|
|
||||
|
|
||||
|
||||
Symposia Epidemiology of Brain Tumors |
Solutia, Inc., St. Louis, MO 63166-6760 [J.J.C.]; and BP Chemicals, Inc., Warrensville Heights, OH 44128-2837 [D.E.S.]
1 Address correspondence and reprint requests to James J. Collins, Solutia, Inc., 10300 Olive Boulevard, St. Louis, MO 63166-6760.
Abstract
Acrylonitrile is a potent CNS tumorigen in rats leading to concern that it may be a tumorigen in humans. There have been 12 epidemiology studies of 37,352 workers exposed to acrylonitrile which evaluate CNS cancers. We summarize and evaluate these epidemiology studies for CNS cancers using the methods of meta-analysis. Our analyses indicate that workers with acrylonitrile exposure have null findings for CNS cancer (relative risk = 1.1, 95% confidence interval 0.8-1.5), which are in stark contrast to the projected risk to humans using the rat findings (relative risk = 3.5, 95% confidence interval 3.0-4.0). We discuss several explanations for the inconsistency between animal and human findings, including the possibility that the acrylonitrile-induced rat CNS tumors may not be relevant to humans. Given the rarity of CNS tumors in humans and a lack of understanding of the causal mechanisms of these tumors in rats, however, a more definitive conclusion will have to await additional experimental and observational data. Nevertheless, the epidemiology evidence indicates that acrylonitrile is not a potent CNS tumorigen.
References
ATSDR (Agency for Toxic Substances and Disease Registry) (1990) Toxicological Profile for Acrylonitrile TP-9002. Atlanta: ATSDR.
Benn, T., and Osborne, K. (1998) Mortality of United Kingdom acrylonitrile workers: An extended and updated study. Scand. J. Work Environ. Health 24 (Suppl. 2),71 -80.
Bigner, D.D., Bigner, S.H., Burger, P.C., Shelburne, J.D., and Friedman, H.S. (1986) Primary brain tumours in Fischer 344 rats chronically exposed to acrylonitrile in their drinking-water. Food Chem. Toxicol. 24,129 -137.[CrossRef][Web of Science][Medline]
Blair, A., and Kazerouni, N. (1997) Reactive chemicals and cancer. Cancer Causes Control 8, 473-490.[CrossRef][Web of Science][Medline]
Blair, A., Stewart, P.A., Zaebst, D.D., Pottern, L., Zey, J.N., Bloom, T.F., Miller, B., Ward, E., and Lubin, J. (1998) Mortality study of industrial workers exposed to acrylonitrile. Scand. J. Work Environ. Health 24 (Suppl. 2),25 -41.
Breslow, N.E., and Day, N.E. (1987)Statistical Methods in Cancer Research: Volume II. The Design and Analysis of Cohort Studies . Lyon: International Agency for Research on Cancer.
Chen, J.L., Walrath, J., O'Berg, M.T., Burke, C.A., and Pell, S. (1987) Cancer incidence and mortality among workers exposed to acrylonitrile. Am. J. Ind. Med. 11,157 -163.[Web of Science][Medline]
Chen, J.L., Fayerweather, W.E., and Pell, S. (1988a) Cancer incidence of workers exposed to dimethylformamide and/or acrylonitrile. J. Occup. Med. 30,813 -818.[CrossRef][Web of Science][Medline]
Chen, J.L., Fayerweather, W.E., and Pell, S. (1988b) Mortality study of workers exposed to dimethylformamide and/or acrylonitrile. J. Occup. Med. 30,819 -822.[CrossRef][Web of Science][Medline]
Collins, J.J., and Acquavella, J.F. (1998) Review and meta-analysis of studies of acrylonitrile workers. Scand. J. Work. Environ. Health 24,71 -80.
