Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 19 (2015) / Chapter Skim
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3 Methacrylaldehyde Acute Exposure Guideline Levels
3 Methacrylaldehyde Acute Exposure Guideline Levels
Pages 62-85
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From page 62... ...
, Chemical Manager Susan Ripple (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances)
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From page 63... ...
Airborne concentrations below the AEGL-1 represent exposure concentrations that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL.
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From page 64... ...
No uncertainty factors were applied because the blinking frequency is not a perceived effect but an objective measurement that precedes perceived irritation. The same AEGL-1 value was used for all durations because mild irritation is not expected to vary over time.
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From page 65... ...
It is highly irritating to mucous membranes, especially the upper respiratory tract and eyes (HSDB 2002)
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From page 66... ...
The subjects were asked to rate perceived irritation of the eye, eyelid, or skin as none, weak, moderate, or strong. A baseline for blinking frequency was established by having four successive stages in each exposure session: an acclimatization stage, which included 3 min of clean air; an initial baseline recording with 8 min of clean air; a 20 min stage of chemical or clean air; and a final 8 min of clean air.
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From page 67... ...
3. ANIMAL TOXICITY DATA The results of toxicity studies of laboratory animals exposed to methacrylaldehyde by inhalation are summarized in Table 3-4.
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1992 5 NOAEL; eyes half-closed during exposure 6 h/d, 5 d/wk for 2 wk 19 LOAEL; multiple clinical signs related to respiratory irritation, respiratory tract lesions Rat 6 h/d, 5 d/wk for 13 wk 1.0 NOEL Coombs et al. 1994 4.9 NOAEL; eyes half-closed during exposure 15.3 LOAEL; multiple clinical signs related to respiratory irritation, respiratory tract lesions, evidence of reversal 4 wk after exposure Rat Unknown 10 Maternal toxicity BG Chemie 1995 20 Maternal and fetal toxicity (reduced birth weight)
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From page 69... ...
Weight gain and food consumption were decreased in both males and females at the highest concentration. Lesions in the respiratory tract comprised of inflammation of the olfactory epithelium and metaplastic changes in the dorsal meatus and dorsal central nasal septum were observed in male and female rats exposed at 15.3 ppm.
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From page 70... ...
Sensory irritation as indicated by a decreased respiratory rate, airflow limitation as indicated by the expiration flow rate at half of the tidal volume, and pulmonary irritation as indicated by the time-of-pause between the end of expiration and the beginning of inspiration were evaluated. Methacrylaldehyde caused a concentrationdependent decrease in respiratory rate of about 30, 40, 50, 55, and 70% at 4.4, 6.6, 10.2, 13.1, and 26.3 ppm, respectively.
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From page 71... ...
Nonlethal inhalation studies indicate that methacrylaldehyde is an irritant and that the upper respiratory tract is the target for toxicity. Signs of respiratory irritation in rats were gasping and closed or half-closed eyes during inhalation exposure.
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From page 72... ...
. To obtain health-protective AEGL values in the absence of an empirically derived scaling exponent, temporal scaling may be performed using default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations (NRC 2001)
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From page 73... ...
The upper respiratory tract is also a target of toxicity for methacrylaldehyde, as evidenced by olfactory lesions found in rats exposed at 15.3 ppm. Data in mice show that methacrylaldehyde suppresses respiration in a manner that indicates significant irritation (Larsen and Nielsen 2000)
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From page 74... ...
A total uncertainty factor of 10 was applied; a factor of 3 to account for interspecies differences and a factor of 3 to account for intraspecies variability. Factors of 10 were considered unnecessary because the toxic effects of methacrylaldehyde appear to be related to contact irritation, so effects are not expected to differ substantially between species or among individuals.
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From page 75... ...
(1994) , in which Sprague-Dawley rats exposed to methacrylaldehyde had clinical signs of ocular irritation.
