Burden of non-melanoma skin cancer attributable to occupational sun exposure in Canada.

PURPOSE: Outdoor workers are exposed daily to solar ultraviolet radiation, an important contributor in the development of non-melanoma skin cancer. This study aimed to quantify the health burden of non-melanoma skin cancers among outdoor workers in Canada. METHODS: Solar ultraviolet radiation exposure and estimates of exposure levels were applied to employment information from Canada census data to determine the exposed population in the risk exposure period (1961-2001). Risk estimates were drawn from meta-analyses selected based on quality and relevance to the current study. Population-attributable fractions were calculated using Levin's equation and attributable cases were estimated based on incidence data reported by the Canadian Cancer Society. RESULTS: In 2011, 6.31% (4556 cases) of non-melanoma skin cancer cases were estimated to be attributable to occupational exposure to solar ultraviolet radiation. The majority of these cases occurred in men in the agriculture or construction industries. CONCLUSIONS: These estimates of the burden of non-melanoma skin cancer in Canada identify the need for further prevention efforts, particularly in agriculture and construction. Introducing workplace sun safety measures could be an important area for policy development.

Evaluation and comparison of three exposure assessment techniques.

This study was conducted to verify the performance of a recently developed subjective rating (SR) exposure assessment technique and to compare estimates made using this and two other techniques (trade mean, or TM, and task-based, or TB, approaches) to measured exposures. Subjects (n = 68) each completed three full-shift noise measurements over 4 months. Individual measured mean exposures were created by averaging each subject's repeated measurements, and TM, TB, and SR estimates were created using noise levels from worksites external to the current study. The bias, precision, accuracy, and absolute agreement of estimates created using the three techniques were evaluated by comparing estimated exposures with measured exposures. Trade mean estimates showed little bias, while neither the TM nor the SR techniques produced unbiased estimates, and the SR estimates showed the greatest bias of the three techniques. Accuracy was essentially equivalent among the three techniques. All three techniques showed poor agreement with measured exposures and were not highly correlated with each other. Estimates from the SR technique generally performed similarly to the TM and TB techniques. Methods to incorporate information from each technique into exposure estimates should be explored.

A retrospective assessment of occupational noise exposures for a longitudinal epidemiological study.

OBJECTIVES: Chronic exposure to high levels of noise may be associated with increased risk of cardiovascular disease. We therefore undertook a quantitative retrospective exposure assessment using predictive statistical modelling to estimate historical exposures to noise among a cohort of 27,499 sawmill workers as part of an investigation of acute myocardial infarction mortality. METHODS: Noise exposure data were gathered from research, industry and regulatory sources. An exposure data matrix was defined and exposure level estimated for job title/mill/time period combinations utilising regression analysis to model determinants of noise exposure. Cumulative exposure and duration of exposure metrics were calculated for each subject. These were merged with work history data, and exposure-response associations were tested in subsequent epidemiological studies, reported elsewhere. RESULTS: Over 14,000 noise measurements were obtained from British Columbia sawmills. A subset, comprising 1901 full-shift dosimetry measurements from cohort mills was used in producing a predictive model (R(2) = 0.51). The model was then used to estimate noise exposures for 3809 "cells" of an exposure data matrix representing 81 jobs at 14 mills over several decades. Various exposure metrics were then calculated for subjects; mean cumulative exposure was 101 dBA*year. Mean durations of employment in jobs with exposure above thresholds of 85, 90 and 95 dBA, were 9.9, 7.0 and 3.2 years, respectively. CONCLUSIONS: The utility of predictive statistical modelling for occupational noise exposure was demonstrated. The model required input data that were relatively easily obtained, even retrospectively. Remaining issues include adequate handling of the use of hearing protectors that likely bias exposure estimation.

Correlation between co-exposures to noise and air pollution from traffic sources.

BACKGROUND: Both air and noise pollution associated with motor vehicle traffic have been associated with cardiovascular disease. Similarities in pollution source and health outcome mean that there is potential for noise to confound studies of air pollution and cardiovascular disease, and vice versa, or for more complex interactions to occur. METHODS: The correlations between 2-week average roadside concentrations of nitrogen dioxide (NO(2)) and nitrogen oxides (NO(X)) and short term average noise levels (L(eq,5min)) for 103 urban sites with varying traffic, environment and infrastructure characteristics were examined. RESULTS: The Pearson correlation coefficient for L(eq,5min) and NO(2) was 0.53, and for L(eq,5min) and NO(X) , 0.64. Factors influencing the degree of correlation were number of lanes on the closest road, number of cars or trucks during noise sampling and presence of a major intersection. CONCLUSIONS: We recommend measurement of both pollutants in future studies of traffic-related pollution and cardiovascular disease to allow for more sophisticated analysis of this relationship.

