Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 12 (2012) / Chapter Skim
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2 Chloroacetaldehyde
2 Chloroacetaldehyde
Pages 48-81
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From page 48... ...
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 49... ...
The toxicity database on chloroacetaldehyde is poor. Apart from a brief statement indicating that a concentration of 10 ppm produced lacrimation and nasal irritation in humans, no information was available on human toxicity.
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From page 50... ...
Slight irritation was also observed in rabbits, rats, and mice, but not guinea pigs, after repeated exposure to chloroacetaldehyde at 5 ppm (7 h/day) (Dow Chemical Company 1952)
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From page 51... ...
AEGL-2 values for other time periods were derived by time scaling. For AEGL-3 values, two studies of the acute lethality of chloroacetaldehyde (Dow Chemical Company 1952; Arts 1987)
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From page 52... ...
The anhydrous monomer is obtained by cracking the cyclic trimer. Commercial aqueous solution of chloroacetaldehyde (45%)
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HUMAN TOXICITY DATA 2.1. Acute Lethality No case reports on human deaths from acute exposure to chloroacetaldehyde were found.
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2.7. Summary of Human Data No information on chloroacetaldehyde toxicity in humans was available, other than a brief statement that chloroacetaldehyde at 10 ppm produced lacrimation and nasal irritation in humans (Dow Chemical Company 1952)
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From page 55... ...
, and 400 ppm (for 0.25 and 0.5 h) (Dow Chemical Company 1952)
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From page 56... ...
, ocular and nasal irritation was found very early during exposure at all concentrations tested (25-400 ppm) (Dow Chemical Company 1952)
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From page 57... ...
Exposed rats exhibited slight nasal irritation and very slight ocular irritation. Growth of the male rats was slightly depressed, while the growth of the female rats was comparable to that of the control animals.
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From page 58... ...
Mice exhibited slight nasal irritation. No effects on growth, organ weights, or gross pathology were found.
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From page 59... ...
The genotoxicity of vinyl chloride has been attributed to its metabolite chloroacetaldehyde, among others. The genotoxicity of chloroacetaldehyde was reviewed by Bartsch et al.
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From page 60... ...
These effects occur soon after onset of exposure and are related to concentration and duration of exposure. Repeated exposure to chloroacetaldehyde at 5 ppm induced slight nasal and ocular irritation.
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From page 61... ...
. In all of these studies, chloroacetaldehyde was investigated as a metabolite of vinyl chloride or the alkylating antitumor agents ifosfamide and cyclophosphamide to understand the mechanism of hepatoxicity, nephrotoxicity, cardiotoxicity, encephalopathy, and chronic fatigue observed after exposure or treatment with those agents.
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From page 62... ...
. Cytotoxicity in isolated rat hepatocytes was enhanced markedly if hepatocyte alcohol or aldehyde dehydrogenase was inhibited before exposure to chloroacetaldehyde.
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From page 63... ...
The major metabolite formed was chloroacetate, which was far less toxic than chloroacetaldehyde and did not result in cardiotoxic symptoms. Their findings suggest that the mechanism of cardiotoxicity might be similar to that found in rat hepatocytes and in a rat renal model (lipid peroxidation, glutathione depletion, reversible thiol-protein-adduct formation, and mitochondrial toxicity with ATP depletion)
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From page 64... ...
DATA ANALYSIS FOR AEGL-1 5.1. Summary of Human Data Relevant to AEGL-1 No information is available on chloroacetaldehyde toxicity in humans other than a brief statement that a concentration of 10 ppm produced lacrimation and nasal irritation in humans within a few minutes of exposure (Dow Chemical Company 1952)
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From page 65... ...
Because no direct information is available on chloroacetaldehyde toxicity in humans, the AEGL-1 values are based on animal data. A single 7-h exposure to chloroacetaldehyde at concentrations of 10 ppm and higher in rats and at 25 ppm and higher in guinea pigs induced ocular and nasal irritation.
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From page 66... ...
