Ferrocene: Disposition following nose-only inhalation by the rat

Ferrocene (FCN) is a volatile solid organometallic proposed for use as an anti-knock additive in gasoline. Such use would provide significant potential for human exposure via inhalation. Nose-only exposure of male F344 rats over 6 h to constant concentrations of 5 and 25 ng of [14C]FCN/mL air was conducted by blending correct proportions of an air stream concentrated with [14C]FCN vapor with one that was FCN free. Fractional pulmonary absorption of FCN was estimated to be ca. 66 and 55% with concentrations of 14C in blood increasing steadily throughout the exposure period to 80 and 370 ng-eq of FCN/mL, respectively. Disappearance of 14C from the blood was multiphasic (terminal t1/2=∼2 d) following inhalation exposure, resulting in blood concentrations of 10 and 50 ng-eq of FCN/mL 72 h after end of exposure. More than 80% of the recovered 14C was in the 0-72 h urine, approximately half of which was a single metabolite (radio-HPLC). Unchanged FCN was excreted in only minor amounts (<5%). Small amounts of 14C were also excreted in feces (ca. 10% of total) and breath (ca. 4% of total). Neither lung nor nasopharynx had tissue to blood ratios of 14C>3 72 h after exposure. Similar disposition was shown after an iv bolus of 1.0 mg of [14C]FCN/kg body weight