Exposure to benzene in a pooled analysis of petroleum industry case-control studies.

Cases of lymphohematopoietic cancer from three petroleum industry cohorts, matched to controls from the respective cohort, were pooled into single study. Average benzene exposure was quantitatively estimated in ppm for each job based on measured data from the relevant country, adjusted for the specific time period, site and job exposure characteristics and the certainty of the exposure estimate scored. The probability of dermal exposure and of peak exposure was also assessed. Before risk was examined, an exposure estimate comparison and rationalisation exercise was performed across the studies to ensure accuracy and consistency of approach. This article evaluates the final exposure estimates and their use in the risk assessments. Overall benzene exposure estimates were low: 90% of participants accumulated less than 20 ppm-years. Mean cumulative exposure was estimated as 5.15 ppm-years, mean duration was 22 years, and mean exposure intensity was 0.2 ppm. 46% of participants were allocated a peak exposure (>3 ppm at least weekly). 40% of participants had a high probability of dermal exposure (based on the relative probability of at least weekly exposure). There were differences in mean intensity of exposure, probability of peak, and/or dermal exposure associated with job category, job site, and decade of exposure. Terminal Operators handling benzene-containing products were the most highly exposed group, followed by Tanker Drivers carrying gasoline. Exposures were higher around 1940-1950 and lower in more recent decades. Overall confidence in the exposure estimates was highest for recently held jobs and for white-collar jobs. We used sensitivity analyses, which included and excluded case-sets on the basis of exposure certainty scores, to inform the risk assessment. The above analyses demonstrated that the different patterns of exposure across the three studies are largely attributable to differences in jobs, site types, and time frames rather than study. This provides reassurance that the previous rationalisation of exposures achieved inter-study consistency and that the data could be confidently pooled.

Sodium chloride concentration affects yield, quality, and sensory acceptability of vacuum-tumbled marinated broiler breast fillets.

The objective of this experiment was to determine the effect of sodium chloride concentration on yield, instrumental quality, and sensory acceptability of broiler breast meat that was vacuum tumbled with a 15% solution (over green weight) for 30 min. Different concentrations (0, 0.25, 0.50, 0.75, 1.00, 1.25, and 1.50%) of NaCl (salt) and 0.35% sodium tripolyphosphate were included in the marinade solution. After marinating, breast fillets were evaluated for marination yields, pH, surface color, cooking loss, tenderness, expressible moisture, proximate composition, purge loss, sodium content, and sensory acceptability. As salt concentration increased, CIE L* decreased linearly, with a concentration of 0.75% having lower (P < 0.05) CIE L* values when compared with the control, 0, and 0.25% NaCl treatments. In addition, there was a linear and quadratic decrease (P < 0.05) in shear force as salt concentration increased, with no further decrease (P < 0.05) when greater than 0.75% NaCl was used. Cooking yield increased (P < 0.05) as the salt concentration increased to 1.0%. All marinated treatments were preferred (P < 0.05) over the control treatment, and all treatments marinated with at least 0.50% sodium chloride had an average rating of like moderately. Cluster analysis indicated that consumer groups varied in their preference of broiler breast meat treatments and that samples that were marinated with between 0.5 to 1.0% NaCl were acceptable to the majority of consumers. Marination with 0.75% NaCl was sufficient to maximize yields and decrease lightness (L*) in vacuum-tumbled, marinated broiler breast that is sold raw, but 1.0% NaCl could be used in a precooked product because it minimizes cook loss. In addition, use of 0.50% NaCl had minimal effects on yields, color, and sensory acceptability when compared with products that were marinated with greater concentrations of NaCl.

Ensuring comparability of benzene exposure estimates across three nested case-control studies in the petroleum industry in support of a pooled epidemiological analysis.

