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4-Vinylphenol-Induced Pneumotoxicity and Hepatotoxicity in Mice

School of Health Sciences, Purdue University, West Lafayette, Indiana, gcarlson{at}purdue.edu

Mary Ullman

School of Health Sciences, Purdue University, West Lafayette, Indiana

Nancy A. Mantick

School of Health Sciences, Purdue University, West Lafayette, Indiana

Paul W. Snyder

School of Veterinary Medicine, Purdue University, West Lafayette, Indiana

4-Vinylphenol (4-hydroxystyrene , 4-ethenylphenol , 4-VP) occurs naturally in some foods and has been used as a flavoring agent in food products. It is used synthetically in the production of polymers and resins. It has also been reported to be a minor metabolite of styrene in rats and humans. Varying doses of 4-vinylpheno l were administered ip to mice. Hepatotoxicity was assessed by measuring serum sorbitol dehydrogenas e (SDH) and by light microscopy. Pneumotoxicity was assessed by measuring proteins, cells, and lactate dehydrogenas e activity in bronchoalveolar lavage fluid (BALF) and by light microscopy. 4-VP caused a dose-dependent increase in serum SDH and mild hepatocellular swelling. It caused an increase in cell number and lactate dehydrogenas e activity in BALF. Microscopically, there was widespread and severe necrosis of the bronchioles by 12 hours. Re-epithelialzation of the bronchioles was evident by 48 hours. These studies indicate that 4-vinylphenol is both hepatotoxi c and pneumotoxic.

Key Words: 4-Vinylphenol • liver • lung • pneumotoxicity • hepatotoxicity.

