Assessment of the hepatotoxicity of acute and short-term exposure to inhaled p-xylene in F-344 rats.
Due to the ubiquitous presence of p-xylene in air and the existing uncertainty regarding its hepatotoxic potential, we examined the effect of acute and short-term exposure to inhaled p-xylene on the liver. Male F-344 rats were exposed to 0 or to 1600 ppm p-xylene, 6 h/d, for 1 or 3 d. Exposure to inhaled p-xylene caused no histopathological evidence of hepatic damage and had little or no effect on the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase, and total bilirubin. Exposure to p-xylene for 1 or 3 d resulted in an increase in relative liver weight on d 1 post-exposure. The concentration of hepatic cytochrome P-450 was increased by both p-xylene exposure regimens on d 1 postexposure and had returned to control levels by d 3 following the single p-xylene exposure and by d 2 following the 3-d exposure. These observations provide consistent evidence that acute and short-term exposure to 1600 ppm p-xylene by inhalation did not produce overt hepatotoxicity but resulted in a significant increase in the concentration of hepatic cytochrome P-450, the principal enzyme system involved in the metabolic biotransformation of xenobiotics.
Simmons
J E
JE
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Allis
J W
JW
Grose
E C
EC
Seely
J C
JC
Robinson
B L
BL
Berman
E
E
D000280:Administration, Inhalation; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001273:Atmosphere Exposure Chambers; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D014992:Xylenes / Q000008:administration & dosage / Q000633:toxicity*
D014992:Xylenes; C031286:4-xylene; D003577:Cytochrome P-450 Enzyme System; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase