Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 10 (2011) / Chapter Skim
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3 Methyl Ethyl Ketone1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA)
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Methyl Ethyl Ketone 141 effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
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142 Acute Exposure Guideline Levels sure at 200 ppm, approaching steady state in the blood by the end of the exposure (Liira et al.
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Methyl Ethyl Ketone 143 The AEGL-3 values were derived using different studies. The 10- and 30min time periods were derived using the studies by Klimisch (1988)
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144 Acute Exposure Guideline Levels products and may be a minor product of normal mammalian metabolism (WHO 1993; Morgott et al.
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Methyl Ethyl Ketone 145 TABLE 3-2 Chemical and Physical Data for Methyl Ethyl Ketone Parameter Data Reference Synonyms MEK, 2-butanone, ethyl ATSDR 1992; methyl ketone, methyl acetone, O'Neil et al. 2001 2-oxobutane CAS registry no.
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146 Acute Exposure Guideline Levels 2.2.2. Clinical Studies Five clinical studies addressed subjective symptoms during MEK exposure.
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Methyl Ethyl Ketone 147 TABLE 3-3 Summary of Human Studies for Methyl Ethyl Ketone Concentration Exposure (ppm) Duration Effect and Type of Study Reference 90-270 4h Concentrations not held constant; underestimation of Nakaaki 1974 (average 150)
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148 Acute Exposure Guideline Levels ketone, or an alcoholic drink, which served as a positive control for the neurobehavioral tests. Two control groups were also used: a chemical-control group and an alcohol-control group.
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Methyl Ethyl Ketone 149 sal swelling as measured by anterior active rhinomenometry was measured. The study was single blind because the subjects were unaware of the exposures, but the staff had little interaction with the subjects.
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150 Acute Exposure Guideline Levels to 224 ppm (Yoshikawa et al.
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Methyl Ethyl Ketone 151 ies)
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152 Acute Exposure Guideline Levels 2.4. Developmental and Reproductive Toxicity No information was found specific to the developmental and reproductive toxicity of MEK in humans.
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Methyl Ethyl Ketone 153 attributable to exposure to MEK was located. The odor recognition threshold for MEK ranges from 6 to 10 ppm (Leonardos et al.
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154 Acute Exposure Guideline Levels TABLE 3-4 Summary of Acute Lethal Inhalation Data in Laboratory Animals Concentration Exposure Species (ppm) Duration Effect Reference Rat 92,239 3h LT50 Klimisch 1988 92,239 30 min No deaths Rat 8,000 8h LC50 Pozzani et al.
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Methyl Ethyl Ketone 155 3.1.2. Mice Adult white mice (strain not identified)
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156 Acute Exposure Guideline Levels TABLE 3-5 Summary of Nonlethal Inhalation Data in Laboratory Animals Concentration Exposure Species (ppm) Duration Effect Reference Baboon 100 24 h, 7 days No effect on match-to-sample task Geller et al.
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Methyl Ethyl Ketone 157 In a 90-day study, groups of 15 male and 15 female Fischer 344 rats were exposed to MEK at 0, 1,250, 2,500, or 5,000 ppm for 6 h/day, 5 days/week, for 90 days (ToxiGenics 1981; Cavender et al.
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158 Acute Exposure Guideline Levels 3.3. Neurotoxicity Geller et al.
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Methyl Ethyl Ketone 159 of Fischer 344 rats at up to 5,000 ppm for 90 days did not result in any signs of neurotoxicity or lesions of the nervous system (ToxiGenics 1981; Cavender et al.1983)
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160 Acute Exposure Guideline Levels (Mast et al. 1989; Schwetz et al.
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Methyl Ethyl Ketone 161 jected intraperitoneally with MEK. MEK was not mutagenic in several strains of Salmonella typhimurium or in Escherichia coli and Saccharomyces cerevisiae, but it induced aneuploidy and chromosome loss in S
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162 Acute Exposure Guideline Levels 4.
