Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 12 (2012) / Chapter Skim
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5 Methyl Bromide1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA)
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172 Acute Exposure Guideline Levels effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
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Methyl Bromide 173 Data from animal studies were available on lethal and sublethal concentrations, neurotoxicity, developmental and reproductive effects, genotoxicity, and potential carcinogenicity. Although genotoxicity studies show that alkylation of DNA and proteins occurs, carcinogenicity has not been established in chronic studies with rats and mice.
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174 Acute Exposure Guideline Levels sponse) of 701 ppm in a 4-h exposure study of rats (Kato et al.
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Methyl Bromide 175 1. INTRODUCTION Methyl bromide is a colorless, highly volatile gas that exists as a liquid below 3.6°C.
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176 Acute Exposure Guideline Levels (O'Neil et al.
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Methyl Bromide 177 Most cases of accidental exposures have involved manufacturing or packaging operations, use of fire extinguishers containing methyl bromide, or fumigation activities. Exposures at high concentrations may occur during fumigation activities, especially when methyl bromide is first released to the environment after fumigation ends, or when fumigated areas are not properly ventilated.
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178 Acute Exposure Guideline Levels colorimetry, have limited sensitivity. For example, Watrous (1942)
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Methyl Bromide 179 neous nausea, dizziness, and vomiting (the one exception experienced only a slight burning sensation in the throat)
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180 Acute Exposure Guideline Levels moment correlation coefficient or Student's t-test. No relationship was found between bromine concentration in blood and subjective symptoms, general neurologic deficits, or serum proteins.
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Methyl Bromide 181 tio of 1.14) , based on state age-adjusted incidence rates.
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182 Acute Exposure Guideline Levels and 2, 8, 12, and 22 h. For 8-h exposures, survival was 100% at 240 ppm and 0% at 470 ppm.
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Methyl Bromide 183 3.1.1. Rats A concentration-time mortality method was used to estimate LC50 values in male SPF-Wistar rats (Zwart 1988; Zwart et al.
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184 Acute Exposure Guideline Levels Sedation was observed in a concentration-dependent manner. No further details of sedation were provided.
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Methyl Bromide 185 The mortality rates of mice exposed at 500 ppm for 105, 120, 130, 140, 150, and 180 min were 0, 0, 11, 15, 85, and 90%, respectively. The post-exposure observation period was not specified.
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186 Acute Exposure Guideline Levels Schwob et al.
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Methyl Bromide 187 TABLE 5-4 Nonlethal Effects of Methyl Bromide in Laboratory Animals Exposed by Inhalation Concentration Exposure Species (ppm) Duration Effect Reference Dog 233, 314, 345, 7h Concentration- and time-dependent Newton 1994a 350, 394 increase in tremors, hunched appearance, and labored breathing.
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188 Acute Exposure Guideline Levels days postexposure. Nasal tissue, brain, spinal cord, and peripheral nerves were examined microscopically at necropsy performed 16-19 days after exposure.
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Methyl Bromide 189 battery of neurotoxicity tests and an automated motor-activity evaluation during the second, fourth, and sixth week of exposure. Tissues of the nervous system were examined at the end of the study.
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190 TABLE 5-5 Repeat-Dose Studies of Methyl Bromide Exposure Concentration (ppm) Duration Effects Reference Dog 0, 55, 156, 268, 283 7 h/d, 4 d 55 ppm: no clinical signs or lesions.
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150 4 h/d, 5 d/wk, 11 wk No clinical signs or deaths; heart lesions. 0, 160 6 h/d, 5 d/wk, 6 wk Early deaths, numerous tissue and organ lesions.
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192 Acute Exposure Guideline Levels Groups of 8 male and 8 female F-344 rats were exposed to methyl bromide at 0 or 150 ppm for 6 h/day for 5 days (Davenport et al.
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Methyl Bromide 193 brain. Necrosis of the olfactory epithelium was more severe and extensive in rats than in mice exposed at the same concentrations.
