Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 19 (2015) / Chapter Skim
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4 Pentaborane Acute Exposure Guideline Levels
4 Pentaborane Acute Exposure Guideline Levels
Pages 86-138
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From page 86... ...
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 87... ...
Dogs exposed at 1.4 ppm a second time (the following day) , however, began to exhibit CNS effects, including decreased activity, miosis, and CAR delays, and additional exposures caused irritability and aggres
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From page 88... ...
An interspecies uncertainty factor of 3 was used because pentaborane causes similar effects (CNS toxicity) in humans and four species of laboratory animals, and acute lethality values varied less than 3-fold among the species.
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From page 89... ...
Two US manufacturers of pentaborane are listed in the Hazardous Substances Data Bank (HSDB 2006) , but no production volumes are specified.
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Autopsy revealed severe necrotizing pneumonia, fatty changes with centrilobular degeneration in the liver, brain degeneration, and lack of mature spermatozoa in the testicles. The second worker had similar effects but survived.
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Serial EEG tracings were used to evaluate CNS effects in 15 male workers exposed to pentaborane at two US aircraft facilities (North American Aviation, Inc. and Edwards Air Force Base)
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From page 92... ...
Severe exposures caused incoordination, muscle spasms and tremors, areas of numbness, drooling, nausea, vomiting, convulsions (30-120 seconds) , opisthotonus, increased blood pressure, tachycardia, fever, and profuse perspiration.
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EEG tracings revealed abnormalities, even in cases when the individuals had no symptoms. More serious symptoms included memory loss, disorientation, incoordination, muscle pain, muscle spasms, and convulsions.
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From page 94... ...
Symptoms included dizziness, drowsiness, headache, nervousness, restlessness, exhaustion, hiccups, cough, nausea, flushing, profuse perspiration, visual disturbances, inability to concentrate, memory loss, incoordination, muscle spasms, and convulsions. EEG tracings revealed abnormalities, even in cases when the individuals had no symptoms.
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From page 95... ...
liquid pentaborane, followed by dilution with air. The concentration of pentaborane in the 0.4-m3 dynamic exposure chamber was determined by a carmine method using air collected in Edgewood collection bubblers.
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method of moving averages; only the deaths that occurred during the first 2 h of exposure were used in the calculation. Using benchmark dose software (EPA Version 1.3.2)
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(1957) determined a mean survival time of 62-67 min for three male CFW rats exposed to pentaborane at 13.6 ppm.
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From page 98... ...
liquid pentaborane, followed by dilution with air, and the concentration of pentaborane was determined by a carmine method using air collected in Edgewood collection bubblers. Toxic signs began with tremors, ataxia, convulsions, and red exudate around the mouth and nose.
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From page 99... ...
Using benchmark dose software (EPA Version 1.3.2) to model data combined from both experiments on mortality that occurred during the 2-week observation period, an LC50 of 12.4 ppm (BMCL05 = 7.9 ppm, BMC01 = 8.6 ppm)
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From page 100... ...
The pentaborane vapor was generated from liquid pentaborane and its concentration was determined by a carmine method in air collected in Edgewood collection bubblers. Toxic signs began with tremors, ataxia, convulsions, red exudate around the mouth and nose, and then death within 24 h after exposure.
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From page 101... ...
. Rat 16.0-285 15-85 4/10-3/3 each Tremors, jitteriness, convulsions, corneal opacity, bulging eyes, decreased breathing, and cyanosis (Svirbely 1954a)
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From page 102... ...
Mortality Effect (Reference) Mouse 16.0-285 11-81 5/5 or 10/10 each Tremors, jitteriness, running-like movements, convulsions, spasms, corneal opacity, bulging eyes, cyanosis, and huddling 4.3-20.2 120 LC50 = 12.4 ppm (Svirbely 1954a)
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From page 103... ...
Nonhuman Primates Sooty mangabey monkeys of unspecified sex and age were exposed to pentaborane for 2 min in both an acute lethality study (described in Section 3.1.1) and a nonlethal toxicity study (Weeks et al.
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From page 104... ...
The study did not report the results of the CAR tests, other than to state that the response time in the CAR test increased to the point that the dogs would not participate for 2-6 days after the last exposure. The boron concentration in the serum of the dogs did not increase, but urinary concentrations increased after each exposure, returning to pre-exposure levels 72 h after the last exposure.
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From page 105... ...
Exposure at 5.2 ppm for 15 min resulted in a slight decrease in mean latency response time, but the investigators noted that the decrease was not significant and no alterations were observed in dogs exposed to pentaborane at 9.1 ppm for 15 min. More severe effects occurred at the high concentrations for all three exposure durations, consisting of convulsions, tremors, and CAR performance delays; some animals did not even perform the CAR test (2- and 5-min exposures)
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No toxic signs. Whole body: 46.0 (n = 2)
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From page 107... ...
each response 58 2/3 convulsions 2/3, no jumps 1 and 2 h after exposure; 3/3, increase in CAR mean latency response time. 15-min exposure 5.2 None 3/3, slight, but not significant, increase in mean response time.
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From page 108... ...
Toxicity increased with exposure duration and concentration, and was cumulative in multiple-exposure studies. Neurotoxic signs included appre
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From page 109... ...
. Both species also had neurotoxic effects and pathologic organ changes.
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From page 110... ...
