Fluoranthene-induced neurobehavioral toxicity in F-344 rats.
Fluroanthene (FLA) is a nonalternant representative of polycyclic aromatic hydrocarbon (PAH) family of toxic chemicals that are widely distributed in the environment. The effects of single acute doses of FLA on locomotor activities and the functional observational battery (FOB) were investigated in 8-week-old male and female F-344 rats. FLA was dissolved in peanut oil and administered by oral gavage as single doses of 0, 100, 200 and 400 mg/kg. Immediately after dosing, animals were placed in activity cages and monitored for nocturnal locomotor activities at 2-hour intervals and for a total of 12 hours for 5 consecutive days post treatment. Significant (p <.001) reductions in horizontal activity, total distance, stereotypy, and vertical activity were observed. Rats administered acute doses of FLA were also subjected to the functional observational battery (FOB) tests that were conducted at 0, 2, 4, 6, 12, 24, 48, 72 and 96 hours after FLA administration. FLA-exposed animals showed significant (p <.05) dysfunction, including ataxia, decreased grip strengths, increased landing foot splay, loss of aerial righting, increased urination and defecation, and decreased responses to sensory stimuli in both sexes. Neurological deficits in the FOB peaked at 6 hours and lasted for 48 hours post treatment. Significant (p <.05) gender-related differences were noted in behavioral end points, with male rats showing greater sensitivity to FLA administration than females, as evidenced by their greater mean severity scores in FOB parameters and lower motor activity counts. These findings suggest that FLA can produce behavioral toxicity in F-344 rats and that motor activity and the FOB may serve as end points for the detection of acute FLA toxicity.
Saunders
Crystal R
CR
Department of Pharmacology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Shockley
Dolores C
DC
Knuckles
Maurice E
ME
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D004785:Environmental Pollutants; D005449:Fluorenes; C007738:fluoranthene