BACKGROUND: Three case-control studies each nested within a cohort of petroleum workers assessed exposure to benzene in relation to risk of haematopoietic cancers. These studies have each been updated and the cases will be pooled to derive a more powerful study. The benzene exposure of new leukemia cases and controls was estimated in accordance with each respective study's original methods. An essential component of the process of pooling the data was comparison and rationalisation of the exposure estimates to ensure accuracy and consistency of approach. This paper describes this process and presents comparative estimates before and after appropriate revision took place. The original petroleum industry studies, in Canada, the UK and Australia, were conducted at different points in time by different study teams, but the industry used similar technology in similar eras in each of these countries. METHODS: A job history for each subject giving job title, dates of starting and leaving the job and location of work, was assembled. For each job or task, the average benzene exposure (Base Estimate (BE) in ppm) was derived from measurements collected at applicable worksites. Estimates of exposure intensity (workplace exposure estimates (WE)) were then calculated for each line of work history by adjusting the BEs for site- and era-specific exposure-related variables such as loading technology and percentage benzene in the product. To ensure that the exposure estimates were comparable among the studies, the WEs were allocated to generic Job Categories, e.g. Tanker Driver (by technology used e.g. bottom loading), Motor Mechanic. The WEs were stratified into eras, reflecting technological changes in the industry. The arithmetic mean (AM), geometric mean (GM) and range of the stratified WEs were calculated, by study, for each generic Job Category. These were then compared. The AMs of the WEs were regarded as substantially similar if they were within 20% in all three studies in one era or for at least two studies in two eras. If the AM of the WE group differed by more than 20%, the data were examined to see whether the difference was justified by differences in local exposure conditions, such as an enclosure versus open work area. Estimates were adjusted in the absence of justification for the difference. RESULTS: Reconciliation of differences resulted in changes to a small number of underlying BEs, particularly the background values, also the BEs attributed to some individuals and changes to the allocation of jobs between Job Categories. Although the studies covered some differing sectors of the industry and different time periods, for 22 Job Categories there was sufficient overlap, particularly in the downstream distribution sector, to make comparisons possible. After adjustment 12 Job Categories were judged to be similar and 10 were judged to be justifiably different. Job-based peak and skin exposure estimates were applied in a uniform way across the studies and a single approach to scoring the certainty of the exposure estimates was identified. CONCLUSIONS: The revised exposure estimates will be used in the pooled analysis to examine the risk of haematopoietic cancers and benzene exposure. This exercise provided an important quality control check on the exposure estimates and identified similarly exposed Job Categories that could be grouped for risk assessment analyses.

A quantitative microbial risk assessment model for Legionnaires' disease: animal model selection and dose-response modeling.

Legionnaires' disease (LD), first reported in 1976, is an atypical pneumonia caused by bacteria of the genus Legionella, and most frequently by L. pneumophila (Lp). Subsequent research on exposure to the organism employed various animal models, and with quantitative microbial risk assessment (QMRA) techniques, the animal model data may provide insights on human dose-response for LD. This article focuses on the rationale for selection of the guinea pig model, comparison of the dose-response model results, comparison of projected low-dose responses for guinea pigs, and risk estimates for humans. Based on both in vivo and in vitro comparisons, the guinea pig (Cavia porcellus) dose-response data were selected for modeling human risk. We completed dose-response modeling for the beta-Poisson (approximate and exact), exponential, probit, logistic, and Weibull models for Lp inhalation, mortality, and infection (end point elevated body temperature) in guinea pigs. For mechanistic reasons, including low-dose exposure probability, further work on human risk estimates for LD employed the exponential and beta-Poisson models. With an exposure of 10 colony-forming units (CFU) (retained dose), the QMRA model predicted a mild infection risk of 0.4 (as evaluated by seroprevalence) and a clinical severity LD case (e.g., hospitalization and supportive care) risk of 0.0009. The calculated rates based on estimated human exposures for outbreaks used for the QMRA model validation are within an order of magnitude of the reported LD rates. These validation results suggest the LD QMRA animal model selection, dose-response modeling, and extension to human risk projections were appropriate.

A tiered approach to assessing children's exposure: a review of methods and data.

From a public health view, there are many important issues to improving children's and adolescent's health, for example, prenatal and childhood nutrition, immunizations, infectious disease control, and drug/alcohol/tobacco control. There has been increasing emphasis worldwide on protecting children from adverse health effects due to environmental factors, including chemicals. For well-studied contaminants (e.g. lead) the risks to children are reasonably known and appropriate risk management actions, in a public health context, can be undertaken. For a number of other chemicals, hazard and exposure data are less complete, and risk-based priorities are consequently less substantive. The US EPA's Voluntary Children's Chemical Evaluation Program proposal prompted additional efforts to develop and improve methods and data for assessing children's exposure. The goal is to efficiently identify the substances and conditions that present the highest potential risks to children, so that resources can be applied efficiently to assure their health improvement. The methods we illustrate use an iterative (tiered) approach for (a) screening level and (b) more detailed exposure assessments relevant to children. We also review and reference the key information sources available for such assessments and analyze the information and method's strengths and limitations.

