Projection of future numbers of mesothelioma cases in the US and the increasing prevalence of background cases: an update based on SEER data for 1975 through 2018.

Historically, mesothelioma, which is almost exclusively a cancer of the pleura or peritoneum, has been referred to as a sentinel disease for asbestos exposure meaning that the disease is an epidemiologic marker for asbestos. This description of mesothelioma often has been misinterpreted to mean that the only risk factor for mesothelioma is asbestos. In addition to a few risk factors other than asbestos, in the US, background mesotheliomas, i.e. mesothelioma cases that are a consequence of spontaneous tumor formation, are the most prevalent number of cases after asbestos-associated cases.1 My analysis of SEER data for 1973 through 2005 published in 2009 projected that around 2040 virtually all mesothelioma cases in the US will be background cases. The update here, which is based on the most current SEER data, 1975 through 2018, and the same methods used in 2009 shows that the pattern of mesothelioma incidence is unchanged. Further, in general agreement with the analysis published in 2009, after 2040 virtually all mesothelioma cases, currently estimated to be approximately 1600 per year, will be background cases.

Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed.

Industrial-grade talc exposure and the risk of mesothelioma.

Industrial-grade talc deposits are complex mixtures of mineral particles and may vary substantially in composition across small geographical areas. Typical industrial-grade talc includes amphibole cleavage fragments, platy talc, serpentine minerals, talc in fibrous form, and a minor presence of transitional fibers. Industrial-grade talc was erroneously determined to be an asbestos-containing material due to an unintended consequence of Occupational Health and Safety Administration's (OSHA's) method for measuring airborne asbestos mandated in 1972. This error was repeated, most notably, by the National Institute for Occupational Safety and Health (NIOSH) in, 1980 for talc mined in northern New York State (NYS) by RT Vanderbilt Company (RTV). Subsequent exposure studies of northern NYS talc conducted through the, 1980s and one study published after, 2000 relied on the conclusion that talc was an asbestos-containing material to infer a causal relationship between talc and mesothelioma. The present review included (1) publications concerning talc's cancer-causing potential issued by organizations concerned with occupational and public health; (2) talc exposure studies and animal and cellular studies of RTV talc; (3) mesothelioma rates in northern NYS; and (4) mesothelioma mortality among RTV mining employees. The review indicated that failure to correctly identify the mineral characteristics of talc resulted in misleading reports concerning the carcinogenic potential of talc. However, the collective data from animal and cellular studies, mesothelioma rates in northern NYS, exposure studies, and a mortality analysis of RTV mining employees do not support a causal relationship between RTV talc and mesothelioma. This conclusion is applicable to all mineral components in RTV talc and to other industrial-grade talcs and mineral aggregates with the same components.

Alternative estimate of source distribution in microbial source tracking using posterior probabilities.

Microbial source tracking (MST) is a procedure used to determine the relative contributions of humans and animals to fecal microbial contamination of surface waters in a given watershed. Studies of MST methodology have focused on optimizing sampling, laboratory, and statistical analysis methods in order to improve the reliability of determining which sources contributed most to surface water fecal contaminant. The usual approach for estimating a source distribution of microbial contamination is to classify water sample microbial isolates into discrete source categories and calculate the proportion of these isolates in each source category. The set of proportions is an estimate of the contaminant source distribution. In this paper we propose and compare an alternative method for estimating a source distribution-averaging posterior probabilities of source identity across isolates. We conducted a Monte Carlo simulation covering a wide variety of watershed scenarios to compare the two methods. The results show that averaging source posterior probabilities across isolates leads to more accurate source distribution estimates than proportions that follow classification.

Time trend of mesothelioma incidence in the United States and projection of future cases: an update based on SEER data for 1973 through 2005.

The time trend of mesothelioma incidence and projections of future cases provide useful information for analyzing proposed public health interventions where asbestos exposure may be an issue, evaluating regulatory proposals, and estimating the remaining potential costs of programs to compensate individuals with asbestos-related diseases. We used the April 2008 release of Surveillance, Epidemiology, and End Results (SEER) data, which covers 1973 through 2005, to analyze the time trends in age-adjusted mesothelioma incidence and to estimate an age and birth-cohort model to project the number of future mesothelioma cases. The increase in the number of SEER cancer registries from 13 to 17 in 2000 had little effect on the time pattern of age-adjusted mesothelioma incidence, and the pattern over time of pleural mesothelioma was indistinguishable from the pattern for total mesothelioma defined as sum of pleural and peritoneal cases. Our analysis suggests that the SEER registries viewed as a sample of the U.S. population over-represents high mesothelioma incidence, a fact that we accounted for in our projections. For 2008 we estimate approximately 2,400 cases, with asbestos the likely cause in 58%. We project that asbestos will no longer be a factor in mesothelioma cases after the year 2042. For 2008 through 2042, we estimate slightly more than 68,000 total cases, with asbestos the likely cause in 34%.