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194 Acute Exposure Guideline Levels NTP 1992)
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Methyl Bromide 195 3.5. Reproductive and Developmental Toxicity Hurtt and Working (1988)
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196 Acute Exposure Guideline Levels In a two-generation study, Sprague-Dawley rats were exposed by wholebody inhalation to methyl bromide at 0, 3, 30, or 90 ppm for 6 h/day, 5 days/week (Mayhew 1986)
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Methyl Bromide 197 missing gall bladder and lung lobe, although increased, were not statistically significant compared with the control group. No maternal or fetal effects were found at the lower concentrations tested in the first study.
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198 Acute Exposure Guideline Levels months. Each group had 90 males and 90 females; 10 rats/sex/group were killed after 13, 52, and 104 weeks.
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Methyl Bromide 199 namely the nose, heart, and brain. The bone was additionally affected.
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200 Acute Exposure Guideline Levels methyl bromide at 90 ppm was a NOAEL for damage to the olfactory epithelium (Hurtt et al.
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Methyl Bromide 201 kot et al.
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202 Acute Exposure Guideline Levels primarily enzyme catalyzed, probably by GST. Formation of formaldehyde appears to be a minor pathway.
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Methyl Bromide 203 tissues and that CNS toxicity might be mediated by CNS glutathione depletion and inhibition of GST activity (Davenport et al.
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204 Acute Exposure Guideline Levels Honma (1987; Honma et al.
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Methyl Bromide 205 mouse tissues (Griem et al.
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206 Acute Exposure Guideline Levels minute volume and basal metabolic rates (rat > dog > man)
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Methyl Bromide 207 (Warholm et al.
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208 Acute Exposure Guideline Levels From the studies summarized in Tables 5-3 to 5-5, it is apparent that there is a threshold concentration at which effects occur or fail to occur. For example, 90 ppm was a NOAEL for olfactory lesions in the rat, both during a 1-day and a 5-day repeat-exposure study, whereas a single exposure at 200 ppm produced such lesions (Hurtt et al.
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Methyl Bromide 209 neurotoxic signs or tissue lesions were observed in dogs exposed at 20 ppm (the highest concentration tested) , 7 h/day, 5 days/week for 6 weeks (Schaeffer 2002)
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210 Acute Exposure Guideline Levels epithelium in humans and rodents and the differences in air flow patterns, olfactory lesions in rats might not be relevant to humans. The developmental study of methyl bromide in rabbits by Breslin et al.
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Methyl Bromide 211 durations using the equation Cn × t = k, with n = 1.2. Because the time-scaled 8h value of 37 ppm is close to the chronic NOAEL of 33 ppm for mice (NTP 1992)
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212 Acute Exposure Guideline Levels TABLE 5-7 AEGL-2 Values for Methyl Bromide 10 min 30 min 1h 4h 8h 940 ppm 380 ppm 210 ppm 67 ppm 67 ppm (3,657 mg/m3)
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Methyl Bromide 213 TABLE 5-8 AEGL-3 Values for Methyl Bromide 10 min 30 min 1h 4h 8h 3,300 ppm 1,300 ppm 740 ppm 230 ppm 130 ppm (12,837 mg/m3)
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214 Acute Exposure Guideline Levels From 1948-1962, the TLV-TWA for methyl bromide was 20 ppm (ACGIH 2004)
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Methyl Bromide 215 ble or other serious health effects or symptoms that could impair an individual's ability to take protection action. The ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing lifethreatening health effects.
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216 Acute Exposure Guideline Levels j MAC (maximaal aanvaarde concentratie [maximal accepted concentration]
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Methyl Bromide 217 ATSDR (Agency for Toxic Substances and Disease Registry)
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218 Acute Exposure Guideline Levels Driscoll, C.D., and J.M. Hurley.
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Methyl Bromide 219 of methyl bromide in F344 rats and BDF1 mice - inhalation studies.
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220 Acute Exposure Guideline Levels A study of nine cases occupationally exposed due to inadvertent spread during fu migation.
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Methyl Bromide 221 Langard, S., T Rognum, O
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222 Acute Exposure Guideline Levels Nolan, R.J., D.L.
