Guidance for Air
The following guidance was developed by the Minnesota Department of Health (MDH) at the request of the Minnesota Pollution Control Agency (MPCA). For more information, contact the Health Risk Assessment Unit.
Note: This information pertains to the acute health-based value for acrolein only. MDH also has developed a subchronic Health Risk Value for this chemical.
Acrolein: Acute Health-Based Value for Air
May 4, 2004
Chemical: Acrolein
CAS number: 107-02-8
Endpoint(s): Eye irritation
Acute Value: 2 ug/m3
Source: Minnesota Department of Health
The Minnesota Department of Health (MDH) has developed an acute air Health-Based Value (HBV) for acrolein (CAS No. 107-02-8). Acrolein is a widespread byproduct of the incomplete combustion of organic material. Therefore, the HBV may be used to assess risks from both ambient exposures and facility emissions.
Although there have been a number of studies that assessed the impacts of acute exposures of animals to acrolein, there have been relatively few experiments done using human subjects. In addition, none of the available human studies are adequate for developing an acute HBV when using the established guidelines for producing and promulgating Health Risk Values (HRVs). Understanding the MPCA's critical need for guidance in assessing acute risks from exposure to acrolein, MDH has used a weight of evidence approach that incorporates data from a human study but relies on evidence from animal studies to validate the resulting HBV. Based on this approach MDH has derived an acute HBV for acrolein of 2 ug/m3 based on mild eye irritation. A description of the techniques and assumptions used in developing this number follows.
The U.S. Environmental Protection Agency, in its recently released Toxicological Review for Acrolein (U.S. EPA, 2003), discusses in some detail a paper that examined the impact of the acute administration of acrolein on human volunteers (Weber-Tschoff et al., 1977). MDH has used the results of this study as the basis for developing the acute HBV as follows:
0.09 ppm x = 2.1 (rounded to 2 ug/m3)
Where:
0.09 ppm = Lowest Observed Adverse Effect Level (LOAEL)
100 = Uncertainty Factor (10 for intraspecies variability, 3 for the use of a mild LOAEL, 3 for human database deficiencies)
2.3 = Conversion Factor (ppm to ug/m3)
*The experimental exposure was for 40 minutes. Consistent with HRV guidelines no time conversion was done.
MDH also examined the more extensive animal literature and identified several studies that support the acute HBV developed for acrolein. It should be noted that acute exposure to acrolein caused similar responses (i.e., eye, throat and respiratory irritation) in all species examined.
Murphy et al. (1963) exposed guinea pigs to 0.1, 0.2, 0.35, 0.6 or 1.0 ppm acrolein for two hours. Respiratory flow resistance during inhalation and exhalation were significantly increased and respiratory rates decreased at 0.35 to 1.0 ppm; the 0.2 ppm exposure is the NOAEL for these effects. When the appropriate pharmacokinetic and time adjustments and an uncertainty factor of 30 (10 for intraspecies, and 3 for interspecies) are used, the resulting HBV is 3.5 ug/m3.Davis et al. (1967) conducted a study where one-hour exposures of guinea pigs to 17 ppm acrolein caused statistically significant increases in respiratory resistance and tidal volume. These changes were coupled with decreases in respiratory rate and minute volumes. When the appropriate pharmacokinetic and time adjustments and an uncertainty factor of 180 (10 for intraspecies, 3 for interspecies, and 6 for use of a LOAEL) are used, the resulting HBV is 50 ug/m3.
Roemer et al. (1963) noted respiratory tract cell proliferation in male Sprague-Dawley rats following an acute 6-hour exposure to 0.2 or 0.6 ppm acrolein provided a LOAEL of 0.2 ppm. When the appropriate pharmacokinetic and time adjustments and an uncertainty factor of 100 (10 for intraspecies, 3 for interspecies, and 3 for use of a mild LOAEL) are used, the resulting HBV is 2.3 ug/m3.
Cassee et al. (1996) exposed rats to various concentrations of acrolein by nose only for 6 hours on 3 consecutive days. The lowest concentration of acrolein (0.25 ppm) produced no effects on the first day of exposure and is therefore a NOAEL for disarrangement, necrosis, thickening, desquamation, and basal cell hyperplasia in rat olfactory nasal epithelium. When the appropriate pharmacokinetic and time adjustments and an uncertainty factor of 30 (10 for intraspecies, 3 for interspecies) are used, the resulting HBV is 9.4 ug/m3.
Since, as previously noted, the mechanism by which acrolein exerts its irritative effects does not appear to vary from species to species, the consistency of the results from the various animal studies examined provides support for the HBV developed using the human data.
Despite the fact that MDH was unable to identify a single study of the acute toxicity of acrolein in air that was sufficient for developing a draft acute HRV, the weight of evidence available from all sources provides confidence that an acute HBV of 2 µg/m3 for acrolein is protective of human health. For questions regarding the development of the acute HBV for acrolein, please contact the Health Risk Assessment Unit at (651) 215-0880.
References
Cassee, F.R., Groton, J.R., and Feron, V.J. (1996). Changes in nasal epithelium in rats exposed by inhalation of mixtures of formaldehyde, acetaldehyde and acrolein. Fund. Appl. Toxicol. 29; 208-218.
Davis, T.R.A., Battista, S.P., and Knesler, C.J. (1967). Mechanism of respiratory effects during exposure of guinea pigs to irritants. Arch. Environ. Health. 15(4); 412-419.
Murphy, S.D., Klingshorn, D.A., and Ulrich, C.E. (1963). Respiratory response of guinea pigs during acrolein inhalation and its modification by drugs. J. Pharmacol. Exp. Therap. 141; 79B93.
Roemer, E., Anton, H.J., Kindt, R., et al. (1963). Cell proliferation in the respiratory tract of the rat after acute inhalation of formaldehyde or acrolein. J. Appl. Toxicol. 13(2); 103-107.
U.S. EPA (2003). Toxicological review of acrolein (CAS No. 107-02-8). EPA/635/R-03/003. U.S. Environmental Protection Agency, Washington, D.C.
Weber-Tschopp, A., Fisher, T., Gierer, R. et al. (1977). Experimentally induced irritating effect of acrolein on men. Int. Arch. Occup. Environ. Health 40; 117-130. In German.