Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 7 (2009) / Chapter Skim
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3 Monochloroacetic Acid
3 Monochloroacetic Acid
Pages 135-177
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From page 135... ...
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 136... ...
Although the AEGL values 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 Monochloroacetic acid (MCAA)
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From page 137... ...
An uncertainty factor of 3 was applied for intraspecies variability because of the limited toxicokinetic variability with respect to local effects and because of the limited toxicodynamic variability with respect to systemic effects, as the enzymes inhibited by MCAA do not vary considerably within and between species. The other exposure duration-specific values were derived by time scaling according to the dose-response regression equation Cn × t = k, using the default of n = 3 for shorter exposure periods and n = 1 for longer exposure periods, due to the lack of suitable experimental data for deriving the concentration exponent.
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a Skin contact with molten MCAA or MCAA solutions should be avoided; dermal penetration is rapid, and fatal intoxications have been observed when 10% or more of the body surface was involved. b Not recommended because of insufficient data.
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From page 139... ...
, although no case of severe intoxication by inhalation has been published in the literature. MCAA or its sodium salt, sodium monochloroacetate, are used primarily in the industrial production of carboxymethylcellulose, herbicides, thioglycolic acid as well as in the production of plastics, pharmaceuticals, flavors, cosmetics, and other organic chemicals (KEMI 1994; ECB 2005)
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From page 140... ...
BG Chemie 1993 1 mg/m3 = 0.26 ppm (at 1,013 hPa, 25°C) a case, in which about 10% of the body surface was contaminated with warm MCAA solution.
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reported that routine medical examinations of workers of two plants, producing MCAA and sodium monochloroacetate, respectively, revealed no respiratory tract irritation, effects on lung-function parameters, or irritation of skin and mucous membranes. The number of potentially exposed workers was 33 in one plant and not stated for the other.
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buildings (<0.26, <0.26, <0.26, <0.26, <0.26, <0.26, <0.26, <0.26, <0.26, <0.26, 0.21, <0.13, <0.13, <0.13, <0.13, <0.13, <0.13 ppm) Abbreviations: SMCA; sodium monochloroacetate; MCAA, monochloroacetic acid.
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From page 143... ...
An inadequately described study reported an irritation threshold of 1.48 ppm (Maksimov and Dubinina 1974; Rodionova and Ivanov 1979) ; no respiratory tract irritation, effects on lung-function parameters or irritation of skin and mucous membranes were reported for more than 33 workers potentially exposed to MCAA concentrations at less than 0.13 ppm for 3 h and at 0.31 ppm for 7 h (Clariant GmbH, unpublished material, 2000)
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From page 144... ...
solution in water Dubinina 1974 580 LD50 10% neutralized solution (no details reported) Mouse 260 LD50 Non-neutralized solution Immobility, ataxia, slight tremors, Berardi and Snyder1983 (8-10 mice/group)
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Mouse 165 LD50 No details reported Respiratory paralysis Morrison and (no details reported) Leake 1941 Goose 50 2 animals No details reported No symptoms Christiansen and Dalgaard-Mikkelsen 75 Same animals, Incoordination, seizures, death after 1961 2 wk later 4-6 h 145
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reported the following 24-h mortality of Sprague-Dawley rats injected neutralized MCAA solution intravenously with 20, 40, 80 and 100 mg/kg in zero of six, one of six, four of 5, and six of six animals, respectively. Intoxication was characterized by a fixed posture, slight tremors, hyperreactivity to stimuli and a dark ruddy eye color.
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From page 147... ...
reported the following 24-h mortality of Swiss-Webster mice injected neutralized MCAA solution intravenously with 100, 125, 160, and 200 mg/kg in zero of seven, one of four, five of seven, and four of four animals, respectively. Signs of intoxication appeared within 2 h of expsoure.
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From page 148... ...
Behavior pattern and nervous system activity was also assessed by specific observation for tremors, convulsions, salivation, lacrimation, and diarrhea, as well as slight lethargy and other signs of altered central nervous system function." During the 2-week observation period, MCAA-exposed rats lost weight initially (day 2) and regained weight during the remainder period (days 4-15)
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From page 149... ...
The pathomorphologic investigation revealed inflammatory changes in the respiratory organs and tracheal catarrh, bronchitis, and bronchopneumonia. In the low-dose group, only very slight effects were found: a lower oxygen uptake on day 3; a lower rectal temperature on days 7 and 14, and a reduction in the chloride concentration of the urine in month 4.
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From page 150... ...
Groups of 10 male and 10 female rats received daily doses of 0, 15, 30, 60 or 120 mg/kg. At 120 mg/kg, 30% of females and 80% of the males died, 7 of the 11 deaths occurred within the first 3 days of treatment, while the other 4 deaths occurred between days 14 and 90.
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3.3. Reproductive and Developmental Toxicity No studies evaluating developmental or reproductive toxic effects after inhalation exposure were located in the literature (MEDLINE and TOXLINE search, November 2003)
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3.6. Summary The only animal study reporting lethal effects after inhalation of MCAA
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. In a single inhalation experiment on rats, eye squint and slight lethargy were observed during MCAA exposure at 66 ppm for 1 h (Dow Chemical Co.
