Thomas A. Hall

A Review and Meta-Analysis of Formaldehyde Exposure and Pancreatic Cancer

BACKGROUND Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract. Two recent studies have suggested that exposure to formaldehyde may increase the risk for pancreatic cancer. METHODS We examine 14 epidemiology studies of workers exposed to formaldehyde where pancreatic cancer rates were reported and use meta-analytic techniques to summarize the findings. We also rank formaldehyde exposures for the industries in these studies. RESULTS We found a small increase of pancreatic cancer risk in the studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest formaldehyde exposures. CONCLUSIONS A small increased risk of pancreatic cancer from formaldehyde exposure cannot be ruled out from the studies examined. However, the null findings among industrial workers and the lack of biological plausibility would argue against formaldehyde as a cause. The increased risk of pancreatic cancer among embalmers, pathologists, and anatomists may be due to a diagnostic bias or to occupational exposures other than formaldehyde in these professions.

Assessment of Medical Personnel Exposure to Nitrogen Oxides During Inhaled Nitric Oxide Treatment of Neonatal and Pediatric Patients

Objective. This study was an assessment of potential exposures of medical personnel to nitrogen oxides during simulated and actual inhaled nitric oxide treatment of newborn and pediatric patients. Design. Breathing zone exposures to nitric oxide (NO) and nitrogen dioxide (NO2) were monitored using data-logging personal dosimeters during simulated and actual administration of NO gas to patients in an intensive care setting. Sample. A total of 28 bedside nurses and 18 respiratory therapists were monitored during 6 different patient treatments. Analysis. The highest measured concentrations of NO and NO2 in the personal breathing zones of the nurses and respiratory therapists were peak readings (<1 minute in duration) of 6.7 parts per million (ppm) NO and 3.1 ppm NO2. Exposures averaged throughout 15 minutes and throughout the work shift were below the limit of detection (0.8-ppm NO and 0.5-ppm NO2). Conclusion. Detectable exposures to NO and NO2were brief, infrequent, and well below Occupational Safety and Health Administration permissible exposure limits or any other exposure guideline, eg, American Conference of Governmental Hygienists Threshold Limit Values.

Theoretical Investigation of the Interrelationship Between Stationary and Personal Sampling in Exposure Estimation

In exposure estimation, personal sampling is the method of choice as it is a nearby representative of the contaminant concentration in the breathing zone. Due to the versatility of the stationary sampling in obtaining much higher sensitivity, in its adaptability to telemetering observations, it may also be an attractive sampling method for many circumstances. However, the two sampling methods differ in many theoretically important ways that go beyond the obvious differences. The theoretical investigation of the stationary and personal sampling methods vis-à-vis sampling for exposure estimation shows that the area sampling can be used to represent personal sampling under restricted conditions. Under the restricted conditions, an area of concentration within specified bounds may be determined in relation to a reasonably well-defined source. The extension of the theory to multiple or ill-defined sources pose potential complications that may be intractable through a theoretical analysis. These limitations and restrictions are inherent to the underlying premises of the two methods; therefore they are not amenable to easy correction. Even though these restrictions may suggest only a limited role for area sampling in exposure assessment, the theory shown also suggests areas of further applied and theoretical research to extend the proper use of area sampling in exposure assessment.

Comments on the Diesel Exhaust in Miners Study

We are writing in response to four recent articles describing the historical reconstruction of diesel exhaust exposures in underground mines (Diesel Exhaust in Miners Study or DEMS) for use in epidemiological analyses of exposure–response relationships between mining-associated diesel exposure and health effects, e.g. lung cancer (Coble et al., 2010; Stewart et al., 2010; Vermeulen et al., 2010a,b). We have particular concerns about the estimation of historical respirable elemental carbon (REC) levels for underground miners. Those estimates were back extrapolated using historical carbon monoxide (CO) area measurements and estimated levels of historical ‘adjusted horsepower (HP)’ of diesel fleets to estimate levels of CO as surrogates of diesel exhaust (DE). As discussed below, those measures are at best imprecise and may not be valid measures of DE. Accordingly, we have concerns about the validity of the articles’ conclusions, which we believe are insufficiently justified. The following communication briefly describes those concerns. 1. Measurements of CO by colorimetric tubes are imprecise and may be unreliable. The historical reconstruction relied on CO data obtained in the DEMS survey, a 1994 Feasibility study, and a compilation of MSHA data from 1976 to 2001 (MIDAS). In the DEMS and Feasibility studies, CO measurements were obtained using long-term (i.e. 8 h) colorimetric tubes. The MIDAS surveys used short-term colorimetric tubes (i.e. 5–15 min) or gas chromatography, but the numbers determined by each of those methods were not described. The precision of CO colorimetric tubes is limited, especially at low exposure levels. Prior to the NIOSH certification program, colorimetric and length-ofstain detector tubes were considered ‘inaccurate’ (Perkins, 1997). Early studies reported that over the range from 25 to 100 p.p.m., all commercially available CO detector tubes were worse than –25% of the true value, while only some brands yielded results within –50% of the true value (Morgenstern et al., 1970). CO tubes are currently required to yield results –35% the true value at 12.5 p.p.m., but precision and accuracy decline as concentrations approach the limit of their recommend use ( 5 p.p.m.). Because of imprecision, inaccuracy, and observer variability, historical and current authorities agree that CO colorimetric tubes should only be used to detect the presence of CO and for range finding purposes, not for quantitative measurements (WHO, 1976; Stern and Mansdorf, 1999; Todd, 2003) and that after CO detection ‘a more accurate . . . method’ should be used (Lodge, 1988). In 1976, the year MIDAS surveys began, WHO recommended that detector tubes only be used ‘for estimating the concentration of CO at concentrations above 5 mg/ m, (i.e. 4.35 p.p.m.) (WHO, 1976). Accordingly, it is notable that the great majority of CO measurements in the DEMS reports were below 4.35 p.p.m.. We are also concerned by a table footnote indicating that some CO values were ‘corrected for measurement technique (detector tube versus bistable)’, but the reports described neither the method for and effects of such ‘correction’, nor the number of samples so ‘corrected’. Thus, the CO measurements are subject to still further uncertainty. 2. The majority of CO measurements were below the recommended range for use of colorimetric tubes. The reports do not describe the actual CO measurements across the seven mines, but summary statistics were provided for samples obtained at the underground production face. Across the seven mines in the DEMS survey, the geometric means of CO samples ranged from 0.8 to 4.5 p.p.m.. Among historical production face CO measurements, the geometric means across all mines grouped by decade ‘typically’ ranged from 1 to 3 p.p.m..

The effectiveness of handheld ventilated sanders in reducing inhalable dust concentrations

Ventilated sanders are commonly used during aircraft surface abrasion but there is limited data on their effectiveness in reducing worker exposures. This study compared two handheld ventilated sander brands, DCM and Dynabrade, in a laboratory glovebox. Both sanders collect particulates by drawing air through holes in the sanding pads; the dust subsequently passes into a vacuum collection system. Aluminum panels coated with aircraft epoxy primer and polyurethane paint were abraded and inhalable dust concentrations were measured inside the glovebox with IOM samplers. The results indicate that both sanders effectively control inhalable dust, with the DCM sander reducing mass concentrations by 93 percent, and the Dynabrade by 98 percent, when the ventilation system is used. The Dynabrade unit, however, was more aggressive and produced over four times as much dust per unit time as the DCM unit. In spite of this, the Dynabrade sander adequately collected this additional dust. Varying abrasive grit size did not significantly affect dust generation, although the differences between the grit sizes used (180 and 240 grit) were not great and may have influenced the results.

Sample size-based indication of normality in lognormally distributed populations.

Occupational and environmental hygiene sampling strategies are usually dictated by factors that limit sample sizes to relatively small numbers. Often, parameters estimated from small sample sizes are then used to make further estimates of the occurrence of extreme events, which are governed by the underlying exposure distribution. We investigated the limitations superimposed by the number of samples in distinguishing an asymmetric (Lognormal) distribution through the rejection of a hypothesized symmetric (Normal) distribution. Sets of 5 to 250 synthetic samples from underlying Lognormal distributions with unit median were generated for 24 separate geometric standard deviations (GSDs), ranging from 1.25 to 7.00. Each simulated combination was repeated in blocks of 200 and each block was repeated tenfold. The synthetic samples were then tested for goodness of fit for Normality by using the Shapiro and Wilks W Test. Results indicated that the number of samples required to distinguish between Normal and Lognormal distributions was inversely related to GSD. When GSD = 1.25, 169 samples were required for 90 percent distinction at alpha = 0.05. The criteria for success for GSD of 2.00 and 4.00 were 25 and 15 samples, respectively. These results led to the conclusion that the general inability to distinguish an underlying distribution may impose serious difficulties in the estimation of extreme events associated with occupational and environmental hygiene-related sampling.

An Investigation of Secondary Exposure Misclassification Effects of Lifelong Occupational History in Exposure Estimation

The effects of exposure misclassification on the interpretation of results of occupational epidemiological studies has been widely investigated and reported. Usually, only the direct effects of misclassification have been considered or simple estimates of misclassification rates have been assigned to various types of exposure estimation processes. Lifelong job profile data obtained from a previously published case-control study provided complete or nearly complete job histories of 511 decedents. An analysis of these work histories and the comparison of exposures related to longest-held job to estimated total lifetime exposures suggest that single job-based exposure estimates may lead to significant exposure misclassification rates. In addition, the appearance of shorter duration jobs in a study population occurring predominantly early in the work history may exacerbate problems associated with exposure misclassification. While few specific suggestions emerge from this analysis, the inclusion of extensive recording of the work history of study subjects emerges as a reasonable basis for the investigation and potential reduction of secondary misclassification of exposures in occupational epidemiological studies.

Assessment of Nitric Oxide and Nitrogen Dioxide Exposure Potential in Healthcare Workers Involved in Nitric Oxide Treatment of Infant and Pediatric Patients

Assessment of Nitric Oxide and Nitrogen Dioxide Exposure Potential in Healthcare Workers Involved in Nitric Oxide Treatment of Infant and Pediatric Patients