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Methacrylaldehyde¹

Acute Exposure Guideline Levels

PREFACE

Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) has been established to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:

AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m³]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.

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¹This document was prepared by the AEGL Development Team composed of Tom Marshall (Oak Ridge National Laboratory), Lisa Ingerman (SRC, Inc.), Julie Klotzbach (SRC, Inc.), Chemical Manager Susan Ripple (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances), and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001).

AEGL-2 is the airborne concentration (expressed as ppm or mg/m³) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.

AEGL-3 is the airborne concentration (expressed as ppm or mg/m³) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.

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. Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.

SUMMARY

Methacrylaldehyde is a colorless liquid at ambient temperature and pressure. It is an intermediate in the production of methacrylonitrile and methacrylic acid, and has been found in the emissions from automobile exhaust, liquid floor wax, steel-protective paints, and trees. Production of methacrylaldehyde in the United States (other than as a chemical intermediate) was discontinued in the late 1970s because better catalysts in propylene oxidation became available for the production of copolymers and resins. Methacrylaldehyde is highly irritating to mucous membranes, especially the upper respiratory tract and eyes (HSDB 2002). Data on the acute lethality of methacrylaldehyde in animals are sparse. Inhalation studies indicate that it is an irritant and that the upper respiratory tract is the target for toxicity in laboratory animals. Irritant effects were evident in studies of durations ranging from a single 6-h exposure to repeated exposures for 2-13 weeks.

The AEGL-1 values for methacrylaldehyde are based on ocular irritation in healthy human subjects (Nojgaard et al. 2005). The nondominant eyes of 10 men were exposed for 20 min to methacrylaldehyde at concentrations of 0, 0.089, 0.189, and 0.286 ppm in eight sessions. Blinking frequency was recorded as a measure of irritation and the subjects described the intensity of any ocular discomfort or irritation during the exposures. The number of complaints about irritation and its intensity were not different at any concentration relative to that described by the control group. The relative change in blinking frequency was statistically higher (18%; p = 0.001) during exposure at 0.286 ppm. The no-

observed-adverse-effect level (NOAEL) for blinking frequency was 0.189 ppm, which served as the point-of-departure for all of the AEGL-1 values for methacrylaldehyde. 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.

The AEGL-2 values are based on sensory irritation observed in a study by Coombs et al. (1994), in which Sprague-Dawley rats were exposed to methacrylaldehyde at 1, 4.9, and 15.3 ppm for 6 h/day, 5 days/week for 13 weeks. Animals exposed at the two highest concentrations were observed keeping their eyes half-closed or closed during exposure and animals exposed at 15.3 ppm occasionally exhibited salivation. No signs of ocular irritation were observed at 1 ppm. Lesions of the upper airways were evidence that the upper respiratory tract is also a target for toxicity. No relevant single exposure or short-term exposure studies were available. Because half-closed or closed eyes may be impairments for escape, 1 ppm was used as the point-of-departure. Typically, two uncertainty factors of 3 would be used for direct-acting irritants; one to account for interspecies differences and one to account for intraspecies variability. However, adjusting the 1-ppm point-of-departure by a total uncertainty factor of 10 would result in values lower than 0.189 ppm, the concentration which did not result in perceived irritation or change in blinking frequency in the Nojgaard et al. (2005) study used as the basis of the AEGL-1 values. Thus, a total uncertainty factor of 3 was used. Time scaling was not performed because half-closed or closed eyes are signs of contact irritation.

The AEGL-3 values are based on a study of a single 6-h exposure to methacrylaldehyde at 77 ppm, which resulted in 90% mortality in rats (Coombs et al. 1992). No deaths were observed in rats exposed at 19 ppm for 6 h/day, 5 days/week for 2 weeks (Coombs et al. 1992) or in rats exposed at 15.3 ppm for 6 h/day, 5 days/week for 13 weeks (Coombs et al. 1994). The concentration of 19 ppm was selected as the point-of-departure for AEGL-3 values. Selecting a no-effect level as the basis of the AEGL-3 values is supported by the steep concentration-response relationship; a 4-fold increase in concentration resulted in a 90% increase in mortality. AEGL-3 values were time-scaled using the equation Cⁿ × t = k (ten Berge et al. 1986). Default values of n = 3 for extrapolating to shorter durations and n = 1 for extrapolating to longer durations were used. The 30-min AEGL-3 value was adopted as the 10-min value because extrapolation from a 6-h point-of-departure to a 10-min guideline is not recommended (NRC 2001). A total uncertainty factor of 10 was applied; a factor of 3 was used to account for interspecies differences and a factor of 3 was used 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.