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In the urine of rats, thiodiglycolic acid, but not S-carboxymethyl-Lcysteine, was found. However, according to the study, S-carboxymethyl-Lcysteine might have been present in bile but could not be identified unequivocally (Dow Chemical Co.
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1992) , and renal nephropathy was found after subchronic oral exposure in rats (Daniel et al.
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(1971) exposed groups of four to five female rats in an exposure chamber to different concentrations of chloroacetic acid methyl ester for different exposure times.
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Although the LD50 values for oral administration are comparable to the LD50 values for MCAA (see Table 3-4) , lethal effects after inhalation exposure to MCAA esters
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local effects due to glutathione binding or enzyme inhibition can be expected to be smaller because the esters have to get hydrolyzed enzymatically to free MCAA first. Although quantitative data for the hydrolysis are lacking, it is likely that due to its rapid distribution in the body, much of the deposited ester will enter systemic circulation before it is hydrolyzed, and thus the concentration of MCAA in respiratory tract tissue is likely to be much smaller during inhalation exposure to MCAA esters than during MCAA exposure.
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found no respiratory tract irritation, effects on lung function parameters, or irritation of skin and mucous membranes in more than 33 workers potentially exposed to MCAA concentrations of less than 0.13 ppm for 3 h and 0.31 ppm for 7 h. Maksimov and Dubinina (1974)
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From page 160... ...
Therefore, due to insufficient data, AEGL1 values were not recommended. Because of the lack of an adequately performed study reporting an odor threshold for MCAA, no level of distinct odor awareness (LOA)
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There is some uncertainty as to the exposure because of the large discrepancy between the nominal exposure concentration of 964 ppm and the analytically measured exposure concentration of 66 ppm. The authors did not discuss whether recrystallization of MCAA took place completely outside the exposure chamber (that is, before the air stream entered the chamber)
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Morrison and Leake (1941) reported that daily oral exposure for 60 days to 300 mL of a 0.05% MCAA solution in water did not result in adverse effects in three human volunteers.
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during inhalation exposure, local concentrations of MCAA in the respiratory tract could cause local tissue damage by enzyme inhibition already in doses lower than those required for systemic effects in oral studies. Experimental findings support a possible local effect on the respiratory tract: (1)
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The data presented in Figure 3-1 suggest that upon inhalation exposure, lethal effects might occur at lower doses compared with oral exposure. Inhalation studies using MCAA esters revealed no mortality after 4 h of exposure at up to 210 or 250 ppm (Torkelson et al.
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All exposures (including single and repeated inhalation exposures and single oral exposures) were converted to daily doses.
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A total uncertainty factor of 10 was used. Other exposureduration-specific values were derived by time scaling according to the doseresponse regression equation Cn × t = k, using the default of n = 3 for shorter exposure periods and n = 1 for longer exposure periods due to the lack of suitable experimental data for deriving the concentration exponent.
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From page 167... ...
Consistency of Data for Monochloroacetic Acid with Derived AEGL Values 100.00 Human - No effect 10.00 Human - Discomfort Human - Disabling Animal - No effect Animal - Discomfort Animal - Disabling Animal - Some Lethality AEGL - 2 Animal - Lethal 1.00 AEGL Concentration (ppm) 0.10 0 60 120 180 240 300 360 420 480 Time (minutes)
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From page 168... ...
Single inhalation exposure studies focusing on lethal effects in animals and irritative effects in animals and humans would allow for more precisely defining the thresholds for the three AEGLs.
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1987. Monochloroacetic Acid: An Acute Vapor Inhalation Limit Study with Fischer 344 Rats.
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1969a. Acute Vapor Inhalation Toxicity Study on Monochloroacetic Acid.
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88.0233. Study con ducted for Berufsgenossenschaft der chemischen Industrie, by Hoechst AG, Pharma Forschung Toxikologie und Pathologie.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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2003. Inhalation exposure to haloacetic acids and haloketones during showering.
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3 for interspecies variability 3 for intraspecies variability Calculations: 10-min AEGL-2 C³ × 0.167 h = 287,496 ppm³-h C = 119.85 ppm 10-min AEGL-2 = 119.85 ppm/10 = 12 ppm (47 mg/m³)
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1987. Monochloroacetic acid: An acute vapor inhalation limit study with Fischer 344 rats.
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Intraspecies: 3, because of the limited toxicokinetic variability with respect to local effects and limited toxicodynamic variability with respect to systemic effects since the enzymes inhibited by MCAA do not vary considerably within and between species. Modifying Factor: Not applicable.
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From page 177... ...
MCAA can bind to sulfhydryl groups, for example, those of reduced glutathione, and may thus cause lung damage through glutathione depletion; and (3) during inhalation exposure, local concentrations of MCAA in the respiratory tract could cause local tissue damage by enzyme inhibition already in doses lower than those required for systemic effects in oral studies.
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