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Toxicological Sciences 58, 161-172 (2000)
Copyright © 2000 by the Society of Toxicology

Respiratory Toxicology

Disposition of [Ring-U-14C]styrene in Rats and Mice Exposed by Recirculating Nose-Only Inhalation

P. J. Boogaard*,1, K. P. de Kloe*, S. C. J. Sumner{dagger}, P. A. van Elburg* and B. A. Wong{dagger}

* Department of Molecular Toxicology, Shell Research and Technology Center, Amsterdam, Shell International Chemicals B.V., P.O. Box 1030 BN Amsterdam, The Netherlands; and {dagger} Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709

The disposition of styrene was studied in a group of 12 Sprague Dawley rats and two groups of 30 CD1 mice exposed separately to 160 ppm [ring-U-14C]styrene of high specific radioactivity of 1.92 TBq x mol–1 (52 Ci x mol–1) for 6 h. A nose-only exposure system was successfully adapted to (1) recirculate a portion of the flow to limit the amount of 14C-styrene required, and (2) avoid any polymerization of the compound. The mean uptake of styrene in rats was 113 ± 7 µmol x kg–1 x h–1 and stable over time. The mean uptake in mice was higher, 189 ± 53 and 183 ± 76 µmol x kg–1 x h–1, for the first and second mouse inhalation experiment, but decreased steadily over time. Some of the mice, but none of the rats, showed signs of overt toxicity. The overall excretion of styrene and its metabolites was quantitatively similar in rats and mice. Urinary excretion was the primary route of excretion while fecal excretion accounted for only a very small part of the radioactivity. There was, however, a significant difference between mice and rats in the exhalation of 14CO2, which must have resulted from opening and subsequent breakdown of the aromatic ring. In mice the exhalation of 14CO2 accounted for 6.4 ± 1.0 and 8.0 ± 0.5% of the styrene retained during the first and second mouse inhalation experiment. In rats, exhalation of 14CO2 accounted for only 2.0 ± 0.7% of the retained styrene. Together with the results from the quantitative whole-body autoradiography (showing significantly higher binding in mouse lung and nasal passages compared to rat) the larger production of 14CO2 might be indicative of the formation of reactive ring-opened metabolites in the mouse lung, which, in turn, might be related to the observed development of bronchioalveolar tumors and nasal effects in mice exposed to styrene.

Key Words: styrene; inhalation exposure; disposition; autoradiography; Sprague Dawley rats; CD1 mice; metabolism; CO2; urine; feces.


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