact with the skin were not allowed to release more than 0.5 µg nickel/cm2/week. It was considered unlikely that nickel allergy would disappear altogether as a proportion of individuals reacted below the level defined by the EU Nickel Directive. Despite this, the EU Nickel Directive part 2 was expected to work as an operational limit that would sufficiently protect European consumers against nickel allergy and dermatitis. This review presents the accumulation of epidemiological studies that evaluated the possible effect of this major public health intervention. Also, it evaluates recent exposure assessment studies that have been performed using the dimethyl glyoxime test. It is concluded that the EU Nickel Directive has started to change the epidemiology of nickel allergy in Europe but it should be revisited to better protect consumers and workers since nickel allergy and dermatitis remain very frequent., (© 2011 John Wiley & Sons A/S.)

Background: Nickel is the most common cause of contact allergy and an important risk factor for hand eczema. Visualization techniques may be powerful in showing exposures. The dimethylglyoxime (DMG) test might be used to establish skin exposure to nickel., Objectives: To develop and evaluate methods for visualization of nickel on the skin by the DMG test and hand imprints., Methods: Nickel solutions at different concentrations were applied in duplicate on the hands in healthy subjects (n = 5). The DMG test and acid wipe sampling for quantification were then performed. Hand imprints were taken after manipulation of nickel-releasing tools (n = 1), and in workers performing their normal tasks (n = 7). The imprints were developed by the DMG test., Results: The DMG test on hands gave positive results in all subjects. The lowest concentration giving rise to a colour change was set to 0.13 µg/cm(2) for DMG testing on skin. DMG test-developed imprints worked well except when hands were heavily contaminated by other particles/dust., Conclusions: The DMG test may be used as a simple and powerful tool for visualization of nickel on skin. DMG test-developed hand imprints may, in the future, be used for semi-quantitative or quantitative exposure assessment., (© 2011 John Wiley & Sons A/S.)

Background: EU legislation has reduced the epidemic of nickel contact allergy affecting the consumer, and shifted the focus towards occupational exposure. The acid wipe sampling technique was developed to quantitatively determine skin exposure to metals., Objectives: To assess the clinical usefulness of the acid wipe sampling technique as part of the diagnostic investigation for occupational nickel allergy-associated hand dermatitis., Patients and Methods: Six patients with vesicular dermatitis on the hands were included. Acid wipe sampling of skin and patch testing with a nickel sulfate dilution series were performed., Results: Nickel was detected in all samples from the hands. In all patients, the nickel content on the hands was higher than on the non-exposed control area., Conclusions: Occupational exposure to nickel-releasing items raised the nickel content on exposed skin as compared with a non-exposed control site. Nickel-reducing measures led to complete symptom relief in all cases. In cases of a positive nickel patch test reaction and hand eczema, patients should perform the dimethylglyoxime (DMG) test on metallic items at home and at work. The acid wipe sampling technique is useful for the diagnosis of occupational hand eczema following screening with the inexpensive DMG test., (© 2010 John Wiley & Sons A/S.)

Background: The EU Nickel Directive, aimed at primary and secondary prevention of nickel allergy by limitation of nickel release from certain items, came fully into force in July 2001., Objectives: To assess the prevalence on the market of items with nickel release and to compare the outcome with previous studies performed in Sweden in 1999 and 2002-2003., Materials and Methods: Nickel release from 659 items covered by the EU Nickel Directive was assessed with the dimethylglyoxime (DMG) test. Special attention, as compared with the previous surveys, was given to cheap jewellery in street markets and sewing materials in haberdashery shops., Results: Nickel release was shown for 9% of the tested items, all of which were intended for direct and prolonged contact with the skin. A high proportion of items bought at haberdashery shops and street markets, 34% and 61%, respectively, showed nickel release., Conclusions: The Swedish market for products intended for direct and prolonged contact with the skin has largely adapted to the Nickel Directive. It is suggested that authorities should monitor the market regularly and give attention to areas where compliance with the requirements is poor, for protection of public health., (© 2010 John Wiley & Sons A/S.)

