Toxicity of Military Smokes and Obscurants: Volume 2 (1999)

Ever since smokeless powder replaced black powder as the standard propellant for guns and firearms, the armed forces have sought methods to blanket battlefields by creating a haze similar to that created by black powder. A variety of smokes and obscurants has been developed and used in wartime operations for screening armed forces from view, deceiving the enemy, signaling friendly forces, and marking positions. White and gray smokes are deployed in grenades to cover or screen individual vehicles, and colored smokes are used to mark specific locations. Obscurants are anthropogenic or naturally occurring particles suspended in air that block or weaken the transmission of particular parts of the electromagnetic spectrum, such as visible and infrared radiation or microwaves. Smokes and obscurants are used by the armed forces to achieve tactical goals during wartime. To ensure defense preparedness, large quantities of smokes and obscurants also are used in military training.

To ensure that exposure to smokes and obscurants during combat training will not have adverse health effects on military personnel, the Office of the Army Surgeon General requested the National Research Council (NRC) to review the data on the toxicity of military smokes and obscurants and recommend exposure guidance levels for military personnel during combat training and for the general public residing or working near military-training facilities.

The NRC assigned this project to the Committee on Toxicology (COT),

which convened the Subcommittee on Military Smokes and Obscurants. For this report, the subcommittee evaluated four obscuring smokes: white phosphorus, brass, graphite, and titanium dioxide. Exposure guidance levels for four other obscuring smokes—fog oil, diesel fuel, red phosphorus, and hexachloroethane—were presented in Volume 1 of Toxicity of Military Smokes and Obscurants (1997), and seven signaling smokes will be presented in a subsequent volume.

The task of the subcommittee was to review the health effects associated with exposure to the smokes and obscurants and to recommend four exposure guidance levels: (1) emergency exposure guidance levels (EEGLs) for a rare, emergency situation resulting in an exposure of military personnel for less than 24 hr; (2) repeated exposure guidance levels (REGLs) for repeated exposure of military personnel during training (referred to as permissible exposure guidance level in Volume 1); (3) short-term public emergency guidance levels (SPEGLs) for a rare, emergency situation potentially resulting in an exposure of the public to a military-training smoke; and (4) repeated public exposure guidance levels (RPEGLs) for possible repeated exposures of the public residing or working near military-training facilities (referred to as permissible public exposure guidance level in Volume 1). All four guidance levels should take into account embryo and fetal development and reproductive toxicity in men and women. In addition, exposures of potentially susceptible subpopulations (e.g., ill or elderly persons and children) are considered in the SPEGL and RPEGL.

For each smoke reviewed in this report, the subcommittee recommends the following exposure guidance levels: EEGLs, REGLs, SPEGLs, and RPEGLs. Table 1-1 summarizes the definitions of these exposure guidance levels and a more detailed description for each is given below.

An EEGL is defined as a concentration of a substance in air (as a gas, vapor, or aerosol) that will permit continued performance of specific tasks during emergency exposures lasting up to 24 hr—an occurrence expected to be infrequent in the lifetime of a person (NRC 1986, 1992a). ''Emergency'' connotes a rare and unexpected situation with potential for significant loss of life, property, or mission accomplishment if not controlled. An EEGL, a single ceiling-exposure concentration for a specified

duration, specifies and reflects the subcommittee's interpretation of available information in the context of an emergency.

An EEGL is acceptable only in an emergency, when some risks or some discomfort must be endured to prevent greater risks (such as fire, explosion, or massive release). Exposure at the EEGL might produce such effects as increased respiratory rate, headache, mild central-nervous-system effects, and respiratory-tract or eye irritation. The EEGL should prevent irreversible harm. Even though some reduction in performance is permissible, it should not prevent proper responses to the emergency (such as shutting off a valve, closing a hatch, or using a fire extinguisher). For example, in normal work situations, a degree of upper-respiratory-tract irritation or eye irritation causing discomfort would not be considered acceptable; during an emergency, it would be acceptable if it did not cause irreversible harm or seriously affect judgment or performance. The EEGL for a substance represents the subcommittee's

judgment based on evaluation of experimental and epidemiological data, mechanisms of injury, and, when possible, operating conditions in which an emergency exposure might occur, as well as consideration of U.S. Department of Defense (DOD) goals and objectives. EEGLs were developed for military use and are intended for healthy military personnel. Therefore, they are not directly applicable to general populations consisting of elderly, very young, and ill persons.

