Comparing the concentration levels of allergens and endotoxins in employees' homes and offices.

OBJECTIVE: The aim of the study was to find out whether allergen and endotoxin concentrations in offices differ from those measured at the homes of employees, and identify the parameters that influence exposure. METHODS: Electrostatic dust collectors (EDCs) were placed in five office buildings (68 rooms, 436 EDCs), as well as the homes of the office workers (145 rooms, 405 EDCs) for 14 days, four times a year. In addition, surface samples were collected from the offices four times a year by vacuuming the carpeted floors. Domestic mite (DM), and the major cat and dog allergens (Fel d 1 and Can f 1) were quantified in all samples using fluorescence enzyme immunoassays. Endotoxin was measured in the EDC samples, using the Limulus amoebocyte lysate assay. The allergen and endotoxin concentrations were log transformed and analysed with multilevel models. RESULTS: Endotoxin concentrations were significantly higher in personal homes compared to levels measured in the offices, and depended on the number of persons living in each household, as well as the presence of a dog. DM allergens were significantly higher in households than in offices, and were significantly higher in bedrooms compared to living rooms. Offices occupied by cat owners had significantly higher Fel d 1 concentrations than offices or homes without. Additionally, Can f 1 concentrations were significantly higher in offices occupied by dog owners compared to those without. CONCLUSIONS: Pet owners appear to transfer cat and dog allergens to their offices. Therefore, in case of allergy complaints at the office, employers and physicians might consider possible contamination by cat and dog allergens.

Skin symptoms in veterinary assistant staff and veterinarians: A cross-sectional study.

BACKGROUND: Veterinary assistants and veterinarians are at an increased risk of developing an occupational skin disease, for example, irritant/allergic contact dermatitis, contact urticaria and hand eczema (HE). OBJECTIVES: We aimed to investigate the prevalence of skin problems and the influence of predisposing factors especially among veterinary assistants. METHODS: We conducted a cross-sectional study among veterinary assistant staff (n = 103) and veterinarians (n = 19). A questionnaire, specific IgE determination and photographs of hands were evaluated for skin symptoms. Logistic regression models assessed predisposing factors. RESULTS: Over 50% (n = 62/122) of our study population reported hand eczema (HE) in the last 12 months (1-year prevalence). Twenty-seven subjects reported redness and contact urticaria directly after animal contact, 35 had a positive history of allergic contact dermatitis. HE was associated with (i) increased frequency of hand washing (11-15 times per day; OR 4.15, confidence interval [CI] 95% 1.18-14.6, p = 0.027, univariate model) and (ii) unprotected contact to fluids and tensides >5 times per day (OR 4.56, CI 95% 1.53-13.6, multivariate model). CONCLUSIONS: We observed a high prevalence of self-reported HE among staff in veterinary practices. Excessive hand washing, unprotected contact with irritants and long-term glove use should be avoided.

Exposure to welding fumes suppresses the activity of T-helper cells.

Welders have an increased susceptibility to airway infections with non-typeable Haemophilus influenzae (NTHi), which implicates immune defects and might promote pneumonia and chronic obstructive pulmonary disease (COPD). We hypothesized that welding-fume exposure suppresses Th1-lymphocyte activity. Non-effector CD4+ T-cells from blood of 45 welders (n = 23 gas metal arc welders, GMAW; n = 16 tungsten inert gas welders, TIG; n = 6 others) and 25 non-welders were ex vivo activated towards Th1 via polyclonal T-cell receptor stimulation and IL-12 (first activation step) and then stimulated with NTHi extract or lipopolysaccharide (LPS) (second activation step). IFNγ and IL-2 were measured by ELISA. In the first activation step, IFNγ was reduced in welders compared to non-welders and in the GMAW welders with higher concentrations of respirable particles compared to the lower exposed TIG welders. IFNγ was not influenced by tobacco smoking and correlated negatively with welding-fume exposure, respirable manganese, and iron. In the second activation step, NTHi and LPS induced additional IFNγ, which was reduced in current smokers compared to never smokers in welders as well as in non-welders. Analyzing both activation steps together, IFNγ production was lowest in smoking welders and highest in never smoking non-welders. IL-2 was not associated with any of these parameters. Welding-fume exposure might suppress Th1-based immune responses due to effects of particulate matter, which mainly consists of iron and manganese. For responses to NTHi this is strongest in smoking welders because welding fume suppresses T-cell activation towards Th1 and cigarette smoke suppresses the subsequent Th1-response to NTHi via LPS. Both effects are independent from IL-2-regulated T-cell proliferation. This might explain the increased susceptibility to infections and might promote COPD development.