Background: Before the introduction of the EU Nickel Directive, concern was raised that manufacturers of jewellery might turn from the use of nickel to cobalt following the regulatory intervention on nickel exposure., Objectives: The aim was to study 354 consumer items using the cobalt spot test. Cobalt release was assessed to obtain a risk estimate of cobalt allergy and dermatitis in consumers who would wear the jewellery., Methods: The cobalt spot test was used to assess cobalt release from all items. Microstructural characterization was made using scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS)., Results: Cobalt release was found in 4 (1.1%) of 354 items. All these had a dark appearance. SEM/EDS was performed on the four dark appearing items which showed tin-cobalt plating on these., Conclusions: This study showed that only a minority of inexpensive jewellery purchased in Denmark released cobalt when analysed with the cobalt spot test. As fashion trends fluctuate and we found cobalt release from dark appearing jewellery, cobalt release from consumer items should be monitored in the future. Industries may not be fully aware of the potential cobalt allergy problem.

Background: It is often difficult to establish clinical relevance of metal exposure in cobalt-allergic patients. Dermatologists and patients may incorrectly assume that many metallic items release cobalt at levels that may cause cobalt dermatitis. Cobalt-allergic patients may be unaware that they are exposed to cobalt from handling work items, causing hand dermatitis., Objectives: To present early findings with a newly developed cobalt spot test., Methods and Results: A cobalt spot test based on disodium-1-nitroso-2-naphthol-3,6-disulfonate was able to identify cobalt release at 8.3 ppm. The test may also be used as a gel test if combined with an agar preparation. We found no false-positive reactions when testing metals and alloys known not to contain cobalt. However, one cobalt-containing alloy, which elicited cobalt dermatitis in cobalt-allergic patients, was negative upon cobalt gel testing., Conclusions: The cobalt test detects amounts of cobalt release that approximate the elicitation concentration seen in cobalt-allergic patients. It may serve as a useful tool in dermatology offices and workplaces.

Background: The accuracy of the dimethylglyoxime (DMG) nickel spot test has been questioned because of false negative and positive test reactions. The EN 1811, a European standard reference method developed by the European Committee for Standardization (CEN), is fine-tuned to estimate nickel release around the limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test., Objectives: To evaluate the sensitivity and specificity of the DMG test., Methods: DMG spot testing, chemical analysis according to the EN 1811 reference method, and X-ray fluorescence spectroscopy (XRF) were performed concomitantly on 96 metallic components from earrings recently purchased in San Francisco., Results: The sensitivity of the DMG test was 59.3% and the specificity was 97.5% based on DMG-test results and nickel release concentrations determined by the EN 1811 reference method., Conclusions: The DMG test has a high specificity but a modest sensitivity. It may serve well for screening purposes. Past exposure studies may have underestimated nickel release from consumer items.

Skin exposure to nickel, cobalt, and chromium may cause sensitization and allergic contact dermatitis and it is known that many alloys and platings may release significant amounts of the metals upon contact with skin. Occupational exposure to these sensitizing metals has been studied in different settings with regards to airborne dust and different biological end points, but little is known about deposition on skin from airborne dust and direct contact with materials containing the metals. In this study, skin deposition was studied in 24 workers in an industry for development and manufacturing of gas turbines and space propulsion components. The workers were employed in three departments, representing different exposure scenarios: tools sharpening of hard metal items, production of space propulsion structures, and thermal application of different metal-containing powders. A novel acid wipe sampling technique was used to sample metals from specific skin surfaces on the hands and the forehead of the workers. Total amounts of nickel, cobalt, and chromium were measured by inductively coupled plasma mass spectrometry. The result showed that nickel, cobalt, and chromium could be detected on all skin surfaces sampled. The highest level of nickel was 15 microg cm(-2) h(-1), the highest for cobalt was 4.5 microg cm(-2) h(-1), and for chromium 0.6 microg cm(-2) h(-1). The three departments had different exposures regarding the metals. The highest levels of nickel on the skin of the workers were found in the thermal applications department, cobalt in the tools sharpening department, and chromium in the space propulsion components department. In conclusion, the workers' exposure to the metals was more likely to come from direct skin contact with items, rather than from airborne dust, based on the fact that the levels of metals were much higher on the fingers than on the back side of the hands and the forehead. The skin exposure levels of nickel and cobalt detected are judged capable to induce sensitization and elicit allergic contact dermatitis.