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108) 2-week Repeat Dose Preliminary Inhalation Toxicity Study in Rats.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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Toxicity end point: No signs of ocular irritation in rats at 1 ppm Time scaling: None Uncertainty factors: 3 for interspecies differences and intraspecies variability
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Toxicity end point: No deaths in rats exposed at 19 ppm for 6 h/day, 5 days/week for 2 weeks Time scaling: Cn × t = k (ten Berge et al.1986) ; default values of n = 3 for extrapolation to shorter durations and n = 1 for longer durations.
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From page 80... ...
80 Acute Exposure Guideline Levels 1-h AEGL-3: C3 × 1 h = 41,154 ppm-h C3 = 41,154 ppm C = 34.5 ppm 34.5 ppm ÷ 10 = 3.5 ppm 4-h AEGL-3: C3 × 4 h = 41.154 ppm-h C3 = 10,288 ppm C = 21.7 ppm 21.7 ppm ÷ 10 = 2.2 ppm 8-h AEGL-3: C1 × 8 h = 114 ppm-h C = 14.25 ppm 14.25 ppm ÷ 10 = 1.4 ppm
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From page 81... ...
Effects: 0.089 ppm = NOAEL 0.189 ppm = NOAEL for increased blinking frequency 0.286 ppm = LOAEL for increased blinking frequency 0.286 ppm = NOAEL for perceived ocular irritation End point/Concentration/Rationale: Blinking frequency as a measure of ocular irritation; NOAEL = 0.189 ppm Uncertainty factors/Rationale: No uncertainty factors were necessary because blinking frequency is not a perceived effect, but an objective measurement that precedes perceived irritation. Modifying factor: None Animal-to-human dosimetric adjustment: None Time scaling: None; the same value was applied to all durations because mild irritation is not expected to vary over time.
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From page 82... ...
Repeated exposure studies in rats show that the eyes and upper respiratory tract are targets for acute and subchronic toxicity. Data in mice show that methacrylaldehyde suppresses respiration in a manner consistent with significant irritation.
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From page 83... ...
Studies of human volunteers and rodents indicate that methacrylaldehyde is a direct-acting irritant. Repeated exposure studies in rats show that the eyes and upper respiratory tract are targets for acute and subchronic toxicity.
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From page 84... ...
84 Acute Exposure Guideline Levels APPENDIX C CATEGORY PLOT FOR METHACRYLALDEHYDE FIGURE C-1 Category plot of toxicity data and AEGL values for methacrylaldehyde. TABLE C-1 Date Used in Category Plot for Methacrylaldehyde Source Species ppm Minutes Category Comments AEGL-1 0.2 10 AEGL AEGL-1 0.2 30 AEGL AEGL-1 0.2 60 AEGL AEGL-1 0.2 240 AEGL AEGL-1 0.2 480 AEGL AEGL-2 0.33 10 AEGL AEGL-2 0.33 30 AEGL AEGL-2 0.33 60 AEGL AEGL-2 0.33 240 AEGL AEGL-2 0.33 480 AEGL AEGL-3 4.2 10 AEGL AEGL-3 4.2 30 AEGL AEGL-3 3.5 60 AEGL (Continued)
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From page 85... ...
1992 Rat 77 360 SL 90% lethality Carpenter et al. 1949 Rat 125 240 SL 2/6, 3/6, or 4/6 deaths Larsen and Nielsen 2000 Mouse 2.0 30 0 Larsen and Nielsen 2000 Mouse 4.4 30 1 30% decrease in respiratory rate Larsen and Nielsen 2000 Mouse 6.6 30 1 40% decrease in respiratory rate Larsen and Nielsen 2000 Mouse 10.2 30 1 50% decrease in respiratory rate Larsen and Nielsen 2000 Mouse 13.1 30 2 55% decrease in respiratory rate Larsen and Nielsen 2000 Mouse 26.3 30 2 70% decrease in respiratory rate For category: 0 = no effect, 1 = discomfort, 2 = disabling, SL = some lethality, 3 = lethality.
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