Nishida N, Farmer J D, Kodavanti P R, Tilson H A, MacPhail R C
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Fundam Appl Toxicol. 1997 Nov;40(1):68-74. doi: 10.1006/faat.1997.2352.
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.
虽然大量研究聚焦于发育阶段接触多氯联苯（包括Aroclor 1254）的神经毒性，但对于成年动物接触多氯联苯的情况了解相对较少。本研究调查了成年大鼠急性和重复接触Aroclor 1254对运动活动和味觉厌恶条件反射的行为影响。雄性Long-Evans大鼠（60日龄）在急性（0、100、300或1000毫克/千克，口服）或重复（0、1、3、10、30或100毫克/千克/天，口服，每周5天，持续4至6周）接触Aroclor 1254后，在光电装置中测试其运动活动。急性接触后，剂量在300毫克/千克及以上时，运动活动呈剂量依赖性降低。1000毫克/千克时出现严重体重减轻和死亡。活动恢复持续9周但不完全。重复接触后，剂量在30毫克/千克及以上时，运动活动呈剂量依赖性降低，100毫克/千克时出现严重体重减轻和死亡。与急性接触不同，接触后3周运动活动完全恢复。另外的大鼠进行禁水（每天30分钟），并在饮用糖精溶液后不久急性口服给予Aroclor 1254（0、10、15、25、30、100或300毫克/千克）。三天后，让它们在饮用糖精或水之间进行选择，并记录对糖精的偏好。剂量在25毫克/千克及以上时，对糖精的偏好降低。额外实验确定了重复进行糖精-Aroclor 1254配对（0、3.75、7.5或15毫克/千克/天，持续14天），最后一次给药1天后进行选择测试的效果。重复接触15毫克/千克产生强烈的味觉厌恶条件反射。重复接触7.5毫克/千克使12只大鼠中的4只产生味觉厌恶条件反射。这些结果表明，Aroclor 1254可导致成年大鼠活动减退和味觉厌恶；急性接触运动活动的无可见效应水平（NOEL）为100毫克/千克，重复接触长达6周的NOEL为10毫克/千克。味觉厌恶条件反射的急性NOEL为15毫克/千克，重复NOEL为7.5毫克/千克。
