Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachus... more Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachusetts are exposed to cumulative, chronic built-environment stressors, and have limited capacity to respond, magnifying their vulnerability to adverse health outcomes. "Neighborhood STRENGTH", our community based participatory research (CBPR) project, comprised four partners: a youth center; an environmental non-profit; a community based health center; and a university. Unlike most CBPR projects that are single topic-focused, our 'holistic', systems-based project targeted five priorities. The three research-focused/action-oriented components were: 1) participatory monitoring of indoor and outdoor pollution; 2) learning about health needs and concerns of residents through community based listening sessions; and 3) engaging in collaborative survey work, including a household vulnerability survey and an asthma prevalence survey for schoolchildren. The two action-focused/research-informed components were: 4) tackling persistent street trash and illegal dumping strategically; and 5) educating and empowering youth to promote environmental justice. We used a coupled CBPR-capacity building approach to design, vulnerability theory to frame, and mixed methods: quantitative environmental testing and qualitative surveys. Process and outcomes yielded important lessons: vulnerability theory helps frame issues holistically; having several topic-based projects yielded useful information, but was hard to manage and articulate to the public; access to, and engagement with, the target population was very difficult and would have benefited greatly from having representative residents who were paid at the partners' table. Engagement with residents and conflict burden varied highly across components. Notwithstanding, we built enabling capacity, strengthened our understanding of vulnerability, and are able to share valuable experiential knowledge.
Managing Uncertainties in Radioactive Site Clean-ups by Robert Goble Abel Russ Octavia Taylor Set... more Managing Uncertainties in Radioactive Site Clean-ups by Robert Goble Abel Russ Octavia Taylor Seth Tuler ... For instance in the familiar case of radiation health effects, much of the assessment effort at radiological sites recently has been performed by an office at ATSDR. ...
In earlier work we assembled a database of classical pharmacokinetic parameters (e.g., eliminatio... more In earlier work we assembled a database of classical pharmacokinetic parameters (e.g., elimination half-lives; volumes of distribution) in children and adults. These data were then analyzed to define mean differences between adults and children of various age groups. In this article, we first analyze the variability in half-life observations where individual data exist. The major findings are as follows. The age groups defined in the earlier analysis of arithmetic mean data (0-1 week premature; 0-1 week full term; 1 week to 2 months; 2-6 months; 6 months to 2 years; 2-12 years; and 12-18 years) are reasonable for depicting child/adult pharmacokinetic differences, but data for some of the earliest age groups are highly variable. The fraction of individual children's half-lives observed to exceed the adult mean half-life by more than the 3.2-fold uncertainty factor commonly attributed to interindividual pharmacokinetic variability is 27% (16/59) for the 0-1 week age group, and 19% (5/26) in the 1 week to 2 month age group, compared to 0/87 for all the other age groups combined between 2 months and 18 years. Children within specific age groups appear to differ from adults with respect to the amount of variability and the form of the distribution of half-lives across the population. The data indicate departure from simple unimodal distributions, particularly in the 1 week to 2 month age group, suggesting that key developmental steps affecting drug removal tend to occur in that period. Finally, in preparation for age-dependent physiologically-based pharmacokinetic modeling, nationally representative NHANES III data are analyzed for distributions of body size and fat content. The data from about age 3 to age 10 reveal important departures from simple unimodal distributional forms-in the direction suggesting a subpopulation of children that are markedly heavier than those in the major mode. For risk assessment modeling, this means that analysts will need to consider "mixed" distributions (e.g., two or more normal or log-normal modes) in which the proportions of children falling within the major versus highweight/fat modes in the mixture changes as a function of age. Biologically, the most natural interpretation of this is that these subpopulations represent children who have or have not yet received particular signals for change in growth pattern. These apparently distinct subpopulations would be expected to exhibit different disposition of xenobiotics, particularly those that are highly lipophilic and poorly metabolized.
Millions of low-income people of diverse ethnicities inhabit stressful old urban industrial neigh... more Millions of low-income people of diverse ethnicities inhabit stressful old urban industrial neighborhoods. Yet we know little about the health impacts of built-environment stressors and risk perceptions in such settings; we lack even basic health profiles. Difficult access is one reason (it took us 30 months to survey 80 households); the lack of multifaceted survey tools is another. We designed and implemented a pilot vulnerability assessment tool in Worcester, Massachusetts. We answer: (1) How can we assess vulnerability to multiple stressors? (2) What is the nature of complex vulnerability-including risk perceptions and health profiles? (3) How can findings be used by our wider community, and what lessons did we learn? (4) What implications arise for science and policy? We sought a holistic picture of neighborhood life. A reasonably representative sample of 80 respondents captured data for 254 people about: demographics, community concerns and resources, time-activity patterns, health information, risk/stress perceptions, and resources/ capacities for coping. Our key findings derive partly from the survey data and partly from our experience in obtaining those data. Data strongly suggest complex vulnerability dominated by psychosocial stress. Unexpected significant gender and ethnic disease disparities emerged: notably, females have twice the disease burden of males, and white females twice the burden of females of color (p < 0.01). Self-reported depression differentiated by gender and age is illustrative. Community based participatory research (CBPR) approaches require active engagement with marginalized populations, including representatives as funded partners. Complex vulnerability necessitates holistic, participatory approaches to improve scientific understanding and societal responses.
