Lethal nonlethal

Synonyms Tear gas Less-than-lethal Nonlethal Lacrimator, Harassing agent Incapacitant 2-Chloro-l-phenylethanone 2-Chloroacetophe-none, chloroacetophenone, phenacyl chloride Chloromethyl phenyl ketone Chemical Formula CgHyClO Chemical Structure ... 

Tear Gas, less than lethal, nonlethal, immobilizers, irritants, lacrimators, harassing agents, RCAs, crowd control agents (Table 1). 

Puskas, J.E. Novel butyl composite for less-lethal ammunition, Kautsch. Gummi Kunstst., 58, 288, 2005. Charles, A. et al. Penetrating bean bag injury Intrathoracic complication of a nonlethal weapon, J. Trauma, 53, 997, 2002. 

Human TClo values of 3 ppm (no duration specified) and 325 micrograms per cubic meter (lig/m3) (0.1 ppm) (no duration specified) have been reported (RTECS 1987). Henderson and Haggard (1943) (as cited in AIHA1993) noted that exposure of humans to arsine at 3-10 ppm for a few hours may result in signs and symptoms of poisoning. Similar to the data set for acute lethality, most information on nonlethal effects of arsine exposure in humans are case reports representing exposure estimates. 

Numerous cases of arsine poisoning have been reported (Elkins and Fahy 1967 DePalma 1969). However, these reports lack definitive exposure concentration data and usually lack exposure duration data as well. Some of the more recent and complete reports involving nonlethal consequences are described in the following section. These reports do not provide quantitative data suitable for AEGL derivations, but they do provide valuable insight into the nature and progression of arsine poisoning in humans. In most cases, the severity of the effects was usually sufficient to necessitate medical intervention to prevent lethality. Some of the more prominent reports and those with the best descriptive data have been summarized, but the overview is by no means exhaustive. 

Numerous case reports are available regarding the lethal and nonlethal toxicity of arsine in humans, but definitive exposure concentration or duration data are lacking. Although the case reports are of limited use for quantitative estimates of exposure limits, they do provide qualitative information about the nature of arsine poisoning in humans. Some estimated human toxicity values are available and are summarized in Table 2-3. 

Male and female F344 rats exposed to arsine at 5 ppm, 6 h/d for 28 d exhibited no mortality or overt signs of toxicity (Fowler et al. 1989). Flowever, there was a 100% mortality within 4 d of exposure to 10 ppm, thereby demonstrating a sharp delimitation and very narrow margin between lethal and nonlethal exposure concentrations. 

Several reports identified nonlethal effects in humans acutely exposed to arsine. These reports, however, lacked definitive exposure data but verified hematologic disorders leading to renal failure as critical effects of arsine exposure. Bulmer et al. (1940) (as cited in Elkins 1959) reconstructed an exposure incident at a gold extraction facility and estimated that subchronic (up to 8 mon) exposure to 0.12 ppm arsine resulted in jaundice and anemia (see Section 2.2.1). The lack of definitive exposure data for humans necessitates the use of animal data for quantitative estimation of AEGL values. Derivation of AEGL-2 values based upon limited human data (Flury and Zernik 1931) was considered but rejected because the data were poorly documented and inconsistent with other data showing lethality at lower cumulative exposures. 

The AEGL values reflect the steep exposure-response relationship exhibited by the toxicity data. Additional information regarding the mechanism(s) of action and metabolism of monomethylhydrazine may provide further insight into understanding and defining the threshold between nonlethal and lethal exposures. 

In the study by Haun et al. (1970), no deaths occurred in mice exposed to monomethylhydrazine at 50 ppm for 240 min. No additional information was provided to assess nonlethal toxicity. At slightly higher exposures (55-63 ppm), mortality was increased (1/40 and 7/40, respectively), suggesting that the 50-ppm exposures were approaching a lethality threshold. 

Acute lethality data for inhalation exposure to monomethylhydrazine are available for monkey, dog, rat, mouse, and hamster. Based upon the available data, hamsters appear to be the most resistant species, and the squirrel monkey and beagle dog are the most sensitive. The lethality of monomethylhydrazine appeared to follow a linear relationship for exposures up to 1 h. Most animal data focus on lethality as the toxicity endpoint with very limited exposure-response information available regarding nonlethal effects. The most significant effect reported in the acute exposure studies was the notable hemolytic response that was reversible upon cessation of exposure. However, the preponderance of the data suggest that there is little margin between exposures associated with nonlethal, reversible effects and those that result in death. 

Data on acute exposures of humans to both isomers of dimethylhydrazine are limited to case reports of accidental exposures. Signs and symptoms of exposure include respiratory irritation, pulmonary edema, nausea, vomiting, and neurologic effects. However, definitive exposure data (concentration and duration) were unavailable for these accidents. The limited data in humans suggest that the nonlethal toxic response to acute inhalation of dimethylhydrazine is qualitatively similar to that observed in animals. No information was available regarding lethal responses in humans. In the absence of quantitative data in humans, the use of animal data is considered a credible approach for developing AEGL values. 

Exposures resulting in nonlethal, irreversible effects of dimethylhydrazine were not well defined. For most studies, responses were described in terms of no visible signs of toxicity or lethality. However, Weeks et al. (1963) described nonlethal (but reversible) effects in dogs exposed to 1,1-dimethylhydrazine at varying concentrations. In this study, dogs were exposed to 1,1-dimethylhydrazine at 1,550 ppm or 4,230 ppm for 5 min or 360, 400, or 1,530 ppm for 15 min. The highest cumulative exposures at each of two exposure periods (Ct =352-383 ppm-h) were associated with marked tremors, convulsions and death, while the lower concentration exposures at each of two periods caused behav... 

The 30-min and 1-, 4-, and 8-h AEGL-3 values were based on the highest concentration causing no mortality in the rat after a 30-min exposure (15 ppm) (Zwart et al. 1990). A UF of 3 was applied for interspecies extrapolation because little species variability is observed for lethal and nonlethal end points after exposure to phosgene. A UF of 3 was applied to account for sensitive human subpopulations due to the steep concentration-response curve and... 

In their literature review, Diller and Zante (1982) also identified nonlethal effects from phosgene exposure (lethal effects are described in Section 2.1). Nonlethal information synthesized from this review is presented in Table 1-4. From the above data and from animal data for initial lung damage, Diller and Zante (1982) synthesized information for nonlethal effects of phosgene in humans (Table 1-5). 

The concept of a death product was introduced by Haber to explain the relationship between the extent of exposure to phosgene and death (Haber 1924). According to Haber s law, the biological effect of phosgene is directly proportional to the exposure, expressed as the product of the atmospheric concentration (C) and the time of exposure (T), or CT=k, where k can be death, pulmonary edema, or other biological effects of phosgene exposure (EPA 1986). Haber s law has subsequently been shown by other investigators to be valid for both nonlethal and lethal effects within certain limits. 

Interspecies 3—little species variability is observed with both lethal and nonlethal end points in many studies after exposure to phosgene... 

Acute inhalation lethality data for the rat, mouse, and rabbit for exposure times of 10 s to 12 h were located. A single inhalation study with the dog did not give an exposure duration. The data are summarized in Table 5-4. Data from studies with nonlethal concentrations are summarized in Table 5-5. Barcroft (1931) reported LC50 values and times to death for eight species of animals, the times to death at a constant concentration. Due to experimental design constraints, the LC50 values are not reported here, but relevant data are discussed in the section on relative species sensitivity (Section 4.4.1). 

---