A SPEGL is defined as a concentration of a substance in air that is acceptable for an unpredicted, single or rare, short-term emergency exposure of the general public. The SPEGL takes into account the likely wide range of susceptibility among individuals in the general public, including potentially susceptible subpopulations, such as children, the elderly, and persons with serious debilitating diseases. Effects of exposure on the developing embryo and fetus and on the reproductive capacity of men and women also are considered in setting a SPEGL.

For purposes of assessing military smokes and other obscurants for the Army, the subcommittee developed two additional guidance levels, REGLs and RPEGLs. The subcommittee defines a REGL as the concentration of a substance in air to which healthy military personnel can be exposed repeatedly, up to a specified total exposure on a weekly basis (usually 8 hr per day, 5 days per week), for several years without experiencing adverse health effects or degradation in performance.

The subcommittee defines a RPEGL as the concentration of a substance in air to which the general public can be exposed repeatedly without experiencing any adverse health effects or discomfort. RPEGLs, like SPEGLs, take into account the likely wide range of susceptibility among individuals in the general public, including potentially susceptible subpopulations (children, the elderly, and the chronically ill), the developing embryo and fetus, and reproductive capacity in men and women.

Exposure guidance levels developed by the subcommittee can be compared with other potentially useful exposure limits, such as the Threshold Limit Value (TLV) time-weighted averages (TWAs) and short-term exposure limits (STELs) recommended by the American Conference of Governmental. Industrial Hygienists (ACGIH) for permissible workplace exposures (ACGIH 1991, 1995). These guidelines are developed for daily occupational exposures of healthy workers. The Occupational Safety and Health Administration (OSHA) is responsible for promulgating and enforcing health standards in the majority of the work environments. These legally binding standards are referred to as permissible exposure limits (PELs; U.S. Department of Labor 1997), and most follow the Na-

tional Institute of Occupational Safety and Health (NIOSH) recommended exposure levels (RELs; EPA 1987). The OSHA and ACGIH values are not relevant for the general public.

The NRC has published guidelines for developing EEGLs, SPEGLs, and other exposure guidance levels for continuous or repeated exposures (NRC 1986, 1992a,b, 1996). For purposes of assessing military smokes and other obscurants, the subcommittee developed comparable procedures for developing REGLs and RPEGLs. The steps in developing exposure guidance levels are similar for EEGLs, SPEGLs, REGLs, and RPEGLs; the differences reflect attributes of the exposed populations and the duration and frequency of exposure. The remainder of this section reviews the steps for developing an EEGL (NRC 1986) and then explains how procedures differ for the remaining three types of exposure guidance levels.

The first step in developing an EEGL is to review all available toxicology information and any documentation for exposure limits proposed by ACGIH and regulatory agencies. Acute toxicity is the primary basis for establishing an EEGL. All end points are evaluated, and the most important are selected. In general, EEGLs reflect experimental and clinical observations and are based on epidemiological, physiological, and toxico-logical data on animals and humans; both immediate and delayed health effects are considered. Special attention is given to training and battlefield conditions that are of concern to the military. If there is any evidence that the substance under consideration is carcinogenic in either animals or humans, a cancer risk assessment is performed to estimate the possible potency of the substance as a carcinogen. The approach used to estimate potency is developed case by case, depending on available data and plausible mechanisms of action.

