Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 36355-01-8 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Hexabromobiphenyl
  • 1,1'-BIPHENYL, HEXABROMO- (9CI)
  • POLYBROMINATED BIPHENYL MIX

Human Toxicity Excerpts

  • EPIDEMIOLOGY STUDIES: A field biochemical epidemiology study was conducted using the Michigan cohort consisting of 51 rural residents exposed to polybrominated biphenyls (PBB). ...PBB serum levels were detected in 36 of the 51 PBB-exposed subjects. The serum half-life of /the major PBB congener, hexabromobiphenyl/ HBB was determined by comparing the current serum HBB values to the subject's previous serum values obtained 5 to 8 years earlier...The /caffeine breath test/ CBT and caffeine urinary metabolite ratio/ CMR were elevated in the subjects exposed to PBBs as compared to the values obtained from urban nonsmokers and were similar to those found in adults who smoke. A gender effect was seen in the PBB-exposed subjects, the median CBT and CMR values of the females being lower than the values of males. There was a correlation between the CBT and the HBB serum values (r2= 0.2, p=0.01) but not between CMR and HBB serum values. The CBT and CMR were easily conducted in the field and appear to be useful metabolic probes of cytochrome P-450I activity in human environmental toxicology. [ Lambert GH, et al; Environ Health Perspect 89: 175-181 (1990) ]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: Firemaster BP-6 induced...cytochrome P-450 and P-448 in liver of rats 192 hr after treatment with single ip injections of 25 mg/kg; major component, 2,2',4,4',5,5'-hexabromobiphenyl /63%/, induced only cytochrome P-450. /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: 20 male and 20 female 2.5 month old Sherman rats...given single...1000 mg/kg... Firemaster FF-1 by gavage as 5% solution in peanut oil. ...Killed...at 2, 6, 10 and 14 month after treatment... hepatocytes in center of liver lobules...enlarged, vacuolated or had foamy cytoplasm.../6 or more months after treatment/. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Toxic effects in rats and mice exposed to Firemaster FF-1 including body weight decrease, liver hypertrophy and fatty infiltration, hepatocyte swelling, cytoplasmic vacuoles and microscopic abscesses. Chloracne-like lesions occurred in rabbit ears exposed to total dose of 60 mg Firemaster FF-1 per ear. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Some ...effects of 2,4,5,2',5'-penta- (congener 1), 2,3,4,2',4',5'-hexa- (congener 5), 2,4,5,3',4',5'-hexa- (congener 6), 2,3,4,5,3',4',-hexa- (congener 7), and 2,3,4,5,2',3',4'-heptabromobiphenyl (congener 9) were evaluated in male rats given a single 90 mg/kg ip injection and killed 7 days later. Only congener 7 depressed body weight gain, spleen and thymus weights, and caused severe histopathological changes in the thymus. Congener 7 caused the largest incr in liver weight and the most changes in liver pathology while congener 1 failed to enlarge this organ and caused the mildest ultrastructural changes. Liver microsomes were isolated and evaluated for enzyme induction from all treated rats except those administered congener 6... . All congeners increased the liver microsomal cytochrome P-450 content, but only congener 7 shifted the carbon monoxide difference spectrum absorption maximum to 448.0 nm. The microsomal ethyl isocyanide difference spectrum 455/430 nm ratio was increased the most by congener 7 (3 fold). All congeners increased cytochrome P-450 reductase and microsomal epoxide hydrase activities by nearly 1.5-3 fold. Congener 7 failed to induce aminopyrine-N-demethylase activity but the remaining congeners increased it by 2 fold. Congener 7 was the most effective inducer of benzo(a)pyrene hydroxylase and p-nitrophenol UDP-glucuronyl transferase. These results add to the suggestion that the presence of an ortho halogen on a polyhalogenated biphenyl does not completely abolish toxicity or 3-methylcholanthrene-type microsomal enzyme induction. /Firemaster/ [Dannan GA et al; Fundam Appl Toxicol 2 (6): 313-321 (1982) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Firemaster BP-6 administered to female Sprague-Dawley rats at 150 mg/kg as single ip injection induced epoxide hydratase and aniline hydroxylase. In contrast, ethylmorphine-n-demethylase and ethoxycoumarin-o-deethylase activities increased. /Firemaster BP-6/ [Dent JG et al; Toxicol Appl Pharmacol 38 (2): 237 (1976) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Isomerically pure di-, tri-, tetra-, penta-, hexa-, and octabromobiphenyls were injected ip into weanling rats at 0.2 mmol/kg/day for 3 days. Hepatic p-nitroanisole o-demethylase activities were increased proportionally as degree of bromination increased. [Ecobichon DJ et al; Toxicol Appl Pharmacol 47 (2): 341 (1979) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Irradiation of ...FireMaster BP-6 in cyclohexane solution at 300 nm for 930 min resulted in a marked diminution of the major components of the mixture. Administration of the photolyzed PBB mixture of FireMaster BP-6 to immature male Wistar rats caused both dose-related decrease in thymus weight and increase in hepatic microsomal benzo(a)pyrene hydroxylase (AHH), 4-dimethylaminoantipyrine N-demethylase and NADPH-cytochrome c reductase activities and cytochrome P-450 content. The dose effecting half-maximal AHH induction for the photolyzed PBBs (9 mg/kg) was approximately 6 times lower than that of FireMaster BP-6 (50 mg/kg). Furthermore, the concentration of photolyzed PBBs (2 um) required to displace 50% of the specifically-bound (3H) TCDD from its high-affinity cytosolic Ah receptor was approximately 150 times lower than that required for FireMaster BP-6 (300 um) ... . The results suggest that the photolysis of the commercial PBB mixture yields products which possess increased biologic activity. /Firemaster BP-6/ [Robertson LW et al; Toxicology 22 (2): 103-114 (1981) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Male Sprague Dawley rats were fed diets containing 0, 0.1, 1, 10, or 100 ppm of 3,3',4,4',5,5'-hexabromobiphenyl (HBB), 2,2',4,4',5,5'-HBB, or Firemaster (FM) BP-6, a commercial mixture of polybrominated biphenyls, for 9 days. Feed consumption and body and organ weights were recorded and histologic and ultrastructural changes were evaluated. Results indicated that 3,3',4,4',5,5'-HBB causes more severe pathologic effects than either FM BP-6 or 2,2',4,4',5,5'-HBB. [Render JA et al; Toxicol and Appl Pharmacol 62 (3):428-44 (1982) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Subchronic dosing with Firemaster FF-1 reduced lethal dose: doses of 100 mg/kg on 5 days/wk for total of 22 doses killed 100% of female rats at 41-43 days and 38% of male rats at 50-73 days. Guinea pigs and mink exposed to commercial hexabromobiphenyl appeared to be more susceptible. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Changes in the bile canaliculus (proliferation of microvilli) were also found in mice fed 1000 mg FM BP-6/kg for 4-14 days. Changes in the hepatocytes of these mice were increase in cell size, decrease in rough-surfaced endoplasmic reticulum (RER), increase in smooth-surfaced endoplasmic reticulum (SER), degeneration of mitochondria, decrease in glycogen, and increase in size and number of nucleoli. Fatty infiltration of the cytoplasm was reported only in another two studies on mice dosed with 30 mg FM FF-1/kg body weight per day or fed 167 mg FM BP-6/kg for 6 weeks. However, in (moribund) mice fed 167 mg FM BP-6/kg feed for 12 weeks, lipid vacuoles were not found within the cytoplasm, but, almost exclusively, within the nucleus. Hepatocellular necrosis has also been observed. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 2, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Rats (No. = 10), given oral doses of FM FF-1 over 6 months, showed dose-related decreases in serum thyroxine (T4) and triiodothyronine (T3). Significant decreases in T4 were seen at doses as low as 0.3 mg PBB/kg bw/day in males, and 1 mg/kg bw/day in females. The reduction in T3 was somewhat less and only significant at high doses (3-10 mg/kg bw/day) in females. A time and dose-dependent reduction in plasma T4 levels was also found in male rats (n = 8-11) administered FM FF-1, by gavage, for 10 or 20 days at 1, 3, or 6 mg/kg bw/day. In addition, the reduced plasma T4 levels were correlated with an increase in thyroid stimulating hormone (TSH) at 20 days. At 6 mg/kg bw/day, the thyroid uptake of iodine was increased, but the incorporation of iodine in monoiodotyrosine was decreased. ...Short-term feeding (7 months) of female rats with commercial hexabromobiophenyl at dietary concentrations of 1-50 mg/kg also resulted in an decrease in serum T3 and T4 levels... . /Commercial mixtures/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ...It was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single ip injection of either peanut oil or 150 mg/kg PBBs (Firemaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body wt ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was incr while epoxide hydratase activity was decr (adults) or not affected (immature rats) in kidney. ...Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. ... /Firemaster BP-6/ [McCormack KM et al; Environ Health Perspect 23: 153-157 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Studies were performed to investigate the effects of FireMaster FF-1, a chemical fire retardant consisting of a mixture of polybrominated biphenyls (PBB), on immune functions in mice and rats. Animals received 22 daily treatments of 0.03, 0.3, 3.0, or 30 mg PBB/kg bw in a period covering 30 days. PBB exposure severely depressed cell mediated immunity in both mice and rats at the higher dosage levels as indicated by depressed responsiveness of splenic lymphocytes to mitogenic stimulation by polyclonal T-cell activators. Additionally, humoral immunity was depressed in mice at the 30.0 ppm dosage level. Assays for humoral immune functions included antibody production, serum immunoglobulin levels, and mitogenic stimulation of splenic lymphocytes to a polyclonal B-cell activator. These studies indicate that PBB exposure can lead to suppression of both humoral and particularly cell-mediated immune responses. /Firemaster FF-1/ [Luster MI et al; Environ Health Perspect 23: 227-232 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Male ...F-344/N rats ...B6C3F1 /mice/ ...were dosed by gavage, 5 day/wk for a total of 22 doses with 0.03-30 mg/kg of Firemaster FF-1, 0.168-16.8 mg/kg of 2,4,5,2',4',5'-hexabromobiphenyl (HBB), or corn oil vehicle. A battery of tests was administered at the end of repeated dosing (30 days...) and 30 days after/wards/ ...(60 day test). FF-1 and, to a much lesser extent, HBB decr body weight and performance on a variety of tests designed to detect neuromuscular dysfunction, ...activity in the open field, forelimb grip strength, and muscular reflexes. Visual placement responses were also decr in some animals, while hypothermia was observed in others. Emotionally, as measured by the number of defecations and urinations in the open field, was not affected ... . At the end of 30 day test, mice were less affected by exposure... than rats; rats tended to worsen during the 30 days of no dosing, while mice tended to improve. These experiments indicate that oral dosing with levels of PBBs below those required to produce signs of acute toxicity produced behavioral or neurological toxicity when given repeatedly. /Firemaster FF-1/ [Tilson HA et al; Environ Health Perspect 23: 257-263 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Female Sprague-Dawley rats were fed polybrominated biphenyls (PBBs) for 15 or 140 days after a 70% partial hepatectomy and diethylnitrosamine administration (10 mg/kg bw) to determine the effect of varying the length of exposure to PBBs on the enhancement of gamma-glutamyl transpeptidase enzyme-altered foci. FireMaster BP-6, a commercial mixture of PBBs, was fed to rats at a dietary concentration of 100 mg/kg for 15 days or 10 mg/kg for 140 days during the promotion phase of a two-stage hepatocarcinogenesis assay. Results indicate that short term exposure to PBBs is as effective as long term exposure in enhancing the development of enzyme-altered foci. /FireMaster BP-6/ [Jensen RK et al; Carcinogenesis 5 (1): 63-66 (1984) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Weanling male rats were exposed to ...a PBB mixture (Firemaster FF-1) in their diet so that they received 1 mg/kg/day for 6 months. They were then fed a normal diet for 4 months. Following this they were placed on diets containing either activated charcoal (AC) or cholestyramine (CSA) for 6 months to evaluate the usefulness of these compounds in reducing the body burdens of the retained PBBs. Periods of restricted caloric intake were also used in an effort to mobilize PBBs stored in fat. Neither compound nor restricted caloric intake was found to be effective in reducing tissue bromine levels... . /Firemaster FF-1/ [McConnell EE et al; Drug Chem Toxicol 3 (3): 277-292 (1980) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ...Four of four rabbits died over a 14-day period after application of 5,000 mg/kg of a commercial hexabromobiphenyl mixture... /by application to abraded and occluded dorsal trunk skin as a 35% (w/v) paste in corn oil/. A dose of 10,000 mg/kg applied for 24 hours killed two of four rabbits. The cause of death was not reported. ...Rabbits treated with 1,000 mg/kg showed no weight gain over 