Tiered Chemical Testing: A Value of Information Approach

In December 2000 the EPA initiated the Voluntary Children's Chemical Evaluation Program (VCCEP) by asking manufacturers to voluntarily sponsor toxicological testing in a tiered process for 23 chemicals selected for the pilot phase. The tiered nature of the VCCEP pilot program creates the need for clearly defined criteria for determining when information is sufficient to assess the potential risks to children. This raises questions about how to determine the "adequacy" of the existing information and assess the need to undertake efforts to reduce uncertainty (through further testing). This article applies a value of information analysis approach to determine adequacy by modeling how toxicological and exposure data collected through the VCCEP may be used to inform risk management decisions. The analysis demonstrates the importance of information about the exposure level and control costs in making decisions regarding further toxicological testing. This article accounts for the cost of delaying control action and identifies the optimal testing strategy for a constrained decisionmaker who, absent applicable human data, cannot regulate without bioassay data on a specific chemical. It also quantifies the differences in optimal testing strategy for three decision criteria: maximizing societal net benefits, ensuring maximum exposure control while net benefits are positive (i.e., benefits outweigh costs), and controlling to the maximum extent technologically feasible while the lifetime risk of cancer exceeds a specific level of risk. Finally, this article shows the large differences that exist in net benefits between the three criteria for the range of exposure levels where the optimal actions differ.     

Engaging Expert Peers in the Development of Risk Assessments

The participation of external technical experts in the development of risk assessment documents and methodologies has expanded and evolved in recent years. Many government agencies and authoritative organizations have experts peer review important works to evaluate the scientific and technical defensibility and judge the strength of the assumptions and conclusions (OMB, 2004; IPCS, 2005; IARC, 2006; Health Canada, 2007; U.S. EPA, 2006). Expert advice has been solicited in other forms of peer involvement, including peer consultation in, for example, the U.S. EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). This article discusses how the principles and practices of peer review can be extended to other types of peer involvement activities (i.e., peer input and peer consultation) to develop high-quality risk assessment work products. A comprehensive process for incorporating peer input, peer consultation, and peer review into risk assessment science is outlined. Four key principles for peer involvement-independence, inclusion of appropriate experts, transparency, and a robust scientific process-are discussed. Recent examples of peer involvement in the development of Health Canada's Priority Substances and Domestic Substance List (DSL) programs under the Canadian Environmental Protection Act (CEPA) serve to highlight the concepts.     

A Framework and Case Study for Exposure Assessment in the Voluntary Children''s Chemical Evaluation Program

A conceptual framework is presented for conducting exposure assessments under the U.S. EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). The VCCEP is a voluntary program whereby companies that manufacture chemicals of potential concern are asked to conduct hazard, exposure, and risk assessments for the chemicals. The VCCEP is unique in its risk-based, tiered approach, and because it focuses on children and requires a comprehensive consideration of all reasonably foreseeable exposure pathways for a particular chemical. The consideration of all potential exposure pathways for some commonly used chemicals presents a daunting challenge for the exposure assessor. This article presents a framework for managing this complicated process, and illustrates the application of the framework with a hypothetical case study. The framework provides guidance for interpreting multiple sources of exposure information and developing a plausible list of exposure pathways for a chemical. Furthermore, the framework provides a means to process all the available information to eliminate pathways of negligible concern from consideration. Finally, the framework provides guidance for utilizing the tiered approach of VCCEP to efficiently conduct an assessment by first using simple, screening-level approaches and then, if necessary, using more complex, refined exposure assessment methods. The case study provides an illustration of the major concepts.     

