Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1998 Feb;106(Suppl 1):191–201. doi: 10.1289/ehp.98106s1191

Methylcyclopentadienyl manganese tricarbonyl: health risk uncertainties and research directions.

J M Davis 1
PMCID: PMC1533284  PMID: 9539013

Abstract

With the way cleared for increased use of the fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) in the United States, the issue of possible public health impacts associated with this additive has gained greater attention. In assessing potential health risks of particulate Mn emitted from the combustion of MMT in gasoline, the U.S. Environmental Protection Agency not only considered the qualitative types of toxic effects associated with inhaled Mn, but conducted extensive exposure-response analyses using various statistical approaches and also estimated population exposure distributions of particulate Mn based on data from an exposure study conducted in California when MMT was used in leaded gasoline. Because of limitations in available data and the need to make several assumptions and extrapolations, the resulting risk characterization had inherent uncertainties that made it impossible to estimate health risks in a definitive or quantitative manner. To support an improved health risk characterization, further investigation is needed in the areas of health effects, emission characterization, and exposure analysis.

Full text

PDF
191

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ali S. F., Duhart H. M., Newport G. D., Lipe G. W., Slikker W., Jr Manganese-induced reactive oxygen species: comparison between Mn+2 and Mn+3. Neurodegeneration. 1995 Sep;4(3):329–334. doi: 10.1016/1055-8330(95)90023-3. [DOI] [PubMed] [Google Scholar]
  2. Archibald F. S., Tyree C. Manganese poisoning and the attack of trivalent manganese upon catecholamines. Arch Biochem Biophys. 1987 Aug 1;256(2):638–650. doi: 10.1016/0003-9861(87)90621-7. [DOI] [PubMed] [Google Scholar]
  3. Aschner M., Aschner J. L. Manganese neurotoxicity: cellular effects and blood-brain barrier transport. Neurosci Biobehav Rev. 1991 Fall;15(3):333–340. doi: 10.1016/s0149-7634(05)80026-0. [DOI] [PubMed] [Google Scholar]
  4. Barbeau A. Etiology of Parkinson's disease: A research strategy. Can J Neurol Sci. 1984 Feb;11(1):24–28. doi: 10.1017/s0317167100045273. [DOI] [PubMed] [Google Scholar]
  5. Bell J. G., Keen C. L., Lönnerdal B. Higher retention of manganese in suckling than in adult rats is not due to maturational differences in manganese uptake by rat small intestine. J Toxicol Environ Health. 1989;26(4):387–398. doi: 10.1080/15287398909531263. [DOI] [PubMed] [Google Scholar]
  6. Bird E. D., Anton A. H., Bullock B. The effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkey. Neurotoxicology. 1984 Spring;5(1):59–65. [PubMed] [Google Scholar]
  7. Brouillet E. P., Shinobu L., McGarvey U., Hochberg F., Beal M. F. Manganese injection into the rat striatum produces excitotoxic lesions by impairing energy metabolism. Exp Neurol. 1993 Mar;120(1):89–94. doi: 10.1006/exnr.1993.1042. [DOI] [PubMed] [Google Scholar]
  8. Calne D. B., Chu N. S., Huang C. C., Lu C. S., Olanow W. Manganism and idiopathic parkinsonism: similarities and differences. Neurology. 1994 Sep;44(9):1583–1586. doi: 10.1212/wnl.44.9.1583. [DOI] [PubMed] [Google Scholar]