An increase of fractional exhaled nitric oxide after specific inhalation challenge is highly predictive of occupational asthma.

PURPOSE: An increase of fractional exhaled nitric oxide (FeNO) has been described after specific inhalation challenges (SICs) with occupational allergens, but the clinical role of FeNO measurements before and after SIC is unknown. It was the aim of this study to assess the diagnostic accuracy of FeNO measurements before and after SIC in subjects with suspected occupational asthma (OA). METHODS: One hundred forty-eight patients with suspected OA were examined by SIC with various occupational allergens. Subjects were assigned to pulmonary responders, nonresponders or doubtful by standard lung function criteria. FeNO was measured before SIC (baseline) and 24 h afterwards. Subjects with negative or doubtful SIC but increase of FeNO were evaluated individually by an overall expert rating. Effect modifiers of FeNO increases were assessed by regression analyses. RESULTS: Thirty-one patients (21%) were classified as pulmonary responders, 105 (71%) as nonresponders and 12 (8%) as doubtful. With the pulmonary responder status as gold standard an increase of FeNO ≥ 13 ppb showed a specificity of 0.9 and a sensitivity of 0.5. Seventeen subjects with negative or doubtful responder status showed such an increase of FeNO, among them 13 subjects with definitive or probable OA after expert rating. Regression analyses revealed no significant modifiers for the FeNO increase. CONCLUSION: An increase of FeNO after SIC is highly predictive of OA and should be regarded as an additional criterion for the interpretation of SIC with occupational agents.

Are multitasking abilities impaired in welders exposed to manganese? Translating cognitive neuroscience to neurotoxicology.

Manganese (Mn) is an essential trace element with well characterized neurotoxic effects in high concentrations. Neurochemically, the initial neurotoxic effect of Mn is the perturbation of striatal γ-aminobutyric acid levels. Specific tasks for the assessment of cognitive functions subserved by fronto-striatal loops are available as the stop-change task (SCT) assessing control of multi-component behavior and action cascading. In a cross-sectional study, fifty male welders and 28 age-matched controls completed the SCT during a whole day examination. Reaction times, responses accuracy, and event-related potentials (ERPs) from electroencephalogram (EEG) recordings were analyzed. The shift exposure of the welders to respirable Mn was stratified by 20 µg/m3 in 23 low-exposed (median = 4.7 µg/m3) and 27 high-exposed welders (median = 86.0 µg/m3). Welders graduation was lower and was therefore included in the analyses. The task-related factor (stop-change delay, SCD) modified the responses as expected; however, the lack of an interaction "SCD × group" revealed no differences between welders and controls. EEG data showed that the "SCD" modulated the amplitude of the P3 ERP in controls stronger than in welders. There was no difference between the two groups of welders and no association between airborne or systemic Mn and the P3 ERP. Moreover, the P3 amplitude was smaller in subjects with lower education. These results showed that multitasking performance and cognitive flexibility are not impaired in welders. The electrophysiological results gave a weak hint that relevant neurobiological processes were different in welders as compared to controls but this may be related to lower education.

Analysis of inflammatory markers and metals in nasal lavage fluid of welders.

Welding fumes may produce adverse health effects in the respiratory tract. To assess the relationship between exposure to welding fumes and inflammation in the upper airways, 190 male welders were examined from the WELDOX study (median age 40 yr, 54.7% smokers, and 32.9% atopics). Inhalable welding fumes were collected in the breathing zone of welders during a single shift. Chromium (Cr), nickel (Ni), manganese (Mn), and iron (Fe) were measured in the welding-fume samples and in postshift nasal lavage fluid (NALF). In addition, the numbers of particles and inflammatory biomarkers, including total and differential cell counts, interleukin (IL)-8, leukotriene (LT) B4, 8-isoprostane (8-iso-PGF2α), tissue inhibitor of metalloproteinase-1 (TIMP-1), and immunoreactive matrix metalloproteinase (MMP)-9, were determined. Metal concentrations in NALF correlated with airborne concentrations. No significant association was found between airborne metal concentrations and biomarkers of inflammation in NALF, whereas increasing metal concentrations in NALF resulted in increased concentrations of total protein, IL-8, MMP-9, and TIMP-1. LTB4 and 8-iso PGF2α were elevated at higher concentrations of Cr or Ni in NALF. The same was true for Fe, although the effects were less pronounced and of borderline significance. In conclusion, our results showed a significant association between the concentrations of metals and soluble inflammatory markers in the NALF of welders. The noninvasive collection of NALF is applicable in field studies, where it may serve as a suitable matrix to simultaneously assess biomarkers of exposure and effect in the upper respiratory tract in workers who are occupationally exposed to airborne hazardous substances.

Allergen quantification in surface dust samples from German day care centers.

Indoor allergens are among the main causes of allergic rhinitis and asthma. Allergen exposure is not limited to private homes. Mite, cat, and dog allergens were measured in day care centers to determine whether these concentrations detected might exert significant influence on human health. In 20 day care centers across North Rhine-Westphalia, Germany, the surfaces of 171 rooms were vacuumed 4 times a year to collect dust (1340 samples in total). In all samples, domestic mite antigens (DM) and the main allergens of cats (Fel d 1) and dogs (Can f 1) were quantified using enzyme immunoassays. Provisional threshold limits (PTL) for increased risks of sensitization and allergic symptoms were estimated according to published values and conversion factors. The influence of room characteristics on allergen concentrations was analyzed in mixed linear models, also considering values below the limit of detection (LOD). Nearly all samples contained allergens (99% DM, 96% Fel d 1, and 96% Can f 1). The concentrations rarely exceeded levels that were previously found to induce symptoms in home environments, but were frequently higher than estimates for enhanced sensitization risk (13% DM, 43% Fel d 1, and 27% Can f 1). Upholstered furnishings had the highest dust and allergen loads, followed by carpets and smooth floors. Allergen concentrations on different surface types that were sampled in the same room at the same time were significantly correlated and analyzed in separate models. The highest DM concentrations were present in bedrooms and in autumn. Further, DM loads on floors decreased significantly in rooms that were renovated within the last 5 years. If there were no records that furnishings were vacuumed, there were then significantly higher Can f 1 loads. Sweeping floors elevated DM and cat allergen concentrations. In addition to mite allergens, cat and dog allergens were detected in nearly all samples from day care centers. Overall, the present results indicate that allergen concentrations may be reduced by renovation and appropriate cleaning procedures.

Allergen Quantification by Use of Electrostatic Dust Collectors (EDCs): Influence of Deployment Time, Extraction Buffer, and Storage Conditions on the Results.

Sampling of endotoxin, beta-glucan, or allergens on electrostatic dust collectors (EDCs) is a convenient method for exposure assessment. However, especially for allergens few experiments on validation of this method concerning deployment time or storage and extraction procedure have been performed. The aim of study was to optimize the EDC procedure for sampling of allergens in indoor environments. EDCs were placed in households or day-care centers and after extraction, allergens were quantified by six immunoassays detecting mite antigens (Domestic mites DM, Dermatophagoides pteronyssinus Dp, Tyrophagus putrescentiae Tp) or the main allergens from cat (Fel d 1), dog (Can f 1) and mouse (Mus m 1). For 20 EDC holders, deployment times of cloths were varied between 7 and 28 days, 36 EDCs were used to test reproducibility, and for 28 EDCs extraction buffers were varied (with or without 0.05% Tween 20, borate, or phosphate buffer). The influence of storage of cloths at room temperature (2-629 days) or extracts at -80°C (7-639 days), and variation of extract storage temperature (-20°C and -80°C) for long time storage (1.5 years) on the outcome of allergen quantification were tested for about 150 EDCs. The allergens on EDC cloths increased proportionally with deployment time, and allergen loads on parallel sampled tissues were significantly correlated (P < 0.0001, Pearson of log-transformed values 0.91-0.99). Extraction without Tween reduced all results (P < 0.0001, -51% DM, -85% Dp, -60% Tp, -99% Fel d 1, -86% Can f 1, -52% Mus m 1), and borate buffer resulted in lower yields of Mus m 1 (-53%), DP (-45%), and Tp (-27%) than phosphate buffer. Storage of cloths at room temperature significantly decreased Can f 1 levels (P < 0.0001, -4.8% loss for every 30 days), whereas storage of extracts at -80°C decreased DM results (P < 0.0001, -1.2% loss for every 30 days). Extracts stored at -20°C gave at mean 12% higher DM results compared to extracts stored at -80°C for 1.5 years. Several mammalian allergens and also DM antigens could be quantified reproducibly on EDCs from indoor environments. Allergen levels on EDC cloths increased proportionally with deployment time in a period of 4 weeks. Allergen yields are strongly influenced by the extraction procedure; the use of detergent Tween 20 and phosphate buffer is recommended.

