用于测定“2,3,7,8-四氯二苯并对二噁英当量”的体外芳烃羟化酶诱导试验的应用：热解溴化阻燃剂

Applications of the in vitro aryl hydrocarbon hydroxylase induction assay for determining "2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents": pyrolyzed brominated flame retardants.

作者信息

Zacharewski T, Harris M, Safe S, Thoma H, Hutzinger O

机构信息

Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A and M University, College Station 77843.

出版信息

Toxicology. 1988 Oct;51(2-3):177-89. doi: 10.1016/0300-483x(88)90148-5.

DOI:10.1016/0300-483x(88)90148-5

PMID:2845603

Abstract

The pyrolysis of brominated flame retardants FR 300 BA (decabromobiphenyl) ether, FireMaster BP-6 (polybrominated biphenyls), Bromkal 70-5-DE (primarily pentabromodiphenylether), Bromkal 70-DE (primarily penta and tetrabromodiphenylether) and Bromkal G1 (pentabromodiphenylether) resulted in the formation of relatively high levels of polybrominated dibenzofurans (PBDFs) and dibenzo-p-dioxins (PBDDs as determined by gas chromatography-mass spectrometric analysis. The dose response EC50 values for the induction of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) by the flame retardant pyrolysates was determined in rat hepatoma H-4-II E cells and compared to the relative induction activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the concentrations of "2,3,7,8-TCDD equivalents" were calculated. The range of "2,3,7,8-TCDD equivalents" levels (micrograms/g or ppm) derived from values obtained from the AHH and EROD bioassays for each of the pyrolyzed flame retardant samples was: 174-194, 480-1400, 2140-4680, 6740-8780 and 3920-5260 ppm for FR 300 BA, FireMaster BP-6, Bromkal 70 DE, Bromkal 70-5 DE and Bromkal G1, respectively. The in vivo dose-response effects of 2 pyrolyzed flame retardants were determined in immature male Wistar rats and compared to the dose-response activities of 2,3,7,8-TCDD. The in vivo responses which were measured included hepatic microsomal AHH and EROD induction, body weight loss and thymic atrophy. For the pyrolyzed FireMaster BP-6 and Bromkal 70-5 DE samples, the range of calculated in vivo "2,3,7,8-TCDD equivalents" (ppm in sample) for the 4 in vivo bioassays was 520-1780 ppm and 3860-8960 ppm, respectively. The excellent overlap between the in vivo and in vitro 2,3,7,8-TCDD equivalents for the 2 flame retardant pyrolysate extracts supports the utility of the in vitro induction bioassay for quantitatively determining "2,3,7,8-TCDD equivalents" for mixtures containing toxic halogenated aryl hydrocarbons.

摘要

溴化阻燃剂FR 300 BA（十溴二苯醚）、FireMaster BP - 6（多溴联苯）、Bromkal 70 - 5 - DE（主要为五溴二苯醚）、Bromkal 70 - DE（主要为五溴和四溴二苯醚）以及Bromkal G1（五溴二苯醚）的热解会导致形成相对高水平的多溴二苯并呋喃（PBDF）和二苯并 - p - 二恶英（PBDD，通过气相色谱 - 质谱分析测定）。通过大鼠肝癌H - 4 - II E细胞测定了阻燃剂热解产物诱导芳烃羟化酶（AHH）和乙氧基异吩恶唑酮 - O - 脱乙基酶（EROD）的剂量反应EC50值，并与2,3,7,8 - 四氯二苯并 - p - 二恶英（TCDD）的相对诱导活性进行比较，计算了“2,3,7,8 - TCDD当量”的浓度。对于每个热解阻燃剂样品，由AHH和EROD生物测定获得的值得出的“2,3,7,8 - TCDD当量”水平范围（微克/克或ppm）分别为：FR 300 BA为174 - 194、FireMaster BP - 6为480 - 1400、Bromkal 70 DE为2140 - 4680、Bromkal 70 - 5 DE为6740 - 8780以及Bromkal G1为3920 - 5260 ppm。在未成熟雄性Wistar大鼠中测定了2种热解阻燃剂的体内剂量反应效应，并与2,3,7,8 - TCDD的剂量反应活性进行比较。所测量的体内反应包括肝微粒体AHH和EROD诱导、体重减轻和胸腺萎缩。对于热解的FireMaster BP - 6和Bromkal 70 - 5 DE样品，4种体内生物测定计算出的体内“2,3,7,8 - TCDD当量”范围（样品中的ppm）分别为520 - 1780 ppm和3860 - 8960 ppm。2种阻燃剂热解产物提取物的体内和体外2,3,7,8 - TCDD当量之间的出色重叠支持了体外诱导生物测定在定量测定含有毒卤代芳烃混合物的“2,3,7,8 - TCDD当量”方面的实用性。