Collins, J.J., Page, L.C., Caporossi, J.C., Utidjian, H.M.D., and Lucas, L.J. (1989) Mortality patterns among employees exposed to acrylonitrile. J. Occup. Med. 31,368 -371.[Web of Science][Medline]
Davis, F.G., Malinski, N., Haenszel, W., Chang, J., Flannery, J., Gershman, S., Dibble, R., and Bigner, D.D. (1996) Primary brain tumor incidence rates in four United States regions, 19851989: A pilot study. Neuroepidemiology 15,103 -112.[CrossRef][Web of Science][Medline]
Delzell, E., and Monson, R.R. (1981) Mortality among rubber workers: III. Cause specific mortality, 19401978. J. Occup. Med. 23,677 -684.[CrossRef][Web of Science][Medline]
Delzell, E., and Monson, R.R. (1982) Mortality among rubber workers: VI. Men with potential exposure to acrylonitrile. J. Occup. Med. 24,767 -769.[Web of Science][Medline]
Dickersin, K., and Berlin, J.A. (1992) Meta-analysis:
State of the science. Epidemiol. Rev.
14,154
-176.
Dickersin, K., Min, Y.I., and Meinert, C.L. (1992)
Factors influencing publication of research results: Follow-up of applications
submitted to two institutional review boards. JAMA
267,374
-378.
Doll, R. (1991) Hazards of cancer in the chemical industry. Br. Ind. Biol. Res. Assoc. Bull. 30,183 -188.
EPA (Environmental Protection Agency) (1990) Health assessment document for acrylonitrile: General review and summary. Sci Total Environ. 90,337 -352.[CrossRef]
Greenland, S. (1987) Quantitative methods in the
review of epidemiologic literature. Epidemiol. Rev.
9, 1-30.
Greenwald, P., Friedlander, B.R., Lawrence, C.E., Hearne, T., and Earle, K. (1981) Diagnostic sensitivity biasan epidemiologic explanation for an apparent brain tumor excess. J. Occup. Med. 23,690 -694.[CrossRef][Web of Science][Medline]
Guirguis, S.S., Cohen, M.B., and Rajhans, G.S. (1984) A review of health risks in acrylonitrile industry. G. Ital. Med. Lav. 6,87 -93.[Medline]
International Agency for Research on Cancer (1979)Evaluation of the carcinogenic risk of chemical to humans: Some monomers, plastics, synthetic elastomers, and acrolein . Vol.19 , IARC, Lyon, France. February.
International Agency for Research on Cancer (1987)Evaluation of the carcinogenic risk of chemical to humans: Overall evaluations of carcinogencity: An updating of IARC monographs . Vol.1 42, Supplement 7, IARC, Lyon, France.
International Classification of Disease Ninth Revision, Clinical Modification (1988). DHHS Publication no. 801260. Washington, D.C.: U.S. Government Printing Office.
Jiang, J., Xu, Y., and Klaunig, J.E. (1998) Induction of oxidative stress in rat brain by acrylonitrile. Tox. Sciences 46,333 -341.[CrossRef]
Kedderis, G.L., and Held, S.D. (1998) Refinement of the human dosimetry description for acrylonitrile. Tox. Sciences 42,1 -S, 142 (Abstract No. 700).
Kiesselbach, N., Korallus, U., Lange, H.J., Neiss, A., and Zwingers, T. (1980) Bayer acrylonitrile study 1977. (1980) Bayer acrylonitrile study 1977. Central J. Indust. Med. Protection Labor, Indust. Hyg. Ergonomics 7,1 -46.
Koerselman, W., and van der Graaf, M. (1984) Acrylonitrile: A suspected human carcinogen. Int. Arch. Occup. Environ. Health 54,317 -324.[CrossRef][Web of Science][Medline]
Marsh, G.M. (1983) Mortality among workers from a plastics producing plant: A matched case-control study nested in a retrospective cohort study. J. Occ. Med. 25,219 -230.
Mastrangelo, G., Serena, R., and Maszia, V. (1993) Mortality from tumours in workers in an acrylic fibre factory.Occup. Med. (Lond.) 43,155 -158.