Background: In recent years, the alarming increase in contact allergy to hair dyes has drawn much attention. It has been shown that many of the currently allowed hair dye substances are potent skin sensitizers., Objectives: To study the prevalence of hair dye substances, categorized as potent skin sensitizer, in oxidative hair dye products on the Swedish market., Materials and Methods: Ingredient labels of 122 oxidative hair dye products from 20 brands were examined. All ingredients were recorded, and the prevalence of hair dye substances categorized as potent skin sensitizers was assessed., Results: According to ingredient labelling, 120 out of 122 examined oxidative hair dye products contained hair dye substances categorized as potent skin sensitizers. More than 80% of the products contained at least four such substances; 37 hair dye substances categorized as potent skin sensitizers were identified, and 10 of these were more prevalent than p-phenylenediamine., Conclusions: Hair dye substances categorized as potent skin sensitizers are very common in oxidative hair dye products. A substantial number of potent skin sensitizers are more frequently used than p-phenylenediamine, while only a few are commercially available as patch test substances.

Background: Cobalt, nickel, and chromium are important skin sensitizers. However, knowledge about cobalt exposure and causes of cobalt sensitization is limited., Objectives: To study release of cobalt, nickel, and chromium from some cobalt-containing hard metal alloys and to test reactivity to the materials in cobalt-sensitized patients., Methods: Discs suitable for patch testing were made of some hard metal alloys. Cobalt, nickel, and chromium release from the materials was determined by immersion in artificial sweat (2 min, 1 hr, 1 day, and 1 week). Patch test reactivity to the discs and to serial dilutions of cobalt and nickel was assessed in previously patch-tested dermatitis patients (19 cobalt positive and 18 cobalt-negative controls)., Results: All discs released cobalt, nickel, and chromium. Some discs released large amounts of cobalt (highest concentration: 290 microg/cm(2)/week). Seven discs elicited three or more positive test reactions., Conclusions: The concentration of released cobalt was high enough to elicit allergic contact dermatitis in cobalt-sensitized patients. As the materials in the discs are used in wear parts of hard metal tools, individuals with contact allergy to cobalt may develop hand eczema when handling such materials.

Background: Occupational exposure to skin irritants, in particular to water, is an important risk factor for hand eczema., Objectives: To assess occupational skin exposure to water in the general population., Methods: As part of a public health survey in Stockholm, Sweden, 18,267 gainfully employed individuals aged 18-64 years completed a questionnaire with previously validated questions regarding occupational skin exposure to water., Results: Altogether 16% reported exposure to water for (1/2) h or more a day, and 13% reported exposure to water more than 10 times a day. Furthermore, 7% reported water exposure of more than 2 h and 6% of more than 20 times a day. Women reported more water exposure than men and many female-dominated occupations were seen to comprise water exposure. Women were also more exposed than men within the same jobs. Young adults were more exposed than older. A total of 18% were employed in high-risk occupations for hand eczema. Fifty-nine per cent of individuals employed in high-risk occupations reported water exposure at work, compared with 11% in low-risk occupations., Conclusions: A total of 20% of the population of working age acknowledged occupational skin exposure to water, which was found to be more common in young adults and women. Using job title as a proxy for water exposure gives an underestimation due to misclassification. In assessing occupational skin exposure to water, both exposure time and frequency should be considered.