The AEGL values for methacrylaldehyde are presented in Table 3-1.

1. INTRODUCTION

Methacrylaldehyde is a colorless liquid at ambient temperature and pressure. It is highly irritating to mucous membranes, especially the upper respiratory tract and eyes (HSDB 2002). Production of methacrylaldehyde in the United States other than as a chemical intermediate was discontinued in the late 1970s because better catalysts in propylene oxidation became available in the production of copolymers and resins. It is an intermediate in the production of methacrylonitrile and methacrylic acid. It has been found in the emissions from automobile exhaust, liquid floor wax, steel protective paints, and trees. The chemical and physical properties of methacrylaldehyde are presented in Table 3-2.

TABLE 3-1 AEGL Values for Methacrylaldehyde

TABLE 3-2 Chemical and Physical Properties of Methacrylaldehyde

2. HUMAN TOXICITY DATA

2.1. Acute Lethality

No studies of the acute lethality of methacrylaldehyde in humans were found.

2.2. Nonlethal Toxicity

2.2.1. Clinical Studies

The nondominant eye of 10 healthy men was exposed for 20 min to methacrylaldehyde at concentrations of 0, 0.089, 0.189, and 0.286 ppm (Nojgaard et al. 2005). Methacrylaldehyde vapors were mixed with clean air that was adjusted to a flow rate that generated the desired concentration. Exposures were conducted using a clear plastic eyepiece though which the vapors passed after mixing with clean air at 20% relative humidity. Concentrations delivered to the eyepiece were measured at a point in the delivery system before reaching the eyepiece. Blinking frequency was recorded as a measure of irritation and the subjects reported the perceived intensity of any eye discomfort or irritation during the exposure sessions. The subjects were recorded by a digital video camera and the same researcher viewed all of the videos and counted the number of blinks per session. 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. The latter stage was divided into 4 min of recovery and 4 min of a final baseline recording. The number of complaints about irritation and its perceived intensity were not different at any concentration relative to the control exposure (see Table 3-3). The relative change in blinking frequency was statistically higher (18%; p = 0.001) during exposure at the highest concentration of 0.286 ppm. The NOAELs were 0.286 ppm for perceived irritation and 0.189 ppm for blinking frequency. A mixture of limolene oxidation products and ozone was tested separately in this study. The results showed that those materials increased blinking frequency by as much as 34%, and also showed that lower relative humidity (20% vs. 50%) exacerbated the response.

2.3. Neurotoxicity

No studies of the neurotoxicity of methacrylaldehyde in humans were found.

TABLE 3-3 Results of Blinking Frequency Tests in Humans Exposed to Methacrylaldehyde

^aChange relative to baseline of each subject calculated using log-transformed data.

^bp = 0.001.

^cCalculated by repeated-analysis using ANOVA software program.

Source: Adapted from Nojgaard et al. 2005.

2.4. Developmental and Reproductive Toxicity

No studies of the developmental or reproductive toxicity of methacrylaldehyde in humans were found.

2.5. Genotoxicity

No studies of the genotoxicity of methacrylaldehyde in humans were found.

2.6. Carcinogenicity

No studies of the carcinogenicity of methacrylaldehyde in humans were found.

2.7. Summary

The single human study on methacrylaldehyde indicates that it is a direct-acting irritant, confirming that effects in people are similar to those observed in animal studies.

3. ANIMAL TOXICITY DATA

The results of toxicity studies of laboratory animals exposed to methacrylaldehyde by inhalation are summarized in Table 3-4.

TABLE 3-4 Result of Toxicity Studies of Methacrylaldehyde

Abbreviations: CI, confidence interval; LOAEL, lowest-observed-adverse-effect level; NOAEL, no-observed-adverse-effect level; NOEL, no-observed-effect level; RD₀, extrapolated threshold concentration for reduction in respiratory rate.

3.1. Acute Lethality

3.1.1. Rats

Carpenter et al. (1949) exposed six Sherman rats (sex not specified) to methacrylaldehyde at a nominal concentration of 125 ppm for 4 h in a glass inhalation chamber, and observed the survivors for 14 days. The report indicates that two, three, or four of the rats died. No other information was provided. The concentration of 125 ppm is assumed to be an approximate LC₅₀ in Sherman rats.

An unconfirmed 4-h LC₅₀ of 195 ppm is reported in a secondary source (BG Chemie 1995). BG Chemie is the German Employment Accident Insurance Fund of the Chemical Industry. The organization, which includes a scientific advisory committee, assesses the hazard of chemicals in the workplace, plans toxicity studies, and contracts the conduct of those studies to laboratories.