  9. Clayton C. A., Perritt R. L., Pellizzari E. D., Thomas K. W., Whitmore R. W., Wallace L. A., Ozkaynak H., Spengler J. D. Particle Total Exposure Assessment Methodology (PTEAM) study: distributions of aerosol and elemental concentrations in personal, indoor, and outdoor air samples in a southern California community. J Expo Anal Environ Epidemiol. 1993 Apr-Jun;3(2):227–250. [PubMed] [Google Scholar]
  10. Cook D. G., Fahn S., Brait K. A. Chronic manganese intoxication. Arch Neurol. 1974 Jan;30(1):59–64. doi: 10.1001/archneur.1974.00490310061010. [DOI] [PubMed] [Google Scholar]
  11. Cotzias G. C., Horiuchi K., Fuenzalida S., Mena I. Chronic manganese poisoning. Clearance of tissue manganese concentrations with persistance of the neurological picture. Neurology. 1968 Apr;18(4):376–382. doi: 10.1212/wnl.18.4.376. [DOI] [PubMed] [Google Scholar]
  12. Cotzias G. C., Miller S. T., Papavasiliou P. S., Tang L. C. Interactions between manganese and brain dopamine. Med Clin North Am. 1976 Jul;60(4):729–738. doi: 10.1016/s0025-7125(16)31856-9. [DOI] [PubMed] [Google Scholar]
  13. Crump K. S. A new method for determining allowable daily intakes. Fundam Appl Toxicol. 1984 Oct;4(5):854–871. doi: 10.1016/0272-0590(84)90107-6. [DOI] [PubMed] [Google Scholar]
  14. Davidsson L., Cederblad A., Lönnerdal B., Sandström B. The effect of individual dietary components on manganese absorption in humans. Am J Clin Nutr. 1991 Dec;54(6):1065–1070. doi: 10.1093/ajcn/54.6.1065. [DOI] [PubMed] [Google Scholar]
  15. Dawson R., Jr, Beal M. F., Bondy S. C., Di Monte D. A., Isom G. E. Excitotoxins, aging, and environmental neurotoxins: implications for understanding human neurodegenerative diseases. Toxicol Appl Pharmacol. 1995 Sep;134(1):1–17. doi: 10.1006/taap.1995.1163. [DOI] [PubMed] [Google Scholar]
  16. Deskin R., Bursian S. J., Edens F. W. The effect of chronic manganese administration on some neurochemical and physiological variables in neonatal rats. Gen Pharmacol. 1981;12(4):279–280. doi: 10.1016/0306-3623(81)90058-6. [DOI] [PubMed] [Google Scholar]
  17. Desole M. S., Esposito G., Migheli R., Fresu L., Sircana S., Zangani D., Miele M., Miele E. Cellular defence mechanisms in the striatum of young and aged rats subchronically exposed to manganese. Neuropharmacology. 1995 Mar;34(3):289–295. doi: 10.1016/0028-3908(94)00140-n. [DOI] [PubMed] [Google Scholar]
  18. Donaldson J., McGregor D., LaBella F. Manganese neurotoxicity: a model for free radical mediated neurodegeneration? Can J Physiol Pharmacol. 1982 Nov;60(11):1398–1405. doi: 10.1139/y82-208. [DOI] [PubMed] [Google Scholar]
  19. Drown D. B., Oberg S. G., Sharma R. P. Pulmonary clearance of soluble and insoluble forms of manganese. J Toxicol Environ Health. 1986;17(2-3):201–212. doi: 10.1080/15287398609530816. [DOI] [PubMed] [Google Scholar]
  20. Eriksson H., Mägiste K., Plantin L. O., Fonnum F., Hedström K. G., Theodorsson-Norheim E., Kristensson K., Stålberg E., Heilbronn E. Effects of manganese oxide on monkeys as revealed by a combined neurochemical, histological and neurophysiological evaluation. Arch Toxicol. 1987;61(1):46–52. doi: 10.1007/BF00324547. [DOI] [PubMed] [Google Scholar]
  21. Eriksson H., Tedroff J., Thuomas K. A., Aquilonius S. M., Hartvig P., Fasth K. J., Bjurling P., Långström B., Hedström K. G., Heilbronn E. Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging. Arch Toxicol. 1992;66(6):403–407. doi: 10.1007/BF02035130. [DOI] [PubMed] [Google Scholar]