Lessons learned while compiling a quantitative exposure database from the published literature.

The published literature was reviewed and then a quantitative hydrocarbon solvent exposure database was compiled. The data was then analyzed to determine trends in documented worker exposures to hydrocarbon solvents. It was found that an all too common limitation of the published literature was the incomplete reporting of results by the authors.

Workshop on harmonization of serving future needs with occupational exposure databases--inhalation modeling, session IIIA.

This workshop was one of several that took place at the International Symposium on Occupational Exposure Databases and Their Application for the Next Millennium held in London from November 1-3, 1999. About 30 delegates participated in the workshop. The agenda for the discussions was provided by a white paper prepared by the organizers. The workshop produced a conceptual outline for a general-purpose prediction model for inhalation exposure, and constructed a list of important input variables for successful model development. Evaluation of prototype models was discussed in some detail, and the workshop concluded with suggestions for taking forward the ideas discussed and maintaining the momentum and interest generated during the symposium.

Predictions of secondary neutrons and their importance to radiation effects inside the International Space Station.

As part of a study funded by NASA MSFC to assess thecontribution of secondary particles in producing radiation damage to optoelectronics devices located on the International Space Station (IS), Monte Carlo calculations have been made to predict secondary spectra vs. shielding inside ISS modules and in electronics boxes attached on the truss (Armstrong and Colborn, 1998). The calculations take into account secondary neutron, proton, and charged pion production from the ambient galactic cosmic-ray (GCR) proton, trapped proton, and neutron albedo environments. Comparisons of the predicted neutron spectra with measurments made on the Mir space station and other spacecraft have also been made (Armstrong and Colborn, 1998). In this paper, some initial results from folding the predicted neutron spectrum inside ISS modules from Armstrong and Colborn (1998) with several types of radiation effects response functions related to electronics damage and astronaut-dose are given. These results provide an estimate of the practical importance of neutrons compared to protons in assessing radiation effects for the ISS. Also, the important neutron energy ranges for producing these effects have been estimated, which provides guidance for onboard neutron measurement requirements.

A tiered approach for assessing children's exposure.

Recently, intense attention has been given to children's health issues, particularly in the use of consumer products. Because of this attention, researchers have been planning and initiating studies specifically aimed at developing both toxicology data and exposure data directed to improve our understanding of industrial and consumer product chemical impacts on children's health. To ensure that this research is focused on the highest priority chemicals, we present a methodology for determining and prioritizing the higher hazard chemicals and scenarios for which children could be disproportionately or highly exposed. This tiered approach includes a screening step for initial chemical selection, a hazard assessment based on no- or lowest-observed-adverse-effect levels, and a margin of exposure (MOE) calculation. The initial chemical screen focuses on the chemical presence in specific media that are special to children, such as foods children regularly eat and drink, residential or school air, products children use, and soil and dust in and around residences. Data from the literature or from models serve as the initial exposure estimate. This methodology would allow us to focus on those chemicals to which children are most exposed that are also associated with, potentially, the highest risk. Use of the MOE calculation allows for comparison among chemicals, prioritization of chemicals for evaluation and testing, and identification of significant data gaps.

Hydrocarbon solvent exposure data: compilation and analysis of the literature.

An occupational exposure database for hydrocarbon solvent end-use applications was constructed from the published literature. The database provides exposure assessment information for such purposes as regulatory risk assessments, support of industry product stewardship initiatives, and identification of applications in which limited exposure data are available. It is quantitative, documented, and based on credible data. Approximately 350 articles containing quantitative hydrocarbon solvent exposure data were identified using a search of computer databases of published literature. Many articles did not report sufficient details of the exposure data for inclusion in the database (e.g., full-shift exposure or task-based exposure data). Others were excluded because only limited summary statistics were provided, which precluded statistical analysis of the data (e.g., arithmetic mean concentration presented, but no sample number). Following evaluation, 16,880 hydrocarbon solvent exposure measurements from 99 articles were entered into a database for analysis. Methods used to identify and evaluate published solvent exposure data are described along with more detailed analysis of worker exposure to hydrocarbon solvents in three major end-use applications: painting and coating, printing, and adhesives. Solvent exposures were evaluated against current ACGIH threshold limit values (TLVs) and trends were identified. Limited quantitative data are available prior to 1970. In general, reported hydrocarbon solvent exposures decreased fourfold from 1960 to 1998, were below the TLVs applicable to specific hydrocarbon solvents at the time, and on average have been below 40% of the TLV since 1980. The database already has proved valuable; however, the utility of published exposure data could be further improved if authors consistently reported essential data elements and supporting information.