In evaluating the noncancer health effects, the subcommittee first assesses relevant toxicological information to determine the no-observed-adverse-effect level (NOAEL) of each smoke for the most sensitive end point. The NOAEL is the highest concentration at which no adverse toxic effect is indicated by the available data. If a NOAEL cannot be deter-

mined from the data, the lowest-observed-adverse-effect level (LOAEL) is determined. The LOAEL is the lowest concentration at which an adverse effect is seen in either human or laboratory animal studies. To estimate a NOAEL from a LOAEL, the subcommittee generally divides the LOAEL by a default uncertainty factor of 10, following the recommendations of the U.S. Environmental Protection Agency (EPA 1994). When NOAEL values obtained from laboratory animals are used to estimate exposure guidelines for humans, the subcommittee adopts the NRC (1977) Safe Drinking Water Committee default assumption that humans are 10-fold more sensitive than animals unless data are available that justify using a different assumption.

SPEGLs are generally set at 0.1 times the EEGL to protect susceptible subpopulations, including infants, the elderly, the chronically ill, and the developing embryo or fetus (NRC 1986).

Although the NRC has not published guidelines for developing REGLs and RPEGLs, the subcommittee follows the same approach as that recommended for EEGLs and SPEGLs; modifications reflect the repeated nature of exposures. In contrast to EEGLs and SPEGLs, the subcommittee uses chronic toxicity as the primary basis for establishing REGLs and RPEGLs. Haber's rule might not be applicable to the longer-term exposure durations. If there is any evidence that the substance is carcinogenic in either animals or humans, the subcommittee estimates the possible potency of the compound as a carcinogen. DOD can use the potency value when comparing risks associated with different concentrations of exposure with risks incurred by personnel wearing masks or not using the obscurant. The subcommittee generally sets RPEGLs at 0.1 times the REGLs to protect more susceptible subpopulations in the general public.

In recommending exposure guidance levels for the various obscurants, the subcommittee has had to rely on the use of uncertainty factors in an

attempt to account for various deficiencies in the toxicology data base for each obscurant. Those deficiencies include absence of a NOAEL, inadequate toxicity information on humans, and absence of information on potential susceptible subpopulations. Default 10-fold uncertainty factors are used in each case (i.e., LOAEL to NOAEL, extrapolation of animal data to humans, and variability in human susceptibility) but might be reduced if, for example, adjustments for species differences in lung dosimetry are made, as is done in the reference concentration method (EPA 1994). In that case, a lower (e.g., 3-fold) uncertainty factor might be applied. Potential sensitivity of the developing embryo and fetus and the reproductive system are accounted for in part by an intraspecies-human-variability uncertainty factor. Deficiencies in reproductive and developmental toxicity data are sometimes accounted for by applying a data-base uncertainty factor in addition to the intraspecies uncertainty factor, because reproductive and developmental end points might be more sensitive than other types of end points (Dourson et al. 1992). Because most smokes are primarily pulmonary toxicants, the subcommittee decided that it was unnecessary to apply an additional uncertainty factor to smokes lacking data on reproductive and developmental toxicity.

Thus, the recommended guidance levels developed are not precise, because the exact magnitude of the uncertainties is unknown. The product of the uncertainty factors results in high confidence that the overall factor is large enough to protect susceptible subpopulations adequately from long-term exposures. There is some conjecture on whether multiplying several uncertainty factors might result in an overly conservative guidance level, but that is difficult to resolve in the absence of more specific data. Several investigators have addressed this issue by reviewing data on variability in susceptibility among species and within the human population (Calabrese 1985; Hattis et al. 1987; Dourson et al. 1992; Burmaster and Harris 1993; Calabrese and Gilbert 1993; Bogen 1994; Baird et al. 1996; Dourson et al. 1996; Renwick and Lazarus 1998). EPA recognizes this problem and has suggested using a maximum of 10,000 for the total uncertainty factor (Dourson 1994).

This report is organized into four chapters, one for each of the obscuring smokes evaluated in this volume. For each smoke, the chapter presents background information on military applications and physical and chemi-

cal properties of the smoke. Each chapter also includes a discussion of toxicokinetics; and a summary of the available toxicity data on the smoke. Following a description of existing recommended exposure limits, each chapter presents the subcommittee's evaluation of the toxicity data and the development of the exposure guidance levels. Sections on research needs and references conclude each chapter.

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