Vehicle-dependent disposition kinetics of fluoranthene in Fisher-344 rats. 2008

Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
Department of Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.

The objective of this study was to evaluate how the vehicles of choice affect the pharmacokinetics of orally administered Fluoranthene [FLA] in rats. Fluoranthene is a member of the family of Polycyclic Aromatic Hydrocarbon chemicals. Fluoranthene exposure to humans may occur as a result of cigarette smoking, consumption of contaminated food and water, heating woods in stoves and boilers, industrial sources such as coal gasification, carbon and graphite electrode manufacturing. Adult male Fisher-344 rats were given single oral doses of 25 and 50 microg/kg FLA in tricaprylin, peanut oil, cod liver oil, Tween 80/isotonic saline (1:5) and 2% Alkamuls-EL620 through gavage. After administration, the rats were housed individually in metabolic cages and sacrificed at 2, 4, 6, 8, 10 and 12 hours post FLA exposure. Blood, lung, liver, small intestine, adipose tissue samples, urine, and feces were collected at each time point. Samples were subjected to a liquid-liquid extraction using methanol, chloroform, and water. The extracts were analyzed by a reverse-phase HPLC, equipped with a fluorescence detector. The results revealed a dose-dependent increase in FLA concentrations in plasma and tissues for all the vehicles used. Plasma and tissue FLA concentrations were greater for peanut oil; cod liver oil, and tricaprylin vehicles compared to Alkamuls (p < 0.05), and Tween 80/isotonic saline (1:5). Most of the FLA administered through peanut oil, cod liver oil and tricaprylin was cleared from the body by 8 hours (90%) and 12 hours (80%) post administration for the 25 microg/kg and 50 microg/kg dose groups, respectively. With both doses employed, the metabolism of FLA was highest when cod liver oil was used as a vehicle and lowest in vehicles containing detergent/water [cod liver oil > peanut oil > tricaprylin > alkamuls > Tween 80/isotonic saline (1:5)]. These findings suggest that uptake and elimination of FLA is accelerated when administered through oil-based vehicles. The low uptake of FLA from Alkamuls and Tween 80/isotonic saline may have been a result of the poor solubility of the chemical. In summary, our findings reiterate that absorption characteristics of FLA were governed by the dose as well as the dosing vehicle. The vehicle-dependent bioavailability of FLA suggests a need for the judicious selection of vehicles in evaluating oral toxicity studies for risk assessment purposes.

UI MeSH Term Description Entries
D008297 Male Males
D010938 Plant Oils Oils derived from plants or plant products. Oils, Plant,Oils, Vegetable,Plant Oil,Vegetable Oil,Vegetable Oils,Oil, Plant,Oil, Vegetable
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002210 Caprylates Derivatives of caprylic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated eight carbon aliphatic structure. Caprylate,Octanoates,Caprylic Acids,Octanoic Acids,Acids, Caprylic,Acids, Octanoic
D003060 Cod Liver Oil Oil obtained from fresh livers of the cod family, Gadidae. It is a source of VITAMIN A and VITAMIN D. Liver Oil, Cod,Oil, Cod Liver
D004777 Environment The external elements and conditions which surround, influence, and affect the life and development of an organism or population. Environmental Impact,Environmental Impacts,Impact, Environmental,Impacts, Environmental,Environments
D005449 Fluorenes A family of diphenylenemethane derivatives.
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.

Related Publications

Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
January 2003, International journal of toxicology,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
March 1982, Toxicology and applied pharmacology,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
November 1991, Journal of gerontology,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
February 2020, Neuroscience,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
June 2005, Xenobiotica; the fate of foreign compounds in biological systems,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
February 2010, Journal of neurochemistry,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
January 1988, Journal of pineal research,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
January 1982, Fundamental and applied toxicology : official journal of the Society of Toxicology,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
September 2004, Ecotoxicology and environmental safety,
Deacqunita L Harris, and Darry B Hood, and Aramandla Ramesh
January 1985, Journal of andrology,
Copied contents to your clipboard!