Recently, the Office of Management and Budget severely criticized the Environmental Protection Ag... more Recently, the Office of Management and Budget severely criticized the Environmental Protection Agency for a number of the standard practices used in estimating cancer risks,(lB2) including particularly the use of "upper confidence limit" estimates of low-dose cancer potency. Instead, OMB suggests that "maximum likelihood estimates" (MLE) would provide an "unbiased" estimate of potency for policy-making purposes. At different places in the document it appears that OMB is using the terms MLE and "expected value" as if they were interchangeable. We and others(=) believe there is merit to the general idea of attempting to convey to decision-makers a fuller picture of the probability density functions for likely risk,3 at least in the context of relatively important societal risk control choices, and with appropriate attention to the specific decision-rules set forth by the legislature
Pandora’s Risk by Kent Osband is an oddity, a book with a quirky title, and even more quirky styl... more Pandora’s Risk by Kent Osband is an oddity, a book with a quirky title, and even more quirky style. It is not at all a standard textbook on financial risk and it will not suit everyone’s taste. It is, however, a truly thoughtful discussion of fundamental issues, both theoretical and practical, that arise in considering financial risks. It is also a book that many environmental and health risk assessors would enjoy and benefit from reading. Why might readers of the Journal of Risk Research want to read this book? Financial risk is a natural field for members of our profession to get acquainted with. The subject is interesting and complex, there is some overlap in concepts, and the policy issues affect all of us as citizens. Beyond that, the financial risk arena offers important lessons for our approaches to thinking about health and environmental risks; and some of us may, in turn, find areas where our profession can contribute in the financial risk arena. But why read Pandora’s Risk rather than a textbook? First, for those who can appreciate its unorthodox approach and style, it is much more enjoyable. The book has a conversational tone; it asks provocative questions (and only sometimes answers them); it does not talk down to the reader nor shy away from mathematics (these are, after all, difficult issues with a quantitative side, but it does consign most of the mathematical development to a lengthy appendix); and every chapter ends with critical commentary from two Titans, Pandora and Prometheus. Second, this pleasurable strategy of presentation encourages readers to participate actively, if vicariously, in the thinking and questioning, particularly about fundamentals. Third, the expansive view taken in the book makes it easier to think about relationships between the risks and risk management we deal with, and financial risks and management. A very short excerpt from a discussion of backdrop for the 2008 financial crash is enough to illustrate all three of these attractions.
International Journal of Sustainable Development & World Ecology, 1996
The term ‘sustainable development’ is a prophetic combination of two words which unites both aspe... more The term ‘sustainable development’ is a prophetic combination of two words which unites both aspects—economic progress and environmental quality—in one vision. This vision of an economic structure that meets all needs of this generation without restricting the needs of future generations is highly attractive, because it reconciles the terms ‘economy’ and ‘ecology’—terms seen so often as opposites—and postulates a generally
Human and Ecological Risk Assessment: An International Journal, 2005
A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the un... more A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the unique exposures of Native American communities continue to be neglected. It is possible to estimate the exposures of these communities through a process of collaborative ...
Human and Ecological Risk Assessment: An International Journal, 2003
ABSTRACT The publication of the National Research Council&#39;s (NRC&#39;s) report Risk A... more ABSTRACT The publication of the National Research Council&#39;s (NRC&#39;s) report Risk Assessment in the Federal Government: Managing the Process, called the “Red Book,” marked a crystallization of the Risk Analysis paradigm. We offer an outsider&#39;s perspective on not only what was gained in this process, but also what was lost (or at least temporarily lost sight of)—the alternative framing of risk issues under the rubrics of policy and decision analysis. More recently, with increasing demands for analyses that juxtapose expected positive and negative consequences of available policy choices, and a newer NRC report on assessing the benefits of air pollution controls, a policy and decision analysis framework may be making a comeback from its long exile from the center of risk and policy discussions. The framework can be usefully informed by progress made in the use and methods of risk assessment.
Background: The National Children's Study is the most ambitious study ever attempted in the Unite... more Background: The National Children's Study is the most ambitious study ever attempted in the United States to assess how environmental factors impact child health and development. It aims to follow 100,000 children from gestation until 21 years of age. Success requires breaking new interdisciplinary ground, starting with how to select the sample of > 1,000 children in each of 105 study sites; no standardized protocol exists for stratification of the target population by factoring in the diverse environments it inhabits. Worcester County, Massachusetts, like other sites, stratifies according to local conditions and local knowledge, subject to probability sampling rules. oBjectives: We answer the following questions: How do we divide Worcester County into viable strata that represent its health-relevant environmental and sociodemographic heterogeneity, subject to sampling rules? What potential does our approach have to inform stratification at other sites? results: We developed a multivariable, vulnerability-based method for spatial sampling consisting of two descriptive indices: a hazards/stressors exposure index (comprising three proxy variables), and an adaptive capacity/sociodemographic character index (five variables). Multivariable, healthrelevant stratification at the start of the study may improve detection power for environment-child health associations down the line. Eighteen strata capture countywide heterogeneity in the indices and have optimal relative homogeneity within each. They achieve comparable expected birth counts and conform to local concepts of space. conclusion: The approach offers moderate to high potential to inform other sites, limited by intersite differences in data availability, geodemographics, and technical capacity. Energetic community engagement from the start promotes local stratification coherence, plus vital researcher-community trust and co-ownership for sustainability.