14 days. Doses of 5,000 and 10,000 mg/kg induced an 11% and 20% weight loss, respectively, whereas, a dose of 100 mg/kg was without effect. /Commercial mixture/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.224-34 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: A decreased heart rate (bradycardia) was measured in White Leghorn cockerels fed 150 mg FireMaster FF-1/kg feed for approximately 9 weeks. Another characteristic sign in chickens was general edema. /FireMaster FF-1/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 2, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: The weight of the thymus was reduced as early as 6 or 15 days after rats were given high doses of FireMaster. Frequently, decreases in thymus weights were accompanied by increases in liver weights. But, in some cases, changes in thymus weights were seen at doses lower than those required for liver changes, or vice versa. Rats and mice both fed FireMaster(R) BP-6 (100 mg/kg feed) for 30 days differed in their thymic response in that rats remained unaffected and mice showed decreased thymic weight. In contrast, rats appeared to be more sensitive than mice when given equal oral doses (30 mg/kg body weight per day for a period of 30 days) of FireMaster(R) FF-1. Two strains of inbred mice are known to differ in their thymic sensitivity to FireMaster(R). /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 2, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: 20 male and 20 female 2.5 month old Sherman rats given single doses of 1000 mg/kg (Firemaster FF-1) by gavage as 5% solution in peanut oil.The rats were fasted for 15 hours prior ro dosing; ...Killed in groups of 5 at 2, 6, 10 and 14 months after treatment. ...Neoplastic liver nodules, described as "hyperplastic"...in 4/5 females killef 10 months after treatment and in 2/5 males and 3/5 females killed after 14 months; no tumors in controls. In addition, in the animals killed 6 or more months after treatment with PBBs, the hepatocytes in the center of the liver lobules were enlarged, vacuolated or had foamy cytoplasm and a general pleomorphism and multinucleation. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 114 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ...It was hypothesized that very short-term administration of /Firemaster BP-6/ (FM) would result in tumor promotion. Female Sprague-Dawley rats weighing 185-215 g were initiated by a two-thirds partial hepatectomy followed by 10 mg diethylnitrosamine/kg bw 24 hr later. Thirty days later, rats were gavaged with FM in corn oil, at total doses of 0, 13, or 130 mg FM/kg bw. Half the dose was given on day 30, and the remaining half was given 24 hr later. At 120 days after gavage the rats were killed and necropsied. Five liver sections from each animal were histochemically stained for gamma-glutamyl transpeptidase-positive enzyme-altered foci (EAF). EAF were significantly increased over control values in initiated rats given 130 mg FM/kg. In animals given 13 mg FM/kg, EAF were increased to a lesser extent but not significantly above controls. Enhancement of these EAF in initiated rats reflects tumor-promoting activity... . /Firemaster BP-6/ [Rezabek MS et al; J Toxicol Environ Health 20 (4): 347-356 (1987) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Noninbred Sherman strain rats were given the polybrominated biphenyl mixture Firemaster FF-1 (PBB). Rats given a single dose of 1,000 mg PBB/kg or 12 doses of 100 mg PBB/kg bw in corn oil by gavage had final (when < or = 26 month old) liver PBB concentrations of 17.1 and 34.8 mg/kg (wet wt), respectively. The respective incidence of hepatocellular carcinomas was 41.4 and 67.8%. No difference in PBB concentrations was found between hepatocellular carcinomas and surrounding liver tissue. In addition, most livers of PBB-dosed rats had adenofibrosis of the liver. Livers of controls were essentially normal. /Firemaster FF-1/ [Kimbrough RD et al; J Natl Cancer Inst 66 (3): 535-542 (1981) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: /Noninbred Sherman strain/ Rats given a single dose of 200 mg PBB/kg MW ... /in corn oil by gavage/ had a 31.2% incidence of neoplastic nodules, whereas none were seen in the controls. The mean PBB concentrations (when 26 months old) were 2.68 mg/kg in liver, 244 mg/kg in adipose tissue, and 0.22 mg/kg in blood. /Firemaster FF-1/ [Kimbrough RD et al; J Natl Cancer Inst 66 (3): 535-542 (1981) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Rats administered 2.5 mg/kg/day of an unspecified hexabromobiphenyl mixture for 7 months showed no significant changes in serum T3, but serum T4 was not evaluated. /Commercial mixture/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.184 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Individual PBB congeners have been examined for tumor promoting activity in rats that were partially hepatectomized and initiated with diethylnitrosamine (DENA). Numbers of hepatic GGT-altered foci and/or neoplastic nodules were increased following promotion with 3,3',4,4'-tetrabromobiphenyl (BB 77) (approx 0.25 mg/kg/day in the diet for 180 days or 8 weekly intraperitoneal injections of approx 7 mg/kg), 2,2',4,4',5,5'-hexabromobiphenyl (BB 153) (approx 0.5 mg/kg/day in the diet for 180 days) or 3,3',4,4',5,5'-hexabromobiphenyl (BB 169) (approx 0.05 mg/kg/day in the diet for 140 days). Dietary exposure to approx 5 mg/kg/day of BB 153 for 480 days similarly promoted hepatic development of altered foci and neoplastic nodules in rats, whereas approx 0.05 mg/kg/day of BB 169 did not, although an apparent synergistic effect was observed when these two congeners were fed together. /3,3',4,4',5,5'-Hexabromobiphenyl/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.223 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Loss of hair (including eye lashes), dry scaly skin, and periorbital edema were reported in a juvenile female rhesus monkey given 25 mg FireMaster FF-1/kg feed for 50 weeks (total dose: approximately 1.5 g), however, the time of onset of these symptoms was not specified. /FireMaster FF-1/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 2, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: FireMaster and BB 153 were also tested as tumor initiators (and promotors) in a two-stage mouse skin tumorogenesis assay. A tumor promoter, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), was applied to the skin of a mouse of a tumor-susceptible strain (SENCAR). After 14 weeks of treatment, neither FM nor BB 153 exhibited tumor initiating (or promoting) activity. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Rhesus monkeys are also among the species more sensitive to FireMaster. At exposures of 1.5-300 mg FM/kg feed, they developed weight loss or a lack of weight gain, hematological and clinical chemistry changes, loss of hair, skin lesions, edema, enlargement of the heart and liver, areas of hemorrhage in the adrenal glands; reduced spermatogenesis, and immune incompetence. Microscopic changes in the liver included enlarged hepatocytes with fatty infiltration. The most severe lesion was hyperplastic gastroenteritis and the accompanying ulcerations. Exposures to 25 or 300 mg FM/kg feed also caused death. The female monkeys fed with lower doses of FireMaster(R) (0.3 mg/kg diet), for over one year, did not develop any of the signs of intoxication noted above, except for weight loss. However, they were affected by reproductive dysfunctions. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 3, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Firemaster BP-6 has teratogenic activity in mice, producing exencephaly when fed to pregnant dams at 100 or 1000 mg/kg of diet on day 7-18 of pregnancy and cleft palates and hydronephrosis when given at 1000 mg/kg of diet. /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 117 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: /Firemaster BP-6 in/ single dose of 40, 200, 400 or 800 mg/kg was administered /to rats/ by gavage on days 6-14 of pregnancy: doses of 400 or 800 mg/kg induced cleft palate and diaphragmatic hernia; number of resorbed and dead fetuses increased markedly with administration of 800 mg on days 7-12... /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 117 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Testing of mouse offspring at 30-120 days of age following maternal exposure to FireMaster FF-1 by gavage on every other day during gestation and through weaning showed altered negative geotaxis and avoidance response latencies at > or =3 mg/kg/day and reduced acoustic startle responsiveness and motor activity at 10 mg/kg/day. /FireMaster FF-1/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.294 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Female F0 generation Sprague-Dawley rats received daily oral doses of 0, 0.2, or 2 mg/kg polybrominated biphenyls (PBB) as FireMaster BP-6 from Day 6 of gestation through Day 24 postpartum. Maternal parameters were assessed, and F1 generation offspring were evaluated for growth and survival, as well as physical and behavioral development. No adverse maternal effects were observed nor were there PBB-related effects on survival of the F1 generation or acquisition of developmental landmarks. Crown-rump length of 0.2 and 2 mg/kg male offspring was significantly less than that of controls and 2 mg/kg male and female offspring gained significantly less weight than did controls for the entire 60-day postnatal observation period. An overall evaluation of behavior by multivariate analysis of variance revealed significant PBB-related effects for acquisition of forward locomotion, cliff avoidance, cage emergence, and open-field activity of male and female offspring from dams administered 2 mg/kg. Delays in acquisition of forward locomotion and supressed open-field activity were the most prominent effects. These indications of growth retardation and neurobehavioral toxicity occurred at concentrations of PBB in offspring body fat in the range of those which have been reported for highly exposed human subjects with neurological sequelae. /FireMaster BP-6/ [Henck JW et al; Neurotoxicol Teratol 16 (4): 391-400 (1994) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Pregnant Sprague Dawley rats were given 0, 0.25, 0.5, 1, 5, and 10 mg of a commercial polybrominated biphenyl, FireMaster BP-6 (PBB), in olive oil by gavage each day from days 7-15 of pregnancy. Laboratory chow and water were given ad libitum. Treatment with PBB had no significant effect on body weight gain, food and water consumption, and urine production. The mothers were killed on day 20, and the only significant effect ...was an incr liver weight of those given 1, 5, and 10 mg PBB. Spleen, kidney, ovarian, gravid uterine, and perirenal fat pad weights were similar to those of control mothers. PBB had no significant effect on number of live/dead fetuses, crown-rump length or fetal weight. No grossly malformed fetuses were observed in PBB-treated mothers. The effects of PBB transfer from mothers to nursing pups was studied by reciprocal exchange of pups between control mothers and mothers treated with 10 mg PBB. When the pups were 21 days old, they were weaned and fed control chow. The following four combinations of prenatal-postnatal exposure were studied: control-control (C:C); control-PBB (C:PBB); PBB-control (PBB:C); and PBB-PBB. Although the birth weights of pups from PBB-treated mothers were similar to those of the controls, body weights of 60-day-old males exposed prenatally and postnatally (PBB:C, C:PBB, and PBB:PBB) were less (p<0.05) than those of the controls (C:C). The weights of the perirenal fat pads of male and female pups exposed to PBB were less (p<0.05) than the control. Liver weights, on a body weight basis, were higher in male and female pups exposed to PBB. Vaginal openings were delayed; the percentages of 36-day-old pups with open vaginas were 50 (C:C), 38 (PBB:C), 28 (C:PBB), and 30 (PBB:PBB). /Firemaster BP-6/ [Harris SJ et al; Environ Health Perspect 23: 295-300 (1978) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: A single dose of 40, 200, 400 or 800 mg/kg bw was administered /to rats/ by gavage on days 6-14 of pregnancy: doses of 400 or 800 mg/kg bw induced cleft palate and diaphragmatic hernia; the number of resorbed and dead foetuses increased markedly with administration of 800 mg on days 7-12; and maternal toxicity occurred in animals given 800 mg/kg. /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 117 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Animal studies of FireMaster FF-1 and FireMaster BP-6 have also shown that hexabromobiphenyl PBB mixtures can induce non-neurological developmental toxicity. Embryolethal effects or increased mortality among nursing young were observed ...in monkeys after exposure before conception and during pregnancy. /Commercial mixture/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.239 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Liver effects, including increased liver weight and hepatic cytochrome P-450 enzymic activity, hepatocyte enlargement, vacuolization, and/or other degenerative changes, occurred in the offspring of rats, mice, and swine fed FireMaster FF-1 or FireMaster BP-6 during gestation and/or lactation. /FireMaster FF-1 or BP-6/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.295 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Increased menstrual cycle duration and prolonged implantation bleeding were observed in female monkeys fed