The studies consistently show that the CNS is the target of pentaborane; toxicity increased with exposure duration and concentration. Neurotoxic signs included apprehensiveness, lethargy, corneal opacity, aggressiveness, miosis, ataxia, tremors, and convulsions.
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From page 111... ...
(1964) found that dogs exposed two or three times on successive days to pentaborane at 3.7-19.8 ppm for 5-60 min had unchanged serum boron concentrations, but their urinary boron increased after each exposure, returning to preexposure concentrations after 72 h.
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From page 112... ...
4.2. Mechanism of Toxicity The mechanism of pentaborane toxicity is unknown, but might involve decreased brain serotonin and norepinephrine concentrations.
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evaluated acute lethality studies conducted with pentaborane, diborane, and decaborane, and concluded that pentaborane was the most toxic. Rats and dogs exposed to diborane had pulmonary edema and hemorrhage, whereas animals exposed to pentaborane (rats and mice)
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From page 114... ...
. Using a value of n derived from a rat lethality study was considered appropriate because neurotoxic effects are on the continuum of effects leading to death, neurotoxicity was the primary toxic effect in both species, and dogs and rats were similarly sensitive to pentaborane.
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From page 115... ...
Occupational exposure studies indicated that the CNS is the target of pentaborane toxicity and that CNS effects can occur at concentrations with an undetectable odor. However, none of the studies determined exposure concentrations, exposure durations, and resulting effects simultaneously.
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From page 116... ...
began to exhibit CNS effects, including decreased activity, miosis, and CAR delays, and additional exposures caused irritability and aggressiveness. This scenario was chosen instead of the 60-min single exposure study in which 3.0 or 3.2 ppm produced no toxic signs (Weir et al.
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A value of n = 1.3 was determined by linear regression analysis of acute lethality data from studies of mice exposed for 5-60 min (Weir et al.
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From page 118... ...
A total uncertainty factor of 10 was applied. An interspecies uncertainty factor of 3 was used because pentaborane caused similar effects (CNS toxicity)
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e TLV-STEL (threshold limit value – short-term exposure limit, American Conference of Governmental Industrial Hygienists)
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.) The American Conference of Governmental Industrial Hygienists established a threshold limit value–time-weighted average (TWA)
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2013 Threshold Limit Values and Biological Exposure Indices Based on the Documentation of the TLVs for Chemical Substances and Physical Agents and BEIs. American Conference of Governmental Industrial Hygienists, Inc., Cincin nati, OH.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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U.S. Army Chemical Warfare Laboratories, Army Chemical Center, MD.
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124 Acute Exposure Guideline Levels Weir, F.W., and F.H. Meyers.
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Dogs exposed a second time (the following day) , however, began to exhibit CNS effects including decreased activity, miosis, and CAR delays.
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From page 126... ...
(5.08) 1.3 × 60 min = 496 ppm-min Uncertainty factors: 3 for interspecies differences; similar effects (CNS toxicity)
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Pentaborane 127 3 for intraspecies variability; the homogenous response among species and the steep concentration-response curve for lethality indicate that there would be little variability among humans. Modifying factor: None Calculations: 10-min AEGL-3 С1.3 × 10 min = 496 ppm-min С = 20 ppm 20 ppm ÷ 10 = 2.0 ppm (5.2 mg/m3)
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From page 128... ...
Results from multiple-exposure studies that have information on effects from the first exposure to pentaborane are also included. No human data on pentaborane were available.
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From page 129... ...
1964 Dog 9.1 15 0 No toxic signs Weeks et al. 1964 Dog 18 15 2 Convulsions, tremors (Continued)
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From page 130... ...
1964 Dog 0.80 60 0 No toxic signs Weir et al. 1964 Dog 3.0 60 0 No toxic signs (whole-body exposure)
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From page 131... ...
Svirbely 1954a Rat 16 81 SL Mortality: 2/5 Svirbely 1954a Rat 24 85 3 Mortality: 3/3 Svirbely 1954a Rat 15.7 120 SL LC50 Svirbely 1954a Rat 20.2 120 3 Mortality: 5/5 Svirbely 1954b Rat 3.3 300 2 Convulsions, gasping, tremors, aggressiveness, salivation, organ lesions Weir et al.
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From page 132... ...
1964 Mouse 19.8 5 2 Convulsions; death after repeated exposures Weir et al. 1964 Mouse 10.2 15 2 Convulsions; death after repeated exposures Weir et al.
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From page 133... ...
Dogs exposed a second time (the following day) began to exhibit CNS effects, including decreased activity, miosis, and CAR delays.
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From page 134... ...
occurred in humans and four species of laboratory animals, and LC50 values varied less than 3-fold among species. Intraspecies: 3, the homogenous response among species and the steep concentrationresponse curve for lethality indicate that there would be little variability among humans.
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From page 135... ...
. For pentaborane, the value of n was determined using lethality data from studies in rats by Weir et al.
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From page 136... ...
136 Acute Exposure Guideline Levels APPENDIX E BENCHMARK DOSE CALCULATIONS (VERSION 2.4.0) Probit Model.
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From page 137... ...
= 4 P-value = 0.1630 Benchmark Dose Computation Specified effect = 0.05 Risk Type = Extra risk Confidence level = 0.95 BMD = 6.54353 BMDL = 5.08379
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From page 138... ...
138 Probit Model, with BMR of 1% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL Probit 1 0.8 Fraction Affected 0.6 0.4 0.2 0 BMDL BMD 0 2 4 6 8 10 12 dose 08:56 08/26 2013
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