3.2. Nonlethal Toxicity

3.2.1. Rats

In a 2-week inhalation exposure study in Sprague-Dawley rats, a single 6-h exposure to methacrylaldehyde at 77 ppm, the highest concentration tested, resulted in death or a moribund condition in nine of 10 rats (five male, four female) within 2 days of exposure (Coombs et al. 1992). The cause of death was lesions in the respiratory tract, which were comprised of necrosis of the olfactory and respiratory epithelium in the nasal turbinates, extensive epithelial ulceration of the larynx and trachea, and necrosis of the bronchiolar epithelium of the lungs. The other two concentrations tested were 5 and 19 ppm, and groups of five male and five female rats were exposed at those concentrations for 6 h/day, 5 days/week for the full 2 weeks. Closed eyes or half-closed eyes were noted in the rats during each exposure period; rats in the 19-ppm group also adopted a hunched position during the exposure. Minimal hyperplasia of the respiratory epithelium of the nasal turbinates and laryngeal epithelia were observed at 19 ppm; no respiratory lesions were observed at 5 ppm.

Coombs et al. (1994) exposed groups of 10 male and 10 female Sprague-Dawley rats by inhalation to methacrylaldehyde at 0, 1, 4.9, and 15.3 ppm for 6 h/day, 5 days/week for 13 weeks. Additional groups of control rats and rats exposed at 15.3 ppm were maintained and observed for 4 weeks after exposure ended. Animals exposed at 4.9 or 15.3 ppm were observed keeping their eyes half-closed during exposure days 1-6 or for most of the study, respectively; salivation was observed occasionally in the 15.3-ppm group. 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. Similar changes were found in the larynx of some animals at that concentration. Clear

signs of repair and recovery from the lesions were found during the 4-week observation period. The NOAEL was 4.9 ppm and the LOAEL was 15.3 ppm for olfactory lesions. For ocular irritation, the NOAEL was 1 ppm.

3.2.2. Mice

Larsen and Nielsen (2000) studied the effects of inhaled methacrylaldehyde on the respiratory tract of male mice (strain not specified; four per group) exposed at 0, 2.0, 4.4, 6.6, 10.2, 13.1, or 26.3 ppm for 30 min. 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 concentration-dependent 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. An RD₅₀ (concentration that reduces the respiratory rate by 50%) of 10.4 ppm and an RD₀ (extrapolated threshold concentration for reduction in respiratory rate) of 1.3 ppm were calculated for that indicator of sensory irritation. No response was seen in the indicators for pulmonary irritation. The investigators concluded that methacrylaldehyde is a potent sensory irritant and that desensitization does not occur in mice because the level of sensory irritation was constant during exposure.

3.3. Developmental and Reproductive Toxicity

No studies of the developmental or reproductive toxicity of methacrylaldehyde were found.

3.4. Genotoxicity

Only in vitro mutagenicity data are available on methacrylaldehyde and the results are equivocal. Methacylaldehyde produced positive results in Salmonella typhimurium strains TA100 (Eder et al. 1990, 1993, 1994) and TA104 (Mersch-Sunderman et al. 1992) without S-9 activation, but had negative results in strain TA 98 (Kato et al. 1989). Neudecker et al. (1991) showed that the addition of S-9 activation reduced methacrylaldehyde mutagenicity even when the liver preparation was boiled or when epoxide hydrolase was inhibited. That indicates that the positive results seen in this bacterial assay are of a direct-acting nature. Methacrylaldehyde was weakly positive in an Escherichia coli WP2 uvrA assay without activation (Kato et al. 1989). Several studies have shown methacrylaldehyde to be inactive in the SOS chromotest (Benamira and Marnett 1992; Mersch-Sunderman 1992; Eder et al. 1990, 1993, 1994). Weak activity for DNA damage was indicated in the comet assay using rat hepatocytes (Kuchenmeister et al. 1998), and a marginally positive result was obtained in studies of DNA adduct formation (Eder et al. 1993).

3.5. Chronic Toxicity and Carcinogenicity

No studies of the chronic toxicity or carcinogenicity of methacrylaldehyde were found.

3.6. Summary

Acute lethality data from animal studies are sparse. 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. At higher concentrations, lesions of the upper airways were evident. Data in mice show that methacrylaldehyde suppresses respiration in a manner that indicates significant irritation. Genotoxicity data are equivocal. No data on the reproductive toxicity, developmental toxicity, or carcinogenicity of methacrylaldehyde were available.