FireMaster FF-1 in approximate daily dose levels of 0.012 mg/kg for 7 months before breeding and during pregnancy. A corresponding decrease in serum levels of progesterone suggests that the reproductive effects in the monkeys are related to PBB-induced endocrine imbalance. /FireMaster FF-1/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.287 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Serum levels of the adrenal hormones corticosterone B, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were decreased in rats fed > or =0.25 mg/kg/day FireMaster BP-6 for 5-7 months. Serum corticosterone levels and adrenal weight did not change in rats exposed to 6 mg/kg/day of an unspecified PBB mixture for a shorter duration of 20 days. ...Implantation was completely blocked in 40-67% of female rats treated with FireMaster BP-6 by gavage in dose levels > or =28.6 mg/kg on alternate days between gestation days 0 and 14. [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.286-7 (September 2004) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Ingestion of FM FF-1 by adult, female rhesus monkeys at concentrations of 0.3 mg/kg feed for 7 months (total dose: approximately 10 mg PBB) caused prolonged menstrual cycles and decreased concentrations of serum progesterone. /FireMaster FF-1/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 3, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Hepatic microsomes, prepared from rats exposed to FM BP-6 (100 mg/kg of feed) from day 8 of gestation until they were killed at 4-21 weeks of age, showed an increased metabolism of progesterone, testosterone, and of the estrogens estradiol, estrone, and ethynylestradiol. In contrast to the increased hydroxylation reaction, reduction of testosterone was inhibited by pretreatment with PBBs. The metabolism of exogenously administered and labelled steroid hormones including progesterone, testosterone, and estradiol, was also enhanced in vivo in rats following perinatal exposure (gestation day 8-28 days postpartum) to 10 or 100 mg FM BP-6/kg feed, as shown by diminished steroid action and reduced radio activity in serum and target organs. In contrast, endogenously produced concentrations of luteinizing hormone, prolactin, or corticosterone were not affected in rats treated with 100 mg FM BP-6/kg feed from gestation day 8 until the ninth week of age. Rats dosed with 1, 3, or 6 mg FM FF-1/kg bw/day for 20 days also did not show any alterations in plasma corticosterone or testosterone levels, but, at 6 mg/kg bw/day, there was a significant reduction in plasma prolactin levels. Long-term, low-dose treatment with FM BP-6 (1, 10, or 50 mg/kg feed for 5-7 months) caused cumulative and dose-dependent decreases in the serum corticosterone levels of female rats, as well as reductions in the circulating levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Mice and rats exhibited neuromuscular dysfunction in a variety of tests after administration of Firemaster FF-1 or 2,2´,4,4´,5,5´-hexabromobiphenyl. Rats appeared to be more severely affected than mice; the effects in rats tended to worsen over 30 days after treatment. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116 (1978)]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: ...The influence of PBB on cognitive function was evaluated. Male rats (Sprague-Dawley) received "hexabrominated biphenyl" (not specified) at 1 mg/kg body weight per day (5 days per week) for a total of 20 doses during a one-month period and were then trained for a simple auditory discrimination task. PBB-treated animals did not significantly differ from controls with respect to accuracy on the discrimination task. However, throughout 24 weeks of discrimination training, PBB rats made many more extra responses and showed longer response times (response latencies), thereby reducing their efficiency. Upon completion of the behavioral study, a group of rats, dosed concurrently with the behavioral animals, was sacrificed immediately after the end of dosing, and the brains were used to prepare both intact synaptosomes and synaptic plasma membranes. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of rats administered 1 mg PBB/kg body weight per day. [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • GENOTOXICITY: /Negative for chromosomal aberration and sister chromatid exchange when tested using Chinese hamster CHO cells (cell culture) with and without metabolic activation/. /from table/ /Commercial mixture/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.239 (September 2004) ]**PEER REVIEWED**
  • GENOTOXICITY: /Negative for gene mutation when tested using Salmonella typhimurium (plate incorporation) with and without metabolic activation/. /from table/ /Commercial mixture/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.239 (September 2004) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Firemaster FF 1 was a mixed inducer of hepatic microsomal drug-metabolizing enzymes such as aryl hydrocarbon hydroxylase in rats, its effects resembling those of a combination of phenobarbital and 3-methylcholanthrene. /Firemaster FF-1/ [Goldstein JA et al; Biochem Pharmacol 28 (19): 2947 (1979) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Firemaster BP-6 (FM), a mixture of polybrominated biphenyls (PBB), and the congeners 2,2',4,4',5,5'-hexabromobiphenyl (245-HBB), 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB), and 3,3',4,4'-tetrabromobiphenyl (34-TBB) were tested for their ability to inhibit cell-cell communication between human teratocarcinoma cells in culture. Both FM and 245-HBB were capable of inhibiting cell-cell communication in these cells, with only slight effects on cell survival. 345-HBB was highly cytotoxic, but did not show the ability to interrupt cell-cell communication. 34-TBB was moderately cytotoxic and was also ineffective at blocking cell-cell communication. [Kavanagh TJ et al; Fundam Appl Toxicol 8 (1): 127-131 (1987) ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: The activity of the enzyme uridine 5'-diphosphoglucuronyltransferase (UDP-GT), responsible for the conjugation of a wide variety of substrates, was significantly increased in microsomes prepared from rats ip injected with 3,3',4'4',5,5'-hexabromobiphenyl at 20 mg/kg body weight. /3,3',4,4',5,5'-Hexabromobiphenyl/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 3, 2005. ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: The influence of FireMaster BP-6 on glutathione peroxidase activity, which is present in most mammalian species, was studied in the rat (liver cytosol). This enzyme is represented, on the one hand, by a selenium-containing enzyme, glutathione peroxidase, which is able to reduce hydrogen peroxide to water and organic hydroperoxides to the corresponding hydroxy compounds, and, on the other hand, by certain isozymes of glutathione transferase. The activity of the selenium-dependent glutathione peroxidase was decreased to about 50% of control values on day 16 following the ip administration of FireMaster BP-6 (500 mg/kg body weight). Inversely, there was a potent induction of glutathione transferases during the 16-day period. [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • ALTERNATIVE IN VITRO TESTS: Adenylate cyclase [ATP pyrophosphatase lyase (cyclizing)] catalyzes the conversion of adenosine triphosphate (ATP) to adenosine 3',5'-cyclic monophosphate (cyclic AMP), which acts as a central regulator of several diverse cell activities. In preliminary experiments, the in vitro effect of FireMaster BP-6 on adenylate cyclase activity in the plasma membranes of rat lung alveoli was determined. At concentrations of 10 ug/mL, the FireMaster mixture stimulated the basal adenylate cyclase activity of plasma membranes 2- to 2.5-fold. /FireMaster BP-6/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: This study was conducted to examine the effects of PBB on the clearance of radiolabel from injected estradiol-17 beta and progesterone along with daily determinations of concentrations of endogenous estradiol-17 beta and progestins in blood plasma. Toxicity was induced by dosing two Holstein cows with 25 g of Firemaster BP-6/day for 39 or 50 days. Single iv injections of 35 microCi (4-14C) progesterone and 400 microCi (2,4,6,7-(3)H) estradiol-17 beta were given on day -5, 10, 30 and 38 or 48 relative to dosing. Last injections were given when severe toxic symptoms were observed in each animal. Clinical signs, blood constituents, and necropsy findings confirmed the toxic syndrome. Clearance of 14C from progesterone was described by a biexponential function of time, while 3H from estradiol was cleared more slowly with a triexponential function. The total clearance rate for radiolabel from progesterone was approximately four times greater than estradiol throughout the experiments. The total clearance rates were similar for both steroids before and 10 days after dosing with PBB. A toxic syndrome was well developed by day 30 of PBB dosing and the total clearance rate of both steroids decreased approximately 50% with precipitous decreases when animals were terminally toxic. Despite the developing toxic syndrome, plasma concentrations of estradiol-17 beta and total progestins were normal and the periodicity of estrous cycles was maintained. /Firemaster BP-6/ [Willett LB et al; J Anim Sci 56 (5): 1135-1144 (1983) ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Offspring of cows experimentally given polybrominated biphenyls(Fire-Master BP-6) were studied from May 1976 through January 1981. Daily doses were 0, 0.25, and 250 mg for 60 days for Groups I, II, and III, and 250 mg for 180 or 202 days for Group V. Concentrations of polybrominated biphenyls in fat of dosed animals in Groups I, II, and III, and V were .05, .20, 25, and 30 ug/g at the end of dosing. ...Seventy-five calves were born to these cows and their offspring, representing first through fifth parturition. Fifteen calves died, 10 of which were in Groups III and V. All deaths in Groups III and V were attributable to dystocia. Incidences of dystocia and calf mortality were related to birth weight of the calf which in turn was correlated with concentrations of polybrominated biphenyls in blood and tissues of the dam. Other variables that influenced birth weight were sex of calf, length of gestation, and parturition number of dam. There were no significant differences in growth and performance of calves from the four dosed groups. Clinical signs of polybrominated biphenyl toxicosis were not evident, and general health of offspring was not influenced. Number of inseminations for conception was greater among offspring from Groups III and V. Mechanisms for this dysfunction have not been determined. /FireMaster BP-6/ [Willett LB, et al; J Dairy Sci 65 (1): 81-91 (1982) ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Fifteen Holstein cows were studied for up to 1500 days to determine whether exposure to polybrominated biphenyls produced latent or subtle toxicosis not evident in previous acute or short studies. Animals for these long studies came from three groups given 0, 0.25, or 250 mg of Firemaster BP-6/day for 60 days in 1975. Another group that received 250 mg of BP-6 for 180 or 202 days in 1976 also was studied. Individual animals were in their second, third, or fourth lactations. Milk production was not different among experimental groups, and mature body weights were similar. Increases in the amount or duration of exposure did not increase number of infections, dysfunctions, or general injuries. Exposure to 250 mg/day for 60, 180, or 202 days increased frequencies of reproductive disorders at parturition, particularly related to and following a high incidence of dystocia. A contributing factor to dystocia was larger birth weights of calves from cows exposed to 250 mg daily as compared to calves from cows exposed to 0 or 0.25 mg polybrominated biphenyls. Although reproductive dysfunctions required more veterinary care, numbers of services per conception were not different among groups. /Firemaster BP-6/ [Willett LB et al; J Dairy Sci 63 (12): 2090-2102 (1980) ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: ...Firemaster FF-1, a commercial mixture of polybrominated biphenyls (PBB), and tissues from chickens and a cow that had previously consumed PBB were fed to mink to ascertain the chronic effects of the commercial and metabolized form of this compound on mink. Diets that contained 6.25 ppm (or more) PBB were lethal to adult mink within 10 months. One to 2.5 ppm dietary PBB fed for 9 months had an adverse effect on litter size, kit weight at birth, and kit survival. The data suggest that the PBB derived from contaminated beef and poultry was more toxic than the original PBB. The clinical signs of PBB poisoning in mink were food rejection, weight loss, and unthrifty appearance, and fatty infiltration of the liver. Based on these findings, mink must be considered highly susceptible to PBB toxicity. PBB residue levels 60 times the amount in the diet were found in the adipose tissue of the PBB-treated animals. /Firemaster FF-1/ [Aulerich RJ, Ringer RK; Arch Environ Contam Toxicol 8 (4): 487-498 (1979) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Abortion or fetal death were reported in offspring of Holstein heifers fed Firemaster BP-6 in daily doses of 25 g/day. After Michigan accident, many calves were born with extraordinarily large heads. /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 118 (1978)]**PEER REVIEWED**
