4-Vinylphenol-Induced Pneumotoxicity and Hepatotoxicity in Mice

Abstract

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.

Effects of styrene and its metabolites on different lung compartments of the mouse—cell proliferation and histomorphology

“…No interpretation can be oVered at this time for the signiWcant decreases of cell proliferation rates in the bronchiolar/bronchi compartments after treatment with phenylacetaldehyde and phenylacetic acid. The absence of signiWcant eVects of 1-phenylethanol and 2-phenylethanol in this study is well in line with the absence of pneumo-and hepatotoxicity in mice observed by Carlson et al (2002a). These authors also reported that there was no pneumotoxicity induced by phenylacetaldehyde in mice.…”

Lung disease associated with occupational styrene exposure

“…Styrene has been shown to cause both lung and liver toxicity in a variety of murine models . Animal studies suggest that styrene is metabolized and oxidized via the P450 system to styrene oxide, which is then metabolized to other metabolites (such as 4‐vinylphenol) or conjugated with glutathione.…”

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Flavouring Group Evaluation 22 (FGE.22): Ring‐substituted phenolic substances from chemical groups 21 and 25 (Commission Regulation (EC) No 1565/2000 of 18 July 2000)

“…Microsomal preparations of mouse liver and lung appeared to be far more active than microsomes from the same tissues in the rat. In addition, metabolism of 4-vinyl-phenol in mouse lung microsomes was also observed to occur with glutathione, also in absence of an active cytochrome P450 system (Carlson et al, 2001;Carlson et al, 2002). However, 4-vinylphenol is not a potent GSH-depleting agent in liver and lung tissue in vivo (Turner et al, 2005 ).…”