No effects on organ weights or gross pathology findings were observed in rats, mice, guinea pigs, or one rabbit exposed to chloroacetaldehyde at 5 ppm for 7 h/day, for eight exposures in 10 days. Pulmonary toxicity was confirmed in a well-performed and adequately reported study of rats exposed to chloroacetaldehyde at concentrations of 44-2,643 ppm (analytically determined)
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From page 67... ...
The concentration-response curve was very steep, and rats were more susceptible than guinea pigs to chloroacetaldehyde. Slight nasal irritation was observed in rats exposed at 5 ppm for 7 h/day for eight exposures in 10 days, but nearly all of the rats exposed once at 25 ppm for 7 h died (Dow Chemical Company 1952)
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From page 68... ...
Application of a total uncertainty factor of 10 results in 9.9 ppm for a 1-h exposure. AEGL-3 values for the other time periods were derived by time scaling according to the dose-response regression equation Cn × t = k, with n = 1.2 based on mortality data (Dow Chemical Company 1952)
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From page 69... ...
b TLV-C (threshold limit value-ceiling, American Conference of Governmental Industrial Hygienists)
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From page 70... ...
However, considering the severity of irritation in relation to the exposure concentrations, as observed in the animal experiments (single and repeated exposure) , exposure to chloroacetaldehyde at 2.3 ppm for up to 30 min will probably not lead to significant ocular or nasal irritation in humans.
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From page 71... ...
:159-168. Dow Chemical Company.
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From page 72... ...
2012. Vinyl Chloride in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol.
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From page 73... ...
1993. Molecular mechanisms of chloroacetaldehyde-induced cytotoxicity in isolated rat hepatocytes.
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From page 74... ...
1.2 × 420 min = 1,261 ppm-min Uncertainty factors: 3 for interspecies differences 3 for intraspecies variability Total uncertainty factor of 10 Modifying factor: A modifying factor of 2 was applied to reduce the lowest-observed-adverse-effect level to a no-effect level. Calculations: 10-min AEGL-1: Set equal to the 30-min AEGL of 2.3 ppm (= 7.4 mg/m3)
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From page 75... ...
1.2 × 60 min = 2,449 ppm-min Uncertainty factors: 3 for interspecies differences 3 for intraspecies variability Total uncertainty factor of 10 Modifying factor: A modifying factor of 2 was applied to reduce the lowest-observed-adverse-effect level, because the pulmonary effects were more severe than those that define AEGL-2 values. Calculations: 10-min AEGL-2: C1.2 × 10 min = 2,449 ppm-min C = 97.9 ppm 97.9 ÷ 10 = 9.8 ppm (rounded)
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From page 76... ...
. Dow Chemical Company.
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From page 77... ...
Effects at 5 ppm: Guinea pigs: no effects Rabbit: slight ocular irritation Rats: slight nasal irritation, very slight ocular irritation Mice: slight nasal irritation End point/Concentration/Rationale: Rabbit, rats, and mice had slight nasal and ocular irritation after 7 h of exposure at 5 ppm (lowest-observed-adverse-effect level)
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From page 78... ...
Lacrimation and nasal irritation reported in humans within a few minutes of exposure to chloroacetaldehyde at 10 ppm (Dow Chemical Company 1952) provides supporting data for deriving AEGL-1 values on the basis of rat data.
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From page 79... ...
(1.5 mg/m3) Animal-to-human dosimetric adjustment: Not applied Time scaling: Cn × t = k; n = 1.2 based on lethality data Data adequacy: No human data were available.
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From page 80... ...
(5.6 mg/m3) Modifying factor: Not applied Animal-to-human dosimetric adjustment: Not applied Time scaling: Cn × t = k; n = 1.2 based on lethality data Data adequacy: Sufficient for deriving AEGL-3 values.
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From page 81... ...
Chloroacetaldehyde 81 APPENDIX C CATEGORY GRAPH OF TOXICITY DATA AND AEGL VALUES FOR CHLOROACETALDEHYDE Chloroacetaldehyde Toxicity 1000 100 Human - No effect Human Discomfort Human - Disabling Animal - No effect ppm 10 Animal - Discomfort Animal Disabling Animal - Some Lethality Animal - Lethal 1 AEGL 0 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-1 Category graph of toxicity data and AEGLs values for chloroacetaldehyde.
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