Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 5 (2007) / Chapter Skim
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Appendix 6 Tetranitromethane Acute Exposure Guideline Levels
Appendix 6 Tetranitromethane Acute Exposure Guideline Levels
Pages 228-274
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Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Subcommittee on Acute Exposure Guideline Levels.
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Tetranitromethane 229 are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows: AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]
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230 Acute Exposure Guideline Levels AEGL-1 values were not developed due to insufficient data. No studies were located with end points clearly within the scope of AEGL-1.
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Tetranitromethane 231 applicable to rare events or single, once-in-a-lifetime exposures, and the data indicate that TNM neoplasms resulted from chronic exposure, and (3) a direct comparison of estimated TNM cancer risk and AEGL values is not appropriate due to large differences in methodology used to obtain these numbers.
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232 Acute Exposure Guideline Levels In humans, exposure to impure TNM has been reported to cause irritation of the eyes, nose, throat, dizziness, chest pain, dyspnea, methemoglobinuria, and cyanosis (Budavari et al.
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. Symptoms from acute exposure included salivation and upper respiratory passage irritation, whereas prolonged exposure resulted in headaches, weariness, sleepiness, slowed pulse, "formation of hemoglobin (not further details provided)
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234 Acute Exposure Guideline Levels source of this information. The data in Sievers (1947)
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Tetranitromethane 235 enced by workers exposed to unknown concentrations of impure TNM (emitted during TNT production) included irritation to the mucous tissue of the eyes, nose, and respiratory passages, dyspnea, expectoration, coughing, chest tightness, and dizziness (Sievers et al.
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236 Acute Exposure Guideline Levels edematous and/or reddened lungs, and microscopic diffuse lung edema. At 10 ppm, one male died on day 8 and had diffuse pneumonitis.
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TABLE 6-3 Tetranitromethane Single-Exposure Animal Studies Exposure Exposure Conc.
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238 TABLE 6-3 Continued Exposure Exposure Conc.
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Tetranitromethane 239 died after 3 days, 3 died after 7 days, and 65 died after 2 weeks. Pathological changes reflecting pulmonary irritation occurred at all doses of TNM: pneumonitis, bronchitis, tracheitis, bronchopneumonia, histiocytic pneumonia, and edema (manifest as increased wet lung/body weight ratios)
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conducted an acute exposure study using mice and determined that the 2-h LC50 was 75 ppm, whereas there was 100% mortality at 114 ppm. No further information was available.
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Tetranitromethane 241 level. A cat exposed in a closed tub (0.022 m3)
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242 Acute Exposure Guideline Levels there was only a trace of TNM in the air (not specified) , and the animals behaved normally during exposure and for the following week of observation.
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Tetranitromethane 243 week 2. No effects were seen in animals exposed to ≤5 ppm other than slightly (10%)
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244 Acute Exposure Guideline Levels ing the study. Signs of toxicity, observed only during the first two exposure days, included occasional coughing, lethargy, an "unthrifty" appearance, and refusal to eat.
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Tetranitromethane 245 3.5. Genotoxicity TNM was strongly mutagenic in Salmonella typhimurium in most conducted assays.
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246 Acute Exposure Guideline Levels in males starting at week 80 and in females starting at week 100. Both sexes had 7-17% lower body weight gains after week 84.
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Tetranitromethane 247 posed for 52 weeks to 0 or 2 ppm, and 10 male mice were exposed to 0.5 ppm; only the lung histopathology results were presented in the NTP (1990) report for these animals.
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. Ocular irritation, lethargy, and methemoglobinemia were reported in acute exposure studies with cats exposed to impure TNM, possibly containing TNT.
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TABLE 6-4 Tetranitromethane Multiple-Exposure Animal Studies Species, Exposure Conc. (Reference)
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TABLE 6-4 Continued 250 Species, Exposure Conc. (Reference)
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In two well-conducted rat and mouse studies (Kinkead et al.