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Methyl Bromide 223 ington, DC [online]
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224 Acute Exposure Guideline Levels Warholm, M., A.K. Alexandrie, J
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Methyl Bromide 225 APPENDIX A TIME-SCALING CALCULATION FOR METHYL BROMIDE Best Fit Concentration x Time Curve 4.5 4 Log Concentration (ppm) 3.5 3 2.5 2 0.5 1 1.5 2 2.5 3 Log Time (minutes)
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226 Acute Exposure Guideline Levels APPENDIX B DERIVATION OF AEGL VALUES FOR METHYL BROMIDE Derivation of AEGL-1 Values AEGL-1 values are not recommended because toxic effects might occur below the odor threshold for methyl bromide. Absence of AEGL-1 values does not imply that exposures below the AEGL-2 values are without adverse effects.
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Methyl Bromide 227 Modifying factor: Not applied Calculations: 10-min AEGL-2: C1.2 = 37,059.7 ppm-min ÷ 10 min C = 940 ppm 30-min AEGL-2: C1.2 = 37,059.7 ppm-min ÷ 30 min C = 380 ppm 1-h AEGL-2: C1.2 = 37,059.7 ppm-min ÷ 60 min C = 210 ppm 4-h AEGL-2: C1.2 = 37,059.7 ppm-min ÷ 240 min C = 67 ppm 8-h AEGL-2: Set equal to the 4-h AEGL-2 of 67 ppm (If based on a chronic NOAEL of 33 ppm for mice (NTP 1992) , a 4-day NOAEL of 55 ppm for clinical signs and tissue lesions in dogs (Newton 1994a)
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228 Acute Exposure Guideline Levels 30-min AEGL-3: C = 166,927.3 ppm-min ÷ 30 min C = 1,300 ppm 1-h AEGL-3 C = 166,927.3 ppm-min ÷ 60 min C = 740 ppm 4-h AEGL-3: C = 166,927.3 ppm-min ÷ 240 min C = 230 ppm 8-h AEGL-3: C = 166,927.3 ppm-min ÷ 480 min C = 130 ppm
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Methyl Bromide 229 APPENDIX C CATEGORY GRAPH OF TOXICITY DATA AND AEGL VALUES FOR METHYL BROMIDE 100000 10000 No Effect Discomfort ppm 1000 Disabling AEGL-3 Some Lethality 100 AEGL-2 Lethal 10 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-1 Category graph of toxicity data on methyl bromide compared with AEGL values. All of the toxicity data pertain to laboratory animals; no clinical data were available.
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230 Acute Exposure Guideline Levels APPENDIX D ACUTE EXPOSURE GUIDELINE LEVELS FOR METHYL BROMIDE Derivation Summary for Methyl Bromide AEGL-1 VALUES AEGL-1 values are not recommended because toxic effects might occur below the odor threshold for methyl bromide. Absence of AEGL-1 values does not imply that exposures below the AEGL-2 values are without adverse effects.
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Methyl Bromide 231 AEGL-2 VALUES Continued 10 min 30 min 1h 4h 8h 940 ppm 380 ppm 210 ppm 67 ppm 67 pm Uncertainty factors/Rationale: Total uncertainty factor: 3 Interspecies: 1, based on studies with methyl chloride, uptake is greater in rodents than in humans; GST concentrations are greater in rodents than humans, resulting in faster production of toxic metabolites. Intraspecies: 3, differences in metabolism among humans are no greater than 3-fold (Nolan et al.
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232 Acute Exposure Guideline Levels AEGL-3 VALUES Continued 10 min 30 min 1h 4h 8h 3,300 ppm 1,300 ppm 740 ppm 230 ppm 130 ppm End point/Concentration/Rationale: BMCL05, 701 ppm, threshold for lethality Uncertainty factors/Rationale: Total uncertainty factor: 3 Interspecies: 1, based on studies with methyl chloride, uptake is greater in rodents than in humans; GST concentrations are greater in rodents than humans, resulting in faster production of toxic metabolites. Intraspecies: 3, differences in metabolism among humans are no greater than 3-fold (Nolan et al.
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