A comparison of the acute neuroactive effects of dichloromethane, 1,3-dichloropropane, and 1,2-dichlorobenzene on rat flash evoked potentials (FEPs).
Previous research showed that acute exposure to dichloromethane (DCM) produced a selective reduction in peak N30 of flash evoked potentials (FEPs) in rats. In contrast, acute exposures to p-xylene or toluene selectively reduced FEP peak N160. The present experiments compared the effects of DCM (log P = 1.25; oil:water partition coefficient), 1,3-dichloropropane (DCP; log P = 2.00), and 1,2-dichlorobenzene (DCB; log P = 3.38) on FEPs recorded from adult Long-Evans rats. Before administration of test compounds, FEPs were recorded for five daily sessions to develop FEP peak N160. Test compounds were dissolved in corn oil and administered i.p. at doses based on proportions of their LD50 values. The doses were: DCM, 0, 57.5, 115, 230, or 460 mg/kg; DCP, 0, 86, 172, 343, or 686 mg/kg; and DCB, 0, 53, 105, 210, or 420 mg/kg. Testing times after dosing varied among compounds and were based on pilot studies to measure both the times of peak effect and recovery. Each solvent produced significant changes in the latency and amplitude of multiple components of the FEP waveforms. However, the predominant effect of DCM was to reduce the amplitude of peak N30 (ED50 = 326.3 mg/kg), that of DCP was to reduce both peaks N30 (ED50 = 231.0 mg/kg) and N160 (ED50 = 136.8 mg/kg), and that of DCB was to reduce peak N160 (ED50 = 151.6 mg/kg). There was no consistent relationship between log P values and the potency of the compounds to alter FEP peaks N30 and N160. The results suggest that organic solvents have multiple acute effects on the function of the central nervous system, which are not predictable solely by the compound's lipid solubility.
Herr
D W
DW
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. Herr.david@epamail.epa.gov
Boyes
W K
WK
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008752:Methylene Chloride / Q000008:administration & dosage / Q000633:toxicity*; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D012997:Solvents / Q000633:toxicity
D002722:Chlorobenzenes; D007306:Insecticides; D012997:Solvents; D008752:Methylene Chloride; C004726:2-dichlorobenzene; C067434:1,3-dichloropropane; D011407:Propane