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Effects of Acute and Repeated Exposures to Aroclor 1254 in Adult Rats: Motor Activity and Flavor Aversion Conditioning
Authors:Nishida, Nobuyuki   Farmer, Jackie D.   Kodavanti, Prasada Rao S.   Tilson, Hugh A.   MacPhail, Robert C.
Affiliation:Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd. Osaka, Japan *Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park North Carolina 27711, Japan

Received December 27, 1996; accepted June 27, 1997

Abstract:While considerable research has focused on the neurotoxicityof developmental exposures to polychlorinated biphenyls, includingAroclor 1254, relatively little is known about exposures inadult animals. This study investigated the behavioral effectsof acute and repeated Aroclor 1254 exposures to adult rats onmotor activity and flavor aversion conditioning. Male Long-Evansrats (60 days old) were tested for motor activity in a photocelldevice after acute (0, 100, 300, or 1000 mg/kg, po) or repeated(0, 1, 3, 10, 30 or 100 mg/kg/day, po, 5 days/week for 4 to6 weeks) exposure to Aroclor 1254. Motor activity was decreaseddose-dependently at doses of 300 mg/kg or more after acute exposure.Severe body weight loss and deaths occurred at 1000 mg/kg. Recoveryof activity occurred over 9 weeks but was incomplete. Afterrepeated exposure, motor activity was decreased dose-dependentlyat doses of 30 mg/kg or more, and severe weight loss and deathsoccurred at 100 mg/kg. In contrast to acute exposure, completerecovery of activity occurred 3 weeks after exposure. Additionalrats were water deprived (30 mm/day) and received acute po administrationof Aroclor 1254 (0, 10, 15, 25, 30, 100, or 300 mg/kg) shortlyafter consuming a saccharin solution. Three days later theywere given the choice between consuming saccharin or water,and saccharin preferences were recorded. Saccharin preferencewas decreased at doses of 25 mg/kg or more. Additional experimentsdetermined the effect of repeated saccharin-Aroclor 1254 pairings(0, 3.75, 7.5, or 15 mg/kg/day, 14 days) followed by a choicetest 1 day after the last dose. Repeated exposure to 15 mg/kgproduced robust flavor aversion conditioning. Repeated exposureto 7.5 mg/kg produced flavor aversion conditioning in four of12 rats. These results demonstrate that Aroclor 1254 causeshypoactivlty and flavor aversions in adult rats; the no observableeffect level (NOEL) for motor activity was 100 mg/kg for acuteexposure and 10 mg/kg for repeated exposure for a period ofup to 6 weeks. The acute NOEL for flavor aversion conditioningwas 15 mg/kg while the repeated NOEL was 7.5 mg/kg.
Keywords:polychlorinated biphenyls   Aroclor 1254     motor activity   flavor-aversion conditioning   rats.
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