  22. Fell J. M., Reynolds A. P., Meadows N., Khan K., Long S. G., Quaghebeur G., Taylor W. J., Milla P. J. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet. 1996 May 4;347(9010):1218–1221. doi: 10.1016/s0140-6736(96)90735-7. [DOI] [PubMed] [Google Scholar]
  23. Gavin C. E., Gunter K. K., Gunter T. E. Mn2+ sequestration by mitochondria and inhibition of oxidative phosphorylation. Toxicol Appl Pharmacol. 1992 Jul;115(1):1–5. doi: 10.1016/0041-008x(92)90360-5. [DOI] [PubMed] [Google Scholar]
  24. Gottschalk L. A., Rebello T., Buchsbaum M. S., Tucker H. G., Hodges E. L. Abnormalities in hair trace elements as indicators of aberrant behavior. Compr Psychiatry. 1991 May-Jun;32(3):229–237. doi: 10.1016/0010-440x(91)90043-c. [DOI] [PubMed] [Google Scholar]
  25. Haar GL Ter, Lenane D. L., Hu J. N., Brandt M. Composition, size and control of automotive exhaust particulates. J Air Pollut Control Assoc. 1972 Jan;22(1):39–46. doi: 10.1080/00022470.1972.10469607. [DOI] [PubMed] [Google Scholar]
  26. Hauser R. A., Zesiewicz T. A., Martinez C., Rosemurgy A. S., Olanow C. W. Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease. Can J Neurol Sci. 1996 May;23(2):95–98. doi: 10.1017/s0317167100038786. [DOI] [PubMed] [Google Scholar]
  27. Iregren A. Psychological test performance in foundry workers exposed to low levels of manganese. Neurotoxicol Teratol. 1990 Nov-Dec;12(6):673–675. doi: 10.1016/0892-0362(90)90085-q. [DOI] [PubMed] [Google Scholar]
  28. Komura J., Sakamoto M. Subcellular and gel chromatographic distribution of manganese in the mouse brain: relation to the chemical form of chronically-ingested manganese. Toxicol Lett. 1993 Mar;66(3):287–294. doi: 10.1016/0378-4274(93)90010-u. [DOI] [PubMed] [Google Scholar]
  29. Kontur P. J., Fechter L. D. Brain regional manganese levels and monoamine metabolism in manganese-treated neonatal rats. Neurotoxicol Teratol. 1988 Jul-Aug;10(4):295–303. doi: 10.1016/0892-0362(88)90031-1. [DOI] [PubMed] [Google Scholar]
  30. Krieger D., Krieger S., Jansen O., Gass P., Theilmann L., Lichtnecker H. Manganese and chronic hepatic encephalopathy. Lancet. 1995 Jul 29;346(8970):270–274. doi: 10.1016/s0140-6736(95)92164-8. [DOI] [PubMed] [Google Scholar]
  31. Laskey J. W., Rehnberg G. L., Hein J. F., Carter S. D. Effects of chronic manganese (Mn3O4) exposure on selected reproductive parameters in rats. J Toxicol Environ Health. 1982 Apr;9(4):677–687. doi: 10.1080/15287398209530195. [DOI] [PubMed] [Google Scholar]
  32. Lauwerys R., Roels H., Genet P., Toussaint G., Bouckaert A., De Cooman S. Fertility of male workers exposed to mercury vapor or to manganese dust: a questionnaire study. Am J Ind Med. 1985;7(2):171–176. doi: 10.1002/ajim.4700070208. [DOI] [PubMed] [Google Scholar]
  33. Lown B. A., Morganti J. B., D'Agostino R., Stineman C. H., Massaro E. J. Effects on the postnatal development of the mouse of preconception, postconception and/or suckling exposure to manganese via maternal inhalation exposure to MnO2 dust. Neurotoxicology. 1984 Spring;5(1):119–129. [PubMed] [Google Scholar]
  34. Lucchini R., Selis L., Folli D., Apostoli P., Mutti A., Vanoni O., Iregren A., Alessio L. Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure. Scand J Work Environ Health. 1995 Apr;21(2):143–149. doi: 10.5271/sjweh.1369. [DOI] [PubMed] [Google Scholar]