Hypertension in noise-exposed sawmill workers: a cohort study.

OBJECTIVE: To investigate the hypothesised association between exposure to high levels of noise and risk of hypertension using quantitative exposure assessment and administrative health data. METHODS: This study followed a cohort of 10 872 sawmill workers in British Columbia from 1991 to 1998. Subjects were linked with provincial hospital discharge, outpatient and vital status databases. Cases were males who died, had at least one hospital admission, or who had three doctor visits within 70 days, for hypertension (ICD-9 codes 401-405). We used four exposure metrics: cumulative exposure, and duration of exposure above thresholds of 85 dBA, 90 dBA and 95 dBA. Relative risks were estimated using Poisson regression with the low-exposure group as controls and adjusting for age, ethnicity and calendar period. RESULTS: 828 cases were identified. The results showed a monotonic increase in hypertension incidence with cumulative exposure. The risk in the highest exposed population was 32% higher than baseline. Similar results were found using duration of exposure metrics. The highest relative risk was 1.5 in workers exposed for more than 30 years at 85 dBA. Exposure-response trends were statistically significant. CONCLUSIONS: The risk of hypertension was positively associated with noise exposure above 85 dB.

Pharmacokinetics of intranasally applied medication during a cold.

The rate at which interferon is cleared from the nose after local administration was measured in volunteers both before and after challenge with virulent strains of human rhinovirus. Interferon was not cleared more rapidly after virus challenge, and there was no relationship between the amount of nasal secretion produced after challenge, and the rate of interferon clearance. These findings suggest that an inverse relationship between the quantity of a locally applied antirhinovirus drug which is recovered in nasal wash, and clinical and laboratory evidence of rhinovirus infection may be taken as evidence for a beneficial effect of the drug.

Inactivation of cytochrome P-450 by 2-isopropyl-4-pentenamide and other xenobiotics leads to heme-derived protein adducts.

When cytochrome P-450 in phenobarbital-induced rat liver microsomes was destroyed by 2-isopropyl-4-pentenamide (AIA) in vitro, 50% of the degraded heme was recovered as heme-derived products irreversibly bound to microsomal proteins. In contrast, less than 50% of the degraded heme was accounted for as N-alkylated porphyrins. Furthermore, 64% of the irreversibly bound products was bound specifically to a 54-kD form of cytochrome P-450. Several other compounds which have been reported to destroy cytochrome P-450 by forming N-alkylated porphyrins also produced heme-derived protein adducts. These findings indicate that the formation of heme-derived protein adducts may represent an important pathway for the irreversible degradation of cytochrome P-450 by many xenobiotics.

Cytogenetic analysis of South Asian berry pickers in British Columbia using the micronucleus assay in peripheral lymphocytes.

Micronuclei in peripheral blood lymphocytes from British Columbia seasonal farmworkers and controls were evaluated using the cytokinesis-block technique. The farmworkers harvested berry crops and were likely occupationally exposed to pesticides. Subjects were 39 female subjects of South Asian descent; 18 farmworkers employed during 1993 and 21 age-matched controls. The mean age was 55.9 years. Micronuceli were also scored for the presence of kinetochores. No significant difference was found between the frequency of micronucleated binucleates in the farmworkers group (19.20/1000 binucleates), and the control group (21.76/1000 binucleates). However, among the farmworkers employed in 1993, there was a positive, but not statistically significant, association between micronucleated cell frequency and weeks worked: 16.44/1000 binucleates in those working less than 20 weeks; 23.78/1000 binucleates in those working 20 to 23 weeks; and 25.43/1000 binucleates in those working more than 23 weeks. In those who had ever been employed as farmworkers, there was an elevated frequency of micronucleated cells in the group with the longest history of employment as a farmworker (25.28/1000 binucleates) compared to those with the shortest employment history (16.48/1000 binucleates). This trend remained evident after adjusting for age, red blood cell folate, meat consumption, coffee consumption and recent vaccination. A positive association between the consumption of meat and micronucleus frequency was also observed. Non-meat eaters were likely life-long vegetarians. Micronuclei in farmworkers had a lower frequency of kinetochore positive micronuclei than controls. This study indicates that South Asian berry pickers in British Columbia may be at risk for genetic damage. More studies in other ethnic groups and in males are needed to generalize the findings of this study. More direct measures of exposure are needed to elucidate the sources of genotoxicity.

Opportunities for a broader understanding of work and health: multiple uses of an occupational cohort database.

