Arnold D L, Bryce F, McGuire P F, Stapley R, Tanner J R, Wrenshall E, Mes J, Fernie S, Tryphonas H, Hayward S
Toxicology Research Division, Health Canada, Ottawa, Ontario.
Food Chem Toxicol. 1995 Jun;33(6):457-74. doi: 10.1016/0278-6915(95)00018-w.
A group of 80 menstruating rhesus (Macaca mulatta) monkeys were randomly allocated to four similar test rooms (20 monkeys/room) and then randomly allocated within each room to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of continuous dosing, approximately 90% of the treated females had attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Commencing on test month 37, each female was paired with an untreated male until either an impregnation occurred or the 29-month breeding phase of the study was completed. The females continued to receive their daily test dose during mating and gestation. To preclude an infant ingesting the mother's dosing capsule, dosing of the dam was discontinued when a nursing infant was approximately 7 wk old. Treatment was restarted when the infant was weaned at 22 wk of age. At parturition, and every 4 wk until weaning, milk and blood samples were obtained from the dam and a blood sample was obtained from the infant for PCB analysis. When the infant was 20 wk old, immunological testing was initiated and an adipose sample was obtained from the infant and dam for PCB analysis. Subsequently, further adipose and blood samples were obtained from the infant and blood specimens were obtained from the dam for PCB analysis. Concurrently, each infant was subjected to anthropometric measurements and detailed clinical examinations until it was approximately 122 wk old. At 122 wk some of the control and all of the treated infants were killed humanely and autopsied. A statistical analysis of the reproduction data provided evidence for a significant decreasing dose-related trend in conception rates and a significant increasing dose-related trend in foetal mortality. Several comparisons between impregnated and non-impregnated females did not implicate 'age' as a confounding factor regarding these results. The major findings with the infants involved some immunological test differences and mild clinical manifestations of PCB ingestion.
将80只处于月经期的恒河猴(猕猴属)随机分配到四个相似的测试房间(每个房间20只猴子),然后在每个房间内再随机分配到五个剂量组之一(每个剂量组/房间4只雌性猴子)。每天,猴子自行摄入含有剂量为0、5、20、40或80微克/千克体重的艾氏剂1254的胶囊。连续给药25个月后,约90%接受治疗的雌性猴子在其脂肪组织中多氯联苯(PCB)浓度方面达到了定性药代动力学稳态。从测试第37个月开始,将每只雌性猴子与一只未接受治疗的雄性猴子配对,直到受孕或研究的29个月繁殖阶段结束。雌性猴子在交配和妊娠期间继续接受每日测试剂量。为防止婴儿摄入母亲的给药胶囊,当哺乳婴儿约7周大时,停止对母猴给药。当婴儿在22周龄断奶时重新开始治疗。分娩时,以及在断奶前每4周,从母猴采集乳汁和血液样本,并从婴儿采集血液样本进行PCB分析。当婴儿20周龄时,开始进行免疫测试,并从婴儿和母猴采集脂肪样本进行PCB分析。随后,从婴儿采集更多的脂肪和血液样本,并从母猴采集血液标本进行PCB分析。同时,对每只婴儿进行人体测量和详细的临床检查,直到其约122周龄。在122周时,对一些对照婴儿和所有接受治疗的婴儿进行人道处死并解剖。对生殖数据的统计分析提供了证据,表明受孕率存在显著的剂量相关下降趋势,胎儿死亡率存在显著的剂量相关上升趋势。受孕和未受孕雌性猴子之间的几项比较并未表明“年龄”是这些结果的混杂因素。婴儿的主要发现包括一些免疫测试差异和PCB摄入的轻微临床表现。