Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 16 (2014) / Chapter Skim
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6 Ketene Acute Exposure Guideline Levels
6 Ketene Acute Exposure Guideline Levels
Pages 267-308
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From page 267... ...
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 268... ...
Ketene is used as an acetylating agent in chemical synthesis, especially in synthesis of acetic acid and acetate esters. Human data on the acute toxicity of ketene are not available.
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From page 269... ...
Thus, whether odor detection and minor irritation would provide adequate warning of ketene exposure is uncertain, especially given the potential for sensitive subpopulations (asthmatics) and delayed severe pulmonary toxicity (including lethality)
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Ketene reacts with water to form acetic acid and will acetylate amino groups, phenolic hydroxyl groups, and sulfhydryl groups in aqueous solution (Cameron and Neuberger 1937)
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. Ketene is used as an acetylating agent in chemical synthesis, especially of acetic acid and acetate esters (Health Council of the Netherlands 2001)
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From page 272... ...
was injected in the chamber from a syringe to obtain the desired concentration. Because no analytic method was available to measure such low concentrations, estimates were calculated from measurements of the rate at which ketene flowed from the reservoir into a measured air stream (nominal concentrations)
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200 0/2 – 250 0/2 – 375 0/2 – 500 0/2 – 750 0/2 – 1,000 1/2 0.8 1,250 2/2 2.8 and 3.07 1,500 1/1 1.3 Guinea pigs (n = 2)
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(day) Mortality Time of Death Monkeys (n = 1)
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1 7h 14 1/10 3 days after tenth exposure 1 7h 55 1/10 1 day after forty-ninth exposure a The same monkey was exposed in both of these experiments, with a 9-day interval between them. b Animals were exposed for 4.5 h on the first day, 5.5 h on the second day, and 6 h on each of 13 other days for 5 days per week.
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From page 276... ...
to ketene at nominal concentrations ranging from 1 to 23 ppm for a various number of exposures (see Section 3.1.1 for technical details and Table 6-4 for information on exposure conditions)
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233 0/1 15 d 367 1/2 8-12 h 623 2/2 26 min and 8-12 h 815 1/1 135 min Rabbits (n = 2) 652 0/2 10 d Guinea pigs (n = 2-4)
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From page 278... ...
Signs of irritation and slight lacrimation during exposure were reported. Toxicity symptoms preceding death was similar to those described for the cat, with effects predominantly on the lungs and central nervous system (see Section 3.1.2 for technical details)
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From page 279... ...
to nominal concentrations of ketene ranging from 1 to 53 ppm for various exposure durations. Mortality rates and times of death are presented in Table 6-4.
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to initial nominal concentrations of ketene (purity: 98-99%) at 100, 200, 250, 375, 500, 750, 1,000, and 1,250 ppm for 10 min under static conditions.
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to nominal concentrations of ketene ranging from 1 to 53 ppm for various exposure durations. Mortality rates and times of death are presented in Table 6-4.
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From page 282... ...
to nominal ketene concentrations ranging from 1 to 53 ppm for various exposure durations. Mortality rates and times of death are presented in Table 6-4.
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four monkeys (one animal per concentration, sex and strain not specified) to ketene at initial nominal concentrations of 50, 200, 750, and 1,500 ppm for 10 min under static conditions.
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. It was not clear whether a microscopic examination was performed on this animal, but it was reported in general that all species tested, except guinea pigs, showed alveolar edema and acute pulmonary congestion after repeated exposure to ketene concentrations above 12 ppm.
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to nominal ketene concentrations of 1-53 ppm for various exposure durations. Mortality rates and times of death are presented in Table 6-4.
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From page 286... ...
to nominal ketene concentrations of 1-53 ppm for various exposure durations. Mortality rates and times of death are presented in Table 6-4.
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From page 287... ...
to ketene at nominal concentrations of 1-53 ppm for various exposure durations. Mortality rates and times of death are presented in Table 6-4.
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. Alveolar edema, acute pulmonary congestion.
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From page 289... ...
The toxicologic profile of inhalation exposure to ketene is generally similar among species tested, involving minor irritation and some central nervous system impairment during exposure, lethality at high exposure concentrations, and severe damage to the lungs (at the alveolar level) that may be manifest as long as 24 h after exposure (Cameron and Neuberger 1937; Potts et al.
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From page 290... ...
4.2. Mechanism of Toxicity As noted above in Section 3.7, clinical signs and pathologic effects of ketene following inhalation exposure are similar to phosgene, involving death at high concentrations and minor irritation during exposure with some lethality after a latency period at lower concentrations.
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From page 291... ...
Although the relative susceptibility was somewhat different from above, the mouse was the most sensitive species in all studies. TABLE 6-8 Susceptibility to Ketene Lowest Concentrations That Induced Edema and Congestion Highest Concentration That Did Not of the Pulmonary Alveoli Species Induce Fatal Pulmonary Edema Followed by Death Data from 10-min Exposure Study by Treon et al.
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(1949) , in which several animal species were exposed to ketene concentrations ranging from 1 to 53 ppm for various exposure durations (10 min to 7 h)
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From page 293... ...
No overt signs of toxicity were observed in mice exposed to ketene at 1 ppm for 7 h; however, the investigators noted serious pulmonary effects following repeated exposure at this concentration. However, it is unknown whether the pulmonary damage occurred following a single exposure or resulted from repeated exposure.
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From page 294... ...
Histopathologic findings in the lungs included alveolar edema and acute pulmonary congestion. Serious effects on the lungs and brain ultimately led to death.
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Human studies examining the toxicity of phosgene, a chemical which appears to have a mode of action similar to ketene, did not identify sensitive subpopulations. AEGL-2 and AEGL-3 values derived for phosgene used an intraspecies uncertainty factor of 3 (NRC 2002)
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(0.15 mg/m3) TABLE 6-10 AEGL Values for Ketene Exposure Duration Classification 10 min 30 min 1h 4h 8h AEGL-1 NRa NRa NRa NRa NRa (nondisabling)
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The AEGL-3 values are approximately 6-times lower than the occupational standards of the Occupational Safety and Health Administration and the National Institute for Occupational Safety and Health. The threshold limit value for ketene is based on the reasoning that 1 ppm was tolerated for several weeks and up to 6 months without apparent injury in several animal species (Treon et al.
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e TLV-STEL (threshold limit value-short-term exposure limit, American Conference of Governmental Industrial Hygienists [ACGIH 2012]
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9. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists)
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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1949. Physiologic response of animals exposed to air-borne ketene.
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302 Acute Exposure Guideline Levels Uncertainty factors: 3 for interspecies differences 3 for intraspecies variability Calculations: (1 ppm)
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From page 303... ...
Human studies examining the toxicity of phosgene, which appears to have a mode of action similar to ketene, did not identify sensitive subpopulations. An intraspecies uncertainty factor of 3 was used to derive AEGL-2 and AEGL-3 values for phosgene (NRC 2002)
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, involved dynamic exposure conditions, involved longer exposure durations (up to 7 h) , and tested a wide concentration range of ketene.
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Ketene 305 APPENDIX C CATEGORY PLOT FOR KETENE FIGURE C-1 Category plot of toxicity data and AEGL values for ketene.
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1949 Guinea pig 1 50 50 1 Treon et al. 1949 Mouse 1 50 50 3 Mortality (10/10)
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1949 Guinea pig 1 23 240 3 Mortality (2/2) Treon et al.
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From page 308... ...
1949 Monkey 1 23 240 2 Adverse clinical effects, ocular irritation, coughing, lethargy Treon et al. 1949 Guinea pig 1 23 240 3 Mortality (2/2)
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