Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 11 (2012) / Chapter Skim
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Pages 257-338
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5 Vinyl Chloride1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA)
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258 Acute Exposure Guideline Levels AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.
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Vinyl Chloride 259 Acute exposure to VC results in narcotic effects (Mastromatteo et al.
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260 Acute Exposure Guideline Levels blood. The extrapolation from a 3.5 h exposure to 10 min is justified because humans exposed at 4,000 ppm for 5 min did not experience headaches (Lester et al.
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Vinyl Chloride 261 scaling according to the dose-response regression equation Cn × t = k, with n = 2, based on data from Mastromatteo et al.
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262 Acute Exposure Guideline Levels Most VC is produced either by hydrochlorination of acetylene, mainly in Eastern European countries, or by thermal cracking of 1,2-dichloroethane. VC is stored either under pressure at ambient temperature or refrigerated at atmospheric pressure (WHO 1999)
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Vinyl Chloride 263 2.2. Nonlethal Toxicity A summary of the acute effects in humans after exposure to VC is presented in Table 5-3.
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264 Acute Exposure Guideline Levels 2.2.1. Neurotoxicity VC was considered a potential anesthetic.
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Vinyl Chloride 265 ing the circulating air duct. A heating tape wrapped around the stainless-steel tubing prevented condensation of VC.
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266 Acute Exposure Guideline Levels polyvinyl-chloride facilities (number of workers not specified)
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Vinyl Chloride 267 Suciu et al.
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268 Acute Exposure Guideline Levels hepatocellular hyperplasia and focal mixed hyperplasia has been observed in VC exposed workers; some of the individuals with focal mixed hyperplasia developed liver angiosarcoma (Tamburro et al.
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Vinyl Chloride 269 2.5. Carcinogenicity No data about cancer induction in humans after a single exposure to VC have been reported.
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270 Acute Exposure Guideline Levels sumed to have occurred after 3.5 h of exposure) (Baretta et al.
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Vinyl Chloride 271 LC100 of 21% (about 210,000 ppm)
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272 Acute Exposure Guideline Levels In the context of a teratology study, John et al.
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Vinyl Chloride 273 ity. Mortality was 100% in animals exposed for 24 h, and 90% in those exposed for 12 h.
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274 Acute Exposure Guideline Levels 3.1.4. Rabbits Rabbits (n = 4)
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TABLE 5-5 Summary of Nonlethal Effects of Vinyl Chloride in Laboratory Animals Species Concentration (ppm) Duration Effect Reference Dog 50,000 5 min EC50, cardiac sensitization in response to epinephrine.
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276 TABLE 5-5 Coninued Species Concentration (ppm) Duration Effect Reference Rat 50,000 6h No clinical or histologic signs of hepatic toxicity.
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Vinyl Chloride 277 Clark and Tinston (1982) conducted a second study on cardiac sensitization to epinephrine in beagle dogs (six male or female, not further specified)
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278 Acute Exposure Guideline Levels Exposure of 18 Sherman rats to VC at 100,000 for 8 h resulted in deep anesthesia, with consciousness regained 5 to 10 min after removal from the exposure chamber. One female rat died after two exposures, and the remaining rats showed signs of toxicity (not specified)
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Vinyl Chloride 279 weight was 15.55 grams (g) in the 2,500-ppm group and 14.27 g in the control group, and the relative liver weight was 37.8 mg/g in the 2,500-ppm group and 34.4 mg/g in the control group.
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280 Acute Exposure Guideline Levels phatase) , subcellular damage, and centrilobular necrosis were found after 2 h.
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Vinyl Chloride 281 Prodan et al.
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282 Acute Exposure Guideline Levels during organogenesis (days 6-15 of gestation for mice and rats and days 6-18 in rabbits, 7 h/day)
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Vinyl Chloride 283 matograph. Section was performed on the day 21 of gestation.
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284 Acute Exposure Guideline Levels delivered in the 1,100-ppm group. The authors considered this effect to be unrelated to exposure, because the values were lower than those of the F1 controlgroup values but comparable to those of the F0 control group.
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Vinyl Chloride 285 rats to [14C] VC at 250 ppm for 5 h, the total amount metabolized per individual rat was 37 μmol.
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286 Acute Exposure Guideline Levels VI rats (7 day old pups and 13-week-old adults) treated with VC.
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Vinyl Chloride 287 al.
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288 Acute Exposure Guideline Levels tumors included eight hepatocellular carcinomas, 15 angiosarcomas of the liver, and two benign cholangioma. No further details were provided.
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Vinyl Chloride 289 A hepatocellular adenoma developed after a single 12-h exposure of rats to VC at 1,500 ppm. That concentration was lethal to most of the animals (Tátrai and Ungváry 1981)
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290 Acute Exposure Guideline Levels tabolism between animals and humans were taken into consideration by use of a pharmacokinetic model. The increased sensitivity of children was taken into consideration.
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Vinyl Chloride 291 liver weights, but no changes were found by light microscopy (Ungváry et al.
