PH19 Environmental Health Toxicology
Exhibit Hall
8:00 AM - Thursday, 13 November 2003
(PH178) Disposition of 5-Nitroacenaphthene in F-344 Rats.
Austin, A1, Nyanda, A1, Ramesh, A1, 1 Meharry Medical College, Nashville, TN, USA
ABSTRACT- Acenaphthene, a polycyclic aromatic hydrocarbon, occurs naturally in the environment by carbonization or pyrolysis of organic materials. With excess NO2 in the atmosphere, acenaphthene becomes nitrated, thus, producing 3- and 5-nitroacenaphthene (3- and 5-NAN). 5-NAN is the predominant compound formed and is present in environmental samples such as ambient air particulates, cigarette tar, diesel exhaust, and in occupational settings such as aluminum smelters, the rubber and tire industry, and power generators. 5-NAN is a suspected carcinogen and/or mutagen. Whether this compound is accumulated in tissues or undergoes rapid biological disposition and/or secreted into the bile, eventually being eliminated through urine or feces is not yet known. The objective of this study is to understand the disposition of pure 5-NAN in F-344 rats. This compound was administered at a dose of 50mg/kg via oral gavage and the animals were sacrificed at specific time intervals ranging from 0 to 15 hours. We used HPLC to quantify trace concentrations of 5-NAN in biological tissues and fluids. The extraction procedure involved homogenization of different tissues and liquid-liquid extractions using water, methanol, and chloroform (3:10:5). After centrifugation of the extracts, the organic phases were concentrated under N2 and reconstituted with acetonitrile. The results of the time course study show that 5-NAN, the parent compound, is detected in the brain at a concentration of 11ng/g but not in the testes or adipose tissue at 1 h. This suggests that 5-NAN crosses the blood-brain barrier but not the testicular-blood barrier. 5-NAN is not sequestered in adipose tissue prior to the 2 h time point. There was a biphasic distribution of 5-NAN in the liver at 0.5, 2, and 6 h time points post-administration with concentrations of 3.49ng/g, 0.88ng/g, and 48ng/g, respectively. A similar biphasic distribution was seen in the small intestine at 0.5, 2, and 6 h time points post-administration with concentrations of 5.74ng/g, 63ng/g, and 16ng/g, respectively. In this study, we were able to show that trace concentrations of 5-NAN are detectable and quantifiable in biological tissues. We believe that 5-NAN, a suspected carcinogen, is sequestered in tissues and can cause organ-specific toxicity in F-344 rats.
Key words: disposition, nitrated polycyclic aromatic hydrocarbon, 5-nitroacenaphthene, acenaphthene