Background: Nickel exposure is the most common cause of contact allergy. The role of contact with nickel-containing coins has been controversial., Objectives: To compare the release of nickel from 1 and 2 EUR coins (both composed of two alloys: Cu 75%, Zn 20%, Ni 5% and Cu 75%, Ni 25%) and Swedish 1 SEK coin (alloy: Cu 75%, Ni 25%) and to assess the deposition of nickel onto skin by coin handling., Methods: Nickel release was determined by immersion in artificial sweat (2 min, 1 hr, 24 hr, and 1 week). Deposition of nickel onto the skin was assessed in three subjects after 1-hr handling of 2 EUR and 1 SEK coins. Samples (n = 48) were taken from fingers and palms by acid wipe sampling and analysed by inductively coupled plasma mass spectrometry., Results: Amounts of nickel released by 1 week from 1 SEK, 1 EUR, and 2 EUR coins were 121, 86, and 99 microg/cm(2), respectively. Corresponding 2 min values were 0.11, 0.25, and 0.22 microg/cm(2). Nickel was deposited onto the skin by 1 hr coin handling (range 0.09-4.1 microg/cm(2)), the largest amounts were on fingers; similar amounts of nickel were deposited from 1 SEK and 2 EUR coins., Conclusions: Nickel is released from 1 and 2 EUR and 1 SEK coins at similar amounts. Nickel is deposited onto skin at substantial and similar amounts by coin handling. Acid wipe sampling is suitable for studies of skin exposure to nickel and in risk assessment.

Background: Nickel, chromium, and cobalt are important skin sensitizers. Better knowledge about skin exposure is needed for more efficient prevention. We have previously developed acid wipe sampling for assessment of skin exposure to metals., Objectives: To apply the acid wipe sampling technique in some occupations where intense contact with metallic items occurs and to gather experience for the design of future workplace studies., Methods: 18 volunteers (carpenters, locksmiths, cashiers, and secretaries as controls) participated. They performed their normal tasks during a job session for exposure. Samples were taken from fingers and palms by acid wipe sampling, and analysis of metals was performed by inductively coupled plasma mass spectrometer., Results: The metals were detected in all samples, and the amount of nickel was larger than that of chromium and cobalt. Fingers were more exposed than palms. 8-h exposure to nickel was calculated and was highest in locksmiths (mean 3.784 mug/cm(2), range 1.846-5.028 mug/cm(2)) followed by carpenters, cashiers, and secretaries., Conclusions: The acid wipe sampling technique is suitable for studies of skin exposure to nickel, chromium, and cobalt in the workplace. The sampling efficiency of acid wipe sampling is high. The amounts of nickel deposited on skin in carpenters, locksmiths, and cashiers are judged capable of eliciting allergic contact dermatitis.

There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future.

Exposure to large airborne organic aerosols may cause respiratory and skin symptoms. The use of human exposure chambers permits safe mechanistic studies of the effect of inhalation or dermal deposition of such particles. The performance of a dynamic and continuous whole-body human exposure chamber using turbulent air mixing during exposure to these organic aerosols of humans and of a new heated mannequin was evaluated. Variability of temporal and spatial distribution of the airborne particle concentration, and aerodynamic aerosol size distribution of the inhalable fraction, were evaluated. The temporal and spatial distribution of these aerosols close to the breathing zone during an exposure session was typically < or = 10%, which is low for airborne particles of this size. In a larger section around a human, only slightly higher spatial variation was found. Variability between exposure sessions was also low (< 10%). Only limited effect of relative humidity for the organic aerosols was observed. The aerodynamic particle size distribution curves differed slightly, but some were comparable to those in occupational environments. The outcome of the performance tests as measured with the heated mannequin was almost the same as with humans, indicating that the mannequin could be used in preparatory tests in this type of chamber.

The aim of this study was to validate questions regarding skin exposure using observation. The study group consisted of 40 individuals in 5 different occupations: nurse in an intensive care unit, car mechanic, hairdresser, kitchen worker, and office worker. The participants completed a questionnaire before the start of a working day. The questionnaire covered total skin exposure times to water, foodstuffs, chemicals, and occlusive gloves and also covered the frequency of hand-washing during a working day. Observers subsequently used a hand-held computer to register the time and the frequency of each exposure. A strong correlation between self-reports and observations was found for questions regarding exposure times to water, foodstuffs, and occlusive gloves and also a moderate correlation for questions regarding frequency of hand-washing. The present observation method was insufficient for estimating total exposure times to chemicals as the true exposure time is influenced by, e.g. the use of contaminated protective gloves and the efficacy with which the chemicals were removed. The inter-observer reliability showed a very strong correlation. We consider the questions regarding skin exposure to water, foodstuffs, protective gloves, and hand-washing to be useful for future studies. The observation method seems to be reliable, useful, and easy to apply.