Assessing Cancer Risks from Short-Term Exposures in Children

For the vast majority of chemicals that have cancer potency estimates on IRIS, the underlying database is deficient with respect to early-life exposures. This data gap has prevented derivation of cancer potency factors that are relevant to this time period, and so assessments may not fully address children's risks. This article provides a review of juvenile animal bioassay data in comparison to adult animal data for a broad array of carcinogens. This comparison indicates that short-term exposures in early life are likely to yield a greater tumor response than short-term exposures in adults, but similar tumor response when compared to long-term exposures in adults. This evidence is brought into a risk assessment context by proposing an approach that: (1) does not prorate children's exposures over the entire life span or mix them with exposures that occur at other ages; (2) applies the cancer slope factor from adult animal or human epidemiology studies to the children's exposure dose to calculate the cancer risk associated with the early-life period; and (3) adds the cancer risk for young children to that for older children/adults to yield a total lifetime cancer risk. The proposed approach allows for the unique exposure and pharmacokinetic factors associated with young children to be fully weighted in the cancer risk assessment. It is very similar to the approach currently used by U.S. EPA for vinyl chloride. The current analysis finds that the database of early life and adult cancer bioassays supports extension of this approach from vinyl chloride to other carcinogens of diverse mode of action. This approach should be enhanced by early-life data specific to the particular carcinogen under analysis whenever possible.     

Statistical Distributions of Daily Breathing Rates for Narrow Age Groups of Infants and Children

Children may be more susceptible to toxicity from some environmental chemicals than adults. This susceptibility may occur during narrow age periods (windows), which can last from days to years depending on the toxicant. Breathing rates specific to narrow age periods are useful to assess inhalation dose during suspected windows of susceptibility. Because existing breathing rates used in risk assessment are typically for broad age ranges or are based on data not representative of the population, we derived daily breathing rates for narrow age ranges of children designed to be more representative of the current U.S. children's population. These rates were derived using the metabolic conversion method of Layton (1993) and energy intake data adjusted to represent the U.S. population from a relatively recent dietary survey (CSFII 1994–1996, 1998). We calculated conversion factors more specific to children than those previously used. Both nonnormalized (L/day) and normalized (L/kg-day) breathing rates were derived and found comparable to rates derived using energy estimates that are accurate for the individuals sampled but not representative of the population. Estimates of breathing rate variability within a population can be used with stochastic techniques to characterize the range of risk in the population from inhalation exposures. For each age and age-gender group, we present the mean, standard error of the mean, percentiles (50th, 90th, and 95th), geometric mean, standard deviation, 95th percentile, and best-fit parametric models of the breathing rate distributions. The standard errors characterize uncertainty in the parameter estimate, while the percentiles describe the combined interindividual and intra-individual variability of the sampled population. These breathing rates can be used for risk assessment of subchronic and chronic inhalation exposures of narrow age groups of children.     

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment

We review approaches for characterizing “peak” exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose–response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to “peak” exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose–response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose–response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no‐threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose–response metrics will be supported. “Peak” exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of “peak” exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short‐term high‐intensity exposures increase risk.     

Identifying Childhood Age Groups for Exposure Assessments and Monitoring

The purpose of this article is to describe a standard set of age groups for exposure assessors to consider when assessing childhood exposure and potential dose to environmental contaminants. In addition, this article presents examples to show how the age groups can be applied in children's exposure assessments. A consistent set of childhood age groups, supported by an underlying scientific rationale, will improve the accuracy and comparability of exposure and risk assessments for children. The effort was undertaken in part to aid the U.S. Environmental Protection Agency (EPA) in implementing such regulatory initiatives as the 1997 Presidential Executive Order 13,045, which required all federal agencies to ensure that their standards take into account special risks to children. The standard age groups include: birth to <1 month; 1 to <3 months; 3 to <6 months; 6 to <12 months; 1 to <2 years; 2 to <3 years; 3 to <6 years; 6 to <11 years; 11 to <16 years; and 16 to <21 years. These age groups reflect a consideration of developmental changes in various behavioral, anatomical, and physiological characteristics that impact exposure and potential dose. It is expected that the availability of a standard set of early-life age groups will inform future analyses of exposure factors data as well as guide new research and data collection efforts to fill knowledge gaps.     

