The Danish urban-rural gradient of allergic sensitization and disease in adults.

BACKGROUND: The reported prevalence of allergic sensitization among children is lower in rural areas than in urban areas of the world. The aim was to investigate the urban-rural differences of allergic sensitization to inhalant allergens in adults depending on childhood exposure living in an industrialized country as Denmark. METHODS: A total of 1236 male participants of 30-40 years of age recruited from two epidemiological studies were divided into four groups with regard to place of upbringing; city, town, rural area and farm. Allergic sensitization was assessed by skin prick tests (SPTs) to 10 inhalant allergens and measurements of serum specific IgE (sIgE) to four inhalant allergens (grass, birch, cat and house dust mite). RESULTS: The prevalence of allergic sensitization to inhalant allergens decreased with decreasing degree of urbanized childhood. The risk of being sensitized to one or more allergens also decreased with decreasing degree of urbanized upbringing measured by sIgE to 4 common allergens as odds ratio with 95% confidence intervals with city as reference; town 0.60 (0.39-0.92), rural area 0.34 (0.22-0.52) and farm 0.31 (0.21-0.46). Furthermore, it was measured by SPT to 10 common allergens; town 0.52 (0.33-0.84), rural area 0.34 (0.21-0.53) and farm 0.29 (0.19-0.45). This urban-rural association was also seen for the risk of sensitization to specific allergens, rhinitis and allergic asthma. CONCLUSION: This is the first study to show an urban-rural gradient of overall allergic sensitization and specific allergen sensitization in adults depending on their childhood exposure. In this highly homogenous western population, exposure to a less urbanized childhood was associated with lower risk of allergic sensitization and disease as an adult.

Exposure levels, determinants and IgE mediated sensitization to bovine allergens among Danish farmers and non-farmers.

BACKGROUND: Bovine allergens can induce allergic airway diseases. High levels of allergens in dust from stables and homes of dairy farmers have been reported, but sparse knowledge about determinants for bovine allergen levels and associations between exposure level and sensitization is available. OBJECTIVE: To investigate levels and determinants of bovine allergen exposure among dairy, pig and mink farmers (bedroom and stable), and among former and never farmers (bedroom), and to assess the prevalence of bovine allergen sensitization in these groups. METHODS: In 2007-2008, 410 settled dust samples were collected in stables and in bedrooms using an electrostatic dust-fall collector over a 14 day period among 54 pig farmers, 27 dairy farmers, 3 mink farmers as well as 71 former and 48 never farmers in Denmark. For farmers sampling was carried out both during summer and winter. Bovine allergen levels (µg/m(2)) were measured using a sandwich ELISA. Determinants for bovine allergen exposure in stables and bedrooms were explored with mixed effect regression analyses. Skin prick test with bovine allergen was performed on 48 pig farmers, 20 dairy farmers, 54 former and 31 never farmers. RESULTS: Bovine allergen levels varied by five orders of magnitude, as expected with substantially higher levels in stables than bedrooms, especially for dairy farmers. Bovine allergen levels in bedrooms were more than one order of magnitude higher for dairy farmers compared to pig farmers. Former and never farmers had low levels of bovine allergens in their bedroom. Bovine allergen levels during summer appeared to be somewhat higher than during winter. Increased bovine allergen levels in the bedroom were associated with being a farmer or living on a farm. Mechanical ventilation in the bedroom decreased bovine allergen level, significant for dairy farmers ß=-1.4, p<0.04. No other significant effects of either sampling or residence characteristics were seen. Allergen levels in dairy stables were associated to type of dairy stable, but not to other stable or sampling characteristics. Sensitization to bovine allergens was only found in one pig farmer. CONCLUSION: This study confirms high bovine allergen levels in dairy farms, but also suggests sensitization to bovine allergens among Danish farmers to be uncommon. Furthermore the importance of a carrier home effect on allergen load is emphasized. Whether the risk for bovine sensitization is related to the allergen level in the stable or the dwelling remains to be determined.

Asbestos exposure and survival in malignant mesothelioma: a description of 122 consecutive cases at an occupational clinic.

BACKGROUND: The natural history and etiology of malignant mesothelioma (MM) is already thoroughly described in the literature, but there is still debate on prognostic factors, and details of asbestos exposure and possible context with clinical and demographic data, have not been investigated comprehensively. OBJECTIVE: Description of patients with MM, focusing on exposure, occupation, survival and prognostic factors. METHODS: Review of medical records of patients with MM from 1984 to 2010 from a Danish Occupational clinic. Survival was estimated using Kaplan-Meier survival analysis and prognostic factors were identified by Cox regression analysis. RESULTS: 110 (90.2%) patients were male, and 12 (9.8%) were female. The median (interquartile rang [IQR]) age was 65 (13) years. Pleural MM was seen in 101 (82.8%) patients, and peritoneal in 11 (9.0%); two (1.6%) had MM to tunica vaginalis testis, and eight (6.6%) to multiple serosal surfaces. We found 68 (55.7%) epithelial tumors, 26 (21.3%) biphasic, and 6 (4.9%) sarcomatoid. 12 (9.8%) patients received tri-modal therapy, 66 (54.1%) received one-/two-modality treatment, and 36 (29.5%) received palliative care. Asbestos exposure was confirmed in 107 (91.0%) patients, probable in four (3.3%), and unidentifiable in 11 (9.0%). The median (IQR) latency was 42 (12.5) years. Exposure predominantly occurred in shipyards. The median overall survival was 1.05 (95% CI: 0.96-1.39) years; 5-year survival was 5.0% (95% CI: 2.0%-13.0%). Female sex, good WHO performance status (PS), epithelial histology and tri-modal treatment were associated with a favorable prognosis. CONCLUSION: MM continuously presents a difficult task diagnostically and therapeutically, and challenges occupational physicians with regard to identification and characterization of asbestos exposure.

Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study.

BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We genotyped 100 new-onset asthma cases and 88 control subjects for three CD14 SNPs, three TLR2 SNPs, and two TLR4 SNPs. Atopy at baseline (defined as a positive skin prick test to one or more common inhalant allergens) was found in 17 asthma cases (17.0%) and in 17 controls (19.3%). RESULTS: The CD14/-260T allele was significantly associated with less atopy [odds ratio (OR) 0.39; 95% confidence interval (CI) 0.21-0.72, additive genetic model], whereas the CD14/-651T allele was positively associated with atopy (OR 2.53; 95% CI 1.33-4.80). Similar results were obtained by haplotype analysis. Stratified analysis by farm childhood showed stronger effects of both CD14 SNPs on atopy among farmers who were born and raised on a farm, although no significant interaction was found. No associations between CD14, TLR2, or TLR4 genotypes and new-onset asthma were found. CONCLUSION: The CD14/-260 and CD14/-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments.

Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking.

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV1) and conventional measures of BHR. The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e. alpha1 75%F, alpha1 75%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF40 and MEF30). BHR was measured by the provocative dose causing a 20% change (PD20) in the FEV1 and alpha1 75%, and also by the method of log dose slopes (LDS). Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD20 FEV1 could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV1 was recorded in 1,725 (88%) subjects. From the prechallenge data, alpha1 75%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV1 showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF40P, and then for LDSFEV1, but LDSMEF40P was measurable in only just over one-half of the subjects. The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.

Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm.

BACKGROUND: Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non-farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the "protective" effect of a farm environment can also be found in adults. MATERIALS AND METHODS: Common atopy and respiratory health were assessed by skin prick tests (SPT), questionnaire and measurement of bronchial hyper-responsiveness (BHR) in the Sund Stald (SUS) study, a cohort study on respiratory health in Danish farming students and conscripts from the same rural areas as controls. Results of SPT were confirmed by IgE serology in all SPT+ subjects and a subset of SPT- subjects. Prevalences of common atopy, respiratory symptoms and bronchial hyper- responsiveness were compared for farmers and controls, and for those who had or had not lived on a farm in early childhood. RESULTS: In multiple logistic regression analyses adjusting for ever smoking and a familial history of allergy, both being a farmer (ORs 0.62-0.75) and having had a farm childhood (ORs 0.55-0.75) appeared to contribute independently to a lower risk of sensitization to common allergens as assessed by SPT and IgE serology. A farm childhood was also inversely associated with high total IgE (OR 0.68), presence of respiratory symptoms (ORs 0.69-0.79) and BHR (OR 0.61) in these analyses. Direction and strength of the association between being a farmer and respiratory symptoms or BHR varied widely (ORs 0.69-1.28). CONCLUSION: The "anti-atopy" protective effect of a farm childhood could be confirmed in Danish farming students: prevalences of positive SPT, specific and total IgE, allergic symptoms and BHR were lower in those being born or raised on a farm. Past exposure to the farm environment in early childhood may therefore also contribute to a lower risk of atopic sensitization and disease at a later age.

The short-term repeatability of histamine bronchial testing in young males. The SUS study.