This paper discusses the merits and disadvantages of a specific proposal for a numerical calculat... more This paper discusses the merits and disadvantages of a specific proposal for a numerical calculation of the reference dose (RfD) with explicit recognition of both uncertainty and variability. It is suggested that the RfD be the lower (more restrictive) value of: The daily dose rate that is expected (with 95% confidence) to produce less than 1/100,000 incidence over background of a minimally adverse response in a standard general population of mixed ages and genders, or The daily dose rate that is expected (with 95% confidence) to produce less than a 1/1000 incidence over background of a minimally adverse response in a definable sensitive subpopulation. Developing appropriate procedures to make such estimates poses challenges. To be a viable replacement for current RfDs, a numerical definition needs to be A plausible representation of the risk management values that both lay people and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;experts&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; believe are intended to be achieved by current RfDs, (while better representing the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;truth&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; that current RfDs cannot be expected to achieve zero risk with absolute confidence for a mixed population with widely varying sensitivities), Estimable with no greater amount of chemical specific information than is traditionally collected to estimate current RfD values, Subjected to a series of comparisons with existing RfDs to evaluate overall implications for current regulatory values, A more flexible value in the sense of facilitating the development of procedures to allow the incorporation of more advanced technical information--e.g., defined data on human distributions of sensitivity; information on comparative pharmacokinetic and/or pharmacodynamics in humans vs. test species, etc. The discussion evaluates the straw man proposal in the light of each of these points, and assesses the risks and uncertainties inherent in present RfDs by applying existing distributional information on various uncertainty factors to 18 of 20 randomly-selected entries from IRIS. The analysis here suggests that current RfDs seem to meet the 1/100,000 risk criterion with only somewhat better than 50% confidence. However, the current RfDs appear to generally fall short of the goal of meeting this risk criterion with 95% confidence, typically by an order of magnitude in dose or somewhat more. The single most important uncertainty is the extent of human interindividual variability in the doses of specific chemicals that cause adverse responses. Our major conclusion is that with some important assumptions, it is currently feasible to both specify quantitative probabilistic performance objectives for RfDs and to make tentative assessments about whether specific current RfDs for real chemicals seem to meet those objectives. Similarly it is also possible to make preliminary estimates of how much risk is posed by exposures in the neighborhood of current RfDs, and what the uncertainties are in such estimates. It is therefore possible to harmonize cancer and noncancer risk assessments by making quantitative noncancer risk estimates comparable to those traditionally made for carcinogenic risks. The benefits from this change will be an increase in the candor of public discussion of the possible effects of exposures to chemicals posing non-cancer risks, and encouragement for the collection of better scientific information related to toxic risks in people--particularly the extent and distributional form of interindividual differences among people in susceptibility.
This article proposes a system of categories for nonmutagenic modes of action for carcinogenesis.... more This article proposes a system of categories for nonmutagenic modes of action for carcinogenesis. The classification is of modes of action rather than individual carcinogens, because the same compound can affect carcinogenesis in more than one way. Basically, we categorize modes of action as: (1) co-initiation (facilitating the original mutagenic changes in stem and progenitor cells that start the cancer process) (e.g. induction of activating enzymes for other carcinogens); (2) promotion (enhancing the relative growth vs differentiation/death of initiated clones (e.g. inhibition of growth-suppressing cell-cell communication); (3) progression (enhancing the growth, malignancy, or spread of already developed tumors) (e.g. suppression of immune surveillance, hormonally mediated growth stimulation for tumors with appropriate receptors by estrogens); and (4) multiphase (e.g., "epigenetic" silencing of tumor suppressor genes). A priori, agents that act at relatively early stages in the process are expected to manifest greater relative susceptibility in early life, whereas agents that act via later stage modes will tend to show greater susceptibility for exposures later in life.
A BSTRACT : A significant data base has been assembled on human variability in parameters represe... more A BSTRACT : A significant data base has been assembled on human variability in parameters representing a series of steps in the pathway from external exposure to the production of biological responses: contact rate (e.g., breathing rates/body weight, fish consumption/body weight); uptake or absorption (mg/ kg)/intake or contact rate; general systemic availability net of first pass elimination and dilution; systemic elimination or half-life; active site availability/ general systemic availability; physiological parameter change/active site availability; functional reserve capacity-change in baseline physiological parameter needed to pass a criterion of abnormal function or exhibit a response. This paper discusses the current results of analyzing these data to derive estimates for distributions of human susceptibility to different routes of exposure and types of adverse effects. The degree of protection is tentatively evaluated by projecting the incidences of effects that would be expected for a tenfold lowering of exposure from a 5% incidence level if the population distribution of susceptibility were truly log-normal out to the extreme tails, and if the populations, chemicals, and responses that gave rise to the underlying data were representative of the cases to which traditional uncertainty factor is applied. The results indicate that, acting by itself, a tenfold reduction in dose from a 5% effect level is associated with effect incidences ranging from slightly less than one in ten thousand, for a median chemical/response, to a few per thousand, for chemicals and responses that have greater human interindividual variability than 19 out of 20 typical chemicals/responses. In practice, for many of the cases where the traditional tenfold factor is applied, additional protection is provided by other uncertainty factors. Nevertheless, the results generate some reason for concern that current application of traditional safety or uncertainty factor approaches may allow appreciable incidences of responses in some cases.