Assessment of Inhalation Exposures and Potential Health Risks to the General Population that Resulted from the Collapse of the World Trade Center Towers

In the days following the collapse of the World Trade Center (WTC) towers on September 11, 2001 (9/11), the U.S. Environmental Protection Agency (EPA) initiated numerous air monitoring activities to better understand the ongoing impact of emissions from that disaster. Using these data, EPA conducted an inhalation exposure and human health risk assessment to the general population. This assessment does not address exposures and potential impacts that could have occurred to rescue workers, firefighters, and other site workers, nor does it address exposures that could have occurred in the indoor environment. Contaminants evaluated include particulate matter (PM), metals, polychlorinated biphenyls, dioxins, asbestos, volatile organic compounds, particle-bound polycyclic aromatic hydrocarbons, silica, and synthetic vitreous fibers (SVFs). This evaluation yielded three principal findings. (1) Persons exposed to extremely high levels of ambient PM and its components, SVFs, and other contaminants during the collapse of the WTC towers, and for several hours afterward, were likely to be at risk for acute and potentially chronic respiratory effects. (2) Available data suggest that contaminant concentrations within and near ground zero (GZ) remained significantly elevated above background levels for a few days after 9/11. Because only limited data on these critical few days were available, exposures and potential health impacts could not be evaluated with certainty for this time period. (3) Except for inhalation exposures that may have occurred on 9/11 and a few days afterward, the ambient air concentration data suggest that persons in the general population were unlikely to suffer short-term or long-term adverse health effects caused by inhalation exposures. While this analysis by EPA evaluated the potential for health impacts based on measured air concentrations, epidemiological studies conducted by organizations other than EPA have attempted to identify actual impacts. Such studies have identified respiratory effects in worker and general populations, and developmental effects in newborns whose mothers were near GZ on 9/11 or shortly thereafter. While researchers are not able to identify specific times and even exactly which contaminants are the cause of these effects, they have nonetheless concluded that exposure to WTC contaminants (and/or maternal stress, in the case of developmental effects) resulted in these effects, and have identified the time period including 9/11 itself and the days and few weeks afterward as a period of most concern based on high concentrations of key pollutants in the air and dust.     

Improving Cancer Dose–Response Characterization by Using Physiologically Based Pharmacokinetic Modeling: An Analysis of Pooled Data for Acrylonitrile-Induced Brain Tumors to Assess Cancer Potency in the Rat

Historically, U.S. regulators have derived cancer slope factors by using applied dose and tumor response data from a single key bioassay or by averaging the cancer slope factors of several key bioassays. Recent changes in U.S. Environmental Protection Agency (EPA) guidelines for cancer risk assessment have acknowledged the value of better use of mechanistic data and better dose–response characterization. However, agency guidelines may benefit from additional considerations presented in this paper. An exploratory study was conducted by using rat brain tumor data for acrylonitrile (AN) to investigate the use of physiologically based pharmacokinetic (PBPK) modeling along with pooling of dose–response data across routes of exposure as a means for improving carcinogen risk assessment methods. In this study, two contrasting assessments were conducted for AN-induced brain tumors in the rat on the basis of (1) the EPA's approach, the dose–response relationship was characterized by using administered dose/concentration for each of the key studies assessed individually; and (2) an analysis of the pooled data, the dose–response relationship was characterized by using PBPK-derived internal dose measures for a combined database of ten bioassays. The cancer potencies predicted for AN by the contrasting assessments are remarkably different (i.e., risk-specific doses differ by as much as two to four orders of magnitude), with the pooled data assessments yielding lower values. This result suggests that current carcinogen risk assessment practices overestimate AN cancer potency. This methodology should be equally applicable to other data-rich chemicals in identifying (1) a useful dose measure, (2) an appropriate dose–response model, (3) an acceptable point of departure, and (4) an appropriate method of extrapolation from the range of observation to the range of prediction when a chemical's mode of action remains uncertain.     