  • IMMUNOTOXICITY: Suppression of cell-mediated immunity occurred in rats and mice given oral doses of Firemaster FF-1, as indicated by depressed responsiveness of splenic lymphocytes to mitogenic stimulation by polyclonal T-cell activators. Indications of humoral immune suppression were observed in mice. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116 (1978)]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Effects of Firemaster FF-1 in cattle include anorexia, decreased milk production, lameness, hematomas, abscesses, abnormal hoof growth, alopecia and skin thickening. Autopsy revealed liver and kidney degeneration. /Firemaster FF-1/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 117 (1978)]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: In cattle, kidneys were severely affected, and doubled in size in animals that were moribund from high doses of FireMaster(R). The kidneys were distended with fluid, and pale tan to gray in color. Perirenal lymph nodes were enlarged and edematous. The principal histological lesions consisted of dilatation of collecting ducts and convoluted tubules, and tubular epithelial degenerative changes. Similar renal lesions were found in calves treated with different doses of FireMaster(R) (0.1-100 mg FM FF-1/kg body weight per day, for 2-12 weeks). The severity of renal damage was related to dose level and length of exposure. Despite the extensive morphological damage, effective renal plasma flow rates and glomerular filtration rates were not affected in cows. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 2, 2005. ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Compared with other species, liver changes observed in cattle were less dramatic. Only an early stage of centrilobular fatty degeneration and glycogen depletion were found in the enlarged livers of lethally (25 g FM BP-6/day) dosed cows. In addition, there were changes in the gallbladder and bile duct. Single calves exposed to FM FF-1 for 6-12 weeks had slightly enlarged hepatocytes (dose: 1 mg/kg body weight per day) or necrosis of individual or small foci of hepatocytes (dose: 100 mg/kg body weight per day). /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 2, 2005. ]**PEER REVIEWED**
  • IMMUNOTOXICITY: Serum immunoglobulin levels in mice were changed following short-or long-term exposure to FireMaster. Suppression of antibody response to sheep erythrocytes (or bovine gamma globulin) was reported after the short-term exposure of mice and after a six-month exposure of rats. ...Interestingly, mice showed no response in the 6-month study. A decrease in antibody titres to tetanus toxoid was observed in guinea-pigs. Although mortality rates following infection with Listeria monocytogenes were not affected by FireMaster exposure in mice exposed long-term, an increased susceptibility to infection with Listeria was suggested, because a decrease in time to death occurred. No effects on mean survival time were observed in mice fed 5 or 167 mg/kg feed for 3 or 6 weeks and then challenged by Plasmodium berghei (murine malaria) infection. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • IMMUNOTOXICITY: An increased susceptibility to endotoxin was found in mice after short-term or perinatal exposure to FireMaster. /FireMaster/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 7, 2005. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ... In cHBB-treated B6 mice, 100% of the pups died within the first 1-5 days post partum. Histologic exam showed lesions in the liver with white-cell infiltrates, indicative of hepatic failure, whereas the mother's liver appeared normal. Northern blot and RT-PCR analysis confirmed CYP1A1 mRNA induction in fetal liver and brain at GD18 in cHBB-treated B6 but no other groups. [Miller KA et al; Toxicologist 66 (1-S): 27 (2002) ]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rabbit dermal 5 g/kg bw /FireMaster BP-6/ /from table/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 1, 2005. ]**PEER REVIEWED**
  • LD50 Rat oral 21.5 g/kg /FireMaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 116]**PEER REVIEWED**
  • LD50 Rat (Fischer-344 N, female) oral 1.43 g/kg bw /FireMaster FF-1/ /from table/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 1, 2005. ]**PEER REVIEWED**
  • LD50 Rat (Fischer-344 N, male) oral 3.28 g/kg bw /FireMaster FF-1/ /from table/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 1, 2005. ]**PEER REVIEWED**
  • LD50 Mouse oral >15 g/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1778]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • In Sprague-Dawley rats, concentration of PBBs were higher in livers of offspring than in livers of their mothers treated with 50 mg/kg of diet Firemaster BP-6 on days 8-21 of gestation. Transfer of PBBs by way of milk was more important than placental transfer in relation to occurrence of PBBs in newborns. /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 118]**PEER REVIEWED**
  • PBB is excreted in milk of ruminants exposed to Firemaster BP-6. In study on placental transfer of Firemaster BP-6, detectable levels were found in tissues of 17 Holstein calves from dams that had been contaminated at least 7-9 months prior to delivery. /Firemaster BP-6/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 118]**PEER REVIEWED**
  • Body fat levels of 120-400 mg/kg /of hexabromobiphenyl believed to be Firemaster FF-1/ were found in aborted calves /in 1973/. In October 1974, measurements made...at 22 /Michigan/ farm premises showed PBBs in poultry tissue and cattle tissue at levels of 4600 and up to 2700 mg/kg, respectively. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V18 113]**PEER REVIEWED**
  • Timed-pregnant albino Hartley strain guinea pigs of approximately 65 days gestation or lactating animals within 6-12 hr of parturition received a single oral dose of Firemaster FF-1 (50 mg/kg bw). The pregnant animals and their fetuses were killed 2 days later at term while the lactating animals and their pups were killed at intervals of 2, 4, 7, 14, 28, 42, and 60 days. Tissues (liver, kidney, lung, perirenal fat) were /analyzed/ ...for 2,4,5,2',4',5'-hexabromobiphenyl (HBB)... content... . Transplacentally-acquired residues of the order of 45 ug HBB/g were found in both maternal and fetal adipose tissue and in fetal liver. HBB residues in maternal kidney, lung and liver were of the order of 4-7 ug/g while, in the fetuses and pups, levels in the kidney and lung were of the order of 1-2 ug/g. Levels of HBB in breast milk 2 days after treatment averaged 22.4 +/- 7.8 ug/g (mean +/- S.D.)... . HBB levels in the pup kidney, lung and adipose tissue reflected redistribution or sequestration in the body fat. The biological half-life of HBB in tissues of both dams and pups appeared to be approximately 22 days. /Firemaster FF-1/ [Ecobichon DJ et al; Toxicology 28 (1-2): 51-63 (1983) ]**PEER REVIEWED**
