Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 14 (2013) / Chapter Skim
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1 Agent BZ (3-Quinuclidinyl Benzilate) Acute Exposure Guideline Levels
1 Agent BZ (3-Quinuclidinyl Benzilate) Acute Exposure Guideline Levels
Pages 13-41
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From page 13... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 14... ...
Data on nonlethal effects of BZ in humans after inhalation exposure are from studies conducted by the military. Subjects in these studies were carefully screened, evaluated, and informed human volunteers (male military personnel)
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1967) , in which responses of test subjects were characterized using a scoring system that integrated various cognitive parameters, blood pressure, and heart rate.
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and to obtain protective AEGL values, time scaling was performed using the default of n = 1 to extrapolate to the 10-min, 30-min, and 1-h durations. AEGL2 values for the 4-h and 8-h durations are not recommended, because data on exposure to BZ for durations longer than a few minutes are lacking and the effects of longer exposures are uncertain.
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From page 17... ...
TABLE 1-1 AEGL Values for Agent BZ Classification 10 min 30 min 1h 4h 8h End Point (Reference) AEGL-1 NR NR NR NR NR Insufficient data.
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: subjects show peak heart rate of 80-95 beats/min, systolic blood pressure elevation <20 mm Hg, sedation might be marked at 4-16 h, transient illusions/hallucinations/confusion and lapses in concentration, some metal slowing, lowest performance score of 40% at 8 h; recovery complete at approximately 72 h. TRI 6.0 (severe)
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: peak heart rate of 110-140 beats/min within 3 h, systolic blood pressure increase of 20-60 mm Hg, onset of stupor within 3 h and performance decrement to zero within 4 h followed by protracted sleepiness, disorganized behavior, continual hallucinations, possible outbursts of fear and anger, delirium subsides within 72 h; complete recovery by120 h. Air concentrations were established to attain estimated doses of BZ ranging from 1.4 to 26 μg/kg.
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TABLE 1-4 Cumulative Exposures and TRI Scores for Male Volunteers Exposed to Agent BZ Minute BZ Subject Number Volume (L) Body Weight TRI Score (CT, mg-min/m3)
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1967) in which responses of test subjects were characterized using a scoring system expressed as a TRI value on the basis of various cognitive parameters, blood pressure, and heart rate.
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. The value was reportedly based on exposure durations of 15-40 min.
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From page 23... ...
Exposure durations and details regarding the experimental protocol were not available.
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Duration Conditions (yards) Effectsa 575 6 min, 41°F, 67% 100 Mydriasis, cycloplegia, 10 sec relative humidity tranquility, erratic behavior, lethargy, hyperactivity, sedation, ataxia, increased heart rate.
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Both the human and animal data are from experiments with short exposure durations (minutes)
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4.3. Structure-Activity Relationships No data regarding structure-activity relationships that would be instrumental in developing AEGL values for BZ were available.
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Effects of BZ were characterized in these studies by a scoring system expressed as TRI values, which were based on cognitive parameters, blood pressure, and heart rate. All exposures were of short duration (about 20 min)
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From page 28... ...
The threshold level is also lower than the one associated with clinical signs that might impair the ability to escape (e.g., progressive deterioration of normal gait and uncomfortable paresthesias of lower extremities reported by subjects exposed to BZ at 46.0-84.7 mg-min/m3 [or 9.2-16.9 mg/m3]
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From page 29... ...
and to obtain protective AEGL values, time scaling was performed using the default of n = 1 to extrapolate to the longer AEGL-specific exposure durations. Nonlethal effects of BZ are totally reversible.
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From page 30... ...
A factor of 10 was applied for interspecies differences because no lethality data are available for humans and LCt50 values for five animal species varied 10-fold. An intraspecies uncertainty factor of 10 was applied to account for possible pharmacokinetic differences and possible increased sensitivity between individuals.
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From page 31... ...
A modifying factor of 3 was applied because of uncertainties in the database, particularly a lack of incidence data (lethality studies only reported LCt50 values) which could be used to estimate a LC01 and a lack of studies involving longer exposure durations (longest duration was 40 min)
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Edgewood Arsenal Technical Report EATR 4140. Medical Research Laboratory, Edgewood Arsenal, MD.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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From page 34... ...
