ToxSci Advance Access originally published online on September 21, 2005
Toxicological Sciences 2005 88(2):614-629; doi:10.1093/toxsci/kfi327
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Effects of Subchronically Inhaled Carbon Black in Three Species. I. Retention Kinetics, Lung Inflammation, and Histopathology
* Department of Environmental Medicine, University of Rochester, Rochester, New York 14642; Department of Pediatrics, University of Rochester, Rochester, New York 14642; Proctor and Gamble Co., Cincinnati, Ohio 45202; and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824
Received July 28, 2005; accepted September 13, 2005
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/m3, nominal concentrations). Rats were also exposed to low surface area Cb (50 mg/m3, 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/m3 respirable HSCb (Printex 90) can be assigned to female rats, mice, and hamsters.
Key Words: Carbon black; particle retention; species comparison; particle overload; inflammation; histopathology.
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