There is a great need to accurately assess skin exposure to contact allergens. We have developed a technique for assessment of skin exposure to nickel, chromium and cobalt using acid wipe sampling by cellulose wipes with 1% nitric acid. Chemical analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS). The recovery of nickel, chromium and cobalt from arms and palms was 93%. The analytical result is expressed in terms of mass per unit area (microg/cm(2)). The developed acid wipe sampling technique is suitable for determination of nickel, chromium and cobalt deposited on the skin. The technique may be used in workplace studies, in studies of individuals in the general population, in dermatitis patients, in identification of risk groups, as well as in developing preventive strategies and in follow-up after intervention.

A semi-quantitative dermal exposure assessment method based on visual observations of fluorescence images was presented by Fenske in 1988. We adapted the method to Nicaraguan working conditions and evaluated its performance. Thirty-two farmers applied chlorpyrifos and methamidophos marked with Tinopal CBS-X(R). Skin fluorescent depositions were observed with a portable UV lamp in a foldaway darkened room. We modified the two components of the original system-extent by weighting the size of exposed body parts according to total body surface and intensity by establishing criteria for reading the fluorescence images. This resulted in body segment scores (BSSs) for specific body parts as well as two summary measures, contaminated body area (CBA) as the percentage of contaminated skin in relation to total body surface and total visual score (TVS) as an overall score combining extent and intensity of contamination. The scoring of intensity was evaluated with quantitative chemical residue analyses. Hands were the most frequently contaminated, and the back had the highest BSS. The CBA ranged between 1 and 66% and the TVS between 0.5 and 270. The farmer with the highest TVS scored 60% of the maximum possible. Residues increased with increasing fluorescence intensities with some misclassification. Fluorescent images reflected work practices and contamination mechanisms. In conclusion, the visual score, as modified by us, provides information on the body segments most contributing to dermal exposure and degree of skin contamination during pesticide applications. Fluorescence patterns reflect exposure routes. The system is low-cost and practical for developing countries. Further improvements are recommended.

Airborne skin exposure to allergens and irritants may cause dermatitis. There are few methods for assessing skin exposure to airborne particles. We have modified and tested a vacuuming sampler for removing particles from the skin. The sampler was compared with two other skin and surface exposure sampling techniques. These were based on surrogate skin (a patch sampler-adhesive tape on an optical cover glass) and a tape stripping removal procedure. All three samplers measure the mass of dust on skin. Dust containing starch was deposited onto the skin in a whole-body exposure chamber. Samples were taken from forearms and shoulders and analysed using optical microscopy. With the different sampling techniques small differences in the results were obtained. Agreement between the vacuuming sampler and the tape stripping technique was good. The comparison between patch and tape stripping procedure indicated a slight overestimation for the patch. The three techniques are applicable for assessing skin exposure to particles and for dose-effect studies. The vacuuming method will be further developed and applied in workplace studies. The technique allows for dust sampling from large areas of skin.

Exposure to wood dust within the woodworking industry has been shown to cause a variety of respiratory disorders. The aim of this study was to investigate the cellular effects in bronchoalveolar lavage (BAL) fluid and peripheral blood from healthy individuals exposed to pinewood dust. Eleven healthy volunteers were exposed to pinewood dust for 1 h in a whole-body exposure chamber. BAL fluid and blood cells were differentially counted and the expression of activation, adhesion and subset markers on alveolar macrophages and T-lymphocytes was determined 2-6 weeks before and 20 h after the exposure. Following pinewood dust exposure, the total BAL fluid cell concentration increased from 81.4 (64.1-97.5) x 10(6) cells x L(-1) (median (interquartile range)) to 195.3 (154.6-341.2) x 10(6) cells x L(-1). The BAL fluid T-lymphocyte concentration increased from 3.8% (3.5-6.5%) to 7.6% (4.9-11.2%), and BAL fluid eosinophil concentration from 0.0% (0.0-0.2%) to 1.8% (0.6-3.5%). Inhalation of pinewood dust leads to the recruitment of inflammatory cells to the airways of healthy individuals. The increase in numbers of eosinophils, T-lymphocytes and mast cells, i.e. cells of crucial importance to airway inflammation, in the lungs may be related to the increased risk of developing respiratory disorders among woodworkers.