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252 Acute Exposure Guideline Levels Rabbits and guinea pigs survived 15-min and 1-h exposures, respectively, to 30,000 ppm nitromethane (CH3NO2) vapor, but all tested rabbits died from a 2-h exposure and all guinea pigs died from a 1-h exposure (Davis 1993)
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The impure TNM therefore likely contained some TNT, and it is unknown which entity caused resulting effects in humans or animals. One effect ascribed to TNM in studies using impure TNM, i.e., the formation of methemoglobin, was shown to be unlikely due to TNM in subsequent rat and mouse studies (Kinkead et al.
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However, since 10 ppm caused significant lung lesions and was a NOEL for lethality in rats and mice, and only a small fraction of the 5 ppm animals were examined histologically, it is unclear if exposure to 2 ppm is within the scope of AEGL-1. Another study for possible use in AEGL-1 derivation is one where cats exposed for 6 h to approximately 0.1-0.4 ppm impure TNM had slight lacrimation (Sievers et al.
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Tetranitromethane 255 mortality was seen at all concentrations except 10 ppm; because 10 ppm is a lethality NOEL in this study and is near the point of departure for AEGL-3, a modifying factor of 3 could be applied to 10 ppm obtain a concentration (3.3 ppm) that would cause only mild reversible lung irritation; (2)
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7.2. Summary of Animal Data Relevant to AEGL-3 Two rat and mouse studies were considered potentially useful for AEGL-3 derivation: (1)
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Tetranitromethane 257 The AEGL-3 point of departure was the lethality BMDL05 of 11 ppm, which was calculated using the log/probit model from EPA's Benchmark Dose Software, Version 1.3.2. with the Kinkead et al.
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258 Acute Exposure Guideline Levels 30-min value was adopted as the 10-min value, to provide AEGL values protective of human health (NRC 2001)
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Tetranitromethane 259 ppm in 1994 based on acute inhalation toxicity data in humans and animals (NIOSH 2005b)
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260 Acute Exposure Guideline Levels pational Safety and Health)
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Tetranitromethane 261 ology for both AEGL-2 and AEGL-3 raises the confidence in the derived values and their relationship to one another across time.
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262 Acute Exposure Guideline Levels HSDB (Hazardous Substances Data Bank)
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2001. Standing Operating Proce dures for Developing Acute Exposure Guideline Levels for Haz ardous Chemicals.
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264 Acute Exposure Guideline Levels ten Berge, W.F., a. Zwart and L.M.
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Tetranitromethane 265 APPENDIX A Derivation of AEGL Values AEGL-1 AEGL-1 values were not developed due to insufficient data. No studies were located with end points clearly within the scope of AEGL-1.
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266 Acute Exposure Guideline Levels C3 × 0.5 h = 0.144 ppm3-h 30-min (and 10-min)
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Tetranitromethane 267 Intraspecies: 3: NOEL for lethality from extreme lung irritation from a gas with a steep dose-response is not likely to vary greatly among humans. Calculations: Concentration 11 ppm 3 × time (4 h)
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268 Acute Exposure Guideline Levels APPENDIX B CANCER ASSESSMENT A preliminary cancer assessment of tetranitromethane (TNM) was performed using the NTP (1990)
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Tetranitromethane 269 For exposures less than 24 h, the fractional exposure (f) becomes 1/f × 24 h (NRC 1985)
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270 Acute Exposure Guideline Levels APPENDIX C ACUTE EXPOSURE GUIDELINES FOR TETRANITROMETHANE (CAS Reg.
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Tetranitromethane 271 All groups had weight loss, which was reversible only at 10 ppm. Rats that died prematurely had moderate to severe lung congestion and hemorrhage; rats surviving the 2 weeks had mild lung congestion.
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272 Acute Exposure Guideline Levels AEGL-3 VALUES Continued Reference: Kinkead, E.R., J.D.
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APPENDIX D Category Plot for Tetranitromethane
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studies for which a single 6 h/day exposure was input into the table (the NTP [1990] 2-week rat and mouse studies, and the Horn [1954]
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