title: Evaluation of potential modes of action of inhaled ethylbenzene in rats and mice.
abstract: Potential factors underlying the tumorigenic activity of ethylbenzene (EB) were examined in F344 rats and B6C3F1 mice inhaling 750 ppm EB vapor 6 h/day, 5 days/week, for one or four weeks. Target tissues (kidneys of rats and livers and lungs of mice) were evaluated for changes in organ weights, mixed function oxygenases (MFO), glucuronosyl transferase activities, S-phase DNA synthesis, apoptosis, alpha2u-globulin deposition, and histopathology. In male rats, kidney weight increases were accompanied by focal increases in hyaline droplets, alpha2u-globulin, degeneration, and S-phase synthesis in proximal tubules. In female rats, only decreased S-phase synthesis and MFO activities occurred. In mice, increased liver weights were accompanied by hepatocellular hypertrophy, mitotic figures, S-phase synthesis, and enzyme activities. S-phase synthesis rates in terminal bronchiolar epithelium were elevated and accompanied by loss of MFO activity. Exposure to a nontumorigenic level of 75 ppm for one week caused few changes. These data, considered with the general lack of EB genotoxicity, suggest a mode of tumorigenesis dependent upon increased cell proliferation and altered population dynamics in male rat kidney and mouse liver and lungs. A similar response in the kidneys of female rats appears to require a longer exposure period than was employed.
authors.affiliation: Toxicology & Environmental Research and Consulting, Building 1803, The Dow Chemical Company, Midland, Michigan 48674, USA. wtstott@dow.com
authors.forename: William T
authors.initials: WT
authors.lastname: Stott
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Rainer
authors.initials: R
authors.lastname: Bahnemann
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Day
authors.forename: Randal J
authors.initials: RJ
authors.lastname: McGuirk
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D019570:Inhalation Exposure; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016196:S Phase / Q000187:drug effects
chemical_list: D001555:Benzene Derivatives; D002273:Carcinogens; D004247:DNA; D006899:Mixed Function Oxygenases; C004912:ethylbenzene