Metabolites of the PAH diol epoxide pathway and other urinary biomarkers of phenanthrene and pyrene in workers with and without exposure to bitumen fumes.

PURPOSE: This study investigates the diol epoxide pathway of phenanthrene (PHE) together with phenolic metabolites of PHE and pyrene (PYR) in workers with and without exposure to bitumen fumes. METHODS: The metabolite concentrations were determined in urine samples collected from 91 mastic asphalt workers and 42 construction workers as reference group before and after shift. During shift, vapours and aerosols of bitumen were measured according to a German protocol in the workers' breathing zone. RESULTS: The median concentration of vapours and aerosols of bitumen in mastic asphalt workers was 6.3 mg/m3. Metabolite concentrations were highest in post-shift urines of smokers with bitumen exposure and showed an increase during shift. The Spearman correlations between the creatinine-adjusted concentrations of metabolites and vapours and aerosols of bitumen in non-smokers were weak (e.g. sum of Di-OH-PYR: 0.28) or negligible (e.g. 1,2-PHE-diol: 0.08; PHE-tetrol: 0.12). Metabolites from the diol epoxide pathway of PHE were excreted in higher concentrations than phenolic metabolites (post-shift, non-smoking asphalt workers: 1,2-PHE-diol 2.59 µg/g crea vs. sum of all OH-PHE 1.87 µg/g crea). 1,2-PHE-diol was weakly correlated with PHE-tetrol (Spearman coefficient 0.30), an endpoint of the diol epoxide pathway. By contrast, we found a close correlation between the sum of 1,6-DiOH-PYR and 1,8-DiOH-PYR with 1-OH-PYR (Spearman coefficient 0.76). CONCLUSIONS: Most urinary PAH metabolites were higher after shift in bitumen-exposed workers, although the association with bitumen was weak or negligible likely due to the small PAH content. The additional metabolites of PHE and PYR complete the picture of the complex metabolic pathways. Nevertheless, none of the PAH metabolites can be considered to be a specific biomarker for bitumen exposure.

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores.

The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were 2.35/10(6) dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m(3) compared to ≤57 µg/m(3). Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores.

CYP2B6*6 is associated with increased breast cancer risk.

The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6_516_G>T (rs3745274) and CYP2B6_785_A>G (rs2279343) and breast cancer risk, we established a specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay. The GENICA breast cancer case-control study showed associations between the variant genotypes CYP2B6_516_TT and CYP2B6_785_GG and breast cancer risk with odds ratios (ORs) of 1.34 (p = 0.001) and 1.31 (p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6_516_T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6_516_G and the CYP2B6_785_G variant had an increased breast cancer risk with ORs of 1.10 (p = 0.027) and 1.10 (p = 0.031), respectively. We conclude that the genetic variants CYP2B6_516_G and CYP2B6_785_G (designated CYP2B6*6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk.

Influence of welding fume on systemic iron status.

Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum ferritin (SF) is a recognized biomarker for iron stores, with high concentrations linked to inflammation and potentially also cancer. However, little is known about iron overload in welders. Within this study, we assessed the iron status and quantitative associations between airborne iron, body iron stores, and iron homeostasis in 192 welders not wearing dust masks. Welders were equipped with personal samplers in order to determine the levels of respirable iron in the breathing zone during a working shift. SF, prohepcidin and other markers of iron status were determined in blood samples collected after shift. The impact of iron exposure and other factors on SF and prohepcidin were estimated using multiple regression models. Our results indicate that respirable iron is a significant predictor of SF and prohepcidin. Concentrations of SF varied according to the welding technique and respiratory protection used, with a median of 103 µg l(-1) in tungsten inert gas welders, 125 µg l(-1) in those wearing air-purifying respirators, and 161 µg l(-1) in other welders. Compared to welders with low iron stores (SF < 25 µg l(-1)), those with excess body iron (SF ≥ 400 µg l(-1)) worked under a higher median concentration of airborne iron (60 µg m(-3) versus 148 µg m(-3)). Even though air concentrations of respirable iron and manganese were highly correlated, and low iron stores have been reported to increase manganese uptake in the gastrointestinal tract, no correlation was seen between SF and manganese in blood. In conclusion, monitoring SF may be a reasonable method for health surveillance of welders. Respiratory protection with air-purifying respirators can decrease iron exposure and avoid chronically higher SF in welders working with high-emission technologies.

Reduction in welding fume and metal exposure of stainless steel welders: an example from the WELDOX study.

PURPOSE: In a plant where flux-cored arc welding was applied to stainless steel, we investigated changes in airborne and internal metal exposure following improvements of exhaust ventilation and respiratory protection. METHODS: Twelve welders were examined at a time in 2008 and in 2011 after improving health protection. Seven welders were enrolled in both surveys. Exposure measurement was performed by personal sampling of respirable welding fume inside the welding helmets during one work shift. Urine and blood samples were taken after the shift. Chromium (Cr), nickel (Ni), and manganese (Mn) were determined in air and biological samples. RESULTS: The geometric mean of respirable particles could be reduced from 4.1 mg/m(3) in 2008-0.5 mg/m(3) in 2011. Exposure to airborne metal compounds was also strongly reduced (Mn: 399 vs. 6.8 µg/m(3); Cr: 187 vs. 6.3 µg/m(3); Ni: 76 vs. 2.8 µg/m(3)), with the most striking reduction inside helmets with purified air supply. Area sampling revealed several concentrations above established or proposed exposure limits. Urinary metal concentrations were also reduced, but to a lesser extent (Cr: 14.8 vs. 4.5 µg/L; Ni: 7.9 vs. 3.1 µg/L). Although biologically regulated, the mean Mn concentration in blood declined from 12.8 to 8.9 µg/L. CONCLUSION: This intervention study demonstrated a distinct reduction in the exposure of welders using improved exhaust ventilation and welding helmets with purified air supply in the daily routine. Data from area sampling and biomonitoring indicated that the area background level may add considerably to the internal exposure.

Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant.

17ß-hydroxysteroid dehydrogenase type 1 (HSD17B1) plays an important role in the biosynthesis of 17ß-estradiol. The current study aimed at confirming the reduced risk of breast cancer in carriers of the non-synonymous HSD17B1_937_A>G (rs605059) polymorphism who used any hormone replacement therapy (HRT) for 10 years or longer. We performed an independent association study using four breast cancer case-control studies from Australia, Germany, and Sweden. In all, 5,777 cases and 8,189 age-matched controls of European descent were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and TaqMan. Risk estimates were calculated by interaction analysis and main effect analysis adjusted for age and study. Main effect analyses for women using any HRT for 10 years or longer (1,428 cases versus 1,724 controls) revealed a protective effect of the HSD17B1_937_G allele on breast cancer risk (OR 0.86, 95 % CI: 0.73-0.99; p = 0.048). Thus, our previous finding of a protective effect of the HSD17B1_937_G allele on HRT-associated breast cancer risk has now been confirmed both in independent large patient cohorts and a comprehensive pooled analysis supporting the hypothesis that a HSD17B1-mediated decreased conversion of estrone to the more potent 17ß-estradiol may reduce the estrogenic effects, thereby reducing the risk of developing breast cancer during long-term HRT use.

Exposure levels of animal allergens, endotoxin, and ß-(1,3)-glucan on a university campus of veterinary medicine.