Objectives: Identification of pesticide exposure determinants has become an issue in explaining exposure variability and improving control measures. Most studies have been conducted in industrialized countries. The aim of this study was to identify relevant dermal exposure determinants among Nicaraguan subsistence farmers., Methods: Field data on possible determinants were collected during 32 pesticide applications through observation and supplementary videorecording. A multistep reduction strategy brought down the 110 potential exposure determinants to 27 variables, which were grouped as worksite, spray equipment, working practices, clothing or hygiene practices related. Dermal exposure was quantified with a modification of Fenske's visual scoring method. Multivariate linear regression modeling within groups and across groups was performed., Results: In the within-group analyses, work practices, spray equipment and worksite related determinants explained 52, 33 and 25% of the exposure variability, respectively. Clothing and hygiene practices were weaker determinants and did not always reduce the exposure. The final model included determinants from all groups except hygiene practices and explained 69% of the exposure variability. A less restricted model increased the explained variability to 75%. Several novel determinants were identified, including spraying on a muddy terrain, dew on plants, sealing the tank lid with a cloth and wiping sweat from the face., Conclusions: This study showed that a combination of observation and visual scoring techniques can provide valuable information on determinants of pesticide exposure and affected body parts under developing country conditions. The results could be used to develop job-specific questionnaires and to design training and preventive programs.

The Nickel Directive aims at the prevention of sensitization and elicitation of nickel dermatitis. It limits nickel release from, and nickel content in, certain items. The Directive came into full force by July 2001. The aim of this study was to investigate the frequency on the market of items that release nickel and of nickel content in piercing posts, 2 years after coming into force of the Directive. Of special interest was to study changes compared to the situation in 1999, when a baseline study had been carried out. Nickel release from 786 items covered by the Nickel Directive was tested with the dimethylglyoxime (DMG) test, and nickel content in 18 piercing posts was analysed. Nickel release was shown from 8% of items intended for direct and prolonged contact with the skin, and 17% of the piercing posts contained too much nickel, a decrease compared to 1999. There has been significant adaptation to the requirements of the Nickel Directive. The DMG test is useful for screening for nickel release and for monitoring the market. Provided there is further adaptation to the requirements, the risk of sensitization and elicitation of nickel dermatitis will be significantly reduced.

Background: Flour dust in bakeries is known to cause allergic as well as nonallergic respiratory symptoms. Fungal alpha-amylase is a commonly used baking additive that has been shown to have allergenic properties. The aim of this study was to investigate any effects on bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL) of healthy individuals exposed to airborne wheat flour dust with or without fungal alpha-amylase added., Methods: Fifteen subjects were exposed during 1 hr in an exposure chamber, ten individuals to wheat flour alone and five with alpha-amylase added. BAL was performed 2-6 weeks before and 1 day after the exposure. BAL cells were differentially counted and flowcytometric analysis of the expression of activation, adhesion, and subset markers on alveolar macrophages (AM) and T cells in BAL fluid and peripheral blood were carried out., Results: Exposure to wheat flour dust increased the total number of cells in BAL fluid from 75.4 (i.q. range 70.4-104.1) to 127.4 (92.1-187.4) cells x 10(6)/L, P < 0.01. There was a significant difference in the change of total BAL cell concentration between the study group exposed to wheat flour only (n = 10; increase with 91.9 x 10(6)/L) and the group exposed to wheat flour with the baking additive fungal alpha-amylase (n = 5; decrease with 5.4 x 10(6)/L). The exposure level of respirable dust was lower in the group that received alpha-amylase and the increase in BAL cell concentration showed a positive correlation with the concentration of respirable dust in the exposure chamber (r = 0.80, P < 0.001). The phenotypic analysis of AM indicated an influx of monocytic cells., Conclusions: The results indicate that the concentration of respirable dust, but not alpha-amylase, is of importance for the recruitment of inflammatory cells to the peripheral airways in healthy individuals exposed to wheat flour dust., (Copyright 2003 Wiley-Liss, Inc.)