We have measured bronchial responsiveness (BR) to histamine on two occasions between 5 and 24 h apart, to determine if conventional and new indices of BR are repeatable. A random sample of 29 healthy male subjects with a mean age of 19 (SD 3.44) years from a larger study repeated a Yan method test of BR, recording both partial and maximal expiratory flow volume (PEFV and MEFV) curves. From the MEFV curves log-dose slopes (LDS) for forced expiratory volume in 1 sec (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%)), mean expiratory flow at 30% and 40% of FVC (MEF30, MEF40), and the first moment of the spirogram (alpha1) truncated at 75% and 90% of FVC were calculated, as well as the provocative dose that induces a 20% fall in FEV1 (PD20FEV1). From the PEFV curves LDS for alpha(1)75% and alpha(1)90%, and MEF30 and MEF40 were derived. Apart from MEF30 and alpha(1)90% the second test was significantly lower (P<0.05) than the first when measuring the repeatability of spirometric indices, whereas the LDS of the indices showed no significant change. The repeatability expressed as intra-class correlation coefficient (ICC) was highest for LDS FEV1 (0.87), second highest for LDS MEF40 (0.67) and LDS MEF30 (0.65). The LDS for moment indices were much less repeatable and the lowest ICC was found in all LDS indices derived from PEFV curves. Within-subject variance was not influenced by atopic status, smoking habits or recordable PD20FEV1. As tests for bronchial hyper-responsiveness (BHR) the LDS of FEV1, MEF40 and MEF30 seem to be acceptable for use in population studies.

S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction.

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.

The shape of the maximum expiratory flow-volume curve reflects exposure in farming.

The objective of the study was to examine the effect of farming exposure, respiratory symptoms and smoking on the shape of the MEFV-curve in 1,691 male farming students and 407 male controls and to relate the slope ratio with FEV(1) and FEV(1) /FVC. Each subject underwent a medical interview and the slope ratios from the MEFV-curve at 75 (SR75), 50 (SR50) and 25 (SR25) %FVC together with FEV1 and FVC were recorded. Histamine bronchial reactivity (Yan method) was measured and skin prick test with inhalant allergens was performed. In smokers, SR75 increased with increasing exposure to: general farming, swine and dairy cattle (p< or =0.020). SR50 increased with increasing exposure to farming (p=0.015). In non-smokers, SR25 increased with increasing exposure to swine and dairy cattle (p=0. 021) and increased SR25 was associated with sensitisation to house dust mite (p=0.017). Data revealed an interaction between smoking and exposure to farming. FEV(1) and FEV(1)/FVC was not associated with farming exposure or production animals. FEV1 and FEV(1)/FVC (p< or =0.003) were lower among subjects wi bronchial hyperresponsiveness and asthma (FEV(1) and asthma only in smokers). SR75 (p=0.037) and SR50 (p=0.024) were increased in subjects with asthma and SR75 was increased in subjects with bronchial hyperresponsiveness, but only in smokers (p=0.002). In conclusion, exposure to farming seems to influence the shape of the MEFV-curve and there are indications of interaction between exposure to organic dust and smoking. These changes are seen only in the slope ratios and not in FEV(1) and FEV(1)/FVC. However, FEV(1) and FEV(1)/FVC are superior to slope ratios in differentiating healthy subjects from those with respiratory symptoms.

Lung status in young Danish rurals: the effect of farming exposure on asthma-like symptoms and lung function.

The aim of this study was to assess the prevalence of asthma (self-reported) and relate this to lung function and factors associated with asthma in young farmers. Two hundred and ten female and 1,691 male farming students together with 407 males controls were studied. Each subject underwent a medical interview; forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded using a dry wedge spirometer. Histamine bronchial reactivity was measured using the Yan method. Skin prick testing was performed using inhalant allergens. Nonsmokers had lower prevalence of asthma (5.4-10.8%) than smokers (11.3-21.0%) (p<0.05). Females reported symptoms of asthma nearly twice as often as males. Sex, smoking and a family history of asthma/allergy were significantly associated with asthma. Controls had higher standardized FEV1 and FVC residuals than male students, both nonsmokers (0.21 and 0.24) versus (-0.06 and -0.05) and smokers (0.29 and 0.33) versus (-0.11 and 0.13) (p<0.032). Bronchial hyperresponsiveness, asthma, siblings with allergy and working with cattle (controls only) were significantly associated with reduced lung function. In conclusion, the prevalence of asthma was significantly related to smoking, female sex, family history of asthma and allergy. Whilst bronchial hyperresponsiveness was associated with reduced lung function and lung function was slightly reduced in the male farming students, there was no association found between occupational farming exposure and either lung symptoms or lung function.