The relationship between low-level benzene exposure and leukemia in Canadian petroleum distribution workers.

This study was conducted to evaluate the relationship between leukemia occurrence and long-term, low-level benzene exposures in petroleum distribution workers. Fourteen cases were identified among a previously studied cohort [Schnatter et al., Environ Health Perspect 101 (Suppl 6):85-89 (1993)]. Four controls per case were selected from the same cohort, controlling for birth year and time at risk. Industrial hygienists estimated workplace exposures for benzene, without knowledge of case-control status. Average benzene concentrations ranged from 0.01 to 6.2 ppm. Company medical records were used to abstract information on other potential confounders such as cigarette smoking. Odds ratios were calculated for several exposure metrics. Conditional logistic regression modeling was used to control for potential confounders. The risk of leukemia was not associated with increasing cumulative exposure to benzene for these exposure levels. Duration of benzene exposure was more closely associated with leukemia risk than other exposure metrics, although results were not statistically significant. A family history of cancer and cigarette smoking were the two strongest risk factors for leukemia, with cumulative benzene exposure showing no additional risk when considered in the same models. This study is consistent with other data in that it was unable to demonstrate a relationship between leukemia and long-term, low-level benzene exposures. The power of the study was limited. Thus, further study on benzene exposures in this concentration range are warranted.

Model calculations of the radiation dose and LET spectra on LDEF and comparisons with flight data.

Ionizing radiation environment models, a 3-D spacecraft mass model, and radiation transport codes have been used to predict the radiation dose and linear energy transfer (LET) spectra measured at various locations on the LDEF satellite. The predictions are compared with thermoluminescent dosimeter measurements of the trapped proton and electron doses and with LET spectra measured by plastic nuclear track detectors. The predicted vs observed comparisons indicate some of the uncertainties of present ionizing radiation environment models for low Earth-orbit missions.

Predictions of the nuclear activation of materials on LDEF produced by the space radiation environment and comparison with flight measurements.

Model calculations have been made to compare with the induced radioactivity measured for materials on the LDEF satellite. Predictions and data comparisons are made for aluminum spacecraft components and for vanadium and nickel samples placed at multiple locations on the spacecraft. The calculated vs observed activations provide an indication of present model uncertainties in predicting nuclear activation as well as the magnitude and directionality of the trapped proton environment for low-Earth orbit missions. Environment model uncertainties based on the activation measurements are consistent with the uncertainties evaluated using other LDEF radiation dosimetry data.

Mass model of the LDEF satellite spacecraft and experiments for ionizing radiation analyses.

A three-dimensional (3D) mass model of the LDEF spacecraft and selected experiments has been developed to allow the influence of material shielding on ionizing radiation measurements and analyses to be determined accurately. This computer model has been applied in a stand-alone mode to provide 3D shielding distributions around radiation dosimeters to aid data interpretation, and has been interfaced with radiation transport codes for a variety of different types of radiation predictions. This paper summarizes the methodology used, the level of detail incorporated, and some example model applications.

Absorbed dose measurements on LDEF and comparisons with predictions.

The radiation environment on LDEF was monitored by cumulative absorbed dose measurements made with TLDs at different locations and shielding depths. The TLDs were included in four experiments: A0015(a) Biostack, P0004 Seeds in Space and P0006 Linear Energy Transfer Spectrum Measurements at the trailing edge (west side) of the satellite; M0004 Fiber Optics Data Link at the leading edge (east side); and A0015(b) Biostack at the Earth side. The shielding depths varied between 0.48 and 15.4 g/cm2, Al equivalent. Both the directional dependence of trapped protons incident on the satellite and the shielding thickness were reflected in absorbed dose values. The trapped proton anisotropy was measured by TLDs at the east and west sides of LDEF. At the east side doses ranged from 2.10 to 2.58 Gy under shielding of 2.90 to 1.37 g/cm2 (M0004) while on the west side doses ranged from 2.66 to 6.48 Gy under shielding of 15.4 to 0.48 g/cm2 (P0006). The west side doses were more than a factor of two higher, where the vertical shielding thicknesses to space were equal. Other west side doses of 3.04 to 4.49 Gy under shielding of 11.7 to 3.85 g/cm2 (A0015(a)) and 2.91 to 6.64 Gy under shielding of 11.1 to 0.48 g/cm2 (P0004) generally agreed with the P0006 results. The Earth side doses of 2.41 to 3.93 Gy under shielding of 10.0 to 1.66 g cm2 (A0015(b)) were intermediate between the east side and west side doses. Calculations utilizing a model of trapped proton spectra were performed by Watts et al. (1993) and comparisons of dose measurement and calculations may be found in a companion paper (Armstrong et al., 1996).