Starch is a main component of wheat flour, which, besides being an occupational allergen can also induce irritative symptoms in the airways. A purified starch product (cornstarch glove powder) was used to investigate whether starch alone could induce airway inflammation. The aim of the study was to investigate a role for starch in wheat flour-induced airway inflammation. Ten healthy individuals were exposed to cornstarch glove powder in a whole-body exposure chamber. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 2-3 weeks before and 1 day after exposure, and the BAL cells were counted differentially. In addition, the expression of activation, adhesion and subset markers on alveolar macrophages and BAL T-cells were investigated using flow cytometry. A three-fold increase in BAL cell concentrations was found, with a selective accumulation and activation of eosinophilic granulocytes, as well as an influx of nonactivated monocytes and polyclonal CD4+ T-cells into the airways. The results show that inhalation of cornstarch glove powder leads to the development of a subclinical inflammation in the airways, with an accumulation of eosinophilic granulocytes. The authors suggest that such exposure may be an interesting model for studying factors contributing to lung accumulations of eosinophil granulocytes in humans.

There is a lack of information concerning whether environmental-related health effects are more or less prevalent or manifested differently in women compared to men. Previously, most research in the area of toxicology and environmental and occupational health involved male subjects. The present work aims at reviewing exposure and health effects of cadmium, nickel, lead, mercury, and arsenic manifested differently in women than in men. The gender difference in exposure to nickel results in a much higher prevalence of nickel allergy and hand eczema in women than in men. The internal cadmium dose is generally higher in women than in men, due to a higher gastro-intestinal absorption at low iron stores. This was probably one major reason why Itai-itai disease was mainly a woman's disease. Yet, data are sparse regarding the risk for women relative to men to develop cadmium-induced kidney damage in populations exposed to low levels of cadmium. Lead is accumulated mainly in bone and increased endogenous lead exposure has been demonstrated in women during periods of increased bone turnover, e.g., menopause. Both lead and mercury exposure in pregnant women has to be kept low in order to prevent neurodevelopment effects in the developing fetus and child. Limited data indicate that women are more affected than men following exposure to methylmercury at adult age, while males seem to be more sensitive to exposure during early development. Regarding arsenic, some data indicate gender differences in the biotransformation by methylation, possibly also in susceptibility to certain arsenic-related cancers. Obviously, gender-related differences in exposure and health effects caused by metals are highly neglected research areas, which need considerable focus in the future., ((c) 2002 Elsevier Science (USA).)

Allergic contact dermatitis is often caused by allergenic substances in products. Legislation can be a useful tool in the prevention of contact dermatitis, by limiting skin exposure to contact allergens in chemical products, cosmetics and hygiene products and nickel-containing objects in contact with the skin. A brief review is given of the most important EU Directives, some national regulations and standardisation projects aiming at the prevention of contact dermatitis. It is essential that medical scientific experts support, with their expert knowledge, national and European authorities.

In a population-based survey of public health issues in Stockholm, Sweden, self-reported hand eczema, history of childhood eczema, nickel allergy, occurrence of skin symptoms on the face and intolerance to cosmetics and hygiene products, were investigated. A postal questionnaire was sent to 15,000 inhabitants aged 19-80 years. The response rate was 73%. The 1-year prevalence of hand eczema was 8% (females 10%, males 6%). History of childhood eczema was reported by 15% and, of these, 42% also stated positively that they had had hand eczema at some time. Hypersensitivity to nickel was owned to 15% of the females and 3% of the males. Of the nickel-sensitive, 30% reported ever having had hand eczema. The combination of nickel allergy and history of childhood eczema resulted in a cumulative prevalence of hand eczema of 56%. Females reported more hand-washings per day than did males, and a relation between number of hand-washings and hand eczema was found. Self-reported 1-year prevalence of skin symptoms on the face was 14% and, of these, 33% also owned to hypersensitivity to cosmetics. Dermatitis appears to be a common health problem. This fact should be made clear to those who give priority and allocate resources to health problems, e.g., by participation of dermatologists in performing population-based surveys.