References

• Bakke OM, Scheline RR (1970). Hydroxylation of aromatic hydrocarbons in the rat. Toxicol Appl Pharmacol 16: 691—700.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Berger PJ, Sanders EH, Gardner PD, Negus NC (1977). Phenolic plant compounds functioning as reproductive inhibitors in Microtus montanus. Science 195: 575—577.[Abstract/Free Full Text]
• Bett KL, Vercellotti JR, Lovegren NV, Sanders TH, Hinsch RT, Rasmussen GK (1994). A comparison of the flavor and compositional quality of peanuts from several origins. Food Chem 51: 21—27.[CrossRef]
• Bond JA (1989). Review of the toxicology of styrene. Critical Rev Toxicol 19: 227—249.[Medline] [Order article via Infotrieve]
• Boogaard PJ, de Kloe KP, Sumner SCJ, van Elburg PA, Wong BA ( 2000). Disposition of [ring-U-14C]styrene in rats and mice exposed by recirculating nose-only inhalation. Toxicol Sci 58: 161—172.[Abstract/Free Full Text]
• Burdock GA (1995). Fenaroli's Handbook of Flavor Ingredients, vol 3, CRC Press, Boca Raton, Florida, p 796.
• Carlson GP, Perez Rivera AA, Mantick NA (2001). Metabolism of the styrene metabolite 4-vinylphenol by rat and mouse liver and lung. J Toxicol Environ Health 63: 541—551.[CrossRef][Web of Science]
• Cruzan G., Cushman JR, Andrews LS, Granville GC, Johnson KA, Bevan C., Hardy CJ, Coombs DW, Mullins PA, Brown WR (2001). Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks. J Appl Toxicol 21: 185—198.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Cruzan G., Cushman JR, Andrews LS, Granville GC, Johnson KA, Hardy CJ, Coombs DW, Mullins PA, Brown WR (1998). Chronictoxicity/oncogenicity study of styrene in CD rats by inhalation exposure for 104 weeks. Toxicol Sci 46: 266—281.[Abstract/Free Full Text]
• Cruzan G., Cushman JR, Andrews LS, Granville GC, Miller RR, Hardy CJ, Coombs DW, Mullins PA (1997). Subchronic inhalation studies of styrene in CD rats and CD-1 mice. Fundam Appl Toxicol 35: 152—165.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Gadberry MG, DeNicola DB, Carlson GP (1996). Pneumotoxicity and hepatotoxicity of styrene and styrene oxide. J Toxicol Environ Health 48: 273— 294.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Gerlach U. (1983). Sorbitol dehydrogenase. In: Methods of Enzymatic analysis, 3rd ed, Bergmeyer HU (ed). Verlag Chemie, Weinheim, pp 112— 117.
• Green T., Toghill A., Foster JR (2001). The role of cytochromes P-450 in styrene induced pulmonary toxicity and carcinogenicity. Toxicology 169: 107—117.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Johanson G., Ernstgard L., Gullstrand E., Lof A., Osterman-Golkar S., Williams CC, Sumner SCJ (2000). Styrene oxide in blood, hemoglobin adducts, and urinary metabolites in human volunteers exposed to 13C8-styrene vapors. Toxicol Appl Pharmacol 168: 36—49.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Morgan DL, Mahler JF, Dill JA, Price HC, O'Connor RW, Adkins B. (1993a). Styrene inhalation toxicity studies in mice. III. Strain differences in susceptibility. Fundam Appl Toxicol 21: 326—333.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Morgan DL, Mahler JF, O'Connor RW, Price HC, Adkins B. (1993b). Styrene inhalation toxicity studies in mice. I. Hepatotoxicity in B6C3F1 mice. Fundam Appl Toxicol 20: 325—335.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pantarotto C., Fanelli R., Bidoli F., Morazzoni P., Salmona M., Szczawinska K. (1978). Arene oxides in styrene metabolism, a new perspective in styrene toxicity? Scand J Work Environ Health 4, suppl. 2: 67—77.[Medline] [Order article via Infotrieve]
• Pfaffli P., Hesso A., Vainio H., Hyvonen M. (1981). 4-Vinylphenol excretion suggestive of arene oxide formation in workers occupationally exposed to styrene. Toxicol Appl Pharmacol 60: 85—90.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ponomarkov V., Tomatis L. (1978). Effects of long-term oral administration of styrene to rats and mice. Scand J Work Environ Health 4 (suppl. 2): 127—135.[Web of Science][Medline] [Order article via Infotrieve]
• Redinbaugh MG, Turley RB (1986). Adaptation of the bicinchoninic acid protein assay for use with microtiter plates and sucrose gradient fractions. Anal Biochem 153: 267—271.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• RTECS, Registry of Toxic Effects of Chemicals (2000). National Institute for Occupational Safety and Health, Cincinnati, OH.
• Vassault A. (1983). Lactate dehydrogenase. UV method with pyruvate and NADH. In: Methods of Enzymatic Analysis, 3rd ed, Bergmeyer HU (ed). Verlag Chemie, Weinheim, pp 118—125.
• Van Winkle LS, Buckpitt AR, Nishio SJ, Isaac JM, Plopper CG (1995). Cellular response in naphthalene-induce d Clara cell injury and bronchiolar epithelial repair in mice. Am J Physiol 269: L800—L818.[Web of Science][Medline] [Order article via Infotrieve]
• Watabe T., Hiratsuka A., Sone T., Ishihama T., Endoh K. (1984). Hepatic microsomal oxidation of styrene to 4-hydroxystyrene 7,8-glycol via 4-hydroxystyrene and its 7,8-oxide as short-lived intermediates. Biochem Pharmacol 33: 3101—3103.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Withycombe DA, Lindsay RC, Stuiber DA (1978). Isolation and identification of volatile components from wild rice grain (Zizania aquatica). J Agric Food Chem 26: 816—822.[CrossRef][Web of Science]

Toxicologic Pathology, Vol. 30, No. 5, 565-569 (2002)
DOI: 10.1080/01926230290105866


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Carlson, G. P. Articles by Snyder, P. W. Search for Related Content PubMed PubMed Citation Articles by Carlson, G. P. Articles by Snyder, P. W. Social Bookmarking                         What's this?