Neutron fluences and dose equivalents measured with passive detectors on LDEF.

Neutron fluences were measured on LDEF in the low energy (< 1 MeV) and high energy (> 1 MeV) ranges. The low energy detectors used the 6Li(n,alpha)T reaction with Gd foil absorbers to separate thermal (< 0.2 eV) and resonance (0.2 eV-1 MeV) neutron response. High energy detectors contained sets of fission foils (181Ta, 209Bi, 232Th, 238U) with different neutron energy thresholds. The measured neutron fluences together with predicted spectral shapes were used to estimate neutron dose equivalents. The detectors were located in the A0015 and P0006 experiments at the west and Earth sides of LDEF under shielding varying from 1 to 19 g/cm2. Dose equivalent rates varied from 0.8 to 3.3 microSv/d for the low energy neutrons and from 160 to 390 microSv/d for the high energy neutrons. This compares with TLD measured absorbed dose rates in the range of 1000-3000 microGy/d near these locations and demonstrates that high energy neutrons contribute a significant fraction of the total dose equivalent in LEO. Comparisons between measurements and calculations were made for high energy neutrons based on fission fragment tracks generated by fission foils at different shielding depths. A simple 1-D slab geometry was used in the calculations. Agreement between measurements and calculations depended on both shielding depth and threshold energy of the fission foils. Differences increased as both shielding and threshold energy increased. The modeled proton/neutron spectra appeared deficient at high energies. A 3-D model of the experiments is needed to help resolve the differences.

Prediction of LDEF exposure to the ionizing radiation environment.

Predictions of the LDEF mission's trapped proton and electron and galactic cosmic ray proton exposures have been made using the currently accepted models with improved resolution near mission end and better modeling of solar cycle effects. An extension of previous calculations, to provide a more definitive description of the LDEF exposure to ionizing radiation, is represented by trapped proton and electron flux as a function of mission time, presented considering altitude and solar activity variation during the mission and the change in galactic cosmic ray proton flux over the mission. Modifications of the AP8MAX and AP8MIN fluence led to a reduction of fluence by 20%. A modified interpolation model developed by Daly and Evans resulted in 30% higher dose and activation levels, which better agreed with measured values than results predicted using the Vette model.

Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers.

OBJECTIVE: To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers. METHODS: This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables. RESULTS: Risks of leukaemia, non-Hodgkin's lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia. CONCLUSION: This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range are warranted.

Retrospective benzene and total hydrocarbon exposure assessment for a petroleum marketing and distribution worker epidemiology study.

A quantitative exposure-estimating algorithm for benzene and total hydrocarbons was developed for a case control study of petroleum marketing and distribution workers. The algorithm used a multiplicative model to adjust recently measured quantitative exposure data to past scenarios for which representative exposure measurement data did not exist. This was accomplished through the development of exposure modifiers to account for differences in the workplace, the materials handled, the environmental conditions, and the tasks performed. Values for exposure modifiers were obtained empirically and through physical/chemical relationships. Dates for changes that altered exposure potential were obtained from archive records, retired employee interviews, and from current operations personnel. Exposure modifiers were used multiplicatively, adjusting available measured data to represent the relevant exposure scenario and time period. Changes in exposure modifiers translated to step changes in exposure estimates. Though limited by availability of data, a validation exercise suggested that the algorithm provided accurate exposure estimates for benzene (compared with measured data in industrial hygiene survey reports); the estimates generally differed by an average of less than 20% from the measured values. This approach is proposed to quantify exposures retrospectively where there are sufficient data to develop reliable current era estimates and where a historical accounting of key exposure modifiers can be developed, but where there are insufficient historic exposure measurements to directly assess historic exposures.