This paper summarizes experiences from long-term ongoing cooperation between Swedish research institutions and institutions at the National Universities in Nicaragua and Costa Rica. 24 researchers and teachers from the Central American institutions and ten Swedish research students have been trained. In addition to three full doctoral and three licentiate (two-year PhD program) theses, the two programs have so far published 15 articles in English-language, international, refereed journals and about three times as many abstracts for conferences in more than ten countries. A "sandwich" model for training is recommended, where the southern researchers come to the wealthier partner for collaborative analyses and write-ups of the publications, while spending 50-75% of their time in their home countries for data collection. Such collaboration should be planned for a time span of at least eight years and include substantial numbers of researchers and students. Means to minimize the risk of brain drain are suggested. The collaboration has been important for the globalization of the research cultures at the participating institutions and has trained international experts.

Nickel allergy is the most frequent contact allergy and is also one of the major background factors for hand eczema. The clinical significance of nickel release from coins was discussed when the composition of euro coins was decided. Current European coinage is dominated by cupro-nickel coins (Cu 75; Ni 25); other nickel-containing and non-nickel alloys are also used. Nickel release from used coinage from the UK, Sweden and France was determined. It was shown that nickel ions are readily available on the surface of used coins. After 2 min in artificial sweat, approximately 2 microg of nickel per coin was extracted from cupro-nickel coins. Less nickel was extracted from non-nickel coins. Nickel on the surface was mainly present as chloride. After 1 week in artificial sweat approximately 30 microg/cm2 was released from cupro-nickel coins: less nickel was released from coins made of other nickel alloys. Theoretically, several microg of nickel salts may be transferred daily onto hands by intense handling of high-nickel-releasing coins.

Legislation can be a useful tool in the prevention of contact dermatitis. This is particularly true for dermatitis due to exposure to the many contact allergens that are chemical substances in products. A brief review is given of the most important European legislation--the EU Nickel Directive, the Cosmetics Directive, the Hazardous Substances Directive and the Hazardous Preparations Directive--and of some national regulations and standardization projects. It is concluded that it is essential that experts on contact dermatitis support, with their expert knowledge, national and European authorities.

Nickel allergy is by far the most frequent contact allergy, affecting 10-15% of women in the general population, and causing dermatitis and hand eczema. The EU Nickel Directive, aimed at the prevention of nickel allergy, comes fully into force by July 2001. The Directive covers piercing materials, items in contact with the skin, and requirements on resistance to wear. We carried out a study of the prevalence on the market, before the Nickel Directive, of items that release nickel and of nickel in piercing posts. Nickel release, as shown by a positive dimethylglyoxime (DMG) test, was detected in 25% of 725 items intended for direct and prolonged contact with the skin. Of 15 posts intended for use during epithelialization after piercing, 60% contained more than 0.05% nickel. These products do not comply with the requirements of the EU Nickel Directive. It is suggested that experts in contact dermatitis participate in the prevention of nickel allergy by explaining its effects: the r le of skin exposure and which parts of an item are in contact with the skin, and the crucial question of nickel release versus nickel content.

The fungicide chlorothalonil is used extensively under several tradenames for the protection of various horticultural and fruit crops and bananas against fungal infections. It is also used as fungicide in wood preservation and as a preservative in paints. Clinical experience has shown chlorothalonil to be a contact allergen and several cases of allergic contact dermatitis attributed to chlorothalonil have been described. 2 previous guinea pig maximization test studies have shown the sensitizing potential of chlorothalonil to be high. The sensitizing property of chlorothalonil was studied by us with the predictive test methods the local lymph node assay and the cumulative contact enhancement test. In the local lymph node assay, chlorothalonil induced a dose-dependent increase in proliferation with a maximal stimulation index of 19.2 and 27.2. In the cumulative contact enhancement test, a statistically significant dose-dependent high sensitization rate was seen with a maximal sensitization rate of 100%. In conclusion, it is evident that chlorothalonil is an extremely potent contact allergen, inducing sensitization using only topical exposure on intact skin.