How Do Cancer Risks Predicted From Animal Bioassays Compare with the Epidemiologic Evidence? The Case of Ethylene Dibromide

Cancer risks for ethylene dibromide (EDB) were estimated by fitting several linear non-threshold additive models to data from a gavage bioassay. Risks predicted by these models were compared to the observed cancer mortality among a cohort of workers occupationally exposed to the same chemical. Models that accounted for the shortened latency period in the gavaged rats predicted upper bound risks that were within a factor of 3 of the observed cancer deaths. Data from an animal inhalation study of EDB also were compatible with the epidemiologic data. These findings contradict those of Ramsey et al. (1978), who reported that extrapolation from animal data produced highly exaggerated risk estimates for EDB-exposed workers. This paper explores the reasons for these discrepant findings.     

信息披露与银行的信誉

银行信誉的重要性来自于信息不对称的存在,强制信息披露能提高稳健型银行的信誉,并且信息披露的程度越高,稳健型银行的信誉也越高,但其对冒险型银行信誉的影响是不确定的.     

OSHA''s Permissible Exposure Limits: Regulatory Compliance Versus Health Risk

Workplace exposures to airborne chemicals are regulated in the U.S. by the Occupational Safety and Health Administration (OSHA) via the promulgation of permissible exposure limits (PELs). These limits, usually defined as eight-hour time-weighted average values, are enforced as concentrations never to be exceeded. In the case of chronic or delayed toxicants, the PEL is determined from epidemiological evidence and/or quantitative risk assessments based on long-term mean exposures or, equivalently, cumulative lifetime exposures. A statistical model was used to investigate the relation between the compliance strategy, the PEL as a limit never to be exceeded, and the health risk as measured by the probability that an individual's long-term mean exposure concentration is above the PEL. The model incorporates within-worker and between-worker variability in exposure, and assumes the relevant distributions to be log-normal. When data are inadequate to estimate the parameters of the full model, as it is in compliance inspections, it is argued that the probability of a random measurement being above the PEL must be regarded as a lower bound on the probability that a randomly selected worker's long-term mean exposure concentration will exceed the PEL. It is concluded that OSHA's compliance strategy is a reasonable, as well as a practical, means of limiting health risk for chronic or delayed toxicants.     

The Spread of a PCB Spill on a Soil Surface

Determining the fate of an oil spill on soil is often the first step in analyzing the risks of human exposure to hazardous viscous liquids such as PCBs. The special surface properties of rigidity and porosity are not among the boundary conditions in previous analyses of spills on water. The present work solves the expressions of mass and momentum conservation using a perturbation approach. Using the example of an Aroclor 1254 spill to illustrate the approach, we find that the radius at the halt of spreading is roughly proportional to spill volume for large spills. Spreading halts when the infiltration equals the spill volume. The radial distribution of infiltration decreases gradually from its central maximum, but falls suddenly to zero approaching the outer edge. Sample results are plotted for Aroclor 1254 spills from 4 to 21 liters in volume.     

Estimation of Potential Health Effects from Acute Exposure to Hydrogen Fluoride Using a "Benchmark Dose" Approach

Communities across the United States are examining the manufacture, use, transport, and storage of hydrogen fluoride (HF) near residential areas as a consequence of a major release of HF in Texas in 1987. Reference exposure levels for routine and accidental HF emissions are calculated using existing animal and human data. The approach employs a logprobit extrapolation of concentration-response data to the 95% lower confidence limit on the toxic concentration producing a "benchmark dose" of 1% response (TC01), called a practical threshold. Species-specific and chemical-specific adjustment factors are applied to develop exposure levels applicable to the general public. Using this method, the 1-hr reference exposure level to protect the public against any irritation from a routine emission (REL-1) is 0.7 ppm and the level to protect against severe irritation from a once-in-a-lifetime (REL-2) release is 2 ppm. This approach is compared to a modified "uncertainty factor" approach.     