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Methyl Ethyl Ketone 163 ter and air and olive oil and air were 134 and 131, respectively; during actual exposures of rats to MEK, the thermodynamic partition concentration was calculated to be 103 (Kessler et al.
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164 Acute Exposure Guideline Levels TABLE 3-6 Blood Concentrations of Methyl Ethyl Ketonea Exposure Concentration Blood Concentration Exposure (ppm)
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Methyl Ethyl Ketone 165 FIGURE 3-1 Methyl ethyl ketone (MEK) concentration (µmol/L)
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166 Acute Exposure Guideline Levels Tada et al.
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Methyl Ethyl Ketone 167 Following accidental ingestion of an unknown amount of MEK, a woman was brought to the hospital with metabolic acidosis (Kopelman and Kalfayan 1983)
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168 Acute Exposure Guideline Levels 4.4. Other Relevant Information 4.4.1.
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Methyl Ethyl Ketone 169 There is concern that exposure to organic solvents may increase the incidence of children born with CNS defects. According to EPA (2003)
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170 Acute Exposure Guideline Levels 4.4.4. Concurrent Exposure Issues Solvent exposure in the workplace generally involves mixtures of chemicals.
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Methyl Ethyl Ketone 171 Exposure of pregnant Wistar rats for 23 h/day, 7 days/week, to a combination of n-hexane at 1,200 ppm and MEK at 300 ppm throughout gestation or during the postnatal period increased the effect of n-hexane alone on birth weight and postnatal weight gain, both of which were reduced (StoltenburgDidinger et al.
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172 Acute Exposure Guideline Levels 1990a,b)
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Methyl Ethyl Ketone 173 6. DATA ANALYSIS FOR AEGL-2 Concentrations above the AEGL-2 may cause irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.
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174 Acute Exposure Guideline Levels day of the study. At 6,000 ppm, mild somnolence was reported in rats, but it was not clear that this effect occurred on the first day of exposure (Altenkirch et al.
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Methyl Ethyl Ketone 175 The values and end point are supported by the study of Altenkirch et al.
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176 Acute Exposure Guideline Levels 7.3. Derivation of AEGL-3 The AEGL-3 values for MEK were derived using different studies.
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Methyl Ethyl Ketone 177 sMCS were tested in the study of Seeber et al.
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178 Acute Exposure Guideline Levels The AEGL-2 was based on an exposure concentration that did not result in neurobehavioral deficits on the first day of a subchronic exposure study with rats (Cavender et al.
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Methyl Ethyl Ketone 179 TABLE 3-11 Extant Standards and Guidelines for Methyl Ethyl Ketone Exposure Duration Guideline 10 min 30 min 1h 4h 8h AEGL-1 200 ppm 200 ppm 200 ppm 200 ppm 200 ppm AEGL-2 4,900 ppma 3,400 ppma 2,700 ppma 1,700 ppm 1,700 ppm b b a a AEGL-3 4,000 ppm 2,500 ppm 2,500 ppma IDLH (NIOSH)
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180 Acute Exposure Guideline Levels longer than 15 min and should not occur more than 4 times per day. There should be at least 60 min between successive exposures in this range.
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Methyl Ethyl Ketone 181 Altenkirch, H., H.M. Wagner, G
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182 Acute Exposure Guideline Levels Cox, G.E., D.E. Bailey, and K
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Methyl Ethyl Ketone 183 Fiserova-Bergerova, V., and M.L.
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184 Acute Exposure Guideline Levels Kale, A., S Praster, W
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Methyl Ethyl Ketone 185 Mitran, E., T Callender, B
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186 Acute Exposure Guideline Levels Patty, F.A., H.H. Schrenk, and W.P.
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Methyl Ethyl Ketone 187 Stoltenburg-Didinger, G., H Altenkirch, and M
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188 Acute Exposure Guideline Levels Wurster, D.E., and R Munies.
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Methyl Ethyl Ketone 189 APPENDIX A DERIVATION OF AEGL VALUES FOR METHYL ETHYL KETONE Derivation of AEGL-1 Values Key studies: Dick et al.