O'Berg, M.T. (1980a) Epidemiologic study of workers exposed to acrylonitrile. J. Occup. Med. 22,245 -252.[Web of Science][Medline]
O'Berg, M.T. (1980b) Epidemiologic study of cancer incidence and mortality among workers exposed to acrylonitrile at a chemical plant which produces textile fibers. University Microfilms International, Ann Arbor, Michigan.
O'Berg, M.T., Chen, J.L., Burke, C.A., Walrath, J., and Pell, S. (1985) Epidemiologic study of workers exposed to acrylonitrile: An update. J. Occup. Med. 27,835 -840.[Web of Science][Medline]
OSHA (Occupational Safety and Health Administration) (1978) Notice issuing final standard for acrylonitrile. Federal Register 4345762 , Oct. 3.
Ott, M.G., Kolesar R.C., Scharnweber, H.C., Schneider, E.J., and Venable, J.R. (1980) A mortality survey of employees engaged in the development or manufacture of styrene-based products. J. Occup. Med. 22,445 -460.[Web of Science][Medline]
Ott, M.G., Teta, M.J., and Greenberg, H.L. (1989) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment. Am. J. Ind. Med. 16,631 -643.[Web of Science][Medline]
Percy, C., Stanek, E., III, and Gloeckler, L. (1981)
Accuracy of cancer death certificates and its effect on cancer mortality
statistics. Am. J. Pub. Health
71,242
-250.
Percy, C.L., Miller, B.A., and Gloeckler, L.A. (1990) Effect of changes in cancer classification and the accuracy of cancer death certificates on trends in cancer mortality. Ann. N.Y. Acad. Sci. 609,87 -99.[Web of Science][Medline]
Poole, C. (1987) Beyond the confidence interval.
Am. J. Pub. Health 77,195
-199.
Rothman, K.J. (1994) Cancer occurrence among workers exposed to acrylonitrile. Scand. J. Work Environ. Health 20,313 -321.[Web of Science][Medline]
SAS (1993) SAS User's Guide: Basics. Version 5. Cary, N.C.: SAS Institute, Inc.
Shadish, W.R., and Haddock, C.K. (1994) Combining estimates of effect size. In: Cooper, H., and Hedges G. (Eds.), The Handbook of Research Synthesis. New York: Russell Sage Foundation. pp. 261-281.
Siemiatycki, J., Dewar, R., Nadon, L., and Gerin, M.
(1994) Occupational risk factors for bladder cancer: Results from
a case-control study in Montreal, Quebec, Canada. Am. J.
Epid. 140,1061
-1080.
Stewart, P.A., Zaebst, D., Zey, J.N., Herrick, R., Dosemeci, M., Hornung, R., Bloom, T., Pottern, L., Miller, B.A., and Blair, A. (1998) Exposure assessment for a study of workers exposed to acrylonitrile. Scand. J. Work Environ. Health 24 (Suppl. 2),42 -53.
Strother, D.E., Mast, R.W., Kraska, R.C., and Frankos, V. (1988) Acrylonitrile as a carcinogen: Research needs for better risk assessment. Ann. N.Y. Acad. Sciences 534,169 -178.[Web of Science][Medline]
Swaen, G.M.H., Bloemen, L.J.N., Slangen, J.J.M., Twisk, J., Scheffers, T., and Sturmans, F. (1992) Mortality update of workers exposed to acrylonitrile. J. Occup. Med. 34,801 -809.[CrossRef][Web of Science][Medline]
Swaen, G.M.H., Bloemen, L.J.N., Twisk, J., Scheffers, T., Slangen, J.J.M., Collins, J.J., Berge, W.J, and Sturmans, F. (1998) Mortality of workers exposed to acrylonitrile in the Netherlands. Scand. J. Work Environ. Health 24 (Suppl. 2),10 -16.
