Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 7 (2009) / Chapter Skim
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1 Acetone Cyanohydrin
1 Acetone Cyanohydrin
Pages 13-49
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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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Although the AEGLs represent threshold levels for the general public, including sensitive subpopulations, it is recognized that certain individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL. SUMMARY Acetone cyanohydrin is a colorless to yellowish liquid with a characteristic bitter almond odor due to the presence of free hydrogen cyanide (HCN)
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to acetone cyanohydrin. This procedure is supported by similar values that would be derived on the basis of available acetone cyanohydrin studies in rats (derivation basis would be exposure at 9.2 ppm for 6 h/d, 5 d/wk for 4 weeks, which did not result in red nasal discharge [Monsanto 1986a]
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1. INTRODUCTION Acetone cyanohydrin is a colorless to yellowish liquid with a characteristic bitter almond odor due to the presence of free HCN (ACGIH 1996)
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At temperatures of 120°C or higher, acetone cyanohydrin decomposes with
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2.2. Nonlethal Toxicity No relevant studies documenting nonlethal effects in humans after a single inhalation exposure to acetone cyanohydrin were located in the available literature.
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2.3. Developmental and Reproductive Toxicity No studies documenting potential developmental or reproductive toxicity of acetone cyanohydrin exposure in humans were located in the available literature.
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. Concentrations in the exposure chamber were calculated by dividing the net amount of acetone cyanohydrin delivered to the chamber per unit time by the airflow per unit time and, in addition, measured by a Miran infrared analyzer (using the C-N triple bond frequency, which detects both acetone cyanohydrin and HCN)
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(time to death) exposure period; using Kincaid 1953 commercially available acetone cyanohydrin Rat Saturated vapor 10 min 6/6 animals died during Sunderman and (about 1,300 ppm)
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Studies using repeated inhalation exposure reported signs of irritation, such as red nasal discharge and perioral wetness. These data are summarized in Table 1-4.
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6 h/d, Red nasal discharge and encrustations during week 1 in 12/24 animals vs. Monsanto 1982c 7 d/wk, 21 d 6/24 controls; 24 females tested Rat 60 [59.6]
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Exposure Time Effect Reference Rat 10 [10.7] 6 h/d, Red nasal discharge and encrustations during week 1 in 9/24 animals vs.
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were determined as 10.0 ± 1.0, 28.5 ± 1.9, and 57.2 ± 3.0 ppm, respectively. For the period of exposure days 1-10, red nasal discharge was observed in 10 of 15 concurrent control animals and in 10 of 15, 12 of 15, and 14 of 15 animals that inhaled 10, 30, or 60 ppm, respectively; perioral wetness and red stain was observed in 2 of 15, 2 of 15, 4 of 15, and 8 of 15 animals, respectively.
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There were no adverse effects of inhaled acetone cyanohydrin in males as indicated by mortality, mean body weights (the high-exposure group showed a lower mean body weight, which was not significantly different from that of the concurrent control group) , clinical observations and necropsy (males were killed about 3 weeks after the end of the exposure period)
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. In the other three studies, exposure at 60 ppm and, in all studies, exposure at 30 ppm caused red nasal discharge and encrustations during the first week of exposure.
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. Cyanide concentrations in liver and brain of CD-1 mice were similar after a single intraperitoneal injection of an equimolar dose of acetone cyanohydrin or sodium cyanide.
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4.2. Mechanism of Toxicity Acetone cyanohydrin behaves as its molar equivalent in cyanide both in vitro and in vivo.
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The authors concluded that the signs of acetone cyanohydrin toxicity resembled those seen after exposure to sodium cyanide.
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. Several studies reporting effects after repeated occupational exposure to cyanides are available; however, accurate empirical exposure data usually were not reported.
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Static monitors on all floors, set to trigger alarms at 10 ppm, failed to sound during the study. Circulating cyanide concentrations in exposed workers, though low, were generally higher than in control workers, and the highest levels were measured in cyanide-exposed nonsmokers compared with the nonsmoking control group (cyanide-exposed nonsmokers, 3.32 µmol; controls, 1.14 µmol; p < 0.001)
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4.4.3. Species Variability Because of the lack of sufficient data, the potential interspecies variability for acute inhalation toxicity of acetone cyanohydrin cannot be assessed directly.
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. However, for a single acute exposure to high acetone cyanohydrin concentrations, the interindividual differences are probably not great because the decomposition of acetone cyanohydrin to cyanide is not dependent on metabolism and the cyanide detoxification pathway becomes quickly saturated at higher exposure concentrations.
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One study in rats (Monsanto 1986a) reported red nasal discharge (which was interpreted as a sign of local irritation in the upper respiratory tract)
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Red nasal discharge in rats occurs at the plexus antebrachii, which is very prominent in the rat. In the rat, extravasation of red blood cells visible as red nasal discharge is caused easily not only by locally acting chemicals, but also by stress, dry air, or upper respiratory tract infections.
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, such as red nasal discharge and encrustations and perioral wetness and red stain. Red nasal discharge was also observed at about 10 ppm in two of the four studies.
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7.3. Derivation of AEGL-3 The derivation of AEGL-3 values was based on the facts that acetone cyanohydrin decomposes spontaneously to HCN and acetone and that the systemic toxicity of acetone cyanohydrin is due to free cyanide.
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They were derived using the following key studies and methods. The derivation of AEGL values was based on the facts that acetone cyanohydrin decomposes spontaneously to HCN and acetone and that the local and systemic toxicity of acetone cyanohydrin is due to free cyanide.
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FIGURE 1-1 Categorical representation of acetone cyanohydrin inhalation data.
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Because acetone cyanohydrin behaves qualitatively and quantitatively both in vitro and in vivo exactly as does its molar equivalent in free cyanide, the TLV for acetone cyanohydrin is assigned to be identical to that for free HCN. c NIOSH REL ceiling (National Institute of Occupational Safety and Health, recommended exposure limits)
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However, the available results of studies in rats are in good agreement with HCN studies. LC50 studies for acetone cyanohydrin performed according to good laboratory practice would strengthen the derived AEGL-3 values.
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1983. Inhalation Pilot Study of Hydrogen Cyanide Exposure in Sprague Dawley Rats.
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1986b. Three-Month Inhalation Toxicity of Acetone Cyanohydrin in Male and Female Sprague-Dawley Rats with cover letter dated 04-25-86.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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1981. The role of cyanide liberation in the acute toxicity of aliphatic nitrieles.
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Red nasal discharge in rats occurs at the plexus antebrachii, which is very prominent in the rat. In the rat, extravasation of red blood cells visible as red nasal discharge is caused easily not only by locally acting chemicals but also by stress, dry air, or upper respiratory tract infections.
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Data Quality and Support for AEGLs: Very similar values would be derived on the basis of available acetone cyanohydrin studies in rats (derivation basis would be an exposure of 29.9 ppm for 6 h/d, 5 d/wk for 4 weeks that caused red nasal discharge as a sign of irritation, and the next higher concentration produced respiratory distress, prostration, convulsions, and tremors [Monsanto 1986a]
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Pp. 211-276 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol.
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