4. SPECIAL CONSIDERATIONS

4.1. Metabolism and Disposition

No studies on the metabolism and disposition of methacrylaldehyde were available. According to HSDB (2002), the fate of methacrylaldehyde is probably similar to other short chain aldehydes that are readily oxidized by aldehyde dehydrogenase to organic acids, which can then serve as substrates for fatty oxidation and the Krebs cycle. A second pathway is for aldehydes to be inactivated by reaction with sulfhydryl groups, particularly glutathione.

4.2. Mechanism of Toxicity

The short chain alkenes related to acrolein are known to react with sulfhydryl groups (Beauchamp et al. 1985). Acrolein is the most toxic of the 2-alkenals (including methacrylaldehyde, crotonaldehyde, pentenal, and hexenal) and is also the most reactive toward sulfhydryl groups. The respiratory irritancy of acrolein and related aldehydes may be due to reactivity toward sulfhydryl groups in receptor proteins in the nasal mucosa.

4.3. Structure-Activity Relationships

Neudecker et al. (1991) showed that relative to acrolein the size of the alkylating substituent influences the direct mutagenicity of the aldehyde, with activity decreasing in the order of 2-methylacrolein, 2-ethylacolein, and 2-propylacrolein.

4.4. Other Relevant Information

4.4.1. Species Variability

Studies in rats and mice (Table 3-4) do not indicate much variability in the toxic effects of methacrylaldehyde. That is likely due to the direct irritating effect of methacrylaldehyde on the airways.

4.4.2. Concentration-Exposure Duration Relationship

The concentration-exposure duration relationship for many irritant and systemically-acting vapors and gases may be described by the equation Cⁿ × t = k, where the exponent n ranges from 0.8 to 3.5 (ten Berge et al. 1986). 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).

5. DATA ANALYSIS FOR AEGL-1

5.1. Human Data Relevant to AEGL-1

The only human toxicity study of methacrylaldehyde shows that the chemical has the potential for ocular irritation (Nojgaard et al. 2005). The nondominant eyes of 10 men were exposed for 20 min to methacrylaldehyde at concentrations of 0, 0.089, 0.189, and 0.286 ppm in eight sessions. Blinking frequency was recorded as a measure of irritation and the subjects described the intensity of any ocular discomfort or irritation during the exposures. The number of complaints about irritation and its intensity were not different at any concentration relative to that described by the control group. The relative change in blinking frequency was statistically higher (18%; p = 0.001) during exposure at 0.286 ppm. The NOAEL for blinking frequency was 0.189 ppm.

5.2. Animal Data Relevant to AEGL-1

Data in rats show that inhaled methacrylaldehyde is a contact irritant. For a 2-week exposure, the NOAEL was 4.9 ppm and the LOAEL was 19 ppm for respiratory-tract lesions (Coombs et al. 1992). A 13-week study in rats demonstrated a NOAEL of 5 ppm and a LOAEL of 15.3 ppm for olfactory lesions and a NOAEL of 1 ppm for ocular irritation (Coombs et al. 1994).

5.3. Derivation of AEGL-1 Values

The point-of-departure for the AEGL-1 values for methacrylaldehyde is the NOAEL of 0.189 ppm for blinking frequency in human subjects (Nojgaard et al. 2005). No uncertainty factors were applied because blinking frequency is not a perceived effect, but is rather an objective measurement that precedes perceived irritation. The same concentration was used for all durations because mild irritation is not expected to vary over time. The AEGL-1 values for methacrylaldehyde are presented in Table 3-5.

6. DATA ANALYSIS FOR AEGL-2

6.1. Human Data Relevant to AEGL-2

No human data relevant to deriving AEGL-2 values for methacrylaldehyde were found.

6.2. Animal Data Relevant to AEGL-2

Data in rats show that inhaled methacrylaldehyde is a contact irritant. For a 2-week exposure to methacrylaldehyde, the NOAEL and LOAEL for respiratory-tract lesions in rats was 5 and 19 ppm, respectively (Coombs et al. 1992). In another study, Sprague-Dawley rats were exposed to methacrylaldehyde at 1, 4.9, and 15.3 ppm for 6 h/day, 5 days/week for 13 weeks. At the two highest concentrations, the animals kept their eyes half-closed or closed during exposure. Salivation (indicative of substantial sensory irritation) was observed occasionally in animals exposed at 15.3 ppm. No signs of ocular irritation were observed at 1 ppm. 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).

