Acute and subchronic oral toxicity of fluoranthene in F-344 rats

We have studied the acute and subchronic oral toxicity of fluoranthene (FLA) in male and female F-344 rats. Single acute FLA doses of 0, 1000, 2000, and 3000 mg/kg body weight (BW) dissolved in peanut oil were administered daily by oral gavage. Subchronic doses of 0, 150, 750, and 1500 mg FLA/kg BW/day were administered for 90 days in the rats' diet. The toxicological endpoints examined included rat body and organ weights, as well as histopathological examinations of liver, kidney, stomach, prostate, testes, and ovaries; hematological parameters including red blood cell (RBC) counts, white blood cell (WBC) counts, hemoglobin (Hgb) concentration, hematocrit (Het) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC); blood chemistry including alanine amino transferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (BUN); and urine chemistry including glucose, bilirubin, specific gravity, pH, protein, urobilinogen, nitrite, occult blood, and leukocytes. In acute toxicity studies, WBC counts were significantly decreased and MCHC was significantly increased in both males and females at all doses. In the subchronic study, several of the blood cell parameters were significantly decreased in males and females after 90 days; RBCs (less than or equal to 12%), WBCs (less than or equal to 40%), Hct (less than or equal to 9%), and Hgb (less than or equal to 12%). Only BUN in males was significantly increased in the high-dose group (1500 mg FLA/kg BW/day) at the 90-day time point. None of the other clinical chemistry parameters were affected. The histopathological examinations showed significant abnormalities (tubular casts) only in the male kidney at the two highest doses after 90 days. We propose a subchronic oral no-observed-adverse-effect level (NOAEL) of 150 mg/kg BW/day for FLA in rats, based on the hematological and renal changes. Overall, our findings indicate that FLA affects specific hematological parameters and kidneys, and has a greater effect on males than females. (C) 2003 Elsevier Inc. All rights reserved.