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Inhalation Health Risk Assessment of MMT
Environmental Research Section A 80, 103—104 (1999) Article ID enrs.1998.3916, available online at http://www.idealibrary.com on
Inhalation Health Risk Assessment of MMT1 J. M. Davis,* A. M. Jarabek,* D. T. Mage,- and J. A. Graham*National Center for Environmental Assessment and -National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Received August 3, 1998
In response to petitions submitted by the Ethyl Corporation to the U.S. Environmental Protection Agency to allow the use of MMT in unleaded gasoline, a team of scientists from the EPA’s Office of Research and Development evaluated the potential health risks associated with possible MMT usage (U.S. EPA, 1994a, b). The assessment comprised hazard identification, dose—response analyses, exposure assessment, and risk characterization components. Particulate manganese emissions resulting from the combustion of gasoline containing MMT were considered the primary health hazard rather than MMT itself. Although Mn has relatively low toxicity when ingested, excessive inhalation exposure to Mn has long been known to affect respiratory, reproductive, and nervous systems. Neurotoxicity has been the most extensively investigated effect of Mn, often characterized by impaired fine control and reduced speed of movements and alterations in gait, posture, and facial expression. EPA’s dose—response analyses centered on derivations of an Mn inhalation reference concentration (RfC), which is defined as an estimate (with uncertainty spanning about an order of magnitude) of a continuous inhalation exposure level for the human population (including sensitive subpopulations) that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. In 1993, the EPA verified an RfC for Mn of 0.05 lg/m3 based on evidence from several occupational epidemiological studies (including Roels et al., 1987; Iregren, 1990; Megler et al., 1994), especially a study of alkaline battery plant workers by Roels et al. (1992). At the request of Ethyl, the EPA conducted intensive analyses using various statistical approaches to derive alternative estimates of RfCs for Mn. Among
the statistical techniques considered were benchmark dose and Bayesian analyses employing various mathematical models and exposure measurements. More than 100 alternative Mn RfC estimates were derived, with eight leading candidates in the range of 0.09 to 0.2 lg/m3. The exposure assessment took advantage of the fact that a well-conducted probabilistic study of personal exposures to particles, including particulate Mn, had been conducted in Riverside, California, in the fall of 1990, a period when MMT was being used in leaded gasoline. Based on data from the particle total exposure assessment methodology (PTEAM) study and other studies, a distribution of personal exposure levels of particulate Mn was projected, assuming that MMT would be used in 100% of unleaded gasoline at a concentration of 0.031 g Mn/gallon, as requested in Ethyl’s petition. According to these projections, approximately 5 to 10% of the Riverside population could experience personal exposure levels of particulate Mn at 0.1 lg/m3 or higher. Figure 1 presents the 1993 verified RfC and eight alternative estimates of RfC values in relation to estimated personal exposure levels of particulate Mn. Although the upper tail of the exposure distribution is in the range of or exceeds several of the RfC values, this does not necessarily signify that a health risk exists. By its definition and the methods used to derive it, the RfC is inherently uncertain, and risks above the RfC cannot be quantified at present. However, this does not imply that no health risk is expected to exist at exposure levels exceeding the RfC. Indeed, the EPA concluded that ‘‘a reasonable basis exists for concern regarding potential public health risks, especially for sensitive subpopulations, if MMT were to be used widely in unleaded gasoline.’’ Several areas of uncertainty make it difficult to state a more definitive conclusion. These uncertainties include limited information on possible
1
This paper reports on a workshop on MMT held at the 1997 Annual Meeting of the Society of Toxicology. 103
0013-9351/99
104
DAVIS ET AL.
FIG. 1. Summary of selected Mn RfC estimates and projected personal exposure levels of Mn. The horizontal marks on the exposure distribution represent medians obtained through two different modeling procedures. (Source: U.S. Environmental Protection Agency, 1994a)
susceptible subpopulations, effects of chronic exposure, reproductive/developmental effects, and differences in the toxicity of different forms of Mn, as well as various limitations in the exposure modeling. Until these uncertainties are reduced through further research and testing, a high degree of uncertainty will attend any judgment of the potential risks to public health associated with the use of MMT. REFERENCES Iregren, A. (1990). Psychological test performance in foundry workers exposed to low levels of manganese. Neurotoxicol. Teratol. 12, 673—675. Mergler, D., Huel, G., Bowler, R., Iregren, A., Belanger, S., Baldwin, M., Tardif, R., Smargiassi, A., and Martin, L. (1994). Nervous system dysfunction among workers with long-term exposure to manganese, Environ. Res 64, 151—180.
Roels, H., Lauwerys, R., Genet, P., Sarhan, M. J., de Fays, M., Hanotian, I., and Buchet, J.-P. (1987). Relationship between external and internal parameters of exposure to manganese in workers from a manganese oxide and salt producing plant. Am. J. Ind Med. 11, 297—305. Roels, H. A., Ghyseleu, P., Buchet, J. P., Ceulemans, E., and Lauwerys, R. R. (1992). Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust. Br. J. Ind. Med. 49, 25—34. U. S. Environmental Protection Agency (1994a). ‘‘Reevaluation of Inhalation Health Risks Associated with Methylcyclopentadienyl Manganese Tricarbonyl (MMT) in Gasoline,’’ EPA Report 600/R-94/062. Office of Research and Development, Research Triangle Park, NC. U.S. Environmental Protection Agency (1994b). ‘‘ORD’s Response to Public Comments on Health and Exposure Issues in Relation to the Waiver Petition of Ethyl Corporation to Add MMT to Unleaded Gasoline,’’ Office of Research and Development. Research Triangle Park, NC.
Inhalation Health Risk Assessment of MMT1 J. M. Davis,* A. M. Jarabek,* D. T. Mage,- and J. A. Graham*National Center for Environmental Assessment and -National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Received August 3, 1998
In response to petitions submitted by the Ethyl Corporation to the U.S. Environmental Protection Agency to allow the use of MMT in unleaded gasoline, a team of scientists from the EPA’s Office of Research and Development evaluated the potential health risks associated with possible MMT usage (U.S. EPA, 1994a, b). The assessment comprised hazard identification, dose—response analyses, exposure assessment, and risk characterization components. Particulate manganese emissions resulting from the combustion of gasoline containing MMT were considered the primary health hazard rather than MMT itself. Although Mn has relatively low toxicity when ingested, excessive inhalation exposure to Mn has long been known to affect respiratory, reproductive, and nervous systems. Neurotoxicity has been the most extensively investigated effect of Mn, often characterized by impaired fine control and reduced speed of movements and alterations in gait, posture, and facial expression. EPA’s dose—response analyses centered on derivations of an Mn inhalation reference concentration (RfC), which is defined as an estimate (with uncertainty spanning about an order of magnitude) of a continuous inhalation exposure level for the human population (including sensitive subpopulations) that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. In 1993, the EPA verified an RfC for Mn of 0.05 lg/m3 based on evidence from several occupational epidemiological studies (including Roels et al., 1987; Iregren, 1990; Megler et al., 1994), especially a study of alkaline battery plant workers by Roels et al. (1992). At the request of Ethyl, the EPA conducted intensive analyses using various statistical approaches to derive alternative estimates of RfCs for Mn. Among
the statistical techniques considered were benchmark dose and Bayesian analyses employing various mathematical models and exposure measurements. More than 100 alternative Mn RfC estimates were derived, with eight leading candidates in the range of 0.09 to 0.2 lg/m3. The exposure assessment took advantage of the fact that a well-conducted probabilistic study of personal exposures to particles, including particulate Mn, had been conducted in Riverside, California, in the fall of 1990, a period when MMT was being used in leaded gasoline. Based on data from the particle total exposure assessment methodology (PTEAM) study and other studies, a distribution of personal exposure levels of particulate Mn was projected, assuming that MMT would be used in 100% of unleaded gasoline at a concentration of 0.031 g Mn/gallon, as requested in Ethyl’s petition. According to these projections, approximately 5 to 10% of the Riverside population could experience personal exposure levels of particulate Mn at 0.1 lg/m3 or higher. Figure 1 presents the 1993 verified RfC and eight alternative estimates of RfC values in relation to estimated personal exposure levels of particulate Mn. Although the upper tail of the exposure distribution is in the range of or exceeds several of the RfC values, this does not necessarily signify that a health risk exists. By its definition and the methods used to derive it, the RfC is inherently uncertain, and risks above the RfC cannot be quantified at present. However, this does not imply that no health risk is expected to exist at exposure levels exceeding the RfC. Indeed, the EPA concluded that ‘‘a reasonable basis exists for concern regarding potential public health risks, especially for sensitive subpopulations, if MMT were to be used widely in unleaded gasoline.’’ Several areas of uncertainty make it difficult to state a more definitive conclusion. These uncertainties include limited information on possible
1
This paper reports on a workshop on MMT held at the 1997 Annual Meeting of the Society of Toxicology. 103
0013-9351/99
104
DAVIS ET AL.
FIG. 1. Summary of selected Mn RfC estimates and projected personal exposure levels of Mn. The horizontal marks on the exposure distribution represent medians obtained through two different modeling procedures. (Source: U.S. Environmental Protection Agency, 1994a)
susceptible subpopulations, effects of chronic exposure, reproductive/developmental effects, and differences in the toxicity of different forms of Mn, as well as various limitations in the exposure modeling. Until these uncertainties are reduced through further research and testing, a high degree of uncertainty will attend any judgment of the potential risks to public health associated with the use of MMT. REFERENCES Iregren, A. (1990). Psychological test performance in foundry workers exposed to low levels of manganese. Neurotoxicol. Teratol. 12, 673—675. Mergler, D., Huel, G., Bowler, R., Iregren, A., Belanger, S., Baldwin, M., Tardif, R., Smargiassi, A., and Martin, L. (1994). Nervous system dysfunction among workers with long-term exposure to manganese, Environ. Res 64, 151—180.
Roels, H., Lauwerys, R., Genet, P., Sarhan, M. J., de Fays, M., Hanotian, I., and Buchet, J.-P. (1987). Relationship between external and internal parameters of exposure to manganese in workers from a manganese oxide and salt producing plant. Am. J. Ind Med. 11, 297—305. Roels, H. A., Ghyseleu, P., Buchet, J. P., Ceulemans, E., and Lauwerys, R. R. (1992). Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust. Br. J. Ind. Med. 49, 25—34. U. S. Environmental Protection Agency (1994a). ‘‘Reevaluation of Inhalation Health Risks Associated with Methylcyclopentadienyl Manganese Tricarbonyl (MMT) in Gasoline,’’ EPA Report 600/R-94/062. Office of Research and Development, Research Triangle Park, NC. U.S. Environmental Protection Agency (1994b). ‘‘ORD’s Response to Public Comments on Health and Exposure Issues in Relation to the Waiver Petition of Ethyl Corporation to Add MMT to Unleaded Gasoline,’’ Office of Research and Development. Research Triangle Park, NC.