Christopher P. Weis

Estimation of relative bioavailability of lead in soil and soil-like materials using young swine

In this article we summarize the results of a series of studies that measured the relative bioavailability (RBA) of lead in a variety of soil and soil-like test materials. Reference material (Pb acetate) or Pb-contaminated soils were administered orally to juvenile swine twice a day for 15 days. Blood samples were collected from each animal at multiple times during the course of the study, and samples of liver, kidney, and bone were collected at sacrifice. All samples were analyzed for Pb. We estimated the RBA of a test material by fitting mathematical models to the dose–response curves for each measurement end point and finding the ratio of doses that gave equal responses. The final RBA for a test material is the simple average of the four end point–specific RBA values. Results from 19 different test materials reveal a wide range of RBA values across different exposure materials, ranging from 6 to 105%. This variability in RBA between different samples highlights the importance of reliable RBA data to help improve risk assessments for Pb in soil. Although the RBA value for a sample depends on the relative amounts of the different chemical and physical forms of Pb present, data are not yet adequate to allow reliable quantitative predictions of RBA from chemical speciation data alone.

Characteristics to Consider when Choosing an Animal Model for the Study of Lead Bioavailability

AbstractMost animal studies conducted to determine the bioavailability of lead have, in the past, employed rodents or lagomorphs as experimental models. In this paper issues and data are presented which raise questions and uncertainties about employing rodents or lagomorphs for investigations into the bioavailability of lead. These issues include: (1) the possible role of coprophagy and feeding behavior in reducing estimates of lead bioavailability; (2) anatomical and physiological differences related to coprophagy which may influence estimates of lead bioavailability derived in rats or rabbits; (3) evidence for relatively high biliary excretion of lead by rats and rabbits; (4) the possibility of a strong developmental component to the active transport of lead. The importance of addressing these and other questions in studies designed to determine the bioavailability of lead is discussed.

A Swine Model for Determining the Bioavailability of Lead from Contaminated Media

Bioavailability is the portion of a chemical dose that enters the systemic circulation from an administered dosage form. Enteric absorption depends on the physical and chemical properties and associated matrix, e.g., soil, slag, food, water, of the chemical. For our purposes, two separate connotations of the term bioavailability will be clarified. Absolute bioavailability is synonymous with the oral absorption fraction (AF0) for a specific chemical from its associated matrix. For example, if lead (Pb) from lead acetate (PbAc) is 50% absorbed from drinking water and lead from lead sulfide (PbS) is 25% absorbed from soil, the absolute bioavailabilities or AF0s of lead would be 50 and 25%, respectively. Relative bioavailability (RBA) refers to the absorption of one chemical form compared to some other reference form. For example, if lead acetate in drinking water is the reference form of lead, then the RBA of lead from lead sulfide would be 25/50, or 50% compared to lead from lead acetate.

Commentary on the contributions and future role of occupational exposure science in a vision and strategy for the discipline of exposure science

Exposure science is a holistic concept without prejudice to exposure source. Traditionally, measurements aimed at mitigating environmental exposures have not included exposures in the workplace, instead considering such exposures to be an internal affair between workers and their employers. Similarly, occupational (or industrial) hygiene has not typically accounted for environmental contributions to poor health at work. Many persons spend a significant amount of their lifetime in the workplace, where they maybe exposed to more numerous chemicals at higher levels than elsewhere in their environment. In addition, workplace chemical exposures and other exogenous stressors may increase epigenetic and germline modifications that are passed on to future generations. We provide a brief history of the development of exposure science from its roots in the assessment of workplace exposures, including an appendix where we detail current resources for education and training in exposure science offered through occupational hygiene organizations. We describe existing successful collaborations between occupational and environmental practitioners in the field of exposure science, which may serve as a model for future interactions. Finally, we provide an integrated vision for the field of exposure science, emphasizing interagency collaboration, the need for complete exposure information in epidemiological studies, and the importance of integrating occupational, environmental, and residential assessments. Our goal is to encourage communication and spur additional collaboration between the fields of occupational and environmental exposure assessment. Providing a more comprehensive approach to exposure science is critical to the study of the “exposome”, which conceptualizes the totality of exposures throughout a person’s life, not only chemical, but also from diet, stress, drugs, infection, and so on, and the individual response.

The Value of Alternatives Assessment

The pages of EHP are replete with studies documenting the potential human health and ecosystem impacts of toxic chemicals. Such research is critical to understanding chemical risks and developing prevention strategies to reduce those risks. Intramural research at the National Institute of Environmental Health Sciences (NIEHS) as well as externally funded studies have led to a better understanding of mechanisms by which toxic chemicals may cause illness along with advanced tools to more rapidly assess risks. As knowledge of the potential impacts of specific chemicals increases, so do market and regulatory pressures to replace those chemicals with safer alternatives. Regrettable substitutions, implemented without adequate screening, can too quickly enter the market if we neglect to develop processes to evaluate those alternatives. For example, research at the NIEHS has shown that many of the substitutes for certain brominated flame retardants may be as concerning as the chemicals they are replacing (Jarema et al. 2015). It is critical, therefore, that we establish thoughtful yet efficient processes to guide the transition to safer chemicals and products. This is the emerging field of alternatives assessment, which focuses on identifying, comparing, and selecting safer alternatives to chemicals of concern on the basis of their hazards, performance, and economic viability. By focusing on function, both chemical and nonchemical options may be considered to achieve the desired property, such as fire retardancy, stain resistance, or degreasing ability. In this issue of EHP, Jacobs et al. (2016) provide a detailed analysis of 20 alternatives assessment frameworks, many developed by governments and industry to guide the selection of safer alternatives. Included in their analysis is the recently published National Research Council (NRC) Framework to Guide Selection of Chemical Alternatives (2014), which, much like the NRC’s famous “Red Book” on risk assessment (1983), can serve as a guide and foundation for this emerging science policy field. In March 2015 the NIEHS, along with the U.S. Environmental Protection Agency, hosted the International Symposium on Alternatives Assessment: Advancing Science and Practice (http://www.saferalternatives.org/). That workshop brought together more than 100 government, academic, industry, and nonprofit scientists from the United States, Canada, and Europe to explore ways to build a more coordinated community of practice around alternatives assessment. Participants discussed gaps in knowledge and methods, and developed the elements of a research agenda to support this growing field. Identifying safer alternatives makes sense for environmental health and safety as well as for economics. At the National Institutes of Health, we are doing this internally through the Substances of Concern Reduction Initiative (http://orf.od.nih.gov/EnvironmentalProtection/Pages/NIH-Substances-of-Concern-Reduction-Initiative.aspx), established to support institute purchasing of safer substitutes for chemicals of concern used in our laboratories, clinical centers, maintenance, and buildings. The NIEHS is committed to using its scientific research to support the design, evaluation, and adoption of safer chemicals. The NRC Framework (2014) identified a number of ways in which high-throughput and in silico research on chemical hazards and potential exposures could significantly enhance the alternatives assessment process, filling in important data gaps. Such research can also help in applying 21st-century toxicology to the design of new green chemistry solutions that are more healthful for people and the environment. Inherent in alternatives assessment is the idea that when we have reasonable evidence that a chemical could be problematic, thoughtful steps are taken to evaluate materials, processes, and technologies to identify a safer substitute. At the NIEHS we look forward to working with the scientific and regulatory communities to help advance this important field.