Issues Related to Time Averaging of Exposure in Modeling Risks Associated with Intermittent Exposures to Lead

Typical exposures to lead often involve a mix of long-term exposures to relatively constant exposure levels (e.g., residential yard soil and indoor dust) and highly intermittent exposures at other locations (e.g., seasonal recreational visits to a park). These types of exposures can be expected to result in blood lead concentrations that vary on a temporal scale with the intermittent exposure pattern. Prediction of short-term (or seasonal) blood lead concentrations arising from highly variable intermittent exposures requires a model that can reliably simulate lead exposures and biokinetics on a temporal scale that matches that of the exposure events of interest. If exposure model averaging times (EMATs) of the model exceed the shortest exposure duration that characterizes the intermittent exposure, uncertainties will be introduced into risk estimates because the exposure concentration used as input to the model must be time averaged to account for the intermittent nature of the exposure. We have used simulation as a means of determining the potential magnitude of these uncertainties. Simulations using models having various EMATs have allowed exploration of the strengths and weaknesses of various approaches to time averaging of exposures and impact on risk estimates associated with intermittent exposures to lead in soil. The International Commission of Radiological Protection (ICRP) model of lead pharmacokinetics in humans simulates lead intakes that can vary in intensity over time spans as small as one day, allowing for the simulation of intermittent exposures to lead as a series of discrete daily exposure events. The ICRP model was used to compare the outcomes (blood lead concentration) of various time-averaging adjustments for approximating the time-averaged intake of lead associated with various intermittent exposure patterns. Results of these analyses suggest that standard approaches to time averaging (e.g., U.S. EPA) that estimate the long-term daily exposure concentration can, in some cases, result in substantial underprediction of short-term variations in blood lead concentrations when used in models that operate with EMATs exceeding the shortest exposure duration that characterizes the intermittent exposure. Alternative time-averaging approaches recommended for use in lead risk assessment more reliably predict short-term periodic (e.g., seasonal) elevations in blood lead concentration that might result from intermittent exposures. In general, risk estimates will be improved by simulation on shorter time scales that more closely approximate the actual temporal dynamics of the exposure.     

Assessment of Health Risk from Exposure to Contaminated Soil

The risk to human health posed by contaminated soil in a residential area depends on the potential extent of exposure to soil and on the toxic properties of the contaminants. A detailed soil exposure analysis is presented for young children, older children, and adults living in a house surrounded by contaminated soil. From this analysis, a lifetime exposure model is derived and used to assess chronic health risks.     

Consumption of Bovine Spongiform Encephalopathy (BSE) Contaminated Beef and the Risk of Variant Creutzfeldt‐Jakob Disease

To date, the variant Creutzfeldt‐Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE‐prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE‐contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrP^res aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age‐specific risk of infection, the hypothesis explains the observations very well from an extreme‐value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.     

Quantifying the Economic Impact of Hydraulic Fracturing Proppant Selection in Light of Occupational Exposure Risk and Functional Requirements

Selection of an effective and economic proppant material for hydraulic fracturing is an important design choice to optimize the production of oil and natural gas. Proppants are made of silica (quartz sand), alumina, resin-coated silica, ceramics, and others. These materials can be toxic to varying degrees and lead to health problems in the employees handling them primarily due to inhalation exposure. Proppants are selected based on grain size, shape, strength, and cost. Current use is dominated by crystalline silica—the proppant that also has the greatest hazard as an inhalation toxin. Existing research describes the effect of silica on human health, but little research has been done to determine the risk-reduction and social-cost-effectiveness associated with using alternative proppants in light of the health risks. This study quantifies the relative risks or benefits to human health by the use of these proppants through an economic analysis considering the health-related economic impact and its technical attributes. Results show that the use of each ton of silica proppant results in $123 of external costs from fatalities and nonfatal illness arising due to exposure to silica for a crew handing 60,000 tons of proppants. If these health-related externalities were incorporated into the cost, silica proppant could be economically replaced by less harmful, more expensive alternatives for hydraulic fracturing crews handling less than 60,000 tons of proppant each year.     

A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population‐Based Epidemiology and Experimental Animal Tests

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real‐life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound‐by‐compound strategy (1.6%).