4-Methoxy-1,1'-biphenyl

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

SPECIES VARIATION IN IN VITRO O-DEMETHYLATION TO 4-HYDROXYBIPHENYL (RECORDED AS NMOL/MG LIVER-HR) RANGED FROM 0.4 RAINBOW TROUT, 0.9 FROG, 1.7 CHICKEN, 8.0 RABBIT, 3.0 RAT, 3.2 MOUSE, 2.3 HAMSTER, TO 2.3 GUINEA PIG. /FROM TABLE/

THE CONVERSION OF BIPHENYL & 4-METHOXYBIPHENYL TO 4-HYDROXYBIPHENYL BY RAT LIVER MICROSOMES WAS MEDIATED BY THE MICROSOMAL MONOOXYGENASE SYSTEM & BOTH SUBSTRATES BOUND TO CYTOCHROME P450 TO GIVE A TYPE I BINDING SPECTRUM, ALTHOUGH THE MAXIMUM & MINIMUM WAVELENGTHS DIFFERED BETWEEN THE 2 SUBSTRATES. THE DIFFERENTIAL EFFECT OF ENZYME INDUCERS, METYRAPONE INHIBITION, & ETHANOL INHIBITION ON BIPHENYL 4-HYDROXYLATION & METHOXYBIPHENYL O-DEMETHYLATION SUGGESTS THAT THESE 2 REACTIONS ARE MEDIATED BY DIFFERENT CYTOCHROME P450 HEMOPROTEINS.

THE MICROSOMAL & SOLUBLE FRACTIONS FROM A TROUT LIVER HOMOGENATE DEALKYLATED 4-METHOXYBIPHENYL. LIVER PREPN FROM THE FROG RANA TEMPORARIA DEALKYLATED 4-METHOXYBIPHENYL ... 2-DEALKYLATION OCCURRED MORE RAPIDLY THAN 4-DEALKYLATION IN THE TROUT PREPN, WHEREAS THE REVERSE WAS TRUE FOR THE FROG PREPN.

The effects of beta-naphthoflavone on 4-methoxybiphenyl and biphenyl metabolism were studied in rats. Male Wistar rats were pretreated with 0 to 80 mg/kg beta-naphthoflavone. Forty hours later, the animals were /sacrificed/ and hepatocytes and liver microsomes were isolated. After incubation with 4-methoxybiphenyl or biphenyl, the rate of production of 4-hydroxybiphenyl was measured. Hepatic microsomes from rats pretreated with 0 or 40 mg/kg beta-naphthoflavone and incubated with biphenyl or 4-methoxybiphenyl were treated with metyrapone, alpha-naphthoflavone or ethanol and the effects on 4-methoxybiphenyl-O-demethylase (MBPD) and biphenyl-4-hydroxylase (BPOH) activity were investigated. The rate of formation of 4-hydroxybiphenyl from 4-methoxybiphenyl hepatocytes and microsomes from non-pretreated rats was essentially the same as that from biphenyl in hepatocytes and microsomes from rats pretreated with beta-naphthoflavone. MBPD and BPOH activities in microsomes from rats not pretreated with beta-naphthoflavone were essentially the same. MBPD activity was inhibited by metyrapone to a significantly greater extent than BPOH activity. BPOH activity, however, was inhibited to a greater extent by ethanol and alpha-naphthoflavone than MBPD activity. Hepatocytes were incubated with biphenyl with or without beta-naphthoflavone pretreatment and the pattern of conjugation of 4-hydroxybiphenyl was determined. In non-pretreated rats, sulfate and glucuronic acid conjugates of 4-hydroxybiphenyl were formed in approximately equal amounts, each presenting 41 to 44% of the total 4-hydroxybiphenyl formed. In the pretreated rats, the sulfate conjugate represented only 22% of the total 4-hydroxybiphenyl formed while the qlucuronic acid conjugate represented 60% of the total. The /results suggest/ that the difference in cellular metabolism between biphenyl and 4-methoxybiphenyl is due to competition between beta-naphthoflavone and biphenyl or their metabolites for common metabolic pathways. The type of cytochrome P450 involved in forming 4-hydroxybiphenyl does not effect the pattern of conjugation.

The response of hepatocytes to 4-hydroxybiphenyl (HP) in the presence of ascorbic acid was investigated in vitro. Livers from male Wistar rats were excised and hepatocyte suspensions were prepared. For assay of 0-demethylation of 4-methoxybiphenyl (MBP) the acidified incubation mixture was incubated with crude beta-glucuronidase. Total HP was extracted and fluorescence was measured. For assay of conjugated metabolites of HP and sequential metabolism of MBP the incubation mixture was extracted to remove unconjugated metabolites of HP and the mixture was treated with crude beta-glucuronidase. Ascorbic acid was added to the cell incubations with preincubated at 37 °C for 5 min before adding the appropriate substrate. During a 60 min incubation of hepatocytes with HP about 55 nanomoles of conjugates were produced; 84% was in the form of glucuronide conjugates. Preincubation with ascorbic acid at 130 to 600 micromoles significantly incr glucuronylation in a dose related manner between 130 and 400 micromoles. Higher ascorbic acid concentrations resulted in sulfation inhibition. Sulfate was the major conjugate produced during the conjugation of HP from MBP in the presence of ascorbic acid. The normal serum concentrations of ascorbic acid did not effect the glucuronylation pathway but high concentrations inhibited sulfation and enhanced glucuronylation to a similar degree. Ascorbic acid did not effect 0-demethylation of MBP nor did it influence cellular lipid peroxidation. The /results suggest/ that high concentrations of ascorbic acid inhibit sulfation of MBP in isolated rat hepatocytes. Inhibition occurs when HP is added directly to the cells or by in situ generation from HP.