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190 Acute Exposure Guideline Levels Uncertainty factors: 1 for interspecies; rodents have higher respiratory rates and cardiac output than humans; metabolism differences will not be significant at high, acute exposures. 3 for intraspecies; differences among humans for CNS effects of anesthetics are not expected to vary greatly.
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Methyl Ethyl Ketone 191 Time-scaling None for 10- and 30-min values None for 4- and 8-h values 1-h value time-scaled from 4-h value using n = 3 (Cn × t = k) Uncertainty factors: 1 for interspecies; rodents have higher respiratory rates and cardiac output than humans; metabolism differences will not be significant at high, acute exposures.
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192 Acute Exposure Guideline Levels APPENDIX B CATEGORY GRAPH OF TOXICITY DATA AND AEGL VALUES 1000000 Human - No Effect Human - Discomfort 100000 Human - Disabling Animal - No Effect 10000 ppm AEGL-3 Animal - Discomfort 1000 AEGL-2 Animal - Disabling Animal - Some Lethality 100 AEGL-1 Animal - Lethal AEGL 10 0 60 120 180 240 300 360 420 480 Minutes FIGURE 3-2 Category graph of toxicity data and AEGL values. TABLE B-1 Data Used in Category Graph Source Species ppm Minutes Categorya NAC/AEGL-1 200 10 AEGL NAC/AEGL-1 200 30 AEGL NAC/AEGL-1 200 60 AEGL NAC/AEGL-1 200 240 AEGL NAC/AEGL-1 200 480 AEGL NAC/AEGL-2 4,900 10 AEGL NAC/AEGL-2 3,400 30 AEGL NAC/AEGL-2 2,700 60 AEGL NAC/AEGL-2 1,700 240 AEGL NAC/AEGL-2 1,700 480 AEGL NAC/AEGL-3 10,000 10 AEGL NAC/AEGL-3 10,000 30 AEGL NAC/AEGL-3 4,000 60 AEGL (Continued)
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Methyl Ethyl Ketone 193 TABLE B-1 Continued Source Species ppm Minutes Categorya NAC/AEGL-3 2,500 240 AEGL NAC/AEGL-3 2,500 480 AEGL Nelson et al. 1943 Human 100 5 0 Human 200 5 1 Human 350 5 1 Shibata et al.
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194 Acute Exposure Guideline Levels APPENDIX C ACUTE EXPOSURE GUIDELINE LEVELS FOR METHYL ETHYL KETONE Derivation Summary for Methyl Ethyl Ketone AEGL-1 VALUES 10 min 30 min 1h 4h 8h 200 ppm 200 ppm 200 ppm 200 ppm 200 ppm Key references: Dick, R.B., E.F. Krieg, Jr., J
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Methyl Ethyl Ketone 195 AEGL-1 VALUES Continued 10 min 30 min 1h 4h 8h 200 ppm 200 ppm 200 ppm 200 ppm 200 ppm Time-scaling: Not applied; a tolerance develops to any irritation Data adequacy: The database on clinical and monitoring studies is extensive. MEK is rapidly metabolized.
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196 Acute Exposure Guideline Levels AEGL-2 VALUES Continued 10 min 30 min 1h 4h 8h a a a 4,900 ppm 3,400 ppm 2,700 ppm 1,700 ppm 1,700 ppm Time-scaling: The 4- and 8-h exposures were set equal to 1,700 ppm; the 10- and 30min and 1-h values were time-scaled with the default n value of 3. Data adequacy: Extensive database of human (irritation, neurotoxicity, and metabolism)
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Methyl Ethyl Ketone 197 AEGL-3 VALUES Continued 10 min 30 min 1h 4h 8h a a b b 4,000 ppm 2,500 ppm 2,500 ppmb Effects: No deaths at 96,239 ppm for 30 min (Klimisch 1988) ; no deaths at 50,000 ppm for 45 min (Zakhari et al.
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