A Distributed Parameter Physiologically-Based Pharmacokinetic Model for Dermal and Inhalation Exposure to Volatile Organic Compounds

Estimates of dermal dose from exposures to toxic chemicals are typically derived using models that assume instantaneous establishment of steady-state dermal mass flux. However, dermal absorption theory indicates that this assumption is invalid for short-term exposures to volatile organic chemicals (VOCs). A generalized distributed parameter physiologically-based pharmacokinetic model (DP-PBPK), which describes unsteady state dermal mass flux via a partial differential equation (Fickian diffusion), has been developed for inhalation and dermal absorption of VOCs. In the present study, the DP-PBPK model has been parameterized for chloroform, and compared with two simpler PBPK models of chloroform. The latter are lumped parameter models, employing ordinary differential equations, that do not account for the dermal absorption time lag associated with the accumulation of permeant chemical in tissue represented by permeability coefficients. All three models were evaluated by comparing simulated post-exposure exhaled breath concentration profiles with measured concentrations following environmental chloroform exposures. The DP-PBPK model predicted a time-lag in the exhaled breath concentration profile, consistent with the experimental data. The DP-PBPK model also predicted significant volatilization of chloroform, for a simulated dermal exposure scenario. The end-exposure dermal dose predicted by the DP-PBPK model is similar to that predicted by the EPA recommended method for short-term exposures, and is significantly greater than the end-exposure dose predicted by the lumped parameter models. However, the net dermal dose predicted by the DP-PBPK model is substantially less than that predicted by the EPA method, due to the post-exposure volatilization predicted by the DP-PBPK model. Moreover, the net dermal dose of chloroform predicted by all three models was nearly the same, even though the lumped parameter models did not predict substantial volatilization.     

A Quantitative Analysis of Factors Affecting PELs and TLVs for Carcinogens

For carcinogens, this paper provides a quantitative examination of the roles of potency and weight-of-evidence (WOE) in setting permissible exposure limits (PELs) at the U.S. Occupational Safety and Health Administration (OSHA) and threshold limit values (TLVs) at the private American Conference of Governmental Industrial Hygienists (ACGIH). On normative grounds, both of these factors should influence choices about the acceptable level of exposures. Our major objective is to examine whether and in what ways these factors have been considered by these organizations. A lesser objective is to identify outliers, which might be candidates for further regulatory scrutiny. Our sample (N=48) includes chemicals for which EPA has estimated a unit risk as a measure of carcinogenic potency and for which OSHA or the ACGIH has a PEL or TLV. Different assessments of the strength of the evidence of carcinogenicity were obtained from EPA, ACGIH, and the International Agency for Research on Cancer. We found that potency alone explains 49% of the variation in PELs and 62% of the variation in TLVs. For the ACGIH, WOE plays a much smaller role than potency. TLVs set by the ACGIH since 1989 appear to be stricter than earlier TLVs. We suggest that this change represents evidence that the ACGIH had responded to criticisms leveled at it in the late 1980s for failing to adopt sufficiently protective standards. The models developed here identify 2-nitropropane, ethylene dibromide, and chromium as having OSHA PELs significantly higher than predicted on the basis of potency and WOE.     

A Tiered Framework for Risk‐Relevant Characterization and Ranking of Chemical Exposures: Applications to the National Children's Study (NCS)

A challenge for large‐scale environmental health investigations such as the National Children's Study (NCS), is characterizing exposures to multiple, co‐occurring chemical agents with varying spatiotemporal concentrations and consequences modulated by biochemical, physiological, behavioral, socioeconomic, and environmental factors. Such investigations can benefit from systematic retrieval, analysis, and integration of diverse extant information on both contaminant patterns and exposure‐relevant factors. This requires development, evaluation, and deployment of informatics methods that support flexible access and analysis of multiattribute data across multiple spatiotemporal scales. A new “Tiered Exposure Ranking” (TiER) framework, developed to support various aspects of risk‐relevant exposure characterization, is described here, with examples demonstrating its application to the NCS. TiER utilizes advances in informatics computational methods, extant database content and availability, and integrative environmental/exposure/biological modeling to support both “discovery‐driven” and “hypothesis‐driven” analyses. “Tier 1” applications focus on “exposomic” pattern recognition for extracting information from multidimensional data sets, whereas second and higher tier applications utilize mechanistic models to develop risk‐relevant exposure metrics for populations and individuals. In this article, “tier 1” applications of TiER explore identification of potentially causative associations among risk factors, for prioritizing further studies, by considering publicly available demographic/socioeconomic, behavioral, and environmental data in relation to two health endpoints (preterm birth and low birth weight). A “tier 2” application develops estimates of pollutant mixture inhalation exposure indices for NCS counties, formulated to support risk characterization for these endpoints. Applications of TiER demonstrate the feasibility of developing risk‐relevant exposure characterizations for pollutants using extant environmental and demographic/socioeconomic data.     

