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4-Vinylphenol (4-hydroxystyrene , 4-ethenylphenol , 4-VP) occurs naturally in some foods and has been used as a avoring 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 bronchoalveola r lavage uid (BALF) and by light microscopy. 4-VP caused a dose-dependen t 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.

Styrene is a widely used chemical in the reinforced plastics industry and in polystyrene production. Its primary metabolic pathway to styrene oxide and then to styrene glycol, which is further metabolized to mandelic acid and phenylglyoxylic acid, has been well studied. However, a few studies have reported finding a minor metabolite, 4-vinylphenol (4-VP), in rat and human urine. The present studies sought to determine if the formation and metabolism of 4-VP in rat and mouse liver and lung preparations could be measured. When styrene was incubated with hepatic and pulmonary microsomal preparations, 4-VP formation could not be measured in these preparations. However, considerable 4-VP metabolizing activity, as determined by the loss of 4-VP, was observed in both mouse and rat liver and lung microsomal preparations. 4-Vinylphenol metabolizing activity in mouse liver microsomes was three times greater than that in rat liver microsomes, and activity in mouse lung microsomes was eight times greater than that in rat lung microsomes. This activity was completely absent in the absence of NADPH. Studies with cytochrome P-450 inhibitors indicated the involvement of CYP2E1 and CYP2F2. Induction of CYP2E1 by pyridine resulted in an increase in 4-VP metabolism by mouse hepatic microsomes but not by pulmonary microsomes. The metabolite(s) formed as a result of this oxidative pathway remain to be identified. In additional studies, glutathione conjugation appeared to be involved in 4-VP metabolism with the highest activity being in mouse lung, with or without the addition of NADPH.