Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 123-31-9 Toxicity Effects

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

Names (NTP)

  • Hydroquinone
  • 1,4-BENZENEDIOL (9CI)

Human Toxicity Excerpts

  • INGESTION OF 1 G BY ADULT HAS CAUSED ... DIZZINESS, SENSE OF SUFFOCATION, INCR RATE OF RESPIRATION, VOMITING, PALLOR, MUSCULAR TWITCHING, HEADACHE, DYSPNEA, CYANOSIS ... & COLLAPSE. URINE IS USUALLY GREEN OR BROWNISH-GREEN IN COLOR & CONTINUES TO DARKEN ON STANDING. ... DEATH ... APPARENTLY INITIATED BY RESP FAILURE. ... ANOXIA ... . [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 1675]**PEER REVIEWED**
  • ACUTE EXPOSURE TO HIGH CONCN OF VAPOR ... /CAUSED/ IRRITATION, PHOTOPHOBIA, LACRIMATION, ... CORNEAL ULCERATION ... . [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 498]**PEER REVIEWED**
  • INGESTION OF 1 G ... CAUSED TINNITUS, NAUSEA,VOMITING, SENSE OF SUFFOCATION, SHORTNESS OF BREATHNESS, CYANOSIS, CONVULSIONS, DELIRIUM, ... IRRITATION OF INTESTINAL TRACT, ... DERMATITIS ... FROM SKIN CONTACT. [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 763]**PEER REVIEWED**
  • STAINING & OPACIFICATION OF CORNEA OCCUR IN WORKERS EXPOSED FOR PROLONGED PERIODS TO CONCN OF VAPOR NOT HIGH ENOUGH FOR PRODN OF SYSTEMIC EFFECTS. [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 763]**PEER REVIEWED**
  • SYSTEMIC ACTIONS LIKE PHENOL, BUT IN ADDITION TREMORS ... ARE PROMINENT, PLUS OCCASIONAL SEVERE HEMOLYTIC ANEMIA (SUBSEQUENT TO METHEMOGLOBINEMIA). [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-190]**PEER REVIEWED**
  • FIVE HUNDRED FORTY-FOUR (544) CREWMEN ABOARD A LARGE USA NAVY VESSEL DEVELOPED GI DISEASE CHARACTERIZED BY ACUTE ONSET OF NAUSEA, VOMITING, ABDOMINAL CRAMPS, & DIARRHEA WHICH WAS FOUND TO BE DUE TO HYDROQUINONE CONTAMINATION OF THE CHILLED WATER SYSTEM BY AUTOMATIC PHOTO DEVELOPING MACHINES ON THE SHIP. [HOOPER RR ET AL; MORB MORTAL WKLY REP 27 (28): 237 (1978)]**PEER REVIEWED**
  • IRRITATING BUT NOT CORROSIVE. HUMAN POISONINGS ... REPORTED FROM MIXT OF HYDROQUINONE & METOL. ... FATAL HUMAN DOSES HAVE RANGED FROM 5-12 G, BUT 300-500 MG HAVE BEEN INGESTED DAILY FOR 3-5 MO WITHOUT ILL EFFECTS. LESIONS OF SKIN (ESP DEPIGMENTATION) & OF EYES ... MAY HAVE BEEN DUE TO LOCAL CONTACT WITH QUINONE. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-190]**PEER REVIEWED**
  • Hydroquinone in photographic workers produces irritation and staining of the cornea which may lead to reduction in vision. [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 820]**PEER REVIEWED**
  • Low-grade long-term exposure has caused discoloration, distortion and opacification of the corneas of workmen. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 498]**PEER REVIEWED**
  • In: workers engaged in the manufacture of hydroquinone ... colorless hydroquinone dust on reaching eye (with a distribution corresponding to palpebral fissure) oxidizes to brown benzoquinone. This material is stored in large granules in or near the basal layer of the corneal epithelium and in smaller granules in the more superficial epithelium. It is visible as a brown band keratopathy. [Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 527]**PEER REVIEWED**
  • Ingestion of 1 g by an adult (smaller quantity by a child) may cause tinnitus, nausea, dizziness, a sense of suffocation, an increased rate of respiration, vomiting, pallor, muscle twitchings, headache, dyspnea, cyanosis, delirium, and collapse. The urine is usually green or brownish green in color and continues to darken on standing. [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. 2591]**PEER REVIEWED**
  • Fatal cases have been reported after ingestion of 5 to 12 g. [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. 2591]**PEER REVIEWED**
  • Cases of dermatitis have resulted from skin contact with hydroquinone. [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. 2591]**PEER REVIEWED**
  • ...Reported cases of keratitis and discoloration of the conjunctiva among men exposed to concentrations ranging from 10 to 30 mg of vapor or dust of hydroquinone per cubic meter of air. [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. 2591]**PEER REVIEWED**
  • Acute neurotoxic effects reported in humans include delirium; twitching; vertigo; tinnitus. /From table/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 104]**PEER REVIEWED**
  • Neurotoxic effects include tremor; convulsions. /From table/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 104]**PEER REVIEWED**
  • Neurotoxic effects include delirium; hallucinations. /From table/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 104]**PEER REVIEWED**
  • Chronic neurotoxic effects include vision disturbances. /From table/ /Quinones/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 129]**PEER REVIEWED**
  • Hydroquinone: dust is irritating to eyes, nose, and mucous membranes. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1098]**PEER REVIEWED**
  • Clinical toxicity following acute ingestion consists of nausea, vomiting, muscular twitching, shortness of breath, cyanosis, confusion, and syncope. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1098]**PEER REVIEWED**
  • Contact with the skin can cause dermatitis, and contact with the eye can cause damage to the cornea. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1098]**PEER REVIEWED**
  • Important chemical causes of toxic vitiligo: hydroquinone. [Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 115]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LD50 OF HYDROQUINONE ... BY STOMACH TUBE TO RATS OF VARIOUS STRAINS ... APPROX 1000 MG/KG BODY WT. FASTING ANIMALS FOR 18 HR PRIOR TO ADMIN OF CMPD PRODUCED 2-3-FOLD INCR IN ITS TOXICITY ... SC DOSE OF 160 MG/KG BODY WT WAS LETHAL TO