Occupational cohort studies conducted to study cancer incidence and mortality require extensive data gathering about workers' job histories, exposures, and health outcomes. Although this process is expensive, the database created can be looked upon as a resource for broad investigations of the relationship between work and health. This paper presents the example of a retrospective cohort study which began in the traditional way, examining the link between a specific pesticide exposure and mortality and cancer incidence. The cohort register has since been used to investigate whether infertility, adverse reproductive outcomes, and childhood cancers might be associated with this exposure. It is also being used as the basis for studying other sawmill exposures including noise and wood dust as well as socioeconomic factors including job strain, job mobility, unemployment, and retraining. This approach allows both the efficient use of occupational cohorts as well as providing the opportunity for investigators to develop a more comprehensive perspective on the determinants of the health status of workers and their families.

Predicting historical dust and wood dust exposure in sawmills: model development and validation.

Nonspecific dust measurements are used as a surrogate for wood dust exposure in sawmills. However, the wood dust component of dust has been found to vary by job and work area. Thus, the use of nonspecific dust exposure levels in epidemiologic studies may introduce exposure misclassification when assessing wood-related health effects. To improve exposure assessment in a retrospective cohort of 28,000 sawmill workers, we developed and evaluated the validity of two empirical models of exposure: one for nonspecific dust and one for wood dust. The dust model was constructed using 1,395 dust measurements collected in 13 sawmills for research or regulatory purposes from 1981 to 1997. Inter-sampler conversion factors were used to obtain inhalable dust equivalents if necessary. The wood dust model was constructed after applying adjustment factors to subtract nonwood components of the dust from the original measurements. The validity of the two models was tested against measurements (n = 213) from a technologically similar mill that was not part of the cohort study. The proportions of variability explained by the dust and wood dust models were 35% and 54%, respectively. When tested against the validation mill, the biases in the dust model were -33% for outdoor jobs and 2% for indoor jobs. The biases in the wood dust model were 2% for outdoor jobs and -3% for indoor jobs. Strong correlations were observed between the predicted and observed geometric means of jobs (0.79 and 0.70 for the dust model and wood dust model, respectively). Testing the validity of predictive models examines the generalizability of the models. The low overall bias, especially in the wood-specific model, increases our confidence in the use of these models for all sawmills to assess both nonspecific particulate and wood-related health effects in the historical cohort study.

Synthesis and turnover of membrane glycoconjugates in monolayer culture of pig and human epidermal cells.

The regression and turnover of the surface glycoconjugates of trypsin-prepared pig and human cultured epidermal cells have been determined using the glycoprotein precursors N-acetyl-D-(I-3H) glucosamine (3H-NAG) and N-(3H)-acetyl-D-mannosamine (3H-NAM). Sialic acid assays have been performed on similar unlabelled cells. The major points which emerged from this study were: (1) Trypsin-damaged cell surfaces are rapidly repaired, probably by normal membrane turnover. There was a 12% regeneration of sialic acid within 2 h and total resynthesis occurred within 24 h. (2) The presence of an internal membrane system, part of which also demonstrates turnover, probably contributed to the speed of surface membrane repair. Some of the glycoprotein/sialic acid of this internal membrane system (30%) remains bound for a considerable length of time. (3) The membrane turnover maintains the cell in equilibrium so that total loss equals the synthesis of glycoprotein. (4) The equilibration of 3H-NAG or 3H-NAM uptake between 24 and 48 h is limited by the relative concentrations of glucose and labelled sugar in the medium at this time. (5) 3H-NAm was a more specific marker of glycoprotein than 2H-NAG. (6) The results for human epidermal cells closely matched those for pig epidermal cells, indicating that pig cells can be used as a model for human cells.

Carbon tetrachloride and 2-isopropyl-4-pentenamide-induced inactivation of cytochrome P-450 leads to heme-derived protein adducts.

When CCl4 was incubated with rat liver microsomes from phenobarbital-treated rats in an aerobic or anaerobic atmosphere, over 69% of the heme moiety of cytochrome P-450 was destroyed. At least 45% of the degraded heme under both reaction conditions was accounted for as heme-derived products irreversibly bound to microsomal proteins. Furthermore, 33% of the irreversibly bound products were bound specifically to a 54-kDa form of cytochrome P-450. A structurally different compound, 2-isopropyl-4-pentenamide, also destroyed the heme moiety of cytochrome P-450 and produced heme-derived adducts of microsomal proteins that accounted for 28% of the destroyed heme. These results represent a novel mechanism for the destruction of cytochromes P-450 by xenobiotics.

A field comparison of inhalable and thoracic size selective sampling techniques.

