Effects of acute and repeated exposures to Aroclor 1254 in adult rats: motor activity and flavor aversion conditioning.
While considerable research has focused on the neurotoxicity of developmental exposures to polychlorinated biphenyls, including Aroclor 1254, relatively little is known about exposures in adult animals. This study investigated the behavioral effects of acute and repeated Aroclor 1254 exposures to adult rats on motor activity and flavor aversion conditioning. Male Long-Evans rats (60 days old) were tested for motor activity in a photocell device after acute (0, 100, 300, or 1000 mg/kg, p.o.) or repeated (0, 1, 3, 10, 30 or 100 mg/kg/day, po, 5 days/week for 4 to 6 weeks exposure to Aroclor 1254. Motor activity was decreased dose-dependently at doses of 300 mg/kg or more after acute exposure. Severe body weight loss and deaths occurred at 1000 mg/kg. Recovery of activity occurred over 9 weeks but was incomplete. After repeated exposure, motor activity was decreased dose-dependently at doses of 30 mg/kg or more, and severe weight loss and deaths occurred at 100 mg/kg. In contrast to acute exposure, complete recovery of activity occurred 3 weeks after exposure. Additional rats were water deprived (30 min/day) and received acute po administration of Aroclor 1254 (0, 10, 15, 25, 30, 100, or 300 mg/kg) shortly after consuming a saccharin solution. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. Saccharin preference was decreased at doses of 25 mg/kg or more. Additional experiments determined the effect of repeated saccharin-Aroclor 1254 pairings (0, 3.75, 7.5, or 15 mg/kg/day, 14 days) followed by a choice test 1 day after the last dose. Repeated exposure to 15 mg/kg produced robust flavor aversion conditioning. Repeated exposure to 7.5 mg/kg produced flavor aversion conditioning in four of 12 rats. These results demonstrate that Aroclor 1254 causes hypoactivity and flavor aversions in adult rats; the no observable effect level (NOEL) for motor activity was 100 mg/kg for acute exposure and 10 mg/kg for repeated exposure for a period of up to 6 weeks. The acute NOEL for flavor aversion conditioning was 15 mg/kg while the repeated NOEL was 7.5 mg/kg.
Nishida
N
N
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Farmer
J D
JD
Kodavanti
P R
PR
Tilson
H A
HA
MacPhail
R C
RC
D000818:Animals; D001140:Aroclors / Q000008:administration & dosage / Q000633:toxicity*; D001362:Avoidance Learning / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D020111:Chlorodiphenyl (54% Chlorine); D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D013649:Taste / Q000187:drug effects*; D013997:Time Factors
D001140:Aroclors; D002273:Carcinogens; D020111:Chlorodiphenyl (54% Chlorine)