  35. Lönnerdal B. Dietary factors affecting trace element absorption in infants. Acta Paediatr Scand Suppl. 1989;351:109–113. doi: 10.1111/j.1651-2227.1989.tb11220.x. [DOI] [PubMed] [Google Scholar]
  36. Mena I., Horiuchi K., Burke K., Cotzias G. C. Chronic manganese poisoning. Individual susceptibility and absorption of iron. Neurology. 1969 Oct;19(10):1000–1006. doi: 10.1212/wnl.19.10.1000. [DOI] [PubMed] [Google Scholar]
  37. Menkes D. B., Fawcett J. P. Too easily lead? Health effects of gasoline additives. Environ Health Perspect. 1997 Mar;105(3):270–273. doi: 10.1289/ehp.105-1470015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mergler D., Huel G., Bowler R., Iregren A., Bélanger S., Baldwin M., Tardif R., Smargiassi A., Martin L. Nervous system dysfunction among workers with long-term exposure to manganese. Environ Res. 1994 Feb;64(2):151–180. doi: 10.1006/enrs.1994.1013. [DOI] [PubMed] [Google Scholar]
  39. Moore W., Hysell D., Miller R., Malanchuk M., Hinners R., Yang Y., Stara J. F. Exposure of laboratory animals to atmospheric maganese from automotive emissions. Environ Res. 1975 Jun;9(3):274–284. doi: 10.1016/0013-9351(75)90007-9. [DOI] [PubMed] [Google Scholar]
  40. Morganti J. B., Lown B. A., Stineman C. H., D'Agostino R. B., Massaro E. J. Uptake, distribution and behavioral effects of inhalation exposure to manganese (MnO2) in the adult mouse. Neurotoxicology. 1985 Spring;6(1):1–15. [PubMed] [Google Scholar]
  41. Murphy V. A., Wadhwani K. C., Smith Q. R., Rapoport S. I. Saturable transport of manganese(II) across the rat blood-brain barrier. J Neurochem. 1991 Sep;57(3):948–954. doi: 10.1111/j.1471-4159.1991.tb08242.x. [DOI] [PubMed] [Google Scholar]
  42. Newland M. C., Weiss B. Persistent effects of manganese on effortful responding and their relationship to manganese accumulation in the primate globus pallidus. Toxicol Appl Pharmacol. 1992 Mar;113(1):87–97. doi: 10.1016/0041-008x(92)90012-h. [DOI] [PubMed] [Google Scholar]
  43. Nishiyama K., Suzuki Y., Fujii N., Yano H., Miyai T. [Experimental study on the effect of a long-term inhalation of manganese particles. 2. Sequential observation of respiratory organs of monkeys and mice]. Nihon Eiseigaku Zasshi. 1975 Apr;30(1):117–117. [PubMed] [Google Scholar]
  44. Piver W. T. Potential dilemma: the methods of meeting automotive exhaust emission standards of the clean air act of 1970. Environ Health Perspect. 1974 Aug;8:165–190. doi: 10.1289/ehp.748165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. RODIER J. Manganese poisoning in Moroccan miners. Br J Ind Med. 1955 Jan;12(1):21–35. doi: 10.1136/oem.12.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rabin O., Hegedus L., Bourre J. M., Smith Q. R. Rapid brain uptake of manganese(II) across the blood-brain barrier. J Neurochem. 1993 Aug;61(2):509–517. doi: 10.1111/j.1471-4159.1993.tb02153.x. [DOI] [PubMed] [Google Scholar]
  47. Roels H. A., Ghyselen P., Buchet J. P., Ceulemans E., Lauwerys R. R. Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust. Br J Ind Med. 1992 Jan;49(1):25–34. doi: 10.1136/oem.49.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Roels H., Lauwerys R., Buchet J. P., Genet P., Sarhan M. J., Hanotiau I., de Fays M., Bernard A., Stanescu D. Epidemiological survey among workers exposed to manganese: effects on lung, central nervous system, and some biological indices. Am J Ind Med. 1987;11(3):307–327. doi: 10.1002/ajim.4700110308. [DOI] [PubMed] [Google Scholar]