We measured inhalable, thoracic, and so-called "total" wood dust exposure in British Columbia lumber mill workers. Particle-size selective sampling was conducted using the GSP and Seven hole inhalable samplers, the PEM thoracic sampler and the 37-mm closed-face cassette "total" sampler. All measurements were full-shift personal samples, obtained from randomly selected workers. We obtained intersampler comparison data for the following pairs of instruments: GSP and 37-mm sampler; GSP and seven-hole sampler (SHS); and PEM and 37-mm sampler. The intersampler measurement ratios were estimated as: GSP/37-mm sampler = 4.2; GSP/SHS = 1.7; and PEM/37-mm sampler = 1.6. The GSP/37-mm sampler ratio is consistent with previously reported findings, while PEM/37-mm sampler and GSP/SHS ratios were both larger than expected. We found that in all comparisons, the measurement ratio had significant variability that was greatest at low ambient dust concentrations. Although it was not possible to attribute the source of the variability to specific sampler types, we concluded that the GSP sampler might be susceptible to "projectile" particles not normally aspirated, and may be vulnerable to direct aspiration of dust from accidentally contacted surfaces. The PEM was designed for environmental monitoring, and it is possible that it is unsuited to the higher particulate concentrations found in some occupational settings. Disparities among inhalable sampling techniques such as that between GSP and SHS should be investigated further in light of the proposed adoption of the inhalable method as an industrial standard.

Inhibition of overall protein and RNA synthesis as a mechanism for the tunicamycin induced decrease in cytochrome P-450 in rat hepatocytes.

In rat hepatocytes maintained in culture, cytochrome P-450 and NADPH cytochrome c reductase activities were decreased by tunicamycin in a dose and time dependent fashion. The effect of tunicamycin was mainly due to inhibition of protein synthesis. Tunicamycin decreased L-[35S] methionine incorporation into many proteins, including a 52 kDa cytochrome P-450 isozyme. Tunicamycin also reduced RNA synthesis. These results indicate that tunicamycin decreased cytochrome P-450 levels in hepatocytes by inhibiting protein and RNA synthesis.

Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated rats.

Four hours after the administration of halothane to phenobarbital-pretreated rats, subcellular fractions of liver were isolated and the proteins in the fractions were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred to nitrocellulose sheets, and immunochemically stained with anti-trifluoroacetylated antibodies. The microsomal fraction contained the highest level of trifluoroacetylated adducts. Its major trifluoroacetylated component was immunochemically identified as a phenobarbital-inducible form of cytochrome P-450 (54 kDa), whereas the other observed trifluoroacetylated protein fraction (59 kDa) was not identified. The plasma membrane fraction also contained a 54-kDa trifluoroacetylated adduct, which was immunochemically related to the 54-kDa cytochrome P-450. Microsomes from untreated rats that were administered halothane contained only the 59-kDa trifluoroacetylated protein fraction. The specificity of the immunochemical staining for the bound oxidative metabolite of halothane was confirmed by the finding that rats treated with deuterated halothane had considerably less stained liver proteins than did those treated with halothane. These results suggest that the CF3COX oxidative metabolite of halothane is so reactive that it binds predominantly to the cytochrome P-450 that produced it.

Exposure to dust, resin acids, and monoterpenes in softwood lumber mills.

A study to assess exposure to potential respiratory hazards in a large lumber mill processing spruce (Picea engelmannii and glauca), pine (Pinus contorta), and fir (Abies lasiocarpa) used a random sampling strategy to assess exposures for all jobs in the sawmill, planer mills, and yard. Personal samples for inhalable particulate were collected to measure exposure to dust and resin acids (abietic acid and pimaric acid). To estimate wood dust exposure, rather than overall dust, the resin acid content within dust was used in combination with observations of job tasks and proximity to dust sources. Passive dosimeters were used to measure exposure to alpha-pinene, beta-pinene, delta3-carene, and other unidentified wood volatiles suspected to be monoterpenes. The GM of the 220 inhalable particulate samples was 1.0 mg/m3 whereas the mean abietic acid, pimaric acid, and estimated wood dust levels were 7.2 microg/m3, 0.6 microg/m3, and 0.5 mg/m3, respectively. The GMs of the 222 monoterpene samples were 0.1 mg/m3 for alpha-pinene, 0.3 mg/m3 for beta-pinene, 0.1 mg/m3 for delta3-carene, and 0.5 mg/m3 for the unidentified wood volatiles. Monoterpene exposures were much lower than those observed in other studies conducted in Sweden and Finland. The results of this exposure assessment highlight the importance of considering the content of airborne particulates in lumber mills as well as potential exposure to wood chemicals.

The use of a continuous cell line for the isolation of influenza viruses.

Cultures of MDCK cells exposed to trypsin were as efficient as cultures of rhesus monkey kidney cells for detecting influenza virus, both in dilutions of infected allantoic fluids and in nose and throat swabs. We suggest that the MDCK cell/trypsin system provides a satisfactory alternative to monkey kidney cultures for the isolation of influenza viruses from clinical specimens.