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Toxicity Effects

CAS Registry Number: 35065-27-1

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 1,1'-Biphenyl, 2,2',4,4',5,5'-Hexachloro- (9ci)
  • 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (PCB 153)
  • 2,2',4,4',5,5'-Hexachlorobiphenyl
  • 2,2'-4,4',5,5'-Hexachlorobiphenyl (Pcb 153) (Toxic Equivalency Factor Evaluation)
  • PCB 153
  • PCB 153- 2,2'-4,4',5,5'-Hexachlorobiphenyl
  • PCB 153- 2,2'-4,4',5,5'-hexachlorobiphenyl (Toxic equivalency factor (TEF) evaluation)
  • PCB-153
  • PCB153
  • Pcb 153 (Toxic Equivalency Factor Evaluation)
  • Toxic Equivalency Factor Evaluation (PCB 153- 2,2'-4,4',5,5'-Hexachlorobiphenyl)
  • Toxic equivalency factor evaluation (PCB 153- 2,2'-4,4',5,5'-hexachlorobiphenyl)

Human Toxicity Excerpts

  • 2,4,5,2',4',5'-Hexachlorobiphenyl induced cytoplasmic inclusions and lipidosis in normal (AG1437) and hypercholesterolemic (GM488) human skin fibroblasts. Quantitative and qualitative microscopic fluorescence analysis showed that the cytoplasmic inclusions are formed as early as 3 hr after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl. The inclusions contain lipids but no detectable nonesterified cholesterol or cholesterol ester. High density lipoproteins, low density lipoproteins, and very low density lipoproteins, facilitate the apparent uptake of 2,2',4,4',5,5'-hexachlorobiphenyl by skin fibroblasts. High density lipoproteins and low density lipoproteins appeared to reverse the induction of cytoplasmic inclusions and lipidosis when cells were pretreated with 2,2',4,4',5,5'-hexachlorobiphenyl, and were then incubated with low density lipoproteins or high density lipoproteins. The results suggest that lipoproteins participate in the uptake and egress of 2,2',4,4',5,5'-hexachlorobiphenyl from skin fibloblasts.[Kling D et al; Environ Res 34 (1): 87-102 (1984)] **PEER REVIEWED** PubMed Abstract
  • Nursing /by women exposed to PCB's/ ... should be discouraged because of the high amount of PCB's excreted with milk. ...[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 1754] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ... The weight of in vitro evidence suggests lipoproteins as the principal carriers of 2,4,5,2',4',5'-hexachlorobiphenyl in plasma from normolipidemic rats and humans. The present study examined the in vivo distribution of 2,4,5,2',4',5'-hexachlorobiphenyl among lipoproteins as well as the influence of time on the absolute amount and proportion of 2,4,5,2',4',5',-hexachlorobiphenyl associated with each density fraction. Plasma obtained between 1 min and 24 hr after an iv injection of 6-(14)C-CB was separated into very low density lipoprotein, low density lipoprotein, and high density lipoprotein fractions by sequential ultracentrifugation. The in vivo results corroborate the in vitro data which suggest low density lipoprotein to be a major transport vehicle for 2,4,5,2',4',5'-hexachlorobiphenyl in plasma. However, the preference of 2,4,5,2',4',5',-hexachlorobiphenyl for low density lipoprotein existed for only a short time following injection. ... Analysis of the decay curves of 2,4,5,2',4',5'-hexachlorobiphenyl among the various lipoproteins further substantiated a change in the distribution of 2,4,5,2',4',5'-hexachlorobiphenyl over time. The decay of 2,4,5,2',4',5'-hexachlorobiphenyl in low density lipoprotein most closely resembled its disappearance from plasma. The content of 2,4,5,2',4',5'-hexachlorobiphenyl remaining in plasma at 24 hr was equally distributed among low density lipoprotein, high density lipoprotein, and the bottom fraction. ...[Spindler-Vomachka M et al; Toxicol Appl Pharm 74 (1): 70-7 (1984)] **PEER REVIEWED**
  • 2,2',4,4',5,5'-Hexachlorobiphenyl (HCB) dissolved in corn oil was administered intragastrically to two groups of 6 to 8 female Sprague Dawley rats at doses of 40 ug/kg/day or 400 ug/kg/day for 3 days each. The animals were killed 6 days after treatment. Control animals were used, but no details of treatment are provided. Lipid peroxidation and glutathione peroxidase (GSH-PX) activity were determined in liver and kidneys. Hepatic aryl hydrocarbon hydroxylase (AHH) activity was determined in two rats 48 hr following the administration of 400 ug/kg of HCB. No changes were noted in these parameters and there was no significant effect on thymus weight or body weight relative to the control group.[Shara MA, Stohs SJ; Arch Environ Contam Toxicol 16: 599-605] **PEER REVIEWED**
  • 2,4,5,2',4',5'-HEXACHLOROBIPHENYL FED TO PREGNANT GUINEA PIGS DID NOT CAUSE FETAL DEATH (TOTAL DOSE 25 MG OR 100 MG).[BRUNSTROEM B ET AL; ACTA PHARMACOL TOXICOL 50 (2): 100-3 (1982)] **PEER REVIEWED**
  • 5-WK OLD MALE MICE WERE ADMIN 10, 30, 100 OR 300 PPM 3,4,5,3',4',5'-HEXACHLOROBIPHENYL (3,4,5-HCB) OR 10, 30, 100, 300 PPM 2,4,5,2',4',5'-HEXACHLOROBIPHENYL (2,4,5-HCB) IN FEED DAILY FOR 28 DAYS. 3,4,5-HCB CAUSED MORTALITY & BODY & ORGAN WT CHANGES AT ALL DOSE LEVELS & PRODUCED EXCESS PORPHYRIN ACCUMULATION. IT CAUSED SC EDEMA, ENLARGEMENT OF LIVER WITH ACCENTUATED HEPATIC LOBULAR MARKINGS, FATTY LIVER, HEPATOCELLULAR SWELLING & NECROSIS, & ATROPHY OF THYMUS. 2,4,5-HCB CAUSED THE SAME LESIONS BUT TO LESSER DEGREE.[BIOCCA M ET AL; TOXICOL APPL PHARMACOL 58 (3): 461-74 (1981)] **PEER REVIEWED** PubMed Abstract
  • Adult female mink were fed diets that contained 2.5 ppm Aroclor 1254, 0.1 or 0.5 ppm 3,4,5,3',4',5'-hexachlorobiphenyl, 2.5 or 5.0 ppm 2,4,5,2',4',5'-hexachlorobiphenyl, or 2,3,6,2',3',6'-hexachlorobiphenyl, or a control diet from 1 month prior to breeding through parturition. All mink fed 0.5 ppm 3,4,5,3',4',5'-hexachlorobiphenyl died within 60 days, while those fed 0.1 ppm showed 50% mortality after 3 month exposure. Only one stillborn kit was whelped in the Aroclor 1254 group. No adverse reproductive effects were observed in the animals fed 2,3,6,2',3',6'-hexachlorobiphenyl or 2,4,5,2',4',5'-hexachlorobiphenyl. ... Aminopyrine N-demethylase activity was elevated by /admin of/ 5.0 ppm 2,4,5,2',4',5'-hexachlorobiphenyl. Benzo(a)pyrene hydroxylase activities were also significantly elevated in milk fed 2,4,5,2',4',5'-hexachlorobiphenyl and 3,4,5,3',4',5'-hexachlorobiphenyl. Norepinephrine concentrations were significantly elevated by ... 5.0 ppm 2,4,5,2',4',5'-hexachlorobiphenyl in the medulla.[Aulerich RJ et al; J Toxicol Environ Health 15 (1): 63-79 (1985)] **PEER REVIEWED** PubMed Abstract
  • CHLORINATED BIPHENYLS DISSOLVED IN CORN OIL WERE INJECTED IP INTO MALE RATS. 2,4,5,2',4',5'-HEXACHLOROBIPHENYL INDUCED A CHANGE IN PROGESTERONE METABOLISM.[NAGATA K ET AL; J PHARMACOBIO-DYN 4 (5): S-64 (1981)] **PEER REVIEWED**
  • From day 45 to day 62 of gestation, three groups of primiparous pregnant Dunkin Hartley guinea pigs were fed once daily 0.1 ml of peanut oil containing 0 (control group), 0.176, or 1.76 mg of 2,4,5,2',4',5'-hexachlorobiphenyl (HCB), which correlated to 0, 3, and 30 mg HCB per animal per treatment period. At day 60 of gestation, the dams were catheterized, and three days later the blood flow was determined by use of labeled microspheres. Blood samples were taken to determine hematological parameters, after which the dams were killed. The levels of HCB in the liver, myometrium, and placenta were determined. HCB accumulated in the placenta of tissue fat (33.9 ug/g) in the animals given the higher dose. In both treatment groups, there was a higher incidence of resorptions and abnormal maternal and fetal livers, compared with the controls. About 50% of the animals in the high-dose group had aberrant placentas. A statistically significant decrease in the placental blood flow and an increase in the lung perfusion were found in the high-dose group.[Hedman C et al; Environ Res 38: 293-300 (1985)] **PEER REVIEWED** PubMed Abstract
  • ISOMERICALLY PURE 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 COMMERCIAL PCB MIXT HAVE CHARACTERISTICS OF BOTH GROUPS. BIPHENYLS CHLORINATED SYMMETRICALLY IN BOTH THE META AND PARA POSITIONS INCREASE THE FORMATION OF CYTOCHROME P448, BUT DECREASE THE AMINOPYRINE N-DEMETHYLASE ACTIVITY. BIPHENYL ISOMERS CHLORINATED IN BOTH THE PARA AND ORTHO POSITIONS INDUCE THE FORMATION OF CYTOCHROME P450 AND N-DEMETHYLASE ACTIVITY. ISOMERS WHICH ARE CHLORINATED IN ONLY 1 RING, OR ARE CHLORINATED IN BOTH RINGS BUT NOT IN THE PARA POSITIONS, HAVE VERY LITTLE ACTIVITY AS INDUCERS OF LIVER ENZYMES.[GOLDSTEIN JA ET AL; CHEM-BIOL INTERACT VOL 17 (1): 69-87 (1977)] **PEER REVIEWED**
  • ORGANOHALOGENS WERE ADMIN TO PREGNANT RATS & ENZYME ACTIVITIES WERE MEASURED IN FETUSES & OFFSPRINGS (6, 20 & 55 DAYS AFTER BIRTH). 3,4,3'4'-TETRACHLOROBIPHENYL (TCB) INDUCED P448-DEPENDENT ENZYMES IN 6 & 20 DAY-OLD RATS WHEREAS 2,4,5,2',4',5'-HEXACHLOROBIPHENYL (HCB) INDUCED P450-DEPENDENT ENZYMES. TCB PRODUCED BEHAVIORAL CHANGES & KIDNEY ABNORMALITIES BUT HCB PRODUCED NO DEVELOPMENTAL EFFECTS. TCB MIGHT ALSO ALTER NORMAL IMPRINTING OF SEXUAL HEPATIC METABOLISM AS EVIDENCED BY FEMINIZATION (DECREASE) OF UDPGT IN ADULT MALE RATS WHICH WERE EXPOSED NEONATALLY TO TCB.[LUCIER GW, MCDANIEL OS; ANN NY ACAD SCI 320: 449-57 (1979)] **PEER REVIEWED** PubMed Abstract
  • TOPICAL APPLICATION OF 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (HCB) OR AROCLOR 1260 (120 MG DAILY, 5 TIMES/WK FOR 28 DAYS) PRODUCED SKIN LESIONS IN RABBITS WITH THE EFFECT BEING MORE SEVERE IN THE LATTER GROUP. BOTH CAUSED ACCUMULATION OF COPROPORPHYRIN. LIVER INJURY & ELEVATION OF SERUM TRANSAMINASE LEVELS WERE MORE SEVERE IN THE HCB-TREATED GROUP.[VOS JG, NOTENBOOM-RAM E; TOXICOL APPL PHARMACOL 23 (4): 563-78 (1972)] **PEER REVIEWED** PubMed Abstract
  • The cytochrome p450 isozymes, cytochrome p450 MC1 and MC2, purified from rats treated with 3-methylcholanthrene, were found by immunohistochemical staining to be strongly induced in the livers of rats treated with 3,3',4,4'-tetrachlorobiphenyl, while the cytochrome p450 isozymes, PB1 and PB2, purified from the livers of rats treated with phenobarbital, were shown to be induced in the livers of rats treated with 2,2',4,4',5,5'-hexachlorobiphenyl. The latter compound also strongly induced reductase nicotinamide adenine dinucleotide phosphate cytochrome p450-reductase. Following induction, all 5 enzymes were located preferentially in the centrilobular and midzonal region of the liver acinus. ... In addition, Diethylnitrosamine alone produced very few islets, the administration of either polychlorinated biphenyls congener (150 umol/kg, ip, once weekly over a period of 8 weeks) subsequent to diethylnitrosamine treatment (50 ppm in the drinking water, 10 days) strongly enhanced the number of islets as well as the relative volume of liver occupied by islet tissue. These effects were evident, both 1 and 9 weeks, after cessation of PCB treatment. ...[Buchmann A et al; Cancer Lett 32 (3): 243-53 (1986)] **PEER REVIEWED** PubMed Abstract
  • The influences of in vivo treatment with two pure polychlorinated biphenyls congeners on the lethal cytotoxicity of bromobenzene and acetaminophen were examined in short-term primary cultures of isolated rat hepatocytes. Lethal injury was measured by release of lactate dehydrogenase into culture medium after 20 hr exposure to the hepatotoxins. The 2,2',4,4',5,5'-hexachlorobiphenyl, a phenobarbital-type inducer of cytochrome p450, resembled phenobarbital in its ability to increase susceptibility of hepatocytes to bromobenzene (0.5 to 1.6 mM) and acetaminophen (1 to 16 mM). This induced sensitivity was consistently inhibited by SKF-525-A (10 uM) but not alpha-naphthoflavone (ANF, 10 uM) in culture.[Hayes MA et al; Toxicol Appl Pharmacol 76 (1): 118-27 (1984)] **PEER REVIEWED** PubMed Abstract
  • The kinetics of liver and kidney retinol and retinyl palmitate levels were examined following single ip injections of DDT, 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, or 2,2',4,4',5,5'-hexachlorobiphenyl to male Sprague Dawley rats. The polychlorinated biphenyls (PCBs) were given in doses of 300 umol/kg, and DDT was given at a dose of 150 umol/kg. ... The induction of various drug metabolizing enzymes or retinyl palmitate hydrolase activity, a key enzyme in hepatic retinyl palmitate hydrolysis, was not implicated in the depletion of hepatic vitamin A. It is suggested that chemical or redox changes in the liver as a result of the toxicity of the xenobiotic may result in the nonenzymatic destruction of the liver vitamin A stores.[Azais V et al; Chemosphere 15 (9-12): 1905-8 (1986)] **PEER REVIEWED**
  • Three groups of primaparous pregnant guinea pigs were fed once daily with a total of either 0 (control group, n= 9), 3 mg (n= 8), or 30 mg (n= 9) of 2,2',4,4',5,5'-hexachlorobiphenyl starting at day 45 of gestation to evaluate the effects of 2,2',4,4',5,5'-hexachlorobiphenyl on placental perfusion. The guinea pigs were separated into their groups randomly. At day 63 of gestation the organ blood flow was determined with microsphere technique in the awake animal. The results show a statistically significant decrease in the placental blood flow and an increase in the pulmonary blood flow in the animals fed with 30 mg 2,2',4,4',5,5'-hexachlorobiphenyl compared to the control group. A higher incidence of resorptions in fetuses was shown in both treatment groups compared to the control group.[Hedman C et al; Environ Res 38 (2): 293-300 (1985)] **PEER REVIEWED** PubMed Abstract
  • Treatment of C57BL/6J mice with 2,2',4,4',5,5'-hexachlorobiphenyl (500 umol/kg) elevated hepatic cytosolic Ah receptor levels 82-107% for up to 14 days. ... Administration of 2,2',4,4',5,5'-hexachlorobiphenyl to DBA/2J mice did not result in detectable hepatic cytosolic Ah receptor levels. Cotreatment of C57BL/6J mice with 2,2',4,4',5,5'-hexachlorobiphenyl (500 umol/kg) at a dose level of 2,3,7,8-tetrachlorodibenzo-p-dioxin (1 nmol/kg) which elicited less than 10% of the maximum induction response resulted in significant synergistic induction of hepatic EROD and AHH (compared to animals treated only with 2,3,7,8-tetrachlorodibenzo-p-dioxin (1 nmol/kg)). ... Cotreatment of DBA/2J mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,2',4,4',5,5'-hexachlorobiphenyl (500 umol/kg) resulted in significant synergistic induction of AHH and EROD at both submaximal (10-500 nmol/kg) and maximal (5000 nmol/kg) induction levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. The only significant interactive effect of 2,2',4,4',5,5'-hexachlorobiphenyl (500 umol/kg) on the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J and DBA/2J was protection from body weight loss observed after cotreatment of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin in DBA/2J mice.[Bannister R, Safe S; Toxicol 44 (2): 159-69 (1987)] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Mouse (C57B1/6J) male oral >64.3 mg/kg/28 day.[USEPA, Office of Drinking Water; Criteria Document (Draft): Polychlorinated Biphenyls p.V-4 (1985) EPA-600/X-84-198-2] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • (14)C-2,4,5,2',4',5'-HEXACHLOROBIPHENYL WAS ADMIN ORALLY TO BILE-CANNULATED RATS. ABSORPTION FROM GI TRACT WAS 28.2% +/- 1.4 WHILE BILIARY EXCRETION WAS 18.6% +/- 1.3. URINARY EXCRETION WAS LOW. DISPOSITION OF RADIOACTIVE RESIDUES IN EVISCERATED CARCASSES INCREASES WITH THE CL CONTENT OF BIPHENYLS.[BERGMAN A ET AL; CHEMOSPHERE 11 (3): 249-54 (1982)] **PEER REVIEWED**
  • ... Male beagle dogs and male Macaca fascicularis monkeys were given a single intravenous bolus in the radial and saphenous vein, respectively, of 6 mg/kg radiolabeled 2,2',4,4',5,5'-hexachlorobiphenyl. Blood and adipose tissue samples of pericardial, perirenal, peritesticular, and subcutaneous fat and omentum were collected at different times. Samples were analyzed for total radioactivity and parent polychlorinated biphenyl (PCB). There were significant differences for 2,2',4,4',5,5'-hexachlorobiphenyl concentrations between the sampled adipose tissue depots at equivalent times and between collection times for the same depot for dog and monkey. Mean concentrations of radiolabel in testicular fat were consistently lower than the concentration in other adipose tissues analyzed. All other concentrations of radiolabel were similar at all times. ... For fat depots that were analyzed, the parent to metabolite ratio for 2,2',4,4',5,5'-hexachlorobiphenyl in dogs was approximately 25.2 and for monkeys, 101. Fat to blood ratios for parent 2,2',4,4',5,5'-hexachlorobiphenyl for dogs and monkeys increased over the time course of the experiment.[Ryerson BA et al; Fund Appl Toxicol 4 (1): 120-4 (1984)] **PEER REVIEWED**
  • ... Normal skin fibroblasts and familial hypercholesterolemic cells were cultured and incubated with 5.5, 27, or 55 micromolar concentrations of radiolabeled hexachlorobiphenyl for 3 or 24 hours. Radiolabeled acetate and glycerol-3-phosphate were used as substrates in different experiments. Cells were analyzed for phospholipids and triglyceride. When acetate was the substrate, synthesis of triglyceride and phospholipids increased dramatically with hexachlorobiphenyl. Incorporation of glycerol-3-phosphate into phospholipids and diglycerides was decreased but no significant change in triglyceride formation was noted. Hypercholesterolemic skin fibroblasts showed increased incorporation of acetate into phospholipids and triglycerides at low concentrations of hexachlorobiphenyl and decreased incorporation at higher concentrations. There was a significant increase in triglyceride content when skin fibroblasts were treated with hexachlorobiphenyl. There was no significant change in phospholipid content of skin fibroblasts after treatment with hexachlorobiphenyl at lower concentrations. ...[Beranek SR et al; Environ Research 34 (1): 103-9 (1984)] **PEER REVIEWED**
  • ... Pharmacokinetic analysis of 4,4'-dichlorobiphenyl, 2,2',3,3',6,6'-hexachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl is presented for the dog and monkey, and the results are compared with previous similar analyses for the rat and mouse. The normalized clearances (ml/min per kg body wt) vary considerably between the dog and the monkey; the rat and the mouse show less species variation. The equilibrium tissue-to-blood distribution ratios for parent and metabolite are generally similar for all 4 species. The fat compartment has the highest parent distribution ratio for all 4 species, and the metabolite distribution ratios are much smaller than the parent distribution ratios. Metabolism appears to be a prerequisite to urinary and biliary excretion for all 3 compounds in each species. Elimination from the body occurs predominantly by the fecal route. The 2,2'4,4'5,5'-hexachlorobiphenyl is more slowly metabolized than the 2,2',3,3',6,6'-isomer in all species. ...[Lutz RJ et al; Drug Metab Dispos 12 (5): 527-35 (1984)] **PEER REVIEWED** PubMed Abstract
  • 2,4,5,2'4',5'-HEXACHLOROBIPHENYL CLEARLY PREDOMINATED IN THE FAT OF CHICKENS FED FAT FROM AROCLOR 1254-TREATED SWINE.[HANSEN LG ET AL; J AGRIC FOOD CHEM 31 (2): 254-60 (1983)] **PEER REVIEWED** PubMed Abstract
  • A physiologically based human pharmacokinetic model of chem intake via ingestion of food and water and inhalation of air is presented. The model takes the form of a series of algebraic equations that describe the steady state, constant exposure, transport rates, and physiological distribution in arterial and venous blood, lung, fat, skin, muscle, liver, gut tissue, gut lumen, and richly perfused tissues. It is assembled using the fugacity concept and is applied to 2,2',4,4',5,5'-hexachlorobiphenyl and styrene. The model can be used to elucidate how tissue concn respond to these intake routes.[Paterson S, Mackay D; Environ Toxicol Chem 6 (5): 395-408 (1987)] **PEER REVIEWED**
  • DISPOSITION OF 2,3,6,2',3',6'-HEXACHLOROBIPHENYL (2,3,6-HCB) & 2,4,5,2',4',5'-HCB (2,4,5-HCB) IN 24-MO OLD MALE SPRAGUE-DAWLEY RATS AFTER IV ADMIN WAS COMPARED TO DATA OBTAINED FROM 2-3 MO OLD RATS. ALTHOUGH THE PATTERN OF HCB DISPOSITION DID NOT CHANGE WITH AGE, IE, METABOLISM & EXCRETION OF 2,3,6-HCB VERSUS PERSISTENCE OF 2,4,5-HCB, THERE WERE DIFFERENCES IN RATES OF ELIM & IN TISSUE LEVELS. THERE WAS ENHANCED METABOLITE RETENTION IN MUSCLE, SKIN, & ADIPOSE TISSUE OF OLDER RATS WHICH SUGGESTED AN AGE-RELATED DECREASE IN TISSUE CLEARANCE. THE LARGER VOLUME OF ADIPOSE TISSUE IN THESE OLDER RATS COULD IN PART EXPLAIN THIS OBSERVATION. THERE WERE FEW CHANGES IN DECAY RATES FROM TISSUES OR IN BILIARY EXCRETION. AGE HAD A GREATER EFFECT ON DISPOSITION OF 2,4,5-HCB THAN ON 2,3,6-HCB.[BIRNBAUM LS; TOXICOL APPL PHARMACOL 70 (2): 262-72 (1983)] **PEER REVIEWED** PubMed Abstract
  • DISPOSITION OF 37 PCB CONGENERS & ADIPOSE TISSUE-PLASMA PARTITION OF 28 PCB CONGENERS WERE STUDIED IN 26 PERSONS OCCUPATIONALLY EXPOSED TO VARIOUS PCBS (20-54% CL). CONCN OF PCBS IN ADIPOSE TISSUE & PLASMA WERE RELATED TO DURATION & INTENSITY OF EXPOSURE. PCB CONCN IN ADIPOSE TISSUE WAS PROPORTIONAL TO THAT IN PLASMA, WITH A PARTITION FOR TOTAL PCBS OF APPROX 190:1 INDICATED FROM REGRESSION ANALYSIS. PCB CONGENERS WITH CL IN BOTH 4-POSITIONS OF BIPHENYL RING WERE MAJOR COMPONENTS IN PLASMA & ADIPOSE TISSUE. CONGENERS WITH UNSUBSTITUTED 3,4-POSITIONS ON 1 OR BOTH OF BIPHENYL RINGS WERE OBSERVED AT LOWER CONCENTRATIONS. IN CONTRAST, THOSE COMPOUNDS WITH SUBSTITUENTS AT 2,4- & 3,4-POSITIONS ON BOTH RINGS WERE PRESENT IN MUCH HIGHER PROPORTIONS IN BLOOD OR ADIPOSE TISSUE THAN IN PCB MIXTURES USED. THESE COMPONENTS ALSO HAD HIGHER ADIPOSE TISSUE-PLASMA PARTITION THAN THOSE WITH UNSUBSTITUTED 3,4-POSITIONS, REGARDLESS OF DEGREE OF CHLORINATION.[WOLFF MS ET AL; TOXICOL APPL PHARMACOL 62 (2): 294-306 (1982)] **PEER REVIEWED** PubMed Abstract
  • EFFECTS OF RESTRICTING FOOD INTAKE ON THE DISTRIBUTION OF 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (6-CB) IN RATS ADMIN A SINGLE DOSE OF 0.6 MG/KG, IV. GRADUAL DISAPPEARANCE OF ADIPOSE TISSUE WAS INDUCED BY RESTRICTING FOOD INTAKE TO 25% OF AD LIBITUM CONSUMPTION. IN FIRST SERIES OF EXPERIMENTS, 6-CB WAS ADMIN SIMULTANEOUSLY WITH START OF FOOD RESTRICTION. FECAL EXCRETION RATE OF 6-CB INCR, REACHED A MAX IN 2ND WK, & THEN LEVELED OFF. AFTER 7 WK, SOME 50% OF THE DOSE WAS EXCRETED & 26% WAS LOCATED IN SKIN. AMOUNTS IN MUSCLE, LIVER, LUNG, KIDNEY, BRAIN, GI CONTENTS, & RESIDUAL ADIPOSE TISSUE WERE BETWEEN 2.5 & 0.1% OF ADMIN DOSE. IN 2ND SERIES OF EXPERIMENTS, 6-CB WAS ADMIN 2 WK AFTER FOOD RESTRICTION STARTED, IE WHEN ADIPOSE TISSUE RESERVES HAD ALREADY LARGELY DISAPPEARED. FECAL EXCRETION RATE WAS MAXIMAL AT OUTSET & GRADUALLY DECR. CUMULATIVE EXCRETION & DISTRIBUTION VALUES FOR SKIN & OTHER TISSUES WERE NOT SIGNIFICANTLY DIFFERENT FROM VALUES DETERMINED IN ABOVE SERIES AFTER 7 WK. PHARMACOKINETIC OF 6-CB IS INFLUENCED BY ADIPOSE TISSUE MASS.[JONDORF WR ET AL; DRUG METAB DISPOS 11 (6): 597-601 (1983)] **PEER REVIEWED** PubMed Abstract
  • IN C57BL & DBA MICE THE ROLE OF ADIPOSE TISSUE AS MODIFIER OF TISSUE DISTRIBUTION, BIOLOGICAL EFFECTS, & ELIMINATION OF 2,4,5,2',4',5'-HEXACHLOROBIPHENYL (2,4,5-HCB) WAS STUDIED. SINCE 2,4,5-HCB WAS PRIMARILY SEQUESTERED BY THE ADIPOSE TISSUE, DBA MICE REQUIRED GREATER DOSES OF 2,4,5-HCB THAN DID C57 MICE TO REACH SIMILAR TISSUE LEVELS OF CHEMICAL. ACCORDINGLY, GREATER 2,4,5-HCB DOSES WERE REQUIRED BY DBA MICE FOR ELEVATION OF DRUG-METABOLIZING ENZYME ACTIVITIES.[AHOTUPA M, MANTYLA E; MOL PHARMACOL 24 (3): 464-70 (1983)] **PEER REVIEWED** PubMed Abstract
  • LAKE TROUT & CHINOOK SALMON SAC FRY WERE EXPOSED TO WATER CONTAINING LOW PPB CONCENTRATIONS OF (14)C-2,4,5,2',4',5'-HEXACHLOROBIPHENYL (2,4,5-HCB). THE 2,4,5-HCB WAS ADDED TO WATER IN STATIC SYSTEM 3 TIMES DAILY FOR 15 DAYS, EACH ADDN BEING A CALCULATED WATER CONCN OF 5 PPB. ALTHOUGH IT DID NOT ACCUMULATE IN WATER, IT DID ACCUMULATE IN FRY OF BOTH SPECIES, REACHING CONCN OF 7.6 PPM IN LAKE TROUT FRY & 3.6 PPM IN CHINOOK SALMON, 1 DAY AFTER THE LAST ADDITION. FOR EACH SPECIES IT WAS FOUND THAT AMT OF 2,4,5-HCB PRESENT AT TIME OF DEATH WAS CONSTANT, NO MATTER WHEN ANIMALS HAD DIED.[BROYLES RH, NOVECK MI; TOXICOL APPL PHARMACOL 50 (2): 299-308 (1979)] **PEER REVIEWED** PubMed Abstract
  • Longterm (280 days) pharmacokinetics of 2,2',4,4',5,5'-hexachlorobiphenyl was studied in rats with const adipose tissue mass. This was achieved by feeding the animals 50% of their mean ad libitum food intake, 2,2',4,4',5,5'-hexachlorobiphenyl was administered as a single iv injection of 0.6 mg/kg. Tissues and excreta were analyzed at various time points from 4 to 280 days. After the redistribution phase, all tissue concentrations declined with terminal half-lives of 431-478 days, and concn in adipose tissue was 1000 times higher than in blood. The corresponding ratios were: for skin 40, lung 30, liver 25, brain 10, and muscle 10. From day 4 on only adipose tissue, skin, and muscle contained significant amts of 2,2'4,4',5,5'-hexachlorobiphenyl. Between 2 and 4 wk adipose tissue and skin reached a max corresponding to 68 and 15% of the dose, respectively. After 280 days these values declined to 38 and 7% of the dose. Fecal excretion during this period was 43% of the dose with a terminal half-life of 478 days. Polar metabolites (1.5% of dose) were detectable in urine only. Extrapolation of fecal excretion kinetics yields a total excretion value of 99% of the dose at infinite time. ...[Wyss PA et al; Drug Metab Dispos 14 (3): 361-5 (1986)] **PEER REVIEWED** PubMed Abstract
  • Male Sprague-Dawley rats were ... treated with a first dose of 0.6 mg/kg 2,4,5,2',4',5'-hexachlorobiphenyl intravenously, followed by an identical dose 14 days later. Similar distribution and elimination patterns were recorded, regardless of the order or number of 2,4,5,2',4',5'-hexachlorobiphenyl doses administered to the animals. The administration of a second dose of unlabeled 2,4,5,2',4',5'-hexachlorobiphenyl did not affect the tissue distribution or excretion of the product administered 14 days earlier. The body weight of the animals increased by 36 % during the first 14 days of the study and by 56% for the entire 28 day experimental period. The percent distribution of the total dose of 2,4,5,2',4',5'-hexachlorobiphenyl in the fat, muscle, skin, liver, and plasma was similar for all groups.[Gallenberg LA, Vodicnik MJ; Drug Metab Dispos 15 (3): 363-6 (1987)] **PEER REVIEWED** PubMed Abstract
  • OF ... 2,2',4,4'5,5'-HEXACHLOROBIPHENYL FED TO RATS, LESS THAN 10% WAS EXCRETED IN FECES, INDICATING A HIGH DEGREE OF ABSORPTION, METABOLISM OR LOCALIZATION IN THE TISSUES. ... FOLLOWING IV INJECTION TO RATS OF ... /2,2',4,4',5,5'-HEXACHLOROBIPHENYL, IT WAS/ FOUND IN HAIR, SUGGESTING THAT THIS MAY SERVE AS A ROUTE OF PCB EXCRETION.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V18 73 (1978)] **PEER REVIEWED**
  • RESULTS FROM A PROCEDURE FOR ANALYZING THE BINDING OF 2,4,5,2',4',5'-HEXACHLOROBIPHENYL (HCB) TO LOW DENSITY LIPOPROTEINS & SERUM ALBUMIN INDICATE THAT ALBUMIN & LOW DENSITY LIPOPROTEIN EFFECTIVELY BIND THIS POLYCHLORINATED BIPHENYL & SUGGEST THAT PLASMA PROTEINS MAY PLAY A ROLE IN ITS DISTRIBUTION TO PERIPHERAL CELLS. LOW DENSITY LIPOPROTEINS BOUND HCB AT SEVERAL NONINTERACTIVE SITES & BOVINE SERUM ALBUMIN AT 1 NONINTERACTIVE SITE.[BECKER MM, GAMBLE W; J TOXICOL ENVIRON HEALTH 9 (2): 225-34 (1982)] **PEER REVIEWED** PubMed Abstract
  • Rats were treated by gavage, with a single dose of 14 C-2,4,5,2',4',5',-hexachlorobiphenyl at 0.6 or 3.6 mg/kg body weight. The rats were examined 1 h, 24 h, 6 weeks, 20 weeks, or 40 weeks after dosing. The highest levels of PCBs were found in the muscle, liver, adipose tissue, and skin, early in study. ... The highest PCB levels were found in the adipose tissue followed by the skin, muscle, and liver. During the 40 week study period, only 16% of the total dose was excreted.[WHO; Environ Health Criteria 140: Polychlorniated Biphenyls and Terphenyls p.226 (1993)] **PEER REVIEWED**
  • Studies of polychlorinated biphenyls (PCB) toxicity in laboratory animals indicate a wide species variability in sensitivity to physiological intoxication by these compounds. For example, rats are largely resistant to PCB intoxication, whereas rhesus monkeys are quite sensitive. Human sensitivity to PCB toxicity appears to be related to the source of exposure. All PCB congeners are highly lipophilic, and most are readily distributed to all tissues. PCBs are cleared from tissues at very different rates. ... Rates of PCB metabolism vary widely, depending on the animal species and the degree and positions of chlorination. The ability of animals to metabolize PCBs increases in the order, fish, birds, and mammals. PCBs that are not readily cleared concentrate in fatty tissue. Pharmacokinetic modeling of PCBs is discussed. A pharmacokinetic model for PCBs in the rat show that compartment sizes and blood flows are independent of the chemical being modeled. The amounts stored in tissues depends on the tissue to blood distribution coefficients and the body burden. The metabolic clearance constants show a considerable range, from 10 ml/min for 4-chlorobiphenyl to 0.045 ml/min for 2,4,5,2',4',5'-hexachlorobiphenyl for a rat weighing 250 g.[Matthews HB, Dedrick RL; Annual Rev Pharmacol Toxicol 24: 85-103 (1984)] **PEER REVIEWED**
  • THE AVAILABILITY OF RADIOLABELED 2,4,5,2',4',5'-HEXACHLOROBIPHENYL (2,4,5-HCB) TO BENTHIC AMPHIPODS WAS DETERMINED FROM EXPTL CONTAMINATED NATURAL SEDIMENTS. AMPHIPODS ACCUM 2,4,5,2',4',5'-HEXACHLOROBIPHENYL PRIMARILY BY DIRECT UPTAKE FROM WATER AS A FUNCTION OF EXPOSURE TIME. ORGANISMS THAT WERE DIRECTLY EXPOSED TO SEDIMENTS HAD CONSISTENTLY HIGHER CONCN THAN DID ORGANISMS EXPOSED ONLY TO THE SEDIMENT-DESORBED RESIDUES IN THE WATER. THE SUBSTRATE ORG MATTER CONTENT & PARTICLE SIZE AFFECTED THE CONCN OF 2,4,5-HCB IN THE WATER & ORGANISM. REMOVAL OF SEDIMENT ORG MATTER ENHANCED 2,4,5-HCB ACCUM BY SUBSTRATE & WATER EXPOSED ORGANISMS. AMPHIPODS ACCUM THE LEAST 2,4,5-HCB WHEN EXPOSED TO SILT-CLAY PARTICLE SIZE FRACTIONS WHICH CONTAINED ORG MATTER. THE SUBSTRATE PARTICLE SIZE WAS LESS IMPORTANT THAN THE ORG MATTER IN DETERMINING 2,4,5-HCB AVAILABILITY TO THE AMPHIPODS.[LYNCH TR, JOHNSON HE; ASTM SPEC TECH PUBL 766 (AQUAT TOXICOL HAZARD ASSESS): 273-87 (1982)] **PEER REVIEWED**
  • THE DISPOSITION OF MULTIPLE ORAL DOSES OF ... 2,4,5,2',4',5'-HEXACHLOROBIPHENYL ... STUDIED IN MICE ... INVESTIGATORS FOUND THAT THE RATE OF METABOLISM & EXCRETION DECREASED WITH INCREASING CHLORINATION, BUT WAS MOST PROFOUNDLY AFFECTED BY ELIMINATION OF ADJACENT UNSUBSTITUTED CARBON ATOMS. ACCUMULATION OCCURRRED MAINLY IN ADIPOSE TISSUE, SKIN, MUSCLE.[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3657] **PEER REVIEWED**
  • TISSUE DISTRIBUTION, METABOLISM & EXCRETION OF LABELED 2,4,5,2',4',5'-HEXACHLOROBIPHENYL WERE STUDIED IN BEAGLE DOGS & CYNOMOLGUS MONKEYS FOLLOWING SINGLE IV ADMIN OF 0.6 MG/KG. ELIMINATION OF THE PARENT PCB FROM BLOOD OF BOTH SPECIES WAS BIPHASIC WITH TERMINAL PHASE ELIMINATION RATE CONSTANT OF 0.045/DAY FOR DOG & 0.015/DAY FOR MONKEY. PERCENTAGE OF DOSE REMAINING WAS FOUND LARGELY AS PARENT CMPD IN ADIPOSE TISSUE (16%), SKIN (6%), & MUSCLE (2%). BY 90 DAYS, THE MONKEY HAD EXCRETED ONLY 18% OF THE DOSE (17% IN FECES, 1% IN URINE).[SIPES IG ET AL; TOXICOL APPL PHARMACOL 65 (2): 264-72 (1982)] **PEER REVIEWED** PubMed Abstract
  • TRANSPLACENTAL TRANSFER OF 2,4,5,2',4',5'-HEXACHLOROBIPHENYL (HCB) WAS MINIMAL IN MICE WHO HAD RECEIVED HCB 2 WK PRIOR TO MATING. HOWEVER, IT WAS RAPIDLY TRANSFERRED TO SUCKLING OFFSPRING THROUGH THE LACTATING MAMMARY GLAND.[VODICNIK MJ, LECH JJ; TOXICOL APPL PHARMACOL 54 (2): 293-300 (1980)] **PEER REVIEWED** PubMed Abstract
  • The disposition and biotransformation of 4,4'-dichlorobiphenyl, 2,2',3,3',6,6'-hexachlorobiphenyl, 2,2',4,4',5,5'-hexachlorobiphenyl were studied in isolated rat hepatocyte suspensions. The PCBs were taken up rapidly by the cells but 2,2',4,4',5,5'-hexachlorobiphenyl was not metabolized (0.1-200 uM). ... Analysis of absorbance differences (DELTA absorbance 390-240 nm) of equimolar concn of congener (100 uM) revealed that 2,2',3,3',6,6'-hexachlorobiphenyl displayed the greatest affinity of binding to cytochrome p450 followed by 4,4'-dichlorobiphenyl, while 2,2',4,4',5,5'-hexachlorobiphenyl showed virtually no binding.[Vickers AE M et al; Biochem Pharmacol 35 (2): 297-306 (1986)] **PEER REVIEWED** PubMed Abstract
  • The distribution, metabolism, and excretion of 14C labeled 2,4,5,2'4'5' hexachloro, or 2,3,6,2'3',6' hexachlorobiphenyl in beagle dogs and cynomolgus monkeys, were studied after a single intravenous dose. The elimination of the test substances from the blood of both species was shown to be biphasic. The results for dichlorobiphenyl showed that the dog eliminated 50% of the dose (urine, 7 %; feces, 43 %) within 24 hr, while the remainder was found mainly in the adipose tissue. By 5 days, 90% had been eliminated. The monkey eliminated less than 15% of the dose within 24 hr, with less than 1% in the feces. The remainder was found in the adipose tissue. Within 28 days, 59% of the dose had been eliminated, chiefly in the urine. Biliary excretion after 24 hr was shown to be 33 % in the dog and only 0.4% in the monkey. The data for 2,4,5,2',4',5' hexachlorobiphenyl showed that the dog eliminated 66% (urine, 3%; feces, 63%) within 3 days; the monkey eliminated 18 % of the dose (of which 17 % was in the feces), 90 days following administration. The remainder was found in the adipose tissue. In the studies with 2,3,6,2',3',6' hexachlorobiphenyl, the dog eliminated 52% of the dose within 24 hr (urine, 11%; feces, 41%) and 70% in 3 days. The monkey eliminated 19% during the first 24 hr, divided equally between urine and feces. By 15 days, 61% had been eliminated, primarily in the feces. The 24 hr biliary excretion was 26% and 2.4% in the dog and the monkey, respectively.[WHO; Environ Health Criteria 140: Polychlorniated Biphenyls and Terphenyls p.238 (1993)] **PEER REVIEWED**
  • The effects of age on intestinal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin were studied using adult male Fischer 344 rats of 3 different age groups: 13 weeks old (young), 13 months old (mature), and 26 months old (senescent). Absorption was measured with an in situ intestinal recirculation perfusion procedure. Absorption expressed in terms of ng 2,3,7,8-tetrachlorodibenzo-p-dioxin absorbed/g intestinal dry weight/hr was 166, 149, and 143 ng/g/hr in the young, mature and senescent groups, respectively . When absorption was calculated in terms of ng 2,3,7,8-tetrachlorodibenzo-p-dioxin absorbed/g mucosal dry weight/hr, the decrease between the senescent rats and the 2 younger age groups, from 544 ng/g/hr (young) to 351 ng/g/hr (senescent), was not statistically significant (p< 0.05). Absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin was unaffected by the presence of 2,4,5,2',4',5'-hexachlorobiphenyl in the perfusate, but that 2,4,5,2',4',5'-hexachlorobiphenyl absorption was (p< 0.01) enhanced by the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin.[Hebert CD, Birnbaum LS; Toxicol Lett 37 (1): 47-55 (1987)] **PEER REVIEWED** PubMed Abstract
  • The transfer of 2,4,5,2',4',5' hexachlorobi[14 C]phenyl across the placenta during the course of pregnancy in Sprague Dawley mice was studied. The PCB was injected intraperitoneally at 100 mg/kg body weight, in corn oil, 2 weeks prior to mating. The concentrations of 14 C PCB in the fetuses from 12 and 18 day pregnant animals were 0.71 and 2.45 mg/kg tissue, respectively. At birth, the total carcass concentration for all newborn animals was less than 3 mg/kg tissue, which represents less than 3 % of the dose present in the mothers at birth.[WHO; Environ Health Criteria 140: Polychlorniated Biphenyls and Terphenyls p.230 (1993)] **PEER REVIEWED**
  • UPTAKE, DISTRIBUTION, & EXCHANGE OF CHLORINATED INSECTICIDES DIELDRIN & CHLORDECONE & BIPHENYLS 2,4,5,2',4',5-HEXACHLOROBIPHENYL & 3-CHLOROBIPHENYL AMONG HUMAN LIPOPROTEINS WAS EXAMINED BY FLUORESCENCE QUENCHING, GEL FILTRATION, & ULTRAFILTRATION. THE CHLORINATED HYDROCARBONS ATTACHED TO ALBUMIN OR ONE OR MORE OF THE LIPOPROTEINS WERE RAPIDLY TRANSFERRED TO ALL OTHER LIPOPROTEINS. THE EXCHANGE WAS COMPLETE IN LESS THAN 1 MIN.[MALIWAL BP, GUTHRIE FE; J LIPID RES 23 (3): 474-9 (1982)] **PEER REVIEWED** PubMed Abstract
  • Uptake of the persistent environmental chemicals 2,2',4,4',5,5'-hexachlorobiphenyl and DDT by Chang liver cells, an established human cell line, was investigated. Monolayer cells were incubated with culture medium to which the lipophilic model cmpd were added. The time course of uptake of either cmpd was biphasic, reaching equil after approx 5 hr of incubation. The ratio of DDT: hexachlorobiphenyl uptake was dependent on the presence of serum proteins. Increasing concn of serum proteins in the culture medium progressively inhibited uptake. Efflux from the cells was not entirely reversible: 10-20% of the chemicals were not released. Uptake was a linear function of the external concn of the cmpd. Absorptive binding to the outer cell plasma membrane could be determined by removing bound chemicals with fetal calf serum (back exchange). With this method, temp-dependent translocation through the cell plasma membrane could directly be demonstrated. The effect of low temp as well as the influence of metabolic inhibitors point out the contribution of energy-driven uptake pathways. Demonstration of low density lipoprotein receptor-like binding protein on Chang liver cells facilitated estimation of the role of receptor-mediated uptake. ...[Mangelsdorf I et al; Biochem Pharmacol 36 (13): 2071-8 (1987)] **PEER REVIEWED** PubMed Abstract

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Metabolism/Metabolites

  • (14)C-labeled 2,4,5,2',4',5'-hexachlorobiphenyl (2,4,5-HCB), a slowly metabolized polychlorinated biphenyl (PCB), was given to rats by gastric incubation. The hepatocyte nuclei were then isolated and treated with specific hydrolytic enzymes to separate the nucleic macromols, (protein, RNA, and DNA). 2,4,5-HCB was shown to bind in vivo to hepatocyte nuclei. Liver nuclear proteins bind 70% of 2,4,5-HCB and 30% is found in the DNA fraction. No radioactivity was found in the nuclear RNA fraction. ...[Daubeze M, Narbonne JF; Toxicol 31 (3-4): 315-8 (1984)] **PEER REVIEWED**
  • A strain of Alcaligenes eutrophus, designated H850, that rapidly degrades a broad and unusual spectrum of polychlorinated biphenyls (PCBs) has been isolated and characterized. .... This strain was isolated from PCB-containing dredge spoils, grows well on biphenyl and 2-chlorobiphenyl but poorly on 3- and 4-chlorobiphenyl. Capillary gas-chromatographic analysis showed that biphenyl- grown resting cells of H850 degraded the components of 38 of the 41 largest peaks of Aroclor 1242 and 15 of the 44 largest peaks of Aroclor 1254, resulting in an overall reduction of PCBs by 81% for Aroclor 1242 (10 ppm) and 35% for Aroclor 1254 (10 ppm) in 2 days. H850 metabolized the predominantly ortho- substituted PCB congeners. ... The congener selectivity patterns indicate that a two-step process consisting of anaerobic dechlorination followed by oxidation by H850 can effectively degrade all of the congeners in Aroclor 1242 and possibly all those in Aroclor 1254.[Bedard DL et al; Appl Environ Micro 53 (5): 1094-102 (1987)] **PEER REVIEWED**
  • IN MICE & RATS, 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (HCB) IS METABOLIZED TO 2,2',4,4',5,5'-HEXACHLORO-3-BIPHENYLOL. IN RABBITS, THE METABOLIC PRODUCTS ARE A MONOHYDROXYLATED DERIVATIVE, A MONOHYDROXY WITH CHLORINE SHIFT, & A MONOHYDROXYMETHOXYLATED DERIVATIVE. PRODUCTS IN CHICKENS ARE A META-HYDROXYLATED DERIVATIVE, A PENTA-CHLOROBIPHENYL DERIVATIVE, & A PENTA-CHLOROTRIHYDROXYLATED DERIVATIVE.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V18 75 (1978)] **PEER REVIEWED**
  • METABOLISM OF (3)H-LABELED 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (2,4,5-HCB) WAS STUDIED IN 2 MONKEYS. 2,4,5-HCB WAS EXCRETED IN THE BILE AS PARENT 2,4,5-HCB, 2,2',4,4',5,5'-HEXACHLORO-3-HYDROXYBIPHENYL, & WATER-SOL CONJUGATES OF 2,4,5-HCB GLUCURONIDE, PROBABLY 2,2',4,4',5,5'-HEXACHLORO-3-HYDROXYBIPHENYL GLUCURONIDE. METABOLISM OF 2,4,5-HCB MAY OR MAY NOT INCLUDE THE FORMATION OF AN ARENE OXIDE.[NORBACK DH ET AL; RES COMMUN CHEM PATHOL PHARMACOL 32 (1): 71-85 (1981)] **PEER REVIEWED** PubMed Abstract
  • METABOLISM OF 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (245-HCB) BY HUMAN HEPATIC MICROSOMES WAS STUDIED. 245-HCB WAS NOT METABOLIZED UNDER VARIOUS CONDITIONS. THE FACT THAT IT WAS NOT METABOLIZED EXPLAINS WHY IT IS THE PREDOMINANT PCB FOUND IN HUMAN ADIPOSE TISSUE.[SCHNELLMANN RG ET AL; BIOCHEM PHARMACOL 32 (21): 3233-9 (1983)] **PEER REVIEWED** PubMed Abstract
  • The biochemical basis for the marked difference in the rate of the hepatic metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl by beagle dogs and Sprague-Dawley rats has been investigated. Control dog liver microsomes metabolize this substrate 15 times faster than control rat liver microsomes. Upon treatment with phenobarbital, at least two cytochrome p450 isozymes are induced in the dog, and the hepatic microsomal metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl is increased on both a per nanomole p450 basis (two-fold) and a per milligram protein basis (five-fold). ... Antibody inhibition studies have shown that /one of the phenobarbitol induced isozymes/, PBD-2, accounts for > 90% of the hepatic microsomal metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl in control and phenobarbital induced dogs, while /the major isozyme induced by phenobarbitol/, PB-B, only accounts for about half of the metabolism of this compound by microsomes obtained from phenobarbital treated rats. ...[Duignan DB et al; Arch Biochem Biophys 255 (2): 290-303 (1987)] **PEER REVIEWED** PubMed Abstract

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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