6.3. Derivation of AEGL-2 Values

The AEGL-2 values for methacrylaldehyde are based on a NOAEL of 1 ppm for ocular irritation in rats (Coombs et al. 1994). Typically, two uncertainty factors of 3 would be applied to determine AEGL values for direct-acting irritants; one to account for interspecies differences and one to account for intraspecies variability. However, adjusting the 1-ppm point-of-departure by a total uncertainty factor of 10 would result in values lower than 0.189 ppm, which is a NOAEL for ocular irritation in humans (Nojgaard et al. 2005) and the basis of the AEGL-1 values for methacrylaldehyde. Thus, a total uncertainty factor of 3 was applied instead. Time scaling was not performed because mild ocular irritation is not expected to vary over time. The AEGL-2 values for methacrylaldehyde are presented in Table 3-6, and the calculations are presented in Appendix A.

TABLE 3-6 AEGL-2 Values for Methacrylaldehyde

7. DATA ANALYSIS FOR AEGL-3

7.1. Human Data Relevant to AEGL-3

No human data relevant to deriving AEGL-3 values for methacrylaldehyde were found.

7.2. Animal Data Relevant to AEGL-3 Values

Data in rats show that inhaled methacrylaldehyde is a sufficiently severe contact irritant that it causes serious effects, including lethality (Table 3-4). A single exposure of rats to methacrylaldehyde at 77 ppm for 6 h resulted in 90% mortality (Coombs et al. 1992). No deaths were observed in rats exposed at 19 ppm for 6 h/day, 5 days/week for 2 weeks or in rats exposed at 15.3 ppm 6 h/day, 5 days/week for 13 weeks (Coombs et al. 1994). Other supporting studies include an assumed 4-h LC₅₀ in Sherman rats of about 125 ppm (nominal) reported by Carpenter et al. (1949), and an unconfirmed 4-h LC₅₀ of 195 ppm reported in a secondary source (BG Chemie 1995).

7.3. Derivation of AEGL-3 Values

On the basis of the study by Coombs et al. (1992), the 2-week NOAEL for lethality of 19 ppm was selected as the point-of-departure for AEGL-3 values for methacrylaldehyde. Time scaling was performed using the equation Cⁿ × t = k (ten Berge et al. 1986). Data on methacrylaldehyde were inadequate for deriving an empirical value for the exponent n, so default values of n = 3 to extrapolate to shorter durations and n = 1 to extrapolate to longer durations were used. 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. Furthermore, use of a factor of 10 for either the interspecies or intraspecies uncertainty factor would result in AEGL-3 values that are less consistent with the available data. (A total uncertainty factor of 30 yields AEGL-3 values of 1.4 ppm for the 10- and 30-min durations, 1.1 ppm for the 1-h duration, 0.7 ppm for the 4-h duration, and 0.47 ppm for the 8-h duration. No effects were observed in rats exposed at 1.0 ppm for 6 h/day, 5 days/week for 13 weeks, and half-closed eyes and respiratory irritation were observed in rats similarly exposed at 4.9 ppm).

The AEGL-3 values for methacrylaldehyde are presented in Table 3-7, and the calculations are provided in Appendix A.

8. SUMMARY OF AEGLS

8.1. AEGL Values and Toxicity End Points

The AEGL values for methacrylaldehyde are presented in Table 3-8. The AEGL-1 values are based on a study of ocular irritation in healthy human subjects, which identified a NOAEL and a LOAEL for blinking frequency (Nojgaard et al. 2005). The AEGL-2 values are based on a study by Coombs et al. (1994), in which Sprague-Dawley rats exposed to methacrylaldehyde had clinical signs of ocular irritation. The AEGL-3 values are based on a concentration of methacrylaldehyde not resulting in deaths in rats exposed for 6 h/day, 5 days/week for 13 weeks (Coombs et al. 1992).

8.2. Other Standards and Guidelines

No other standards or guidelines for methacrylaldehyde were found.

8.3. Data Adequacy and Research

Human data appropriate for derivation of AEGL-1 values for methacrylaldehyde were available from a well-conducted study. However, no information was available concerning effects in young, elderly, or asthmatic individuals. Minimal animal data were available for derivation of AEGL-2 or AEGL-3 values.

TABLE 3-7 AEGL-3 Values for Methacrylaldehyde

TABLE 3-8 AEGL Values for Methacrylaldehyde

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APPENDIX A

DERIVATION OF AEGL VALUES FOR METHACRYLALDEHYDE

APPENDIX B

ACUTE EXPOSURE GUIDELINE LEVELS FOR METHACRYLALDEHYDE

Derivation Summary

AEGL-1 VALUES

AEGL-2 VALUES

AEGL-3 VALUES

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

For category: 0 = no effect, 1 = discomfort, 2 = disabling, SL = some lethality, 3 = lethality.