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The present study has been undertaken to examine whether exposure to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound, influences the metabolism of fluoranthene (FLA), another PAH compound. Microsomes were isolated from the adipose tissue of mice that received 50 μg/kg BaP and incubated with FLA (3 µM) alone; FLA in combination with BaP at equimolar concentrations, and a control group that received nothing. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA metabolites by reverse-phase HPLC with fluorescence detection. The rate of FLA metabolism (pmol of metabolite/min/mg protein) was increased when microsomes from BaP-treated mice were exposed to FLA alone and FLA in combination with BaP, compared to controls. On the other hand, the difference in FLA metabolic rate between microsomes that were exposed to FLA + BaP was higher than the ones that received FLA. The microsomes from BaP-pre-treated mice produced a considerably higher proportion of FLA 2, 3-diol, and 2, 3 D FLA when microsomes were incubated with FLA. There were no differences in the FLA metabolite types formed when BaP-pre-treated mice were co-incubated with BaP and FLA than with FLA alone. The enhanced biotransformation of FLA as a result of prior and concomitant exposure to BaP may have implications for assessment of risks arising from human exposure to PAH mixtures. [ABSTRACT FROM AUTHOR]

We have studied the acute and subchronic oral toxicities of benzo[a]pyrene (BaP) in male and female F-344 rats. Single acute BaP doses of 0, 100, 600, and 1000 mg /kg dissolved in peanut oil were administered by oral gavage. Subchronic doses of 0, 5, 50, and 100 mg/kg/day were administered for 90 days in the animal diet. The major toxicological endpoints examined included animal body weight, selected tissue weights, and histopathological examinations (liver, kidney, stomach, prostate, testes, and ovaries). In addition, we examined blood elements: red blood cells (RBC), white blood cells (WBC), hemoglobin (Hgb), hematocrit (Hct), mean cell volume (MCV), mean cell hematocrit (MCH), and mean cell hemoglobin concentration (MCHC), blood chemistry (ALT, AST, and BUN), and urine chemistry (glucose, bilirubin, specific gravity, pH, protein, urobilinogen, nitrite, occult blood, and leucocytes). In the acute study, WBC were significantly decreased and mean cell-hemoglobin concentration was significantly increased, both in males only. The liver:body weight ratio was significantly increased in males and females (up to 30%). None of the blood chemistry or urine parameters were significantly affected. In the subchronic study, mean body weight was significantly decreased in males only (13%), and the liver:body weight ratio in males was significantly increased. Several of the blood elements were significantly decreased in males and females after 90 days; RBCs (up to 10%), Hct (up to 12%), and Hgb (up to 12%). For blood chemistry parameters (AST, ALT, BUN), only BUN in males was significantly increased in the high dose group (100 mg/kg) at the 90 day time point. The histopathological examination of selected tissues showed significant abnormalities (tubular casts) only in the male kidney, at the 2 highest doses, after 90 days. These studies indicate that the acute and subchronic toxicities of BaP are relatively low, BaP affects specific blood elements and organs, and BaP has a greater effect on males than females. The induction of non-carcinogenic kidney abnormalities in males only may be indicative of renal dysfunction and further substantiates an apparent sex difference in tolerance to BaP. [ABSTRACT FROM PUBLISHER]