Detail of "32598-13-3"

Reference

Chlorinated biphenyl induction of aryl hydrocarbon hydroxylase activity: a study of the structure-activity relationship

Chlorinated biphenyl induction of aryl hydrocarbon hydroxylase activity: a study of the structure-activity relationship. Poland, Alan; Glover, Edward (Dep. Pharmacol. Toxicol., Univ. Rochester Sch. Med. Dent., Rochester, N. Y., USA). Mol. Pharmacol., 13(5), 924-38 (English) 1977. CODEN: MOPMA3. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Of 16 halogenated biphenyls examd. for their capacity to induce hepatic aryl hydrocarbon hydroxylase [9037-52-9] activity in the chicken embryo, only 3 congeners, 3,4,3',4'-tetrachlorobiphenyl (I) [32598-13-3], 3,4,5,3',4',5'-hexachlorobiphenyl [32774-16-6], and 3,4,5,3',4',5'-hexabromobiphenyl [60044-26-0], were active. They were approx. equipotent in the chicken embryo, with ED50 values of .apprx. 90 nmoles/kg. These 3 chlorobiphenyl congeners also induced hepatic aryl hydrocarbon hydroxylase activity in C57BL/6J mice and rats, and they competitively bound the hepatic cytosol binding species thought to be the receptor for the induction of this enzyme. Among the halogenated biphenyls, there appear to be 2 structural requirements for induction of aryl hydrocarbon hydroxylase activity: the presence of at least 2 adjacent halogen atoms in the lateral positions of each benzene ring (positions 3,4,3',4' or 3,4,5,3',4',5') and the absence of halogen atoms adjacent to the biphenyl bridge (positions 2,6,2', and 6'); such substitutions lead to marked nonplanarity of the mol. The halobiphenyl congeners that induced aryl hydrocarbon hydroxylase activity did not induce aminopyrine N-demethylase [9037-69-8] activity (a measure of phenobarbital-like activity); however, some of the congeners that failed to induce aryl hydrocarbon hydroxylase activity did induce aminopyrine N-demethylase. This suggests that while the com. mixt. of chlorobiphenyls, Aroclor 1254 [11097-69-1], induces a mixed pattern of microsomal monooxygenase activity resembling the combined administration of 3-methylcholanthrene and phenobarbital, any given chlorobiphenyl congener appears to produce only a 3-methylcholanthrene-like or a phenobarbital-like response (or the congener may be devoid of both activities). I, the prototype of the halobiphenyls that induce hepatic aryl hydrocarbon hydroxylase activity, is an approximate isostereomer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran, and 2,4,3',4'-tetrachloroazoxybenzene, all of which induce hepatic aryl hydrocarbon hydroxylase activity but which are over 100-fold more potent. Conversion I to a more rigid, planar analog, 2,3,6,7-tetrachlorobiphenylene [7090-41-7], produced a compd. roughly equipotent to TCDD in inducing hepatic aryl hydrocarbon hydroxylase activity in the chicken embryo.

Separation of pure polychlorinated biphenyl isomers into two types of inducers on the basis of induction of cytochrome P-450 or P-448

Separation of pure polychlorinated biphenyl isomers into two types of inducers on the basis of induction of cytochrome P-450 or P-448. Goldstein, Joyce A.; Hickman, Patricia; Bergman, Hinda; McKinney, James D.; Walker, Michael P. (Environ. Res. Cent., EPA, Research Triangle Park, N. C., USA). Chem.-Biol. Interact., 17(1), 69-87 (English) 1977. CODEN: CBINA8. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) A number of isomerically pure polychlorinated biphenyls (PCBs) were tested as inducers of hepatic drug-metabolizing enzymes in the rat. The chlorinated biphenyl isomers can be categorized into 2 distinct groups of inducers, while commerical PCB mixts. have characteristics of both groups. Biphenyls chlorinated symmetrically in both meta and para positions (3,4,3',4'-tetrachloro [32598-13-3], and 3,4,5,3',4',5'-hexachloro [32774-16-6] biphenyls) increased the formation of cytochrome P-448 [9035-50-1]; the ratio of the 455 to 430 peaks of the ethyl isocyanide difference spectrum, and aryl hydrocarbon hydroxylase [9037-52-9] and glucuronyl transferase [37329-64-9] activities, but decreased aminopyrine N-demethylase [9037-69-8] activity. These isomers were also the most toxic, as measured by weight loss. Biphenyl isomers chlorinated in both the para and ortho positions induced the formation of cytochrome P-450 [9035-51-2] rather than P-448, regardless of the chlorination of the meta position. These isomers, which include 2,4,2',4'-tetrachloro [2437-79-8] and 2,4,5,2',4',5'-hexachloro [35065-27-1], 2,3,4,2',3',4'-hexachloro [38380-07-3] and 2,4,6,2',4',6'-hexachlorobiphenyl [33979-03-2], increased cytochrome P-450 and N-demethylase activity, but produced only a slight increase in aryl hydrocarbon hydroxylase activity, and did not alter the peak of the CO-difference spectrum or the ratio of the 455/430 peaks of the ethyl isocyanide difference spectrum. Isomers which are chlorinated in only one ring, or are chlorinated in both rings but not in the para positions, had very little activity as inducers of liver enzymes. Of the dichlorobiphenyls tested, 3,3'- [2050-67-1] and 4,4'-dichlorobiphenyl [2050-68-2] had only slight activity at very high doses.