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292 Acute Exposure Guideline Levels Induction of liver tumors has been reported in rats after subacute (5 weeks and 33 days) exposure (Maltoni et al.
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Vinyl Chloride 293 Whole-body exposure (excluding the head) of Rhesus monkeys to radioactive VC indicated that very little VC is absorbed through the skin (about 0.031 and 0.023% at 800 and 7,000 ppm, respectively, after 2-2.5 h)
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294 Acute Exposure Guideline Levels and proteins or spontaneously rearrange to 2-chloroacetaldehyde, which might bind to proteins and DNA. 2-Chloroethylene oxide can also be transformed to glycol aldehyde by epoxide hydrolase or react with glutathione, leading to the formation N-acetyl-S-(2-hydroxyethyl)
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Vinyl Chloride 295 Saturation of metabolism also has been observed after oral exposure to VC at high doses. Watanabe et al.
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296 Acute Exposure Guideline Levels noma have been found after short-term exposure to VC (Maltoni et al. 1981, 1984; Froment et al.
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Vinyl Chloride 297 TABLE 5-7 Lethal Concentrations of Vinyl Chloride in Laboratory Animals Species LC50 Reference Mouse 117,500 ppm Prodan et al. 1975 Rat 150,000 ppm Lester et al.
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298 Acute Exposure Guideline Levels 4.3.4. Concurrent Exposure Issues Concurrent administration of ethanol and VC in rats resulted in an increase in liver angiosarcoma, compared with data from animals exposed only to VC.
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Vinyl Chloride 299 5.2. Summary of Animal Data Relevant to AEGL-1 Lacrimation occurred shortly after mice, rats, guinea pigs, and rabbits were exposed to VC (42,900-280,000 ppm)
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300 Acute Exposure Guideline Levels 6.
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Vinyl Chloride 301 Viola (1970) reported that rats exposed to VC at 30,000 ppm for 4 h/day were slightly soporific (no further details)
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302 Acute Exposure Guideline Levels Narcotic effects seem to predominate in rats, mice, and guinea pigs acutely exposed to high concentrations of VC. These effects are relevant AEGL2 effects because they have the potential to impair escape.
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Vinyl Chloride 303 7.
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304 Acute Exposure Guideline Levels tor of 1 was applied. Only small interindividual differences in pharmacokinetics of VC are expected, as the concentration of VC required to elicit the effect is greater than that required for saturation of the metabolic pathways.
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Vinyl Chloride 305 TABLE 5-11 Summary of AEGL Values for Vinyl Chloride Classification 10 min 30 min 1h 4h 8h AEGL-1 450 ppm 310 ppm 250 ppm 140 ppm 70 ppm (nondisabling)
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306 Acute Exposure Guideline Levels TABLE 5-12 Extant Standards and Guidelines for Vinyl Chloride Exposure Duration Guideline 10 min 30 min 1h 4h 8h AEGL-1 450 ppm 310 ppm 250 ppm 140 ppm 70 ppm AEGL-2 2,800 ppm 1,600 ppm 1,200 ppm 820 ppm 820 ppm AEGL-3 12,000 ppm 6,800 ppm 4,800 ppm 3,400 ppm 3,400 ppm a PEL-TWA (OSHA)
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Vinyl Chloride 307 eral population can be exposed to for up to 4 h without any health risks. The value is based on the observation that no acute toxic effects or irritating effects have been observed during exposure to 500 ppm for 4 h.
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308 Acute Exposure Guideline Levels Boffetta, P., L Matisane, K.A.
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Vinyl Chloride 309 Clewell, H.J., P.R. Gentry, J.M.
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310 Acute Exposure Guideline Levels Feron, V.J., B.J.
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Vinyl Chloride 311 Bethesda, MD [online]
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312 Acute Exposure Guideline Levels Maltoni, C., G Lefemine, A
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Vinyl Chloride 313 Schaumann, O
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314 Acute Exposure Guideline Levels Viola, P.L., A Bigotti, and A
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Vinyl Chloride 315 APPENDIX A DERIVATION OF AEGL VALUES FOR VINYL CHLORIDE Derivation of AEGL-1 Values Key study: Baretta, E.D., R.D. Stewart, and J.E.
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316 Acute Exposure Guideline Levels 4-h AEGL-1: C × 240 min = 103,110 ppm-min C = 429.63 ppm 430 ppm ÷ 3 = 140 ppm [360 mg/m3]
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Vinyl Chloride 317 Calculations: 10-min AEGL-2: C2 × 10 min = 7.2 × 108 ppm2-min C = 8,485.28 ppm 8,485 ppm ÷ 3 = 2,800 ppm [7,300 mg/m3]
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318 Acute Exposure Guideline Levels Time scaling: C2 × t = k for extrapolation to 10 min, 30 min, 1 h, and 2 h Steady-state concentration occurs after 2 h, so flat-line response assumed for extrapolation to 4 and 8 h k = (50,000 ppm) 2 × 5 min = 1.25 × 1010 ppm2-min Calculations: 10-min AEGL-3: C2 × 10 min = 1.25 ×1010 ppm2-min C = 35,355.34 ppm 35,355 ppm ÷ 3 = 12,000 ppm [31,000 mg/m3]
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Vinyl Chloride 319 APPENDIX B TIME-SCALING CALCULATIONS The relationship between dose and exposure duration to produce a toxic effect for any given chemical is a function of the physical and chemical properties of the substance and the toxicologic and pharmacologic properties of the individual substance. Historically, the relationship according to Haber (1924)
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320 Acute Exposure Guideline Levels TABLE B-1 Observations of Side Position in Mice Exposed to Vinyl Chloride Concentration Time (min) Log concentration Log time 100,000 20 5 1.301 200,000 5 5.301 0.699 300,000 2 5.477 0.301 TABLE B-2 Observations of Side Position in Guinea Pigs Exposed to Vinyl Chloride Concentration Time (min)
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Vinyl Chloride 321 Although the end points for AEGL-2 (anesthesia) and AEGL-3 (cardiac sensitization)
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322 Acute Exposure Guideline Levels APPENDIX C CANCER ASSESSMENT OF VINYL CHLORIDE The most recently published cancer risk estimate from EPA (2000a,b) appears to be the best unit risk estimate currently available for VC.
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Vinyl Chloride 323 To account for uncertainty regarding the variability in the stage of the cancer process at which VC or its metabolites may act, a multistage factor of 6 is applied (NRC 2001)
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TABLE C-1 Dose in the Liver of Active Metabolite 24 Hours After Exposure to Vinyl Chloride 324 Dose in Liver, mg/L Concentration (mg/m3)
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Vinyl Chloride 325 FIGURE C-1 External concentration and dose to liver of vinyl chloride calculated by physiologically-based pharmacokinetic modeling by EPA. Source: Gary Foureman, EPA, personal commun., June 2003.
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326 Acute Exposure Guideline Levels TABLE C-4 Incidence of Tumors in Studies by Maltoni et al.
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Vinyl Chloride 327 5 week × 7 days/week × 30 = 1,050 days 33.0 μg/m3 × 1,050 days = 34.7 mg/m3 (14 ppm) An additional factor to adjust for uncertainties with assessing potential cancer risks under short-term exposures is not applied, as exposure was shortterm in the underlying study.
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328 Acute Exposure Guideline Levels A similar result is obtained if the tumor data from Froment et al.
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Vinyl Chloride 329 APPENDIX D OCCUPATIONAL EPIDEMIOLOGIC STUDIES OF VINYL CHLORIDE Two large studies of workers employed in industries using VC monomer and polyvinyl chloride before 1974 were evaluated. Both studies were retrospective cohort mortality studies.
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330 Acute Exposure Guideline Levels TABLE D-1 Liver Cancer Incidence for All European Countries by Duration of Employment Duration of Incidence Employment Number of Number of (observed/ SMR (years) Individualsa Person (years)
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Vinyl Chloride 331 states were used to calculate SMRs. For the Canadian province, mortality-rate data from Michigan was used because it is the state closest to the Canadian plant.
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332 Acute Exposure Guideline Levels TABLE D-3 Liver and Biliary-Tract Cancer Incidence in the United States by Duration of Employment Duration of Incidence Employment Number of Number of (observed/ (years) Individuals Person (years)
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Vinyl Chloride 333 TABLE D-4 Standardized Mortality Ratios for Malignant Tumors of the Liver by Duration of Exposure Employment Duration (months) Cases SMR Confidence Interval <12 0 -- -- 13-60 2 874 Beyond 95th confidence interval 61-120 3 1,525 Beyond 99th confidence interval >121 7 2,528 Beyond 99th confidence interval Total 12 Source: Adapted from Weber et al.
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334 Acute Exposure Guideline Levels APPENDIX E ACUTE EXPOSURE GUIDELINE LEVELS FOR VINYL CHLORIDE Derivation Summary for Vinyl Chloride AEGL-1 VALUES 10 min 30 min 1h 4h 8h 450 ppm 310 ppm 250 ppm 140 ppm 70 ppm Reference: Baretta, E.D., R.D. Stewart, and J.E.
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Vinyl Chloride 335 AEGL-2 VALUES 10 min 30 min 1h 4h 8h 2,800 ppm 1,600 ppm 1,200 ppm 820 ppm 820 ppm References: Lester, D., L.A. Greenberg, and W.R.
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336 Acute Exposure Guideline Levels AEGL-2 VALUES Continued 10 min 30 min 1h 4h 8h 2,800 ppm 1,600 ppm 1,200 ppm 820 ppm 820 ppm (continued) Mastromatteo et al.
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Vinyl Chloride 337 AEGL-3 VALUES Continued 10 min 30 min 1h 4h 8h 12,000 ppm 6,800 ppm 4,800 ppm 3,400 ppm 3,400 ppm End point/Concentration/Rationale: Considering possible sensitive subpopulations and increased excitement in case of emergency reaction, epinephrine-induced cardiac reactions might occur and could be enhanced by exposure to high concentrations of VC. The respective effects are well known for certain unsubstituted and halogenated hydrocarbons.
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