OBJECTIVES: The study aimed to determine the allergen, endotoxin and ß-(1,3)-glucan concentrations at various areas on a university campus of veterinary medicine. METHODS: Dust samples were collected four times a year for three years using electrostatic dust collectors (EDC) at 25 different locations on a campus of veterinary medicine and in laboratories of inorganic chemistry as a control area representing animal-free environment. Major animal allergens from dog, cat, horse, cattle and mouse, domestic mite (DM) allergens, and ß-(1,3)-glucan were measured using enzyme immunoassays and endotoxin using the limulus amoebocyte lysate (LAL) assay. Seasonal, annual and local influences on exposure levels were analyzed using Bayesian mixed models. RESULTS: With the exception of mouse allergens, all other determinants were found in almost all locations on the campus and in the control area, but in up to 10.000-fold variable concentrations. By far the highest levels of feline, canine, equine and bovine allergens were detected in buildings where the respective species were examined. The highest levels of mouse and DM allergens, ß-(1,3)-glucan and endotoxin occurred together and were associated with locations where large animals were present. In buildings without animals, allergen levels were considerably lower but still elevated at several locations compared to the control area, especially for dog and horse allergens, and ß-(1,3)-glucan. Significant seasonal effects were observed for dog, cat, horse and DM allergens, and ß-(1,3)-glucan. Variations between years were less apparent than between seasons (except for ß-(1,3)-glucan). CONCLUSIONS: The strongest influencing factor on the concentration of mammalian allergens was the presence of the corresponding animal at the collection site. Seasonal influence on allergen concentrations was observed, while the overall exposure remained constant over the years. At locations with horses, elevated levels of mite allergens, endotoxin, and ß-(1,3)-glucan can be expected, probably due to passive transfer from stable environment.

Impact of interleukin-13 and -18 promoter polymorphisms in health care workers with natural rubber latex allergy.

It is a matter of debate whether single nucleotide polymorphisms (SNP) in the promoter region of interleukin (IL)-13, an IgE regulator, and IL-18, an inducer of immune responses, modulating the respective protein expression, are accompanied by an increased risk of atopy, allergic asthma, and total IgE levels. The suspected associations were noted in health care workers (HCW) with and without latex allergy. IL-13 (-1055C>T) and three IL-18 (-656T>G, -607C>A, -137G>C) SNP were studied in 523 HCW with natural rubber latex (NRL) exposure and diagnosis in the late 1990s. Three hundred and thirty-four HCW displayed NRL sensitization and allergic symptoms, 93 with latex-allergic asthma, and 189 HCW with neither symptoms nor NRL sensitization. SNP analyses were performed by real-time polymerase chain reaction (PCR) using newly developed LightCycler assays. Analysis of IL-13 -1055C>T by analysis of variance (ANOVA) revealed significantly elevated total IgE levels in HCW carrying the CT or TT variant compared with the CC variant. None of the studied SNP showed an association with NRL-specific IgE. The IL-18 variants -656GG and -607CC displayed 99.5% linkage disequilibrium. Frequencies of alleles -656GG and -607CC were elevated in HCW with NRL asthma (48.4%) compared with HCW without symptoms (37.6%). In contrast, IL-18 -137G>C variants displayed an overall homogenous distribution. The association between the IL-13 -1055T allele and elevated total IgE levels confirms the role of a genetic background for total IgE regulation. The studied IL-18 SNP demonstrated no significant association with the clinical outcome, total IgE, or specific IgE in HCW with natural rubber latex allergy.

Modulation of oxidative DNA damage by repair enzymes XRCC1 and hOGG1.

