Regional distribution and kinetics of vinyl acetate hydrolysis in the oral cavity of the rat and mouse.
Vinyl acetate is an ester that is used to make polyvinyl acetate based polymers that are used in the manufacture of latex paints and adhesives. Chronic oral exposure to high concentrations of vinyl acetate induces oral tumors in rodents. Since carboxylesterase-dependent hydrolysis of VA to acetic acid and acetaldehyde has been implicated in the nasal inhalation carcinogenesis of this ester, the potential for oral mucosa of the F344 rat and BDF mouse to hydrolyze VA was examined. Homogenates were prepared by scraping the mucosa from four regions of the oral cavity: dorsal interior (all tissues interior to the teeth), dorsal tongue surface, ventral interior (sublingual area and lower interior tissues) and exterior (all tissues exterior to the teeth). The oral cavity was rinsed once with saline prior to dissection to determine if oral secretions possessed metabolic capacity. Aliquots of the homogenates or rinse fluid were incubated for 30 min with varying concentrations of vinyl acetate (0.05-10 mM), and the production of acetaldehyde was quantitated by HPLC. All tissue regions possessed VA hydrolysis activity. In both species the hydrolysis activity was greatest in the dorsal interior region (Vmax of 90 and 6 nmol/min in the rat and mouse, respectively, Km values of 0.5 and 0.9 mM). Activity in the other oral regions was 2-15-fold lower. Activity was observed in the rinse fluid, but was 20-fold or more lower than the dorsal interior region. Finally, solutions of vinyl acetate were placed in the mouth of anesthetized rats for 10 min and then analyzed for acetaldehyde concentrations. Acetaldehyde was detected in these solutions providing evidence that metabolism of this ester occurs in vivo in oral tissues.
Morris
John B
JB
Toxicology Program, Department of Pharmaceutical Sciences, University of Connecticut, Box U-2092, Storrs, CT 06269, USA. morris@uconnvm.uconn.edu
Symanowicz
Peter
P
Sarangapani
Ramesh
R
D000079:Acetaldehyde / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D004396:Coloring Agents / Q000493:pharmacokinetics; D005070:Evans Blue / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014753:Vinyl Compounds / Q000493:pharmacokinetics* / Q000633:toxicity
D004396:Coloring Agents; D014753:Vinyl Compounds; D005070:Evans Blue; D000135:Acid Phosphatase; D000079:Acetaldehyde; C011566:vinyl acetate