Review of the U.S. Army's health risk assessments for oral exposure to six chemical-warfare agents. Introduction.

The U.S. Army is under a congressional mandate and the Chemical Weapons Convention of January 1993 to destroy its entire stockpile of chemical munitions. In addition to stockpiled munitions, nonstockpile chemical materiel (NSCM) has been identified for destruction. NSCM includes a host of lethal wastes from past disposal efforts, unserviceable munitions, chemically contaminated containers, chemical-production facilities, newly located chemical munitions, known sites containing substantial quantities of buried chemical weapons and wastes, and binary weapons and components. There are eight stockpile sites located in the continental United States and one on an island in the Pacific Ocean, and 82 NSCM locations have been identified. There are concerns, based on storage and past disposal practices, about soil and groundwater contamination at those sites. Six of the most commonly found chemical-warfare agents at stockpile and NSCM sites are the nerve agents GA, GB, GD, and VX and the vesicating (blistering) agents sulfur mustard and lewisite. To ensure that chemical contamination is reduced to safe concentrations at stockpile and NSCM sites before they are used for residential, occupational, or wildlife purposes, the U.S. Army requested that health-based exposure limits for GA, GB, GD, VX, sulfur mustard, and lewisite be developed to protect the public and the environment. Oak Ridge National Laboratory (ORNL) was asked to conduct the health risk assessments and propose chronic oral reference doses (RfDs) and, where appropriate, oral slope factors (SFs) for the six agents. RfDs are toxicological values developed for noncancer effects and used as reference points to limit human oral exposure to potentially hazardous concentrations of chemicals thought to have thresholds for their effects. RfDs are estimates (with uncertainty spanning an order of magnitude or greater) of daily oral chemical exposures that are unlikely to have deleterious effects during a human lifetime. For chemicals identified as carcinogens (e.g., sulfur mustard), SFs are also calculated. SFs are estimates of upper-bound lifetime cancer risk from chronic exposure to an agent. The Army's Surgeon General adopted the proposed RfDs and SFs developed by ORNL as interim values to ensure that consistent health-based criteria were applied in ongoing initiatives requiring decisions on the safety of contaminated sites. The Army's Surgeon General also requested that the National Research Council (NRC) independently review the scientific validity of these values. The NRC assigned this task to the Committee on Toxicology (COT), and a multidisciplinary subcommittee of experts was convened to assess the scientific validity of the interim RfDs developed for GA, GB, GD, VX, sulfur mustard, and lewisite and the SF developed for sulfur mustard. Specifically, the subcommittee was asked to (1) determine whether all the relevant toxicity data were considered appropriately; (2) review the uncertainty, variability, and quality of the data; (3) determine the appropriateness of the assumptions used to derive the RfDs (e.g., the application of uncertainty factors); and (4) identify data gaps and make recommendations for future research. Although multiple agents are present at stockpile and NSCM sites, the subcommittee was asked to evaluate the agents only on an individual basis. Furthermore, although the most likely routes of exposure to chemical-warfare agents at these sites are the inhalation and dermal routes, the subcommittee was only asked to evaluate toxicological risk from the oral route at this time. The Army is in the process of developing inhalation exposure guidelines. The subcommittee was also not asked to address issues related to risk management, such as technology, detection, and feasibility.