Part of the explanation for the persistent epidemiological findings of associations between morta... more Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are very much more susceptible to particle-induced responses than others. This study assembles a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied include data drawn from epidemiologic studies of the doses of methacholine, flour dust, and some other agents inducing acute changes in lung function in different people. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters is greater than the variability in pharmacokinetic (breathing rate, deposition and clearance) parameters. Quantitatively the results to date indicate human interindividual variability of breathing rates and the major pharmacokinetic parameters-total deposition, and tracheobronchial clearance are generally in the region of Log(GSD) = 0.1 to 0.2. Deposition to the deep lung (alveolar region) appears to be somewhat more variable [Log(GSD) of about 0.3]. Among pharmacodynamic parameters, changes in FEV1 in response to ozone and metabisulfite (an agent that is said to act primarily on neural receptors in the lung) are in the region of Log(GSD) of 0.2 to 0.4. However similar responses to methacholine, an agent that acts on smooth muscle, seem to have still more variability (0.4 to somewhat over 1.0 depending on the type of population studied). Similarly high values are suggested for particulate allergens. Central estimates of this kind of variability, and the close correspondence of the data to lognormal distributions, indicate that 99.9 th percentile individuals are likely to respond at doses that are 150-450 less than would be needed in median individuals. It seems plausible that acute responses with this amount of variability could form part of the mechanistic basis for epidemiological observations of enhanced mortality in relation to ambient exposures to fine particles.
Part of the explanation for the persistent epidemiological findings of associations between morta... more Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are very much more susceptible to particleinduced responses than others. This study assembles a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied include data drawn from epidemiologic studies of the doses of methacholine, flour dust, and some other agents inducing acute changes in lung function in different people. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters is greater than the variability in pharmacokinetic (breathing rate, deposition and clearance) parameters.
A BSTRACT : A significant data base has been assembled on human variability in parameters represe... more A BSTRACT : A significant data base has been assembled on human variability in parameters representing a series of steps in the pathway from external exposure to the production of biological responses: contact rate (e.g., breathing rates/body weight, fish consumption/body weight); uptake or absorption (mg/ kg)/intake or contact rate; general systemic availability net of first pass elimination and dilution; systemic elimination or half-life; active site availability/ general systemic availability; physiological parameter change/active site availability; functional reserve capacity-change in baseline physiological parameter needed to pass a criterion of abnormal function or exhibit a response. This paper discusses the current results of analyzing these data to derive estimates for distributions of human susceptibility to different routes of exposure and types of adverse effects. The degree of protection is tentatively evaluated by projecting the incidences of effects that would be expected for a tenfold lowering of exposure from a 5% incidence level if the population distribution of susceptibility were truly log-normal out to the extreme tails, and if the populations, chemicals, and responses that gave rise to the underlying data were representative of the cases to which traditional uncertainty factor is applied. The results indicate that, acting by itself, a tenfold reduction in dose from a 5% effect level is associated with effect incidences ranging from slightly less than one in ten thousand, for a median chemical/response, to a few per thousand, for chemicals and responses that have greater human interindividual variability than 19 out of 20 typical chemicals/responses. In practice, for many of the cases where the traditional tenfold factor is applied, additional protection is provided by other uncertainty factors. Nevertheless, the results generate some reason for concern that current application of traditional safety or uncertainty factor approaches may allow appreciable incidences of responses in some cases.
New Solutions: A Journal of Environmental and Occupational Health Policy, 2003
In 1990 the U.S. Congress passed a law providing compensation to former uranium miners who became... more In 1990 the U.S. Congress passed a law providing compensation to former uranium miners who became ill while the U.S. Government was the sole purchaser of uranium. Ten years later, in 2000, the law was amended to correct widely perceived problems. We reviewed the content of the Radiation Exposure Compensation Act (RECA) laws and regulations, cataloged complaints about the 1990 law, compared the law to the scientific knowledge base in 1990 and in the present, reviewed the 2000 amendments to RECA, and drew lessons about how such compensation programs might be better structured. We concur with popular sentiment that the 1990 law had numerous flaws, the central one being that it failed to compensate many miners who by most other standards would have been deemed deserving. This problem arose through setting exposure criteria very high (at six to 15 times elevated risk), with a disproportionate burden placed on miners who had smoked. The additional burden on smokers was exacerbated by a very stringent definition of smokers (one pack-year in a lifetime). Federal compensation laws should prioritize payment to deserving claimants rather than excluding un-deserving claimants. Thus, a doubling of risk should be an upper limit for setting an eligibility threshold and a lower &amp;amp;amp;amp;quot;significant contributory effect&amp;amp;amp;amp;quot; standard could be considered more appropriate. Uncertainties in exposure and in dose response should be considered and resolved with a bias toward compensation. Beyond setting appropriate criteria, an active effort is needed to inform potentially eligible people and to assist them in qualifying; the eligibility criteria and the requirements for documentation should be appropriate for Native Americans and other cultural groups. Built-in evaluation mechanisms are needed for all compensation programs to assess whether they are meeting their stated objectives.
Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachus... more Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachusetts are exposed to cumulative, chronic built-environment stressors, and have limited capacity to respond, magnifying their vulnerability to adverse health outcomes. "Neighborhood STRENGTH", our community based participatory research (CBPR) project, comprised four partners: a youth center; an environmental non-profit; a community based health center; and a university. Unlike most CBPR projects that are single topic-focused, our 'holistic', systems-based project targeted five priorities. The three research-focused/action-oriented components were: 1) participatory monitoring of indoor and outdoor pollution; 2) learning about health needs and concerns of residents through community based listening sessions; and 3) engaging in collaborative survey work, including a household vulnerability survey and an asthma prevalence survey for schoolchildren. The two action-focused/research-informed components were: 4) tackling persistent street trash and illegal dumping strategically; and 5) educating and empowering youth to promote environmental justice. We used a coupled CBPR-capacity building approach to design, vulnerability theory to frame, and mixed methods: quantitative environmental testing and qualitative surveys. Process and outcomes yielded important lessons: vulnerability theory helps frame issues holistically; having several topic-based projects yielded useful information, but was hard to manage and articulate to the public; access to, and engagement with, the target population was very difficult and would have benefited greatly from having representative residents who were paid at the partners' table. Engagement with residents and conflict burden varied highly across components. Notwithstanding, we built enabling capacity, strengthened our understanding of vulnerability, and are able to share valuable experiential knowledge.
Managing Uncertainties in Radioactive Site Clean-ups by Robert Goble Abel Russ Octavia Taylor Set... more Managing Uncertainties in Radioactive Site Clean-ups by Robert Goble Abel Russ Octavia Taylor Seth Tuler ... For instance in the familiar case of radiation health effects, much of the assessment effort at radiological sites recently has been performed by an office at ATSDR. ...
In earlier work we assembled a database of classical pharmacokinetic parameters (e.g., eliminatio... more In earlier work we assembled a database of classical pharmacokinetic parameters (e.g., elimination half-lives; volumes of distribution) in children and adults. These data were then analyzed to define mean differences between adults and children of various age groups. In this article, we first analyze the variability in half-life observations where individual data exist. The major findings are as follows. The age groups defined in the earlier analysis of arithmetic mean data (0-1 week premature; 0-1 week full term; 1 week to 2 months; 2-6 months; 6 months to 2 years; 2-12 years; and 12-18 years) are reasonable for depicting child/adult pharmacokinetic differences, but data for some of the earliest age groups are highly variable. The fraction of individual children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s half-lives observed to exceed the adult mean half-life by more than the 3.2-fold uncertainty factor commonly attributed to interindividual pharmacokinetic variability is 27% (16/59) for the 0-1 week age group, and 19% (5/26) in the 1 week to 2 month age group, compared to 0/87 for all the other age groups combined between 2 months and 18 years. Children within specific age groups appear to differ from adults with respect to the amount of variability and the form of the distribution of half-lives across the population. The data indicate departure from simple unimodal distributions, particularly in the 1 week to 2 month age group, suggesting that key developmental steps affecting drug removal tend to occur in that period. Finally, in preparation for age-dependent physiologically-based pharmacokinetic modeling, nationally representative NHANES III data are analyzed for distributions of body size and fat content. The data from about age 3 to age 10 reveal important departures from simple unimodal distributional forms-in the direction suggesting a subpopulation of children that are markedly heavier than those in the major mode. For risk assessment modeling, this means that analysts will need to consider &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;mixed&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; distributions (e.g., two or more normal or log-normal modes) in which the proportions of children falling within the major versus highweight/fat modes in the mixture changes as a function of age. Biologically, the most natural interpretation of this is that these subpopulations represent children who have or have not yet received particular signals for change in growth pattern. These apparently distinct subpopulations would be expected to exhibit different disposition of xenobiotics, particularly those that are highly lipophilic and poorly metabolized.
Millions of low-income people of diverse ethnicities inhabit stressful old urban industrial neigh... more Millions of low-income people of diverse ethnicities inhabit stressful old urban industrial neighborhoods. Yet we know little about the health impacts of built-environment stressors and risk perceptions in such settings; we lack even basic health profiles. Difficult access is one reason (it took us 30 months to survey 80 households); the lack of multifaceted survey tools is another. We designed and implemented a pilot vulnerability assessment tool in Worcester, Massachusetts. We answer: (1) How can we assess vulnerability to multiple stressors? (2) What is the nature of complex vulnerability-including risk perceptions and health profiles? (3) How can findings be used by our wider community, and what lessons did we learn? (4) What implications arise for science and policy? We sought a holistic picture of neighborhood life. A reasonably representative sample of 80 respondents captured data for 254 people about: demographics, community concerns and resources, time-activity patterns, health information, risk/stress perceptions, and resources/ capacities for coping. Our key findings derive partly from the survey data and partly from our experience in obtaining those data. Data strongly suggest complex vulnerability dominated by psychosocial stress. Unexpected significant gender and ethnic disease disparities emerged: notably, females have twice the disease burden of males, and white females twice the burden of females of color (p < 0.01). Self-reported depression differentiated by gender and age is illustrative. Community based participatory research (CBPR) approaches require active engagement with marginalized populations, including representatives as funded partners. Complex vulnerability necessitates holistic, participatory approaches to improve scientific understanding and societal responses.