  • ...Dermal absorption in rabbits can be inferred from reports of lethality and liver effects observed after application of a commercial mixture of hexabromobiphenyl to abraded and occluded dorsal skin. /Commercial mixture/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.245 (September 2004) ]**PEER REVIEWED**
  • Tissue levels of young exposed to PBBs only via nursing have been determined for rats... . When pups of non-treated female rats were nursed by dams fed FireMaster BP-6 (50 mg/kg bw) on days 1-14 postpartum, hepatic /hexabromobiphenyl/ concentrations were on average approximately eight times higher than those in the dams on day 14 postpartum. /FireMaster BP-6/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**
  • In birds, eggs are the medium of PBB transfer to the offspring. The ratio of egg PBB contents to dietary level has been reported to be 1:1 and 1.3 - 1.5:1 in chickens (White Leghorn hens) and Japanese quail, respectively. After 63 days of feeding FireMaster(R) BP-6 in the diet, the PBB level in body fat of White Leghorn hens was about 4 times the level in eggs. /FireMaster BP-6/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**
  • ...A 50% recovery of /hexabromobiphenyl/ HxBB /was found/ after 168 hr in the feces of two cows given single intraruminal doses (3 g) of FireMaster BP-6. However, relatively high concentrations of radioactivity or of HxBB, found, in some cases, in the feces during the first few days after dosing or during daily dosing, may have been due to incomplete absorption. Approximately 60% of the total dose was also recovered in the feces of rhesus monkeys. Elimination of PBBs was primarily via the bile and the intestine into the feces and, in general, was found to be a slow process. Biliary concentrations have been measured in a Rhesus monkey, in rats, and in cattle. In rats, excretion of HxBB in the bile accounted for 0.68% of the total PBB dose between 0 and 4 hr after iv administration. Twenty- four hours after an iv dose, 0.032% of the total dose was excreted in the bile in 1 hr, and, 7 or 42 days after dosing concentrations were too low to quantify. Because of this small amount cleared with the bile, enterohepatic recirculation of HxBB in rats is not important. Concen trations of HxBB in the bile of cattle were two-three times greater than the concentration in the plasma. [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**
  • There have been some studies on the means to enhance the elimination of PBBs. PBBs used were: FireMaster(R) FF-1 and [14C-]HxBB. The treatments included activated carbon in rats and cows, cholestyramine in rats and monkeys, colestipol in chickens, mineral oil in rats, monkeys, and chickens, high-fiber diets in rats, and phenobarbital in cows. The effects of restricted caloric intake, alone, or in combination with other treatments, was investigated in rats and chickens. The procedures were found not to be, or to be only partially, effective in reducing the body burden of PBBs (measured as concentrations of HxBB, total bromine levels, or 14C-activity). [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**
  • Another domestic species in which the kinetics have been examined is the chicken. Whole carcass analysis of male White leghorn chickens showed that, during the 2 weeks that FireMaster FF-1 was fed at 0.1 or 1.0 mg/kg, the chickens retained 88 and 69%, respectively, of the FF-1 that was consumed. Withdrawal rates were determined in a similar study on egg- and meat-type chickens fed diets containing 1 or 10 mg FF-1/kg. Body burdens of BB 153 in chickens, previously fed 10 mg/kg, did not decrease significantly during a withdrawal period of 42 days (e.g., 3% loss by day 21 of withdrawal). In contrast, chickens, previously fed 1 mg/kg, eliminated up to 40% of the BB 153. Withdrawal of PBBs from the adipose tissue of laying hens fed FireMaster FF-1 at different dietary levels (0.2, 1, 5, 25, 125, or 625 mg/kg) has been followed... . BB 153 levels remained unchanged over the 56 days of withdrawal. /In another study/... a 50% reduction /was calculated/ after more than 16 weeks. Withdrawal from other tissues and from eggs was more rapid. /FireMaster FF-1/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of November 1, 2005. ]**PEER REVIEWED**

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Metabolism/Metabolites

  • The NADPH-dependent metabolism of a PBB mixture was studied in vitro with liver microsomes of rats induced with /phenobarbital/ (PB), PBB, or /3-methylcholanthrene/ (3-MC). Of the 12 major components of the mixture, only 2,2',4,5,5'-pentabromobiphenyl (BB 101) and a hexabromobiphenyl were metabolized by microsomes from PB- or PBB-treated rats. [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.257 (September 2004) ]**PEER REVIEWED**
  • The major urinary metabolite of FireMaster BP-6 /in pigs/ was a pentabromobiphenylol (1% of the dose), which could have resulted from direct hydroxylation of the minor pentabromobiphenylol isomers in FireMaster BP-6 or by debromination/hydroxylation of the major congener, 2,2',4,4',5,5'-hexabromobiphenyl (BB 153). /FireMaster BP-6/ [DHHS/ATSDR; Toxicological Profile for Polybrominated Biphenyls and Polybrominated Diphenyl Ethers p.256 (September 2004) ]**PEER REVIEWED**
  • The feces of dogs fed FireMaster BP-6 contained a metabolite identified as 6-hydroxy-2,2',4,4',5,5'-hexabromobiphenyl. However, the authors did not exclude microbial metabolism in the dog's gut, because no hydroxyhexabromobiphenyl was found in the liver of the dog, though PBB was present. /Investigators/ mentioned that dogs were able to metabolize 2,2',4,4',5,5'-hexachlorinated biphenyl, but were unable to metabolize the analogous PBB at an appreciable rate. /FireMaster BP-6/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**
  • Some investigations implied that fish may debrominate the more highly brominated components of PBB mixtures. Juvenile Atlantic salmon (Salmo salar) experimentally exposed to FireMaster BP-6, in water or in food, contained several mono- to pentabromobiphenyls, not present in FireMaster BP-6. /FireMaster BP-6/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**
  • Analyses of fish captured from natural waters may also indicate the possibility of the debromination reaction in fish, unless selective accumulation or elimination takes place. ...In fish from FireMaster BP-6-contaminated waters, only hexabromobiphenyl was detected. /FireMaster BP-6/ [WHO; Environ Health Criteria 152: Polybrominated biphenyls (1994). Available from: http://www.inchem.org/documents/ehc/ehc/ehc152.htm as of October 31, 2005. ]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008