Effects of inhaled 1,1,1-trichloroethane on the regional brain cyclic GMP levels in mice and rats.
As it is known that volatile organic compounds (VOCs) exhibit differential dispositions among anatomically discrete brain regions in rodents as well as in humans, potential toxicological consequences of this pharmacokinetic feature were evaluated using measurements of cyclic GMP (glucose monophosphate). With the knowledge of 1, 1, 1-trichloroethane (TRI) uptake and distribution in the various brain regions, cyclic GMP was evaluated due to (1) known susceptibility to the effects of organic solvents, (2) pivotal physiological role in perpetuating changes in neurochemical pathways, and (3) possible involvement with neurobehavioral functions, whose disruption is one of the primary health effects associated with solvent exposures. Male CD-1 mice and Sprague-Dawley rats inhaled 5000 ppm TRI for 40 and 100 min in dynamic inhalation exposure chambers, and the brain was procured from the animals immediately following termination by microwave irradiation. After 40 min of TRI inhalation, significant decreases in cyclic GMP levels were found in the cerebellum of both species, 55% and 58%, respectively, relative to the controls. There was a further decrease in both species after 100 min of TRI inhalation. Smaller decreases in cyclic GMP were seen in the cortex of both species at both time points of measurement. A decrease in cyclic GMP was observed in the medulla oblongata of mice but not in rats after 40 min of exposure. Due to its signal transduction functions, it might be expected that the effects of TRI on cyclic GMP levels could directly impact neurological function. Comparison of the results from this study with the regional brain distribution of TRI and its effects on behavioral performance seen in previous studies by this laboratory appeared to indicate that alterations in brain cyclic GMP levels are only involved with the neurobehavioral toxicity of TRI in an indirect fashion; consequently, behavioral effects and decreases in cyclic GMP do not appear to be directly related to regionally differential dispositions of TRI in rodent brain.
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Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens 30602-2352, USA.
Dallas
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D000280:Administration, Inhalation; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D014240:Trichloroethanes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D006152:Cyclic GMP