Use of Markov Chain Monte Carlo Analysis with a Physiologically-Based Pharmacokinetic Model of Methylmercury to Estimate Exposures in U.S. Women of Childbearing Age

A Bayesian approach, implemented using Markov Chain Monte Carlo (MCMC) analysis, was applied with a physiologically‐based pharmacokinetic (PBPK) model of methylmercury (MeHg) to evaluate the variability of MeHg exposure in women of childbearing age in the U.S. population. The analysis made use of the newly available National Health and Nutrition Survey (NHANES) blood and hair mercury concentration data for women of age 16–49 years (sample size, 1,582). Bayesian analysis was performed to estimate the population variability in MeHg exposure (daily ingestion rate) implied by the variation in blood and hair concentrations of mercury in the NHANES database. The measured variability in the NHANES blood and hair data represents the result of a process that includes interindividual variation in exposure to MeHg and interindividual variation in the pharmacokinetics (distribution, clearance) of MeHg. The PBPK model includes a number of pharmacokinetic parameters (e.g., tissue volumes, partition coefficients, rate constants for metabolism and elimination) that can vary from individual to individual within the subpopulation of interest. Using MCMC analysis, it was possible to combine prior distributions of the PBPK model parameters with the NHANES blood and hair data, as well as with kinetic data from controlled human exposures to MeHg, to derive posterior distributions that refine the estimates of both the population exposure distribution and the pharmacokinetic parameters. In general, based on the populations surveyed by NHANES, the results of the MCMC analysis indicate that a small fraction, less than 1%, of the U.S. population of women of childbearing age may have mercury exposures greater than the EPA RfD for MeHg of 0.1 μg/kgg/day, and that there are few, if any, exposures greater than the ATSDR MRL of 0.3 μgg/kgg/day. The analysis also indicates that typical exposures may be greater than previously estimated from food consumption surveys, but that the variability in exposure within the population of U.S. women of childbearing age may be less than previously assumed.     

The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models

Physiologically‐based pharmacokinetic (PBPK) models are often submitted to or selected by agencies, such as the U.S. Environmental Protection Agency (U.S. EPA) and Agency for Toxic Substances and Disease Registry, for consideration for application in human health risk assessment (HHRA). Recently, U.S. EPA evaluated the human PBPK models for perchlorate and radioiodide for their ability to estimate the relative sensitivity of perchlorate inhibition on thyroidal radioiodide uptake for various population groups and lifestages. The most well‐defined mode of action of the environmental contaminant, perchlorate, is competitive inhibition of thyroidal iodide uptake by the sodium‐iodide symporter (NIS). In this analysis, a six‐step framework for PBPK model evaluation was followed, and with a few modifications, the models were determined to be suitable for use in HHRA to evaluate relative sensitivity among human lifestages. Relative sensitivity to perchlorate was determined by comparing the PBPK model predicted percent inhibition of thyroidal radioactive iodide uptake (RAIU) by perchlorate for different lifestages. A limited sensitivity analysis indicated that model parameters describing urinary excretion of perchlorate and iodide were particularly important in prediction of RAIU inhibition; therefore, a range of biologically plausible values available in the peer‐reviewed literature was evaluated. Using the updated PBPK models, the greatest sensitivity to RAIU inhibition was predicted to be the near‐term fetus (gestation week 40) compared to the average adult and other lifestages; however, when exposure factors were taken into account, newborns were found to be populations that need further evaluation and consideration in a risk assessment for perchlorate.     

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 U.S. EPA Geographic Information System for Mapping Environmental Releases of Toxic Chemical Release Inventory (TRI) Chemicals

This study characterizes the environmental releases of toxic chemicals of the Toxic Chemical Release Inventory (TRI) in the southeastern United States by using the U.S. Environmental Protection Agency (EPA) Geographic Information System (GIS) to map them. These maps show that the largest quantities of TRI releases in the Southeast are usually near densely populated areas. This GIS mapping approach takes the first steps in defining those areas in the region which may be potential exposure zones and which could be strategic targets for future risk screening efforts in this geographic area.     

Assessing Health Risks Associated with DDT Residues in Soils in California: A Proposition 65 Case Study

Population growth in California has increased the pressure to convert agricultural land to commercial, industrial, or residential uses. In the ensuing property transactions, buyers and sellers must address the presence of toxic materials in soils such as pesticides, several of which are known to the State of California to cause cancer under Proposition 65. While this statute does not specifically address soil contaminants, the potential scope of its enforcement is sufficiently broad that owners of former agricultural properties may be obliged to provide warning of exposure to potential buyers, occupants, or construction workers about exposure to residues in soil from pesticide applications. However, Proposition 65 provides no guidance on how to assess exposures to chemicals in soil. The U.S. EPA Risk Assessment Guidance for Superfund (RAGS) provides a method for assessing soil-related exposure pathways that is consistent with the intent of Proposition 65. Using this approach, we have calculated the lifetime average concentrations of DDT in soil corresponding to the no-significant-risk level stipulated under Proposition 65 (1 × 10⁻⁵) for a hypothetical residential exposure scenario. The concentration of DDT in soil corresponding to a no-significant-risk ranges from 7.9-18.8 mg/kg, depending upon which exposure pathways are deemed to be complete for residential land use. It is argued that Proposition 65 forces the assessment and possible cleanup of such a situation through the threat of creating a health risk perception that could affect the market value of a property.     

Re-evaluation of the Reference Dose for Methylmercury and Assessment of Current Exposure Levels

Methylmercury (Me-Hg) is widely distributed through freshwater and saltwater food chains and human consumption of fish and shellfish has lead to widespread exposure. Both the U.S. EPA Reference Dose (0.3 μg/kg/day) and the FAO/WHO Permissible Tolerable Weekly Intake (3.3 μg/kg/week) are currently based on the prevention of paraesthesia in adult and older children. However, Me-Hg exposure in utero is known to result in a range of developmental neurologic effects including clinical CNS symptoms and delayed onset of walking. Based on a critical review of developmental toxicity data from human and animal studies, it is concluded that current guidelines for the prevention of paraesthesia are not adequate to address developmental effects. A dose of 0.07 μ/kg/day is suggested as the best estimate of a potential reference dose for developmental effects. Data on nationwide fish consumption rates and Me-Hg levels in fish/seafood weighted by proportion of the catch intended for human consumption are analyzed in a Monte Carlo simulation to derive a probability distribution of background Me-Hg exposure. While various uncertainties in the toxicologic and exposure data limit the precision with which health risk can be estimated, this analysis suggests that at current levels of Me-Hg exposure, a significant fraction of women of childbearing age have exposures above this suggested reference dose.     

Aldrin and Dieldrin: A Reevaluation of the Cancer and Noncancer Dose‐Response Assessments

The dose‐response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg‐day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg‐day)^?1, respectively (i.e., about 5‐ and 2.3‐fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA.     

Building a performance-based environmental management system: EPA's reinvention efforts revisited

A new U.S. Environmental Protection Agency (EPA) report recommends the Agency do more to help well-meaning companies comply with the law and encourage those that are willing and able to do even more. Since 1996, major stakeholders have achieved consensus on the need and desire to create a ‘performance-base’ environmental managemeny system. Whereas most agree that a performance-based system is necessary for the future, few agree on when or how the EPA should design and implement it. The design of a new performance track, one developed and operated in parallel with the existing regulatory system, utilizing emerging environmental management techniques and complementary policy developments, is close at hand, but needs reinvigorated support to be applied on a greater scale and with more confidence.In this article, the first in a two part series, Monsma and Mazurek show why the design and implementation of a new, federal performance-based environmental management track should not be deterred. Drawing from the lessons of prominent EPA pilot programs such as 33/50, the Common Sense Initiative, and Project XL, the authors identify a set of lessons for a performance-based system. In part two of the series (to appear next issue) the authors will discuss the political economics of reinvention and try to determine the best means out of the current maze.