Summary of the Workshop on Issues in Risk Assessment: Quantitative Methods for Developmental Toxicology

This report summarizes the proceedings of a conference on quantitative methods for assessing the risks of developmental toxicants. The conference was planned by a subcommittee of the National Research Council's Committee on Risk Assessment Methodology ⁴ in conjunction with staff from several federal agencies, including the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, U.S. Consumer Products Safety Commission, and Health and Welfare Canada. Issues discussed at the workshop included computerized techniques for hazard identification, use of human and animal data for defining risks in a clinical setting, relationships between end points in developmental toxicity testing, reference dose calculations for developmental toxicology, analysis of quantitative dose-response data, mechanisms of developmental toxicity, physiologically based pharmacokinetic models, and structure-activity relationships. Although a formal consensus was not sought, many participants favored the evolution of quantitative techniques for developmental toxicology risk assessment, including the replacement of lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) with the benchmark dose methodology.     

Significance of the Dermal Route of Exposure to Risk Assessment

The skin is a route of exposure that needs to be considered when conducting a risk assessment. It is necessary to identify the potential for dermal penetration by a chemical as well as to determine the overall importance of the dermal route of exposure as compared with inhalation or oral routes of exposure. The physical state of the chemical, vapor or liquid, the concentration, neat or dilute, and the vehicle, lipid or aqueous, is also important. Dermal risk is related to the product of the amounts of penetration and toxicity. Toxicity involves local effects on the skin itself and the potential for systemic effects. Dermal penetration is described in large part by the permeability constant. When permeability constants are not known, partition coefficients can be used to estimate a chemical's potential to permeate the skin. With these concepts in mind, a tiered approach is proposed for dermal risk assessment. A key first step is the determination of a skin-to-air or skin-to-medium partition coefficient to estimate a potential for dermal absorption. Building a physiologically-based pharmacokinetic (PBPK) model is another step in the tiered approach and is useful prior to classical in vivo toxicity tests. A PBPK model can be used to determine a permeability constant for a chemical as well as to show the distribution of the chemical systemically. A detailed understanding of species differences in the structure and function of the skin and how they relate to differences in penetration rates is necessary in order to extrapolate animal data from PBPK models to the human. A study is in progress to examine anatomical differences for four species.     

One parent or two? The intertwining of American marriage and fertility patterns

Marriage and fertility in the United States have become less firmly entwined as more women bear children without marrying and more couples with children divorce. Today a sizeable number of children are expected to spend a portion of their childhood in one-parent households. Despite the trends in illegitimacy and divorce, the actual effect of out-of-wedlock childbearing on the living arrangements of children has not been fully explicated. Using the National Survey of Family Growth Cycle III, this paper estimates the probability that children aged 0–13 in 1982 are living in two-parent households, controlling for their mothers' marital statuses at their births. We find that marital status at birth is an important predictor of household structure at later ages for both white and black populations; however, the childhood environment is actually quite elastic as women marry, divorce, remarry, and redivorce.     

RURAL POVERTY, URBAN POVERTY, AND PSYCHOLOGICAL WELL-BEING

Data from the National Survey of Families and Households are used to compare the psychological well-being of the rural and urban poor. Overall, the urban poor are higher in perceived health than the rural poor, although no differences are apparent in happiness or depression. Significant interactions are present between rural/urban poverty and sex, race, and family status. The psychological well-being of poor African Americans is higher in rural than urban areas, whereas the well-being of poor whites is higher in urban than rural areas. This trend is especially pronounced for depression among males. In addition, single men without children have especially high depression scores in rural areas, whereas married women without children have especially low depression scores in urban areas. The results are interpreted in terms of the environmental quality of inner-city neighborhoods and attitudes toward poverty in urban and rural communities.     

Mapping water quality by local scoring

The mean density of bacteria in a water body is commonly monitored using quantal assay. This paper describes the use of local scoring in estimating the spatial distribution of mean density from quantal assay results at a set of point locations. An application to estimating the mean density of fecal conform bacteria in a coastal pond is presented. Model diagnostics based on a parametric bootstrap are also presented.     

Lumpers and Splitters: The Public Opinion Information that Politicians Collect and Use

Are the decisions of American policymakers informed by generaltrends in the public’s ideology or by the public’spolicy-specific preferences? In this article we discuss twoexplanations for the types of public opinion information thatpoliticians collect and use. Using a unique data set of privatepolls from the White House of Richard Nixon, we find that whenopinion data on specific policies were available, the presidentrelied on them and not on general ideology data. On less importantissues, however, we find that the president often chose notto collect policy-specific data and instead relied on generalideology data. The differential collection and use of informationby policymakers reflect varying strategic calculations. Theyalso have profound implications for representative democracyand the demands placed on citizens and governors.