  49. Roels H., Lauwerys R., Genet P., Sarhan M. J., de Fays M., Hanotiau I., Buchet J. P. Relationship between external and internal parameters of exposure to manganese in workers from a manganese oxide and salt producing plant. Am J Ind Med. 1987;11(3):297–305. doi: 10.1002/ajim.4700110307. [DOI] [PubMed] [Google Scholar]
  50. Roels H., Meiers G., Delos M., Ortega I., Lauwerys R., Buchet J. P., Lison D. Influence of the route of administration and the chemical form (MnCl2, MnO2) on the absorption and cerebral distribution of manganese in rats. Arch Toxicol. 1997;71(4):223–230. doi: 10.1007/s002040050380. [DOI] [PubMed] [Google Scholar]
  51. Saric M. Occupational and environmental exposures and nonspecific lung disease--a review of selected studies. Isr J Med Sci. 1992 Aug-Sep;28(8-9):509–512. [PubMed] [Google Scholar]
  52. Seth P. K., Chandra S. V. Neurotransmitters and neurotransmitter receptors in developing and adult rats during manganese poisoning. Neurotoxicology. 1984 Spring;5(1):67–76. [PubMed] [Google Scholar]
  53. Shinotoh H., Snow B. J., Hewitt K. A., Pate B. D., Doudet D., Nugent R., Perl D. P., Olanow W., Calne D. B. MRI and PET studies of manganese-intoxicated monkeys. Neurology. 1995 Jun;45(6):1199–1204. doi: 10.1212/wnl.45.6.1199. [DOI] [PubMed] [Google Scholar]
  54. Smyth L. T., Ruhf R. C., Whitman N. E., Dugan T. Clinical manganism and exposure to manganese in the production and processing of ferromanganese alloy. J Occup Med. 1973 Feb;15(2):101–109. [PubMed] [Google Scholar]
  55. Tholin K., Sandström B., Palm R., Hallmans G. Changes in blood manganese levels during pregnancy in iron supplemented and non supplemented women. J Trace Elem Med Biol. 1995 Mar;9(1):13–17. doi: 10.1016/S0946-672X(11)80003-9. [DOI] [PubMed] [Google Scholar]
  56. Tjälve H., Henriksson J., Tallkvist J., Larsson B. S., Lindquist N. G. Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol Toxicol. 1996 Dec;79(6):347–356. doi: 10.1111/j.1600-0773.1996.tb00021.x. [DOI] [PubMed] [Google Scholar]
  57. Wennberg A. Neurotoxic effects of selected metals. Scand J Work Environ Health. 1994;20(Spec No):65–71. [PubMed] [Google Scholar]
  58. Wilson D. C., Tubman R., Bell N., Halliday H. L., McMaster D. Plasma manganese, selenium and glutathione peroxidase levels in the mother and newborn infant. Early Hum Dev. 1991 Oct;26(3):223–226. doi: 10.1016/0378-3782(91)90162-v. [DOI] [PubMed] [Google Scholar]
  59. Wolters E. C., Huang C. C., Clark C., Peppard R. F., Okada J., Chu N. S., Adam M. J., Ruth T. J., Li D., Calne D. B. Positron emission tomography in manganese intoxication. Ann Neurol. 1989 Nov;26(5):647–651. doi: 10.1002/ana.410260510. [DOI] [PubMed] [Google Scholar]
  60. Yamada M., Ohno S., Okayasu I., Okeda R., Hatakeyama S., Watanabe H., Ushio K., Tsukagoshi H. Chronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brain. Acta Neuropathol. 1986;70(3-4):273–278. doi: 10.1007/BF00686083. [DOI] [PubMed] [Google Scholar]
  61. Zayed J., Gérin M., Loranger S., Sierra P., Bégin D., Kennedy G. Occupational and environmental exposure of garage workers and taxi drivers to airborne manganese arising from the use of methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline. Am Ind Hyg Assoc J. 1994 Jan;55(1):53–58. doi: 10.1080/15428119491019267. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES