National Academies Press: OpenBook
« Previous: Front Matter
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 1
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 2
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 3
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 4
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 5
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 6
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 7
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 8
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 9
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 10
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 11
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 12
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 13
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 14
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 15
Suggested Citation:"Summary." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
×
Page 16

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

SUMMARY 1 Summary No reliable acute-exposure1 standards have been established for the particular purpose of protecting soldiers from toxic exposures to chemical- warfare (CW) agents. Some human-toxicity estimates are available for the most common CW agents—organophosphorus nerve agents and vesicants; however, most of those estimates were developed for offensive purposes (that is, to kill or incapacitate the enemy) and were intended to be interim values only. The U.S. Army's original purpose for developing human-toxicity estimates for CW agents was to enable it to predict the number of casualties that would occur during an offensive action in which the goal was to kill or incapacitate a certain fraction of the enemy forces (for example, killing or incapacitating a minimum of 50% of the least-sensitive (most-resistant) individuals). Such an approach would actually result in more than half of the exposed individuals dying (the "bonus effect"), because a certain percentage of those exposed would be expected to be more susceptible than the least-sensitive individual. Thus, exposure under the Army's original estimates would result in substantial "over- kill." These estimates understate the toxicity of the agents and therefore are inappropriate for protecting soldiers. 1 A one-time, short-term exposure; for example, < 1 hr.

SUMMARY 2 Because of the possibility of a chemical attack by a foreign power, the Army's Office of the Surgeon General asked the Army's Chemical Defense Equipment Process Action Team (CDEPAT) to review the toxicity data for the nerve agents GA (tabun), GB (sarin), GD (soman), GF, and VX, and the vesicant agent sulfur mustard (HD) and to establish a set of exposure limits that would be useful in protecting soldiers from toxic exposures to those agents. In the 1994 report entitled Review of Existing Toxicity Data and Human Estimates for Selected Chemical Agents and Recommended Human Toxicity Estimates Appropriate for Defending the Soldier, the team concluded that some of the existing human-toxicity estimates are too high and are inappropriate for use in protecting soldiers. In those cases, CDEPAT proposed new estimates for various routes of exposure—percutaneous vapor, vapor inhalation, and percutaneous liquid exposures. The proposed human-toxicity estimates are only for healthy male military personnel. They must not be used for civilians. Before making a decision on acceptance of the human-toxicity estimates proposed by CDEPAT, the Department of the Army requested that the National Research Council (NRC) independently review the CDEPAT report to determine the scientific validity of the proposed estimates. The NRC assigned this project to the Committee on Toxicology (COT) of the Board on Environmental Studies and Toxicology. The COT convened the Subcommittee on Toxicity Values for Selected Nerve and Vesicant Agents, which prepared this report. Members of the subcommittee were selected for their recognized expertise in the fields of toxicology, medicine, pathology, biostatistics, and risk assessment. The subcommittee was charged to review the Army's proposed human-toxicity estimates for GA, GB, GD, GF, VX, and HD. Specifically, the subcommittee was charged with the following tasks: 1. Review the scientific protocols and quality of the toxicity data used in revising the human-toxicity estimates for acute exposures. 2. Review the toxicity estimates for mild and nonsevere effects and for severe and lethal effects. 3. Review the methods used in deriving the human-toxicity estimates for acute exposures. 4. Determine the appropriateness of the assumptions made in deriving the human-toxicity estimates for acute exposures. The subcommittee was not asked to recommend new toxicity estimates

SUMMARY 3 or to address the policy or operational consequences of lowering the proposed human-toxicity estimates. The subcommittee's evaluations of CDEPAT's proposed estimates for GA, GB, GD, GF, VX, and HD are summarized in Tables I through 6. The subcommittee's conclusions concerning the scientific validity of the proposed CDEPAT estimates are grouped in four categories: (1) some estimates were judged to be scientifically valid; (2) other estimates were judged adequate to serve as interim estimates until further research is conducted; (3) some estimates need to be lowered; and (4) a few estimates need to be raised. The toxicity data that CDEPAT used to derive its proposed estimates were generated primarily from a data base developed from the 1930s to the 1960s. The existing human-toxicity estimates were based on experiments performed 30–40 years ago using various animal species in often poorly controlled studies with vastly different protocols. In reviewing the available toxicity data for the six CW agents, the subcommittee recognized that the quality of the relevant toxicity data is marginal, but it also recognized that the Army needs "best estimates" to protect its troops from exposure. For each chemical agent, data were available for only a few adverse health effects, such as death, incapacitation, cholinesterase (ChE) inhibition, miosis (a decrease in pupil size), and rhinorrhea (running nose), vesication, and erythema. Thus, even though the subcommittee concluded that some of CDEPAT's proposed estimates are scientifically valid, those conclusions are based on a limited toxicity data base. By current standards of toxicology, the toxicity data base for the agents is inadequate, and such inadequacy is a major obstacle to the Army in developing human-toxicity estimates with statistical confidence and in developing risk-management strategies. The subcommittee recommends that the Army convene an expert panel to develop a research strategy for deriving more scientifically sound toxicity values for the agents of concern. The panel should first consider the use of such techniques as structure-activity relationships, the uncertainty factors, and in vitro systems for estimating human-toxicity values for CW agents. If these approaches do not appear to be useful, animal and human experimentation may be recommended. Although additional research is clearly desirable to provide improved confidence in existing data, such research should not be performed on laboratory animals until expert judgment documents the need on a case-by-case basis. It must be documented that the data to be obtained from laboratory animals is needed to make a significant improvement in the protection of human health.

TABLE 1 Evaluation of Human-Toxicity for GA Human-Toxicity Estimates for GA SUMMARY Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LCt50 a Percutaneous, 20,000 mg- 15,000 mg- Proposed estimate is Proposed estimate supported by human data vapor min/m3 min/m3 scientifically valid Inhalation, 135 mg- 70 mg-min/ Proposed estimate should Because of inadequate data on GA for this route, vapor min/m3 m3 be lowered CDEPAT derived the estimate by assuming that GA is 0.5 times as toxic as GB; approach reasonable but estimate should be lowered because of recommended lowering of LCt50 for GB for this route; further research recommended ECt50 b Threshold Percutaneous, None 2,000 mg- Proposed estimate is ChE inhibition data used for proposing new effects vapor min/m3 scientifically valid recommendation Severe Inhalation, None 50 mg-min/ Proposed estimate should CDEPAT's proposed estimate based on a study that effects vapor m3 be lowered indicated the ratio of ICt50e/LC50 is 0.75; that assumption used to establish ECt50 . for severe effects; the subcommittee recommends that the ECt50 estimate be lowered to correspond to the lowered estimate for LCt50 ; further research recommended Mild effects Inhalation, 0.9 mg- 0.5 mg-min/ Proposed estimate should Human data show that humans can tolerate higher vapor min/m3 m3 be raised exposures; further research recommended 4

Human-Toxicity Estimates for GA Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation SUMMARY Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LD50 c Percutaneous, 1,500 mg 1,500 mg for Proposed estimate should No uncertainty factors used in lieu of limited animal data liquid for 70-kg 70-kg man be lowered for proposed estimate; further research recommended man ED50 d Percutaneous, None 880 mg for Proposed estimate should In the absence of adequate human or animal data for this liquid 70-kg man be lowered effect, CDEPAT established the estimate by assuming ID50 f/LD50 ratio of 0.6 to estimate ED50; the subcommittee recommends that the ED50 estimate be lowered to correspond to the lowered estimate for LD50; further research recommended a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt : Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 e ICt : Vapor exposure that produces incapacitation in 50% of the exposed population. 50 f ID : Liquid dose causing incapacitation in 50% of the exposed population. 50 5

TABLE 2 Evaluation of Human-Toxicity Estimates for GB Human-Toxicity Estimates for GB SUMMARY Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LCt50 a Percutaneous, 15,000 mg- 10,000 mg- Proposed estimate is Proposed estimate supported by studies in monkeys and vapor min/m3 min/m3 scientifically valid humans Inhalation, 70 mg-min/ 35 mg-min/ Proposed estimate should Estimate too high because human studies show 100% vapor m3 m3 be lowered lethality at 40 mg-min/m3 ECt50 b Threshold Percutaneous, None 1,200 mg- Proposed estimate is Estimate supported by studies of ChE inhibition in effects vapor min/m3 scientifically valid humans; further research recommended Severe Inhaiation, 35 mg-min/ 25 mg-min/ Proposed estimate should ECt50 /LCt50 ratio of 0.7 used to develop estimate; LCt50 effects vapor m3 m3 be lowered for this route of exposure was lowered; therefore, ECt50 should be lowered correspondingly; further research recommended Mild effects Inhalation, 2 mg-min/ 0.5 mg-min/ Proposed estimate should No effects in humans at 0.5 mg-min/m3; effects begin to vapor m3 m3 be raised appear at 2 mg-min/m3 ; further research recommended LD50 c Percutaneous, 1,700 mg 1,700 mg for Low confidence in Estimate based on a ratio of ChE inhibition in rabbits liquid for 70-kg 70-kg man proposed estimate; and humans; however, human data concerning the man proposed estimate should relation between ChE inhibition and adverse effects are serve as interim value inconsistent; further research recommended 6

Human-Toxicity Estimates for GB Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation SUMMARY Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA ED50 d Severe Percutaneous, None 1,000 mg for Proposed estimate should In the absence of adequate data on GB for this effect, effects liquid 70-kg man serve as interim value CDEPAT assumed that the ratio of lD50c/LD50 is 0.6 and used that to estimate the ED50 values; further research recommended a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt : Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 c ID : Liquid dose causing incapacitation in 50% of the exposed population. 50 7

TABLE 3 Evaluation of Human-Toxicity Estimates for GD Human-Toxicity Estimates for GD SUMMARY Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LCt50 a Percutaneous, None 2,500 mg- Proposed estimate is Proposed estimate based on assumption that GD is 4 vapor min/m3 scientifically valid times more toxic than GB for percutaneous exposure Inhalation, 70 mg-min/ 35 mg-min/ Proposed estimate should Proposed estimate based on the assumption that GD and vapor m3 m3 be lowered GB are equipotent via this route; subcommittee recommends that LCt50 estimate for GD be lowered to correspond to lowered estimate for GB; further research recommended ECt50 b Threshold Percutaneous, None 300 mg-min/ Proposed estimate should In the absence of adequate human or animal data, effects vapor m3 serve as an interim value proposed estimate based on assumption that GD is 4 times more toxic than GB for percutaneous exposure; further research recommended Severe Inhalation, 35 mg-min/ 25 mg-min/ Proposed estimate should In the absence of adequate human or animal data, effects vapor m3 m3 be lowered proposed estimate based on assumption that potencies of GD and GB are comparable; ECt 50 estimate for GD should be lowered to correspond to the lowered estimate for GB; further research recommended 8

Human-Toxicity Estimates for GD Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation SUMMARY Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA Mild Inhalation, None 0.2 mg-min/ Proposed estimate should In the absence of adequate human or animal data, effects vapor m3 be raised proposed estimate based on assumption that GD is 2.5 times more potent than GB for miotic effects; subcommittee recommends that the LCt50 estimate for GD be raised to correspond to the recommended raised estimate for GB; further research recommended LD50 c Percutaneous, 350 mg for 350 mg for Proposed estimate should Because of wide range of LD50 values in animals, liquid 70-kg man 70-kg man serve as an interim value subcommittee's confidence in the proposed estimate is low; CDEPAT's proposed estimate of 350 mg for 70-kg man should serve as an interim value; further research recommended ED50 d Severe Percutaneous, None 200 mg for Proposed estimate should In the absence of adequate human or animal data, effects liquid 70-kg man serve as an interim value proposed estimate was derived using the ID50 e/LD50 ratio of 0.6; the subcommittee recommends that CDEPAT's proposed estimate serve as an interim value; further research recommended a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt : Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 c ID : Liquid dose causing incapacitation in 50% of the exposed population. 50 9

