title: Effects of subchronically inhaled carbon black in three species. I. Retention kinetics, lung inflammation, and histopathology.
abstract: Exposure to high concentrations of carbon black (Cb) produces lung tumors in rats, but not mice or hamsters, presumably due to secondary genotoxic mechanisms involving persistent lung inflammation and injury. We hypothesized that the lung inflammation and injury induced by subchronic inhalation of Cb are more pronounced in rats than in mice and hamsters. Particle retention kinetics, inflammation, and histopathology were examined in female rats, mice, and hamsters exposed for 13 weeks to high surface area Cb (HSCb) at doses chosen to span a no observable adverse effects level (NOAEL) to particle overload (0, 1, 7, 50 mg/m(3), nominal concentrations). Rats were also exposed to low surface area Cb (50 mg/m(3), nominal; LSCb). Retention and effects measurements were performed immediately after exposure and 3 and 11 months post-exposure; retention was also evaluated after 5 weeks of exposure. Significant decreases in body weight during exposure occurred only in hamsters exposed to high-dose HSCb. Lung weights were increased in high-dose Cb-exposed animals, but this persisted only in rats and mice up to the end of the study period. Equivalent or similar mass burdens were achieved in rats exposed to high-dose HSCb and LSCb, whereas surface area burdens were equivalent for mid-dose HSCb and LSCb. Prolonged retention was found in rats exposed to mid- and high-dose HSCb and to LSCb, but LSCb was cleared faster than HSCb. Retention was also prolonged in mice exposed to mid- and high-dose HSCb, and in hamsters exposed to high-dose HSCb. Lung inflammation and histopathology were more severe and prolonged in rats than in mice and hamsters, and both were similar in rats exposed to mid-dose HSCb and LSCb. The results show that hamsters have the most efficient clearance mechanisms and least severe responses of the three species. The results from rats also show that particle surface area is an important determinant of target tissue dose and, therefore, effects. From these results, a subchronic NOAEL of 1 mg/m(3) respirable HSCb (Printex 90) can be assigned to female rats, mice, and hamsters.
authors.affiliation: Department of Environmental Medicine, University of Rochester, NY 14642, USA. Alison_Elder@urmc.rochester.edu
authors.forename: Alison
authors.initials: A
authors.lastname: Elder
authors.forename: Robert
authors.initials: R
authors.lastname: Gelein
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Driscoll
authors.forename: Jack
authors.initials: J
authors.lastname: Harkema
authors.forename: Günter
authors.initials: G
authors.lastname: Oberdörster
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000493:pharmacokinetics* / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000336:Aerosols; D002244:Carbon