Temporal stability of chemical hormesis (CH): Is CH just a temporary stop on the road to thresholds and toxic responses?

Chemical hormesis (CH) is currently described as a nonmonotonic, bidirectional dose-response relationship for chemicals, where a stimulatory, (beneficial?) response at low dose or exposure is followed by an inhibitory response at higher doses/exposures (or vice-versa). CH is depicted as U(J)-shaped or inverse U(J)-shaped curves, i.e.

Structured Development and Promotion of a Research Field: Hormesis in Biology, Toxicology, and Environmental Regulatory Science.

The ability of powerful and well-funded interest groups to steer scientific research in ways that advance their goals has become a significant social concern. This steering ability is increasingly being recognized in the peer-reviewed scientific literature and in findings of deliberative scientific bodies. This paper provides a case study that illustrates some of the major strategies that can be used to structure and advance a controversial research field.

Limits to chemical hormesis as a dose-response model in health risk assessment.

This review presents and discusses the extent to which chemical hormesis meets five important requirements for performance of any dose-response model in the toxicological and regulatory sciences. These include (1) the requirement that there be a documented and accepted mechanistic basis for the dose-response model's plausible role and use in health risk assessment; (2) the requirement that any newly proposed dose-response methodology can be compared with current models as to reliability and scientific validity; (3) the requirement that the underlying reliability and stability of the model be established as to its temporal aspects, that is, minimal temporal lag between stressor contact and biological or toxicological response and temporal stability expressed throughout the prevailing relationship; (4) the requirement that the dose-response model be as broadly applicable as other dose-response methodologies being applied in human health risk assessment; and, (5) the requirement that any dose-response model proposed as default methodology can be characterized as to variability and uncertainty and will have a minimal likelihood of harm to the health of impacted populations. This review includes a brief treatment of definitions of hormesis and its place in nonmonotonic dose-response relationships.

How prevalent is chemical hormesis in the natural and experimental worlds?

Hormesis is described as a biological phenomenon showing bidirectional (biphasic) responses to chemical or other stressors: stimulation at low doses and inhibition at high doses or vice-versa. The label applies to either radiation or chemical hormesis. This review addresses certain critical but persisting quantitative questions about chemical hormesis.

Ad hoc and fast forward: the science of hormesis growth and development.

Background: Hormesis is a binary response phenomenon with low-dose stimulation (or inhibition) of effects by substances producing opposite high-dose responses. Hormesis, after decades of obscurity, has undergone a renaissance in recent years, with rapid growth benefiting greatly from the systematized efforts of such proponents as the hormesis group at the University of Massachusetts-Amherst led by Edward J. Calabrese.

Hormesis and its place in nonmonotonic dose-response relationships: some scientific reality checks.

Objective: This analysis is a critical assessment of current hormesis literature. I discuss definitions, characterization, generalizability, mechanisms, absence of empirical data specific for hormesis hypothesis testing, and arguments that hormesis be the "default assumption" in risk assessment.

Data Sources: Hormesis, a biological phenomenon typically described as low-dose stimulation from substances producing higher-dose inhibition, has recently garnered interest in several quarters.

Lead remediation and changes in human lead exposure: some physiological and biokinetic dimensions.

This paper presents a qualitative and quantitative analysis of the various aspects of lead remediation effectiveness with particular reference to human health risk assessment. One of the key elements of lead remediation efforts at such sites as those under the Superfund program deals with populations at elevated exposure and toxicity risk in the proximity of, or at, the site of remediation, especially remediation workers, workers at other tasks on sites that were remediated down to some action level of lead concentration in soils, and groups at risk in nearby communities. A second element has to do with how one measures or models lead exposure changes with special reference to baseline and post-remediation conditions.

Estimation of cumulative lead releases (lead flux) from the maternal skeleton during pregnancy and lactation.

Recent longitudinal studies with human subjects and nonhuman primates using high-precision stable lead isotopes show that lead is mobilized from the maternal skeleton during pregnancy and the postpartum period. We have now calculated the cumulative lead release (lead flux in micrograms) mobilized from the skeleton during these periods by means of analysis of monthly PbB samples from recent immigrants to Australia. Results included a statistically significant inverse relationship (P = .

Uses and limits of empirical data in measuring and modeling human lead exposure.

This paper examines the uses and limits of empirical data in evaluating measurement and modeling approaches to human lead exposure. Empirical data from experiment or observation or both have been used in studies of lead exposure. For example, experimental studies have elucidated and quantified physiologic or biokinetic parameters of lead exposure under controlled conditions.

Risk and revisionism in arsenic cancer risk assessment.

Oral exposures of nonoccupational populations to environmental inorganic arsenic are associated with skin and internal cancers as well as various noncarcinogenic effects. Cancer risk assessments have been based largely on epidemiological studies of a large population exposed to inorganic arsenic in well water in Taiwan. Criticisms and skepticism of the use of the Taiwanese data for estimating arsenic cancer risks outside of Taiwan, including potential use by the U.

New directions in the toxicokinetics of human lead exposure.

An important determinant of body lead (Pb) burden and Pb toxicity in exposed humans is Pb metabolism, or more correctly, Pb toxicokinetics. It affects the former through the quantitative processes of uptake, distribution and retention/excretion and the latter via delivery of toxic doses to cellular/molecular sites of action. Pb toxicokinetics has useful application in understanding Pb's behavior in populations.

Defining lead as the premiere environmental health issue for children in America: criteria and their quantitative application.

The principal environmental health issue for American children is pervasive lead poisoning from the many decades of lead contamination. Available scientific evidence cementing lead's premiere ranking is voluminous, multifaceted, and compelling. This evidence, however, requires organization into a clear and coherent body of science before it can be fully recognized or comprehended by either the scientific community or the general public and its representatives: public health officials, regulators, policy makers, and legislators.

Methods for reducing lead exposure in young children and other risk groups: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

As part of a Congressionally mandated report on U.S. childhood lead poisoning prepared by the Federal government (U.

Determination of numbers of lead-exposed women of childbearing age and pregnant women: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In a Congressionally mandated study carried out under the aegis of the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) and summarized in this article, the authors have provided estimates of the numbers of American women of childbearing age and the numbers of American pregnant women whose lead exposure is sufficiently elevated to pose an intrauterine toxicity risk.

Determination of numbers of lead-exposed U.S. children by areas of the United States: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In response to Congressional mandate and under the aegis of the Federal Agency for Toxic Substances and Disease Registry (ATSDR), a comprehensive report to Congress on childhood lead poisoning in the United States was prepared. We have examined numbers of lead-exposed U.S.

Determination of numbers of lead-exposed American children as a function of lead source: integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In 1986, the U.S. Congress [Section 118(f), Superfund Amendments and Reauthorization Act (SARA)] directed the Agency for Toxic Substances and Disease Registry to provide to it a quantitative assessment of the contributions of various sources of lead to childhood exposure.