TABLE 4 Evaluation of Human-Toxicity Estimates for GF Human-Toxicity Estimates for GF SUMMARY Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LCt50 a Percutaneous, 15,000 mg- 2,500 mg- Proposed estimate should Rationale for the CDEPAT estimate not supported by vapor min/m3 min/m3 serve as an interim value data; further research recommended Inhalation, None 35 mg-min/ Proposed estimate should In the absence of adequate data, proposed estimate based vapor m3 be lowered on assumption that GF, GD, and GB are equipotent; approach is reasonable; because LCt50 for GB was recommended to be lowered, proposed value for GF should be lowered correspondingly; further research recommended ECt50 b Threshold Percutaneous, None 300 mg-min/ Proposed estimate should Proposed estimate based on assumption that GF and GD effects vapor m3 serve as an interim value are equipotent; approach is reasonable; further research recommended Severe Inhalation, None 25 mg-min/ Proposed estimate should In the absence of adequate data, proposed estimate based effects vapor m3 be lowered on assumption that GF, GD, and GB are equipotent; approach is reasonable; because ECt50s for severe effects for GB and GD were recommended to be lowered, proposed value for GF should be lowered correspondingly; further research recommended 10

Human-Toxicity Estimates for GF Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation SUMMARY Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA Mild Inhalation, None 0.2 mg-min/ Proposed estimate should In the absence of adequate human or animal data, the effects vapor m3 be raised proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; because ECt50 for mild effects for GD was recommended to be raised, proposed value for GF should be raised correspondingly; further research recommended LD50 c Percutaneous, None 350 mg for Proposed estimate should In the absence of adequate human or animal data, liquid 70-kg man serve as an interim value proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; further research recommended ED50 d Severe Percutaneous, None 200 mg for Proposed value should In the absence of adequate human or animal data, the effects liquid 70-kg man serve as an interim value proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; further research recommended a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt : Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 11

TABLE 5 Evaluation of Human-Toxicity Estimates for VX Human-Toxicity Estimates for VX SUMMARY Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LCt50 a Percutaneous, None 150 mg-min/ Proposed estimate should Degree of confidence in data is low to moderate; further vapor m3 be considered an interim research recommended value Inhalation, 30 mg-min/ 15 mg-min/ Proposed estimate should Degree of confidence in data is low to moderate; further vapor m3 m3 be lowered research recommended ECt50 b Threshold Percutaneous, None 10 mg-min/ Proposed estimate should Degree of confidence in data is low; a no-observed- effects vapor m3 be considered an interim adverse-effect level (NOAEL) was not defined; further value research recommended Severe Percutaneous, None 25 mg-mill/ Proposed estimate should Degree of confidence low to moderate; further research effects vapor m3 be considered an interim recommended value Inhalation, 25 mg-min/ 10 mg-min/ Proposed estimate should Insufficient data; further research recommended vapor m3 m3 be considered an interim value Mild effects Inhalation, 0.09 mg- 0.09 mg- Proposed estimate is Available human data support the proposed estimate vapor min/m3 min/m3 scientifically valid LD50 c Percutaneous, 10 mg/70- 5 mg/70-kg Proposed estimate should Animal data indicate that the proposed estimate is too liquid kg man man be lowered high; furthermore, no uncertainty factor used in lieu of variability associated with dermal penetration of various regions of body; further research recommended 12

Human-Toxicity Estimates for VX Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation SUMMARY Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA ED50 d Severe Percutaneous, 5 mg/70-kg 2.5 mg/70kg Proposed estimate should The ED50 is based on the ID50 e/LD50 ratio; the effects liquid man man be lowered subcommittee recommends that the LD50 be lowered, therefore, the ED50 should be lowered correspondingly; further research recommended a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt : Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 e ID : Liquid dose causing incapacitation in 50% of the exposed population. 50 13

TABLE 6 Evaluation of Human-Toxicity Estimates for HD Human-Toxicity Estimates for HD SUMMARY Toxicity Route and Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type Form of Estimates Proposed Evaluation of Proposed Exposure Estimates Estimates for GA LCt50 a Percutaneous, 10,000 mg 5,000 mg- Proposed estimate should Estimate might be too high because data from the most- vapor min/m3 min/m3 be lowered sensitive species (rats and mice) not used; further research recommended Inhalation, 1,500 mg 900 mg-min/ Proposed estimate is CDEPAT averaged LCt50 data in several animal species; vapor min/m3 m3 scientifically valid in the absence of data on humans, that approach is reasonable ECt50 b Threshold Percutaneous, None 50 mg-min/ Proposed estimates In the absence of details on studies on which estimates effects vapor m3 (moderate should serve as interim were based, proposed estimate should be considered temperature); values interim value; further research recommended 25 mg-min/ m3 (hot temperature) Severe Percutaneous, 2,000 mg- 500 mg-min/ Proposed estimates are Estimates based on human studies effects vapor min/ m3 m3 (moderate scientifically valid (moderate temperature); temperature) <200 mg- 1,000 mg min/m3 (hot min/ m3 (hot temperature) temperature) 14

Human-Toxicity Estimates for HD Toxicity Route and Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation SUMMARY Type Form of Estimates Proposed Evaluation of Proposed Exposure Estimates Estimates for GA Inhalation, 200 mg-min/ 100 Mg-Min/ Proposed estimate is Proposed estimate supported by human data vapor m3 (moderate m3 moderate scientifically valid temperature) temperature) Mild Inhalation, >50 mg min/ 25 mg-min/ Proposed estimate is Proposed estimate supported by human data effects vapor m3 m3 scientifically valid LD50 c Percutaneous, 7,000 mg for 1,400 mg for Proposed estimate is Proposed estimate supported by a study in dogs liquid 70-kg man 70kg man scientifically valid ED50 d Severe Percutaneous, None 610 mg for Proposed estimate is Proposed estimate supported by human data effects liquid 70-kg man scientifically valid; however, it should be rounded to 600 mg for a 70-kg man to avoid appearance of precision that is not there a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 15

SUMMARY 16 The experimental designs should include the following: • Define if and when experiments with humans are appropriate. • In the absence of human experimentation, define the most appropriate animal model for each specific toxicity value and agent, including the end points to be observed. • Define the adequacy of the design in determining the toxicity values for healthy female as well as healthy male military personnel. • Define the requirements for observation of reversibility of adverse health effects. • Identify adverse health effects at the low end of the dose-response curve to determine threshold exposure levels. • Identify confidence limits for the proposed estimates as a measure of the uncertainty of the estimated incidence of toxic effects. • Identify potentiation or antagonistic effects from exposures to mixtures of chemical agents. • Identify more-sensitive biological markers of exposure and effects for CW agents.

Next: 1 - Introduction and Background »
Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents Get This Book
×
Buy Paperback | $50.00 Buy Ebook | $39.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

No reliable acute-exposure1 standards have been established for the particular purpose of protecting soldiers from toxic exposures to chemical warfare (CW) agents. Some human-toxicity estimates are available for the most common CW agents--organophosphorus nerve agents and vesicants; however, most of those estimates were developed for offensive purposes (that is, to kill or incapacitate the enemy) and were intended to be interim values only. Because of the possibility of a chemical attack by a foreign power, the Army's Office of the Surgeon General asked the Army's Chemical Defense Equipment Process Action Team (CDEPAT) to review the toxicity data for the nerve agents GA (tabun), GB(sarin), GD (soman), GF, and VX, and the vesicant agent sulfur mustard (HD) and to establish a set of exposure limits that would be useful in protecting soldiers from toxic exposures to those agents. This report is an independent review of the CDEPAT report to determine the scientific validity of the proposed estimates.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!