Thiess, A.M., Frentzel-Beyme, R., Link, R., and Wild, H. (1980) Mortalitatsstudie bei chemiefacharbeitern verschiedener produktionsbetriebe mit exposition auch gegenuber acrylnitril. Zentralbl. Arbeitsmed. Arbeitsschutz. Propyl Ergonomie 30,259 -267.
Thomas, T.L. (1994) Primary brain tumors associated with chemical exposure. In: Bleeker, M.L., and Hansen, J.A. (Eds.), Occupational neurology and clinical neurotoxicology. New York: Williams and Wilkins. pp.187 -206.
Thomas, T.L., and Waxweiler, R.J. (1986) Brain tumors and occupational risk factors: A review. Scand. J. Work Environ. Health 12,1 -15.
Thomas, T.L., Stewart, P.A., Stermhagen, A., Correa, P., Norman, S.A., Bleecker, M.L., and Hoover, R.N. (1987) Risk of astrocytic brain tumors associated with occupational chemical exposures. Scand. J. Work Environ. Health 13,417 -423.[Web of Science][Medline]
Velema, J.P., and Percy, C.L. (1987) Age curves of central nervous system tumor incidence in adults: Variation of shape by histologic type. J. Nat. Cancer Inst. 79,623 -629.
Ward, C.E., and Starr, T.B. (1993) Comparison of cancer risks projected from animal bioassays to epidemiologic studies of acrylonitrile-exposed workers. Regul. Toxicol. Pharmacol. 18,214 -232.[CrossRef][Web of Science][Medline]
Waxweiler, R.J., Smith, A.H., Falk, H., and Tyroler, H.A. (1981) Excess lung cancer risk in a synthetic chemicals plant. Environ. Health Perspect. 41,159 -165.[Web of Science][Medline]
Werner, J.B., and Carter, J.T. (1981) Mortality of United Kingdom acrylonitrile polymerization workers. Br. J. Ind. Med. 38,247 -253.[Web of Science][Medline]
Whysner, J., Ross, P.M., Conaway, C.C., Verna, L.K., and Williams, G.M. (1998a) Evaluation of possible genotoxic mechanisms for acrylonitrile tumorigenicity. Regul. Toxicol. Pharmacol. 27,217 -239.[CrossRef][Web of Science][Medline]
Whysner, J., Steward, R.E., Chen, D., Conaway, C.C., Verna, L.K., Richie, J.P., Ali, N., and Williams, G.M. (1998b) Formation of 8oxodeoxyguanosine in brain DNA of rats exposed to acrylonitrile. Arch. Toxicol. 72,429 -438.[CrossRef][Web of Science][Medline]
Wood, S.M., Buffler, P.A., Burau, K., and Krivanek, N. (1998) Cohort study of DuPont employees exposed to acrylonitrile. Scand. J. Work Environ. Health 24 (Suppl. 2),54 -62.[Web of Science][Medline]
Young, J.L., Percy, C.L., and Asire, A.D. (1981)Surveillance, epidemiology, and end results: Incidence and mortality data, 197377 . NCI monograph 57, NIH publication no. 812330. Washington, D.C.: U.S. Government Printing Office.
Zhou, B., and Wang, T. (1991) Historical cohort study of causes of death in a chemical fiber factory. J. Chinese Med. Univ. 20,35 -37.
This article has been cited by other articles:
![]() |
S. M. Rappaport, L. L. Kupper, and Y. S. Lin On the Importance of Exposure Variability to the Doses of Volatile Organic Compounds Toxicol. Sci., February 1, 2005; 83(2): 224 - 236. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Sweeney, M. L. Gargas, D. E. Strother, and G. L. Kedderis Physiologically Based Pharmacokinetic Model Parameter Estimation and Sensitivity and Variability Analyses for Acrylonitrile Disposition in Humans Toxicol. Sci., January 1, 2003; 71(1): 27 - 40. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|