Recently, the Office of Management and Budget severely criticized the Environmental Protection Ag... more Recently, the Office of Management and Budget severely criticized the Environmental Protection Agency for a number of the standard practices used in estimating cancer risks,(lB2) including particularly the use of "upper confidence limit" estimates of low-dose cancer potency. Instead, OMB suggests that "maximum likelihood estimates" (MLE) would provide an "unbiased" estimate of potency for policy-making purposes. At different places in the document it appears that OMB is using the terms MLE and "expected value" as if they were interchangeable. We and others(=) believe there is merit to the general idea of attempting to convey to decision-makers a fuller picture of the probability density functions for likely risk,3 at least in the context of relatively important societal risk control choices, and with appropriate attention to the specific decision-rules set forth by the legislature
Pandora’s Risk by Kent Osband is an oddity, a book with a quirky title, and even more quirky styl... more Pandora’s Risk by Kent Osband is an oddity, a book with a quirky title, and even more quirky style. It is not at all a standard textbook on financial risk and it will not suit everyone’s taste. It is, however, a truly thoughtful discussion of fundamental issues, both theoretical and practical, that arise in considering financial risks. It is also a book that many environmental and health risk assessors would enjoy and benefit from reading. Why might readers of the Journal of Risk Research want to read this book? Financial risk is a natural field for members of our profession to get acquainted with. The subject is interesting and complex, there is some overlap in concepts, and the policy issues affect all of us as citizens. Beyond that, the financial risk arena offers important lessons for our approaches to thinking about health and environmental risks; and some of us may, in turn, find areas where our profession can contribute in the financial risk arena. But why read Pandora’s Risk rather than a textbook? First, for those who can appreciate its unorthodox approach and style, it is much more enjoyable. The book has a conversational tone; it asks provocative questions (and only sometimes answers them); it does not talk down to the reader nor shy away from mathematics (these are, after all, difficult issues with a quantitative side, but it does consign most of the mathematical development to a lengthy appendix); and every chapter ends with critical commentary from two Titans, Pandora and Prometheus. Second, this pleasurable strategy of presentation encourages readers to participate actively, if vicariously, in the thinking and questioning, particularly about fundamentals. Third, the expansive view taken in the book makes it easier to think about relationships between the risks and risk management we deal with, and financial risks and management. A very short excerpt from a discussion of backdrop for the 2008 financial crash is enough to illustrate all three of these attractions.
International Journal of Sustainable Development & World Ecology, 1996
The term ‘sustainable development’ is a prophetic combination of two words which unites both aspe... more The term ‘sustainable development’ is a prophetic combination of two words which unites both aspects—economic progress and environmental quality—in one vision. This vision of an economic structure that meets all needs of this generation without restricting the needs of future generations is highly attractive, because it reconciles the terms ‘economy’ and ‘ecology’—terms seen so often as opposites—and postulates a generally
Human and Ecological Risk Assessment: An International Journal, 2005
A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the un... more A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the unique exposures of Native American communities continue to be neglected. It is possible to estimate the exposures of these communities through a process of collaborative ...
Human and Ecological Risk Assessment: An International Journal, 2003
ABSTRACT The publication of the National Research Council&#39;s (NRC&#39;s) report Risk A... more ABSTRACT The publication of the National Research Council&#39;s (NRC&#39;s) report Risk Assessment in the Federal Government: Managing the Process, called the “Red Book,” marked a crystallization of the Risk Analysis paradigm. We offer an outsider&#39;s perspective on not only what was gained in this process, but also what was lost (or at least temporarily lost sight of)—the alternative framing of risk issues under the rubrics of policy and decision analysis. More recently, with increasing demands for analyses that juxtapose expected positive and negative consequences of available policy choices, and a newer NRC report on assessing the benefits of air pollution controls, a policy and decision analysis framework may be making a comeback from its long exile from the center of risk and policy discussions. The framework can be usefully informed by progress made in the use and methods of risk assessment.
Background: The National Children's Study is the most ambitious study ever attempted in the Unite... more Background: The National Children's Study is the most ambitious study ever attempted in the United States to assess how environmental factors impact child health and development. It aims to follow 100,000 children from gestation until 21 years of age. Success requires breaking new interdisciplinary ground, starting with how to select the sample of > 1,000 children in each of 105 study sites; no standardized protocol exists for stratification of the target population by factoring in the diverse environments it inhabits. Worcester County, Massachusetts, like other sites, stratifies according to local conditions and local knowledge, subject to probability sampling rules. oBjectives: We answer the following questions: How do we divide Worcester County into viable strata that represent its health-relevant environmental and sociodemographic heterogeneity, subject to sampling rules? What potential does our approach have to inform stratification at other sites? results: We developed a multivariable, vulnerability-based method for spatial sampling consisting of two descriptive indices: a hazards/stressors exposure index (comprising three proxy variables), and an adaptive capacity/sociodemographic character index (five variables). Multivariable, healthrelevant stratification at the start of the study may improve detection power for environment-child health associations down the line. Eighteen strata capture countywide heterogeneity in the indices and have optimal relative homogeneity within each. They achieve comparable expected birth counts and conform to local concepts of space. conclusion: The approach offers moderate to high potential to inform other sites, limited by intersite differences in data availability, geodemographics, and technical capacity. Energetic community engagement from the start promotes local stratification coherence, plus vital researcher-community trust and co-ownership for sustainability.
This paper discusses the merits and disadvantages of a specific proposal for a numerical calculat... more This paper discusses the merits and disadvantages of a specific proposal for a numerical calculation of the reference dose (RfD) with explicit recognition of both uncertainty and variability. It is suggested that the RfD be the lower (more restrictive) value of: The daily dose rate that is expected (with 95% confidence) to produce less than 1/100,000 incidence over background of a minimally adverse response in a standard general population of mixed ages and genders, or The daily dose rate that is expected (with 95% confidence) to produce less than a 1/1000 incidence over background of a minimally adverse response in a definable sensitive subpopulation. Developing appropriate procedures to make such estimates poses challenges. To be a viable replacement for current RfDs, a numerical definition needs to be A plausible representation of the risk management values that both lay people and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;experts&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; believe are intended to be achieved by current RfDs, (while better representing the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;truth&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; that current RfDs cannot be expected to achieve zero risk with absolute confidence for a mixed population with widely varying sensitivities), Estimable with no greater amount of chemical specific information than is traditionally collected to estimate current RfD values, Subjected to a series of comparisons with existing RfDs to evaluate overall implications for current regulatory values, A more flexible value in the sense of facilitating the development of procedures to allow the incorporation of more advanced technical information--e.g., defined data on human distributions of sensitivity; information on comparative pharmacokinetic and/or pharmacodynamics in humans vs. test species, etc. The discussion evaluates the straw man proposal in the light of each of these points, and assesses the risks and uncertainties inherent in present RfDs by applying existing distributional information on various uncertainty factors to 18 of 20 randomly-selected entries from IRIS. The analysis here suggests that current RfDs seem to meet the 1/100,000 risk criterion with only somewhat better than 50% confidence. However, the current RfDs appear to generally fall short of the goal of meeting this risk criterion with 95% confidence, typically by an order of magnitude in dose or somewhat more. The single most important uncertainty is the extent of human interindividual variability in the doses of specific chemicals that cause adverse responses. Our major conclusion is that with some important assumptions, it is currently feasible to both specify quantitative probabilistic performance objectives for RfDs and to make tentative assessments about whether specific current RfDs for real chemicals seem to meet those objectives. Similarly it is also possible to make preliminary estimates of how much risk is posed by exposures in the neighborhood of current RfDs, and what the uncertainties are in such estimates. It is therefore possible to harmonize cancer and noncancer risk assessments by making quantitative noncancer risk estimates comparable to those traditionally made for carcinogenic risks. The benefits from this change will be an increase in the candor of public discussion of the possible effects of exposures to chemicals posing non-cancer risks, and encouragement for the collection of better scientific information related to toxic risks in people--particularly the extent and distributional form of interindividual differences among people in susceptibility.
This article proposes a system of categories for nonmutagenic modes of action for carcinogenesis.... more This article proposes a system of categories for nonmutagenic modes of action for carcinogenesis. The classification is of modes of action rather than individual carcinogens, because the same compound can affect carcinogenesis in more than one way. Basically, we categorize modes of action as: (1) co-initiation (facilitating the original mutagenic changes in stem and progenitor cells that start the cancer process) (e.g. induction of activating enzymes for other carcinogens); (2) promotion (enhancing the relative growth vs differentiation/death of initiated clones (e.g. inhibition of growth-suppressing cell-cell communication); (3) progression (enhancing the growth, malignancy, or spread of already developed tumors) (e.g. suppression of immune surveillance, hormonally mediated growth stimulation for tumors with appropriate receptors by estrogens); and (4) multiphase (e.g., "epigenetic" silencing of tumor suppressor genes). A priori, agents that act at relatively early stages in the process are expected to manifest greater relative susceptibility in early life, whereas agents that act via later stage modes will tend to show greater susceptibility for exposures later in life.
A BSTRACT : A significant data base has been assembled on human variability in parameters represe... more A BSTRACT : A significant data base has been assembled on human variability in parameters representing a series of steps in the pathway from external exposure to the production of biological responses: contact rate (e.g., breathing rates/body weight, fish consumption/body weight); uptake or absorption (mg/ kg)/intake or contact rate; general systemic availability net of first pass elimination and dilution; systemic elimination or half-life; active site availability/ general systemic availability; physiological parameter change/active site availability; functional reserve capacity-change in baseline physiological parameter needed to pass a criterion of abnormal function or exhibit a response. This paper discusses the current results of analyzing these data to derive estimates for distributions of human susceptibility to different routes of exposure and types of adverse effects. The degree of protection is tentatively evaluated by projecting the incidences of effects that would be expected for a tenfold lowering of exposure from a 5% incidence level if the population distribution of susceptibility were truly log-normal out to the extreme tails, and if the populations, chemicals, and responses that gave rise to the underlying data were representative of the cases to which traditional uncertainty factor is applied. The results indicate that, acting by itself, a tenfold reduction in dose from a 5% effect level is associated with effect incidences ranging from slightly less than one in ten thousand, for a median chemical/response, to a few per thousand, for chemicals and responses that have greater human interindividual variability than 19 out of 20 typical chemicals/responses. In practice, for many of the cases where the traditional tenfold factor is applied, additional protection is provided by other uncertainty factors. Nevertheless, the results generate some reason for concern that current application of traditional safety or uncertainty factor approaches may allow appreciable incidences of responses in some cases.
Part of the explanation for the persistent epidemiological findings of associations between morta... more Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are very much more susceptible to particle-induced responses than others. This study assembles a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied include data drawn from epidemiologic studies of the doses of methacholine, flour dust, and some other agents inducing acute changes in lung function in different people. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters is greater than the variability in pharmacokinetic (breathing rate, deposition and clearance) parameters. Quantitatively the results to date indicate human interindividual variability of breathing rates and the major pharmacokinetic parameters-total deposition, and tracheobronchial clearance are generally in the region of Log(GSD) = 0.1 to 0.2. Deposition to the deep lung (alveolar region) appears to be somewhat more variable [Log(GSD) of about 0.3]. Among pharmacodynamic parameters, changes in FEV1 in response to ozone and metabisulfite (an agent that is said to act primarily on neural receptors in the lung) are in the region of Log(GSD) of 0.2 to 0.4. However similar responses to methacholine, an agent that acts on smooth muscle, seem to have still more variability (0.4 to somewhat over 1.0 depending on the type of population studied). Similarly high values are suggested for particulate allergens. Central estimates of this kind of variability, and the close correspondence of the data to lognormal distributions, indicate that 99.9 th percentile individuals are likely to respond at doses that are 150-450 less than would be needed in median individuals. It seems plausible that acute responses with this amount of variability could form part of the mechanistic basis for epidemiological observations of enhanced mortality in relation to ambient exposures to fine particles.
Part of the explanation for the persistent epidemiological findings of associations between morta... more Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are very much more susceptible to particleinduced responses than others. This study assembles a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied include data drawn from epidemiologic studies of the doses of methacholine, flour dust, and some other agents inducing acute changes in lung function in different people. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters is greater than the variability in pharmacokinetic (breathing rate, deposition and clearance) parameters.
A BSTRACT : A significant data base has been assembled on human variability in parameters represe... more A BSTRACT : A significant data base has been assembled on human variability in parameters representing a series of steps in the pathway from external exposure to the production of biological responses: contact rate (e.g., breathing rates/body weight, fish consumption/body weight); uptake or absorption (mg/ kg)/intake or contact rate; general systemic availability net of first pass elimination and dilution; systemic elimination or half-life; active site availability/ general systemic availability; physiological parameter change/active site availability; functional reserve capacity-change in baseline physiological parameter needed to pass a criterion of abnormal function or exhibit a response. This paper discusses the current results of analyzing these data to derive estimates for distributions of human susceptibility to different routes of exposure and types of adverse effects. The degree of protection is tentatively evaluated by projecting the incidences of effects that would be expected for a tenfold lowering of exposure from a 5% incidence level if the population distribution of susceptibility were truly log-normal out to the extreme tails, and if the populations, chemicals, and responses that gave rise to the underlying data were representative of the cases to which traditional uncertainty factor is applied. The results indicate that, acting by itself, a tenfold reduction in dose from a 5% effect level is associated with effect incidences ranging from slightly less than one in ten thousand, for a median chemical/response, to a few per thousand, for chemicals and responses that have greater human interindividual variability than 19 out of 20 typical chemicals/responses. In practice, for many of the cases where the traditional tenfold factor is applied, additional protection is provided by other uncertainty factors. Nevertheless, the results generate some reason for concern that current application of traditional safety or uncertainty factor approaches may allow appreciable incidences of responses in some cases.
New Solutions: A Journal of Environmental and Occupational Health Policy, 2003
In 1990 the U.S. Congress passed a law providing compensation to former uranium miners who became... more In 1990 the U.S. Congress passed a law providing compensation to former uranium miners who became ill while the U.S. Government was the sole purchaser of uranium. Ten years later, in 2000, the law was amended to correct widely perceived problems. We reviewed the content of the Radiation Exposure Compensation Act (RECA) laws and regulations, cataloged complaints about the 1990 law, compared the law to the scientific knowledge base in 1990 and in the present, reviewed the 2000 amendments to RECA, and drew lessons about how such compensation programs might be better structured. We concur with popular sentiment that the 1990 law had numerous flaws, the central one being that it failed to compensate many miners who by most other standards would have been deemed deserving. This problem arose through setting exposure criteria very high (at six to 15 times elevated risk), with a disproportionate burden placed on miners who had smoked. The additional burden on smokers was exacerbated by a very stringent definition of smokers (one pack-year in a lifetime). Federal compensation laws should prioritize payment to deserving claimants rather than excluding un-deserving claimants. Thus, a doubling of risk should be an upper limit for setting an eligibility threshold and a lower &amp;amp;amp;amp;quot;significant contributory effect&amp;amp;amp;amp;quot; standard could be considered more appropriate. Uncertainties in exposure and in dose response should be considered and resolved with a bias toward compensation. Beyond setting appropriate criteria, an active effort is needed to inform potentially eligible people and to assist them in qualifying; the eligibility criteria and the requirements for documentation should be appropriate for Native Americans and other cultural groups. Built-in evaluation mechanisms are needed for all compensation programs to assess whether they are meeting their stated objectives.
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