Peak expiratory flow and the resistance of the mini-wright peak flow meter.

The purpose of this study was to examine whether the resistance of the peak flow meter influences its recordings. One hundred and twelve subjects, (healthy nonsmokers and smokers and subjects with lung diseases) performed three or more peak expiratory flow (PEF) manoeuvres through a Fleisch pneumotachograph with and without a mini-Wright peak flow meter added in random order as a resistance in series. The results were as follows. In comparison with a pneumotachograph alone, peak flow measured with an added mini-Wright meter had a smaller within-test variation, defined as the difference between the highest and second highest values of PEF in a series of blows. The mean (SE) variation was 14 (1.3) L.min-1 and 19 (1.5) L.min-1 with and without meter added, respectively. In comparison with the pneumotachograph alone, the addition of the mini-Wright meter caused PEF to be underread, especially at high flows. The difference (PEF with meter minus PEF without meter) = -0.064 (average PEF) -8 L.min-1; R2 = 0.13. The mean difference was -7.8 (1.1) %, and increased numerically for a given PEF, when maximal expiratory flow when 75% forced vital capacity remains to be exhaled (MEF75%FVC) decreased. The reproducibility criteria for repeated measurements of peak flow are more appropriately set at 30 L.min-1 than the commonly used 20 L.min-1, because a within-test variation of less than 30 L.min-1 was achieved in 76% of the subjects without PEF meter inserted and in 88% with meter inserted, with no difference between healthy untrained subjects and patients. The resistance of the peak expiratory flow meter causes less variation in recordings but reduces peak expiratory flow, especially at high values and when the peak is large as compared with the rest of the maximal expiratory flow-volume curve.

Urinary 1-hydroxypyrene, a PAH biomarker in foundry workers.

Exposure to PAH in foundry workers has been studied by urinary 1-hydroxypyrene (HPU) levels, quantitatively measured by reversed phase HPLC. Seventy male foundry workers and 68 matched controls were investigated. Polycyclic aromatic hydrocarbon (PAH) exposure was defined by 17 breathing zone hygienic samples, consisting of 16 selected PAH compounds. Mean total PAH concentration (SD) was 10.40 (4.04) mu g/m3. A multiple regression model of tobacco consumption, age, airborne PAH-exposure and foundry work on log HPU showed a significant correlation, p < 0.001, r2 = 0.69. Only foundry work (p < 0.0001) and airborne PAH exposure (p = 0.0478) contributed significantly to the model. These data suggest that HPU is a sensitive biomarker for low-dose PAH exposure.

Exposure of iron foundry workers to polycyclic aromatic hydrocarbons: benzo(a)pyrene-albumin adducts and 1-hydroxypyrene as biomarkers for exposure.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in foundry workers has been evaluated by determination of benzo(a)pyrene-serum albumin adducts and urinary 1-hydroxypyrene. Benzo(a)pyrene binding to albumin and 1-hydroxypyrene were quantitatively measured by enzyme linked immunosorbent assay (ELISA) and reverse phase high performance liquid chromatography (HPLC), respectively. 70 male foundry workers and 68 matched controls were investigated. High and low exposure groups were defined from breathing zone hygienic samples, consisting of 16 PAH compounds in particulate and gaseous phase. Mean total PAH was 10.40 micrograms/m3 in the breathing zone, and mean dust adsorbed PAH was 0.15 microgram/m. All carcinogenic PAH was adsorbed to dust. Median benzo(a)pyrene-albumin adduct concentrations (10-90% percentiles) were similar in foundry workers (smokers 0.55 (0.27-1.00) and non-smokers 0.58 (0.17-1.15)) pmol/mg albumin and age matched controls (smokers 0.57 (0.16-1.45) and non-smokers 0.70 (0.19-1.55) pmol/mg albumin). Median 1-hydroxypyrene concentrations were significantly higher (P < 0.0001) in smoking and non-smoking foundry workers (0.022 (0.006-0.075) and 0.027 (0.006-0.164)) mumol/mol creatinine than in smoking and non-smoking controls (0 (0-0.022) and 0 (0-0.010) mumol/mol creatinine). Dose-response relations between total PAH, pyrene, carcinogenic PAHs, and 1-hydroxypyrene for smokers, and polycyclic aromatic hydrocarbons adsorbed to dust for non-smokers are suggested. Exposure to PAHs adsorbed to dust showed an additive effect. There was no correlation between the concentrations of 1-hydroxypyrene and benzo(a)pyrene-albumin adducts. The change in 1-hydroxypyrene over a weekend was also studied. Friday morning median 1-hydroxypyrene concentrations were significantly higher in both smokers and non-smokers (0.021 (0-0.075) and 0.027 (0.06-0.164)) mumol/mol creatinine than Monday morning median concentrations (0.007 (0-0.021) and 0.008 (0-0.021) mumol/mol creatinine). Smoking did not affect the concentrations of 1-hydroxypyrene or benzo(a)pyrene-albumin adducts. These data suggest that 1-hydroxypyrene is a sensitive biomarker for low dose PAH exposure. Exposure to PAHs may be aetiologically related to increased risk of lung cancer in foundry workers.

