Chhabra R S, Bucher J R, Haseman J K, Elwell M R, Kurtz P J, Carlton B D
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1993 Nov;21(4):451-60. doi: 10.1006/faat.1993.1121.
Chronic toxicity and carcinogenicity studies of a polybrominated biphenyl mixture (PBB) were conducted in F344/N rats and B6C3F1 mice of each sex. The major objective of the study was to determine if exposure to PBB during the perinatal period, in addition to conventional exposure of animals for 2 years, enhances the sensitivity of the bioassay to identify the carcinogenic potential of this chemical. The studies were designed to determine the toxic and carcinogenic effects of dietary PBB in rats and mice receiving (i) perinatal exposure up to 8 weeks of age followed by control diet for 2 years, (ii) exposure for 2 years beginning at the age of 8 weeks, and (iii) combined perinatal/adult exposure to PBB (perinatal exposure to 8 weeks of age followed by adult exposure for 2 years). During the perinatal period, rats were exposed to PBB at dose levels ranging from 1 to 10 ppm and adult exposure concentrations ranged from 3 to 30 ppm in the diet. In the mice, the dose levels ranged from 3 to 30 ppm in both perinatal and adult exposure portions of the chronic studies. A total of eight dose groups (including controls) were used with 60 animals in each group. Liver was the major target organ of PBB toxicity. Perinatal exposure alone (through dietary administration of 10 ppm PBB to the dams) had no effect on the incidences of neoplasms in female F344/N rats, but in male rats, perinatal exposure was associated with a marginally increased incidence of hepatocellular adenomas that may have been related to chemical administration. In male and female B6C3F1 mice, perinatal exposure to 30 ppm PBB resulted in significantly increased incidences of hepatocellular neoplasms. In adult-only dietary exposure studies, PBB was carcinogenic in male and female F344/N rats and male and female B6C3F1 mice based on increased incidences of hepatocellular neoplasms. Combined perinatal and adult dietary exposure to PBB confirmed the findings of the adult-only exposures for the increased incidences of hepatocellular neoplasms in rats and mice. In male rats, there were no enhancing effects of combined perinatal and adult exposure. However, perinatal exposure enhanced the susceptibility of female rats receiving adult exposure of 10 or 30 ppm to the induction of liver neoplasms. For male and female rats, a combined analysis of the incidences of leukemia in the adult-only, perinatal-only, and combined perinatal and adult exposure groups revealed an apparent association between increasing incidences of mononuclear cell leukemia and exposure to PBB.(ABSTRACT TRUNCATED AT 400 WORDS)
对多溴联苯混合物（PBB）进行了慢性毒性和致癌性研究，受试动物为不同性别的F344/N大鼠和B6C3F1小鼠。该研究的主要目的是确定围产期接触PBB，除了传统的动物2年接触外，是否会增强生物测定对识别该化学品致癌潜力的敏感性。这些研究旨在确定在大鼠和小鼠中，通过饮食给予PBB的毒性和致癌作用，这些动物接受：（i）至8周龄的围产期接触，随后2年给予对照饮食；（ii）8周龄开始接触2年；（iii）围产期/成年期联合接触PBB（至8周龄围产期接触，随后成年期接触2年）。在围产期，大鼠接触PBB的剂量水平为1至10 ppm，成年期接触浓度在饮食中为3至30 ppm。在小鼠中，慢性研究的围产期和成年期接触部分的剂量水平均为3至30 ppm。总共使用了八个剂量组（包括对照组），每组60只动物。肝脏是PBB毒性的主要靶器官。仅围产期接触（通过给母鼠饮食给予10 ppm PBB）对雌性F344/N大鼠的肿瘤发生率没有影响，但在雄性大鼠中，围产期接触与肝细胞腺瘤发生率略有增加有关，这可能与化学品给药有关。在雄性和雌性B6C3F1小鼠中，围产期接触30 ppm PBB导致肝细胞肿瘤发生率显著增加。在仅成年期饮食接触研究中，基于肝细胞肿瘤发生率增加，PBB对雄性和雌性F344/N大鼠以及雄性和雌性B6C3F1小鼠具有致癌性。围产期和成年期联合饮食接触PBB证实了仅成年期接触研究中大鼠和小鼠肝细胞肿瘤发生率增加的结果。在雄性大鼠中，围产期和成年期联合接触没有增强作用。然而，围产期接触增强了接受10或30 ppm成年期接触的雌性大鼠对肝脏肿瘤诱导的易感性。对于雄性和雌性大鼠，对仅成年期、仅围产期以及围产期和成年期联合接触组的白血病发生率进行综合分析发现，单核细胞白血病发生率增加与接触PBB之间存在明显关联。（摘要截断于400字）
