4-Vinylphenol-induced pneumotoxicity and hepatotoxicity in mice.

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-vinylphenol were administered ip to mice. Hepatotoxicity was assessed by measuring serum sorbitol dehydrogenase (SDH) and by light microscopy. Pneumotoxicity was assessed by measuring proteins, cells, and lactate dehydrogenase 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 dehydrogenase 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 hepatotoxic and pneumotoxic.