Experiments conducted by Ketchum and colleagues were of short durations; 6-8 min in animal studies and possibly no more than 5 min in tests with human volunteers. The concentration-time relationship for many irritant and systemically acting vapors and gases may be described by the equation Cn × t = k, where the exponent n ranges from 0.8 to 3.5 (ten
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From page 35... ...
and to obtain protective AEGL values, time scaling was performed using a default of n = 1 for extrapolating from shorter exposures to longer duration. Uncertainty factors: 1 for interspecies differences, because data were from human volunteers.
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From page 36... ...
and to obtain protective AEGL values, time scaling was performed using the default of n = 1 for extrapolating from shorter exposures to longer duration. Uncertainty factors: 10 for interspecies differences; no lethality data are available for humans and LCt50 values for five animal species varied 10-fold.
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From page 37... ...
Agent BZ (3-Quinuclidinyl Benzilate) 37 1-h AEGL-3: C = 3,700 mg-min/m3 ÷ 60 min = 61.67 mg/m3 C = 61.67 mg/m3 ÷ 300 = 0.21 mg/m3 4-h AEGL-3: Not recommended because of uncertainties regarding longer-term exposures.
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From page 38... ...
Test species/Strain/Sex/Number: Human volunteers, males, n = 8 Exposure route/Concentrations/Durations: Aerosol inhalation Effects: Cognitive and behavioral effects, mild effects on heart rate and blood pressure. ICt50 of 60.1 mg-min/m3 (95% CI: 41.3-87.5 mg-min/m3; presumably for 5 min)
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From page 39... ...
Uncertainty factors/Rationale: Total uncertainty factor: 100 Interspecies: 10, no lethality data are available for humans and LCt50 values for five animal species varied 10-fold. Intraspecies: 10, the anticholinergic mechanism by which BZ operates is not likely to vary between individuals because the structure of muscarinic receptors are highly conserved in humans; however, individuals with pre-existing conditions may be sensitive to the anticholingeric effects of BZ.
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From page 40... ...
of mg-min/m3. Data points were derived for the lowest and highest exposure durations for which the CT values were determined, as well as for AEGL-specific durations within or near the respective range of the experimental exposure durations.
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From page 41... ...
Exposures mg/m3 Minutes Category Comments NAC/AEGL-3 1.2 10 AEGL NAC/AEGL-3 0.41 30 AEGL NAC/AEGL-3 0.21 60 AEGL NAC/AEGL-3 NR 240 AEGL NAC/AEGL-3 NR 480 AEGL Ketchum 1963 Human 1 2 30 2 Human 1 5 30 2 Human 1 0.8 60 2 Human 1 1.2 60 2 Department of Monkey 1 6,167 6 SL LCt50 the Army 1974 Monkey 1 1,480 25 SL LCt50 Dog 1 4,167 6 SL LCt50 Dog 1 1,563 16 SL LCt50 Rat 1 12,800 5 SL LCt50 Rat 1 2,133 30 SL LCt50 Mouse 1 2,400 5 SL LCt50 Mouse 1 632 19 SL LCt50 Rabbit 1 2,133 15 SL LCt50 Rabbit 1 800 40 SL LCt50 Guinea pig 1 24,600 5 SL LCt50 Guinea pig 1 4,100 30 SL LCt50 Ketchum et Monkey 1 93 6.17 1 Mydriasis, al. 1967 cycloplegia, tranquility, erratic behavior, lethargy, hyperactivity, sedation, ataxia Dog 1 93 6.17 1 Mydriasis, cycloplegia, tranquility, erratic behavior, lethargy, hyperactivity, sedation, ataxia, increased heart rate Dog 1 5 8 0 Rabbit 1 93 6.17 1 Mydriasis, cycloplegia Dog 1 1,000 8 SL RCt50 Dog 1 25 8 1 Rabbit 1 10 8 1 RCt50 Rabbit 1 1,000 8 SL For category: 0 = no effect; 1 = discomfort; 2 = disabling; SL = some lethality; 3 = lethal.
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