Exposure to airborne amphibole structures and health risks: Libby, Montana.

Libby, Montana is the site of a large vermiculite deposit that was mined between 1920 and 1990 to extract vermiculite for commercial applications such as insulation, gardening products, and construction materials. The Libby vermiculite deposit also contains amphibole minerals including tremolite, actinolite, richterite, and winchite. Historically, Libby mine workers experienced high exposures to amphibole structures, and, as a group, have experienced the health consequences of those occupational exposures. It has been suggested that Libby residents also have been and continue to be exposed to amphibole structures released during the vermiculite mining operations and therefore are at increased risk for disease. The Agency for Toxic Substance and Disease Registry (ATSDR) conducted two epidemiological-type studies of residents living in Libby and the surrounding areas to assess these risks. The Environmental Protection Agency (EPA) collected and analyzed exposure data in Libby and used those data to project risks of asbestos-associated disease for Libby residents. The EPA has placed the Libby Asbestos Site, which includes the mine and the town of Libby, on its National Priority List of hazardous waste sites in need of clean up. This article presents a review of the exposure studies conducted in Libby and an analysis of health risks based on the data collected in those studies. Libby mine workers have experienced elevated levels of asbestos-associated disease as a consequence of their occupational exposures to amphibole structures. Libby residents' exposures typically are substantially lower than mine workers' historical exposures, and the health risk projections for residents are, accordingly, substantially lower.

A comparison of ARA and DNA data for microbial source tracking based on source-classification models developed using classification trees.

The literature on microbial source tracking (MST) suggests that DNA analysis of fecal samples leads to more reliable determinations of bacterial sources of surface water contamination than antibiotic resistance analysis (ARA). Our goal is to determine whether the increased reliability, if any, in library-based MST developed with DNA data is sufficient to justify its higher cost, where the bacteria source predictions are used in TMDL surface water management programs. We describe an application of classification trees for MST applied to ARA and DNA data from samples collected in the Potomac River Watershed in Maryland. Conclusions concerning the comparison of ARA and DNA data, although preliminary at the current time, suggest that the added cost of obtaining DNA data in comparison to the cost of ARA data may not be justified, where MST is applied in TMDL surface water management programs.

Influence of seasonality and exposure on the accumulation and reproductive effects of p,p'-dichlorodiphenyldichloroethane and dieldrin in largemouth bass.

Two studies investigated the accumulation and reproductive effects of p,p'-dichlorodiphenyldichloroethane (DDE) and dieldrin over 30 or 120 d of oral exposure in captive Florida, USA, largemouth bass (Micropterus salmoides floridanus). The 30-d exposures were conducted during the peak reproductive season, and the 120-d study was conducted to simulate exposure throughout the ovarian cycle. Whole body chemical residue concentrations were similar, regardless of exposure duration, for the medium and high feed concentrations of either chemical; however, the low-dose residue concentrations were much lower, yet similar to natural exposures. No clear dose-response relationships were identified between chemical dose and morphological (length, weight, hepatosomatic index) or reproductive endpoints (sex steroid concentration, gonadosomatic index, percentage of fry hatching). Reproductive parameters were variable within treatment groups, indicating that circulating sex steroids and percent hatch endpoints have high natural variability among fish of the same age and reproductive stage. However, in general there was a decrease in plasma estradiol and 11-ketotestosterone for female and male fish, respectively, that were exposed to dieldrin. Overall, results suggest that exposure throughout ovarian (follicular) development to either DDE or dieldrin alone does not result in the depressed endocrine status and poor reproductive success reported in highly organochlorine pesticide-contaminated environments in Central Florida, USA.

Classification tree method for bacterial source tracking with antibiotic resistance analysis data.

Various statistical classification methods, including discriminant analysis, logistic regression, and cluster analysis, have been used with antibiotic resistance analysis (ARA) data to construct models for bacterial source tracking (BST). We applied the statistical method known as classification trees to build a model for BST for the Anacostia Watershed in Maryland. Classification trees have more flexibility than other statistical classification approaches based on standard statistical methods to accommodate complex interactions among ARA variables. This article describes the use of classification trees for BST and includes discussion of its principal parameters and features. Anacostia Watershed ARA data are used to illustrate the application of classification trees, and we report the BST results for the watershed.

Mesothelioma: risk apportionment among asbestos exposure sources.

The mesothelioma epidemic in the United States, which peaked during the 2000-2004 period, can be traced to high-level asbestos exposures experienced by males in occupational settings prior to the full recognition of the disease-causing potential of asbestos and the establishment of enforceable asbestos exposure limits by the Occupational Safety and Health Administration (OSHA) in 1971. Many individuals diagnosed with mesothelioma where asbestos has been identified as a contributing cause of the disease have filed claims seeking compensation from asbestos settlement trusts or through the court system. An individual with mesothelioma typically has been exposed to asbestos in more than one setting and from more than one asbestos product. Apportioning risk for mesothelioma among contributing factors is an ongoing problem faced by occupational disease compensation boards, juries, parties responsible for paying damages, and currently by the U.S. Senate in its efforts to formulate a bill establishing an asbestos settlement trust. In this article we address the following question: If an individual with mesothelioma where asbestos has been identified as a contributing cause were to be compensated for his or her disease, how should that compensation be apportioned among those responsible for the asbestos exposures? For the purposes of apportionment, we assume that asbestos is the only cause of mesothelioma and that every asbestos exposure contributes, albeit differentially, to the risk. We use an extension of the mesothelioma risk model initially proposed in the early 1980s to quantify the contribution to risk of each exposure as a percentage of the total risk. The percentage for each specific discrete asbestos exposure depends on the start and end dates, the intensity, and the asbestos fiber type for the exposure. We provide justification for the use of the mesothelioma risk model for apportioning risk and discuss how to assess uncertainty associated with its application.

Risk assessment for asbestos-related cancer from the 9/11 attack on the World Trade Center.

OBJECTIVE: We sought to estimate the lifetime risk of asbestos-related cancer for residents of Lower Manhattan attributable to asbestos released into the air by the 9/11 attack on New York City's World Trade Center (WTC). METHODS: Exposure was estimated from available data and reasoned projections based on these data. Cancer risk was assessed using an asbestos risk model that differentiates asbestos fiber-types and the US Environmental Protection Agency's model that does not differentiate fiber-types and combines mesothelioma and lung cancer risks. RESULTS: The upper limit for the expected number of asbestos-related cancers is less than one case over the lifetime of the population for the risk model that is specific for fiber-types and 12 asbestos-related cancers with the US Environmental Protection Agency's model. CONCLUSIONS: The cancer risk associated with asbestos exposures for residents of Lower Manhattan resulting from the collapse of the WTC is negligible.

Interactive effects of p,p'-dichlorodiphenyldichloroethylene and methoxychlor on hormone synthesis in largemouth bass ovarian cultures.

p,p'-Dichlorodiphenyldichloroethylene (DDE) and methoxychlor were tested alone and in combination to assess the similarity of their actions on hormone synthesis in gonadal tissue from largemouth bass (Micropterus salmoides floridanus), a species whose reproductive fitness has relevance to ecosystem health in Florida (USA). Gonads were harvested from adult female bass (age, two to three years) during the peak reproductive season (January-May), minced, and incubated in culture medium with or without test agents for 48 h. Duplicates of each treatment were performed in each of three experiments using tissue from a different female. Both 17beta-estradiol and testosterone were measured in aliquots of culture medium by validated radioimmunoassay procedures. Dose-response relationships of individual agents were characterized over a 6-log concentration range (1 X 10(-2) to 1 X 10(4) ppb). Both DDE and methoxychlor, tested individually, produced a dose-dependent decrease in testosterone levels. 17beta-Estradiol levels were unaffected. Mixtures of the agents were tested at all concentration combinations of 0.01, 1, 100, and 10,000 ppb in culture medium. Statistical tests indicated that of 16 dose combinations tested, 15 were antagonistic, and only 1 was additive based on the Loewe additivity model of no interaction. These results imply that methoxychlor and DDE inhibit testosterone production by different mechanisms in bass ovaries.

Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003.

Using 1973-2000 mesothelioma incidence data released by the Surveillance, Epidemiology, and End Results Program in April 2003, the authors estimated the parameters of a birth-cohort and age model to determine whether previously reported patterns of mesothelioma in the United States have changed. Compared with analyses based on data through 1992, a slower decline was found in male cases immediately after a peak in 2000-2004, but no other notable changes in the time pattern were detected. Analysis confirmed that the annual number of male mesothelioma cases, which increased steeply from the 1970s through the mid-1990s, has leveled off in terms of both the age-adjusted rate and the absolute numbers of cases. After a peak of approximately 2,000 cases, a return to background levels is expected by 2055. The total projected number of male mesothelioma cases in 2003-2054 is approximately 71,000. The maximum lifetime risk for males, which occurs for the 1925-1929 birth cohort, is 1.8 x 10(-3). The age-adjusted rate for females is constant, as are the female lifetime mesothelioma risk across birth cohorts (3.6 x 10(-4)) and the annual risk (3.9 x 10(-6)). The time pattern of cases for females supports the existence of a threshold exposure for mesothelioma and a quantifiable background rate.