Burgin D E, Diliberto J J, Derr-Yellin E C, Kannan N, Kodavanti P R, Birnbaum L S
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
Environ Health Perspect. 2001 Nov;109(11):1163-8. doi: 10.1289/ehp.011091163.
Aroclor 1254 is a commercial mixture of polychlorinated biphenyls (PCBs), which is defined as being 54% chlorine by weight. However, the congener composition varies from lot to lot. Two lots which have been used in toxicity studies, 124-191 and 6024 (AccuStandard), were analyzed for their congener composition. Lot 6024 has approximately 10 times the dioxin toxic equivalents (TEQ) of lot 124-191. The purpose of this study was to determine if the difference in the TEQ of the two lots explains the different in vivo responses seen on a weight basis. Male Long-Evans rats (70 days old) were treated orally with a single dose of 0-1,000 mg/kg of each lot. Hepatic ethoxy-, methoxy-, and pentoxyresorufin O-deethylase (EROD, MROD, and PROD, respectively) activities as well as serum thyroxine (T(4)) concentrations and measures of oxidative stress were determined 4 days after treatment. Results, on a weight basis, indicate that lot 6024 led to a greater induction of EROD, MROD, and PROD but not total T(4) reduction. The differences in TEQ between the lots explained the differential induction of EROD and MROD but did not account for the induction of PROD nor decreases in T(4). PROD induction is not due to dioxin-like congeners, whereas the decrease in serum T(4) levels may involve multiple mechanisms. Effects on the antioxidants ascorbic acid and uric acid were seen only at the highest mass dose for both lots and were not explained by the difference in TEQ. These results illustrate that the differences in the TEQ explain the differences in the strict dioxin-like effects (EROD, MROD induction), but the non-dioxin-like congeners cause other effects that are not associated with the aryl hydrocarbon receptor (e.g., PROD). In addition, supra-additive effects also occur in the mixture (T(4), oxidative stress). Thus, current results demonstrate that overall toxicity cannot be predicted on the basis of the TEQ values. It is also critical that the lot number is reported in studies conducted with Aroclor 1254 because the congener composition and therefore the effects observed can be very different.
多氯联苯混合物1254（Aroclor 1254）是一种商业用多氯联苯（PCBs）混合物，其氯含量按重量计为54%。然而，不同批次的同系物组成有所不同。对用于毒性研究的两个批次，即124 - 191和6024（AccuStandard），分析了它们的同系物组成。6024批次的二噁英毒性当量（TEQ）约为124 - 191批次的10倍。本研究的目的是确定这两个批次的TEQ差异是否能解释以体重计所观察到的不同体内反应。雄性Long - Evans大鼠（70日龄）经口给予每个批次0 - 1000 mg/kg的单剂量。在处理后4天测定肝脏乙氧基、甲氧基和戊氧基试卤灵O - 脱乙基酶（分别为EROD、MROD和PROD）活性以及血清甲状腺素（T(4)）浓度和氧化应激指标。结果按体重计表明，6024批次导致EROD、MROD和PROD的诱导作用更强，但总T(4)没有降低。批次间TEQ的差异解释了EROD和MROD的不同诱导情况，但不能解释PROD的诱导以及T(4)的降低。PROD的诱导并非由于类二噁英同系物，而血清T(4)水平的降低可能涉及多种机制。仅在两个批次的最高质量剂量下观察到对抗氧化剂抗坏血酸和尿酸的影响，且不能用TEQ的差异来解释。这些结果表明，TEQ的差异解释了严格的类二噁英效应（EROD、MROD诱导）的差异，但非类二噁英同系物会导致其他与芳烃受体无关的效应（如PROD）。此外，混合物中还会出现超加和效应（T(4)、氧化应激）。因此，目前的结果表明不能根据TEQ值预测总体毒性。在使用Aroclor 1254进行的研究中报告批次号也很关键，因为同系物组成以及因此观察到的效应可能会非常不同。
