Health-based Provisional Advisory Levels (PALs) for homeland security.

The Homeland Security Presidential Directive #8 (HSPD-8) for National Emergency Preparedness was issued to " establish policies to strengthen the preparedness of the United States to prevent and respond to threatened or actual domestic terrorist attacks, major disasters, and other emergencies by requiring a national domestic all- hazards preparedness goal. "In response to HSPD-8 and HSPD-22 (classified) on Domestic Chemical Defense, the US Environmental Protection Agency (US EPA) National Homeland Security Research Center (NHSRC) is developing health-based Provisional Advisory Levels (PALs) for priority chemicals (including chemical warfare agents, pesticides, and toxic industrial chemicals) in air and drinking water. PALs are temporary values that will neither be promulgated, nor be formally issued as regulatory guidance.

Practical application of kinetic data in risk assessment--an IPCS initiative.

In this paper, guidance developed in a project of the International Programme on Chemical Safety (IPCS) initiative on Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals is considered in the context of its application in the assessment of the adequacy of physiological-toxicokinetic (PTK) modeling to inform quantitatively extrapolations for interspecies differences and human variability in dose-response assessment. This guidance was developed in the context of a framework, which permits the incorporation of quantitative chemical-specific data, relating to either toxicokinetics or toxicodynamics to replace part or all of the usual 100-fold default uncertainty factor for interspecies differences or human variability in the development of tolerable or reference doses or concentrations. However, since the guidance relates specifically to adequacy of kinetic or dynamic data to replace default for interspecies and human variability, it is also applicable to other approaches of dose-response analyses such as estimation of cancer potency or risk.

The use of toxicokinetic and toxicodynamic data in risk assessment: an international perspective.

Risk assessment of chemicals is a process which is usually based on data derived from animal testing in which the exposure of animals results in toxicological effects. By extrapolation, the dose/exposure in humans, which will not result in toxicological effects ('safe dose', 'safe exposure'), is estimated. Traditional approaches use 'safety factors' or 'uncertainty factors' to extrapolate from animal to man and from the 'mean' subject to the general population, including sensitive subgroups.

IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis.

The International Programme on Chemical Safety (IPCS) is leading an activity to harmonize approaches to cancer risk assessment as a part of its larger project on the Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals. Through a series of workshops and the evaluation of case studies, a number of key components of risk assessments relating to harmonization were identified: transparency, terminology, weight of evidence, flexibility, and accessibility/communication. A major impediment to harmonization identified in the consideration of weight of evidence was the evaluation of mode of action.