The influence of DNA repair gene polymorphisms (XRCC1: Arg194Trp, Arg280His, Arg399Gln; APE1: Asp148Glu; hOGG1: Ser326Cys) on oxidative DNA damage is controversial and was investigated in 214 German workers with occupational exposure to vapors and aerosols of bitumen,compared to 87 German construction workers without exposure, who were part of the Human Bitumen Study. Genotypes were determined by real-time polymerase chain reaction (PCR), and actual smoking habits by a questionnaire and cotinine analysis. Oxidative DNA damage in white blood cells (WBC) collected pre- and postshift was measured as 8-oxodGuo adducts/10(6) dGuo by a hjigh-performance liquid chromatography electron capture detection (HPLC-ECD) method, followed by calculation of the difference between post- and preshift values (Δ8-oxodGuo/10(6) dGuo). The 214 bitumen exposed workers showed higher median Δ8-oxodGuo values than the 87 references. In the whole study group (n=301) there was a trend for increasing adduct values for XRCC1 Arg(GG)399Gln(AA) during a shift, especially in nonsmokers (n=108. Referents (n=87) displayed a similar trend for hOGG1 Ser(CC)326Cys(GG). In contrast, XRCC1 Arg(GG)280His(AA) showed a decrease of median Δ8-oxodGuo/10(6) dGuo values in workers with exposure to vapors and aerosols of bitumen (n=214), especially in smokers (n=145). XRCC1 Arg194Trp and APE1 Asp148Glu displayed no marked association with Δ8-oxodGuo levels. Data indicate that the combination of different variants in DNA damage repair enzymes may modulate the production of 8-oxoguanine adducts in WBC produced by xenobiotics during a shift.

Pre- and postshift levels of inflammatory biomarkers and DNA damage in non-bitumen-exposed construction workers-subpopulation of the German Human Bitumen Study.

Circadian variations in immune defense and tissue repair may interfere with shift effects of occupational exposure when investigating biomarkers in cross-shift studies. This investigation compared biomarkers of inflammation and DNA damage in 59 nonsmoking and 59 smoking male construction workers pre- (6-10 a.m.) versus postshift (4-7 p.m.). Cellular compositions were analyzed in blood, induced sputum (IS), and nasal lavage fluid (NALF) and soluble inflammatory biomarkers were analyzed in IS and NALF. DNA damage was measured as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) adducts and DNA strand breaks (alkaline Comet assay) in white blood cells (WBC). Apoptosis was quantified as percent apoptotic cells by annexin V and 7-amino-actinomycin staining in blood lymphocytes using flow cytometry. In nonsmokers higher preshift than postshift levels of interleukin-8 (IL-8) in IS and more DNA strand breaks were detected. However, more DNA adducts were found postshift. Among smokers, the cellular composition of IS and NALF differed between pre- and postshift samples, in particular more neutrophils pre- than postshift. In contrast, more cells in early apoptosis were observed post shift in both smokers and nonsmokers. These results indicate a potential influence of circadian rhythms on several biomarkers used in epidemiological studies. Data suggest interference with shift-work effects of occupational exposure in cross-shift studies and also the need to consider smoking as a modifying variable.

Exposure to inhalable, respirable, and ultrafine particles in welding fume.

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements

Animal Allergens, Endotoxin, and ß-(1,3)-Glucan in Small Animal Practices: Exposure Levels at Work and in Homes of Veterinary Staff.

OBJECTIVES: In veterinary settings, high exposures to animal allergens and microbial agents can be expected. However, occupational exposure levels are largely unknown. The objective of this study was to estimate the allergen, endotoxin, and ß-(1,3)-glucan concentrations in small animal practices and in the homes of practice employees. METHODS: Dust samples were collected using electrostatic dust fall collectors in diverse rooms of 36 small animal practices, as well as in employees' homes. Major animal allergens (Fel d 1, Can f 1, Ory c 3, Cav p 1, Equ c 1, Bos d 2), domestic mite (DM) allergens, and ß-(1,3)-glucan levels were measured using enzyme immunoassays. Endotoxin was determined using the Limulus amoebocyte lysate assay. Influences on exposure levels were analyzed using multilevel models. RESULTS: The levels of Can f 1, Fel d 1, Ory c 3, and Cav p 1 were up to 30 times higher in practices compared with homes without animals, but significantly lower compared with the homes with the respective pet. Although horses were not treated in the practices, Equ c 1 was found in 87.5% of samples, with the highest concentrations measured in changing rooms. DM levels were significantly lower in practices than in all private homes, and endotoxin levels were similar to those in homes with pets. In the practice itself, exposure levels were significantly influenced by animal presence, type of the room, and area per employee; whereas, room volume and diverse cleaning measures had mostly no effect. CONCLUSIONS: Exposure to animal allergens is high in veterinary practices, but it does not reach levels of households with pets. Domestic mite allergen and endotoxin exposure seem to be low for workers in veterinary practices. The high Equ c 1 detection rate strongly indicates dispersal of allergens, most likely through clothing and hair.