Correlation between work process-related exposure to polycyclic aromatic hydrocarbons and urinary levels of alpha-naphthol, beta-naphthylamine and 1-hydroxypyrene in iron foundry workers.

In two Danish iron foundries the concentration of polycyclic aromatic hydrocarbons (PAH) in 24 personal air samples of workers employed in selected processes, i.e. melters, melted iron transporters, casters, machine molders, hand molders, shake-out workers and finishing workers, were measured and correlated to levels of 1-hydroxypyrene, alpha-naphthol and beta-naphthylamine in the urine of exposed workers. The highest total airborne PAH concentrations (sum of 15 selected PAH compounds: 9.6-11.2 micrograms/m3) were associated with casting, machine molding, and shake-out. The highest concentrations of the sum of six selected airborne carcinogenic PAH compounds were found for melting, casting and machine and hand molding. As seen in other working environments involving low-level PAH exposure, the content of naphthalene was high, in general exceeding 85% of the total content of PAH compounds. The present study demonstrates that 1-hydroxypyrene is a useful and direct biomarker of low-dose occupational exposure to PAH compounds. Molding and casting had the highest pyrene levels in iron foundries. Furthermore, the data shows that levels of beta-naphthylamine in urine are significantly elevated in iron foundry workers. Hand molders, finishing workers and truck drivers tended to have the highest levels. Concerning alpha-naphthol the highest concentrations were measured in urine from casters and shake-out workers. With regard to epidemiologic studies demonstrating that molders and casters have a higher risk of lung cancer, the present study suggests that the elevated risk may be due to exposure to carcinogenic PAH compounds in iron foundries, particularly in some high-risk work processes, e.g. casting and molding. In addition, the present study suggests that biological monitoring of 1-hydroxypyrene and beta-naphthylamine may be used to estimate the individual exposure, which seems to be correlated with exposure during individual work processes.

[A study of skin and mucosal irritation and incidence of allergy among office staff exposed to self-copying paper]. / En undersøgelse af hud- og slimhindeirritation samt forekomst af allergi hos kontorpersonale udsat for selvkopierende papir.

At a public office with a staff of 129, twenty people work for short periods with large amounts of self-copying paper. A controlled study has shown a significantly higher incidence of pruritus and nasal congestion amongst staff exposed to large amounts of self-copying paper or its components, no drying of the skin after working with the paper and no increased degree of irritation of the skin were found in the study group at dermatological examination. No differences were found between the study group and the control group with respect to allergy or skin status or working conditions apart from the contact with self-copying paper. The study confirms that contact with fresh self-copying paper may result in pruritus and skin irritation, but allergy to the paper or microcapsule contents could not be demonstrated in this study.

Renal effects of acute exposure to toluene. A controlled clinical trial.

Urinary excretion rates of beta 2-microglobulin and albumin were measured in 43 male printing trade workers and 43 age-matched male controls before and during exposure to toluene, 382 mg/m3, for 6 1/2 hours in a climate chamber. There were no significant changes in renal excretion rates of albumin and beta 2-microglobulin during toluene exposure indicating that no causal relationship exists between moderate exposure to organic solvents and renal injury.

Renal effects of chronic exposure to organic solvents. A clinical controlled trial.

Chronic effects of organic solvents on renal function were measured by creatinine clearances and urinary excretion rates of beta 2-microglobulin and albumin. Forty-three male printing trade workers occupationally exposed to different organic solvents for 9-25 years were compared with 43 age-matched male controls. No differences were found either in creatinine clearances or average basal levels of beta 2-microglobulin and albumin excretion rates, whereas a positive relation could be demonstrated between alcohol consumption on the day before the trial and urinary excretion rate of albumin. This investigation did not reveal any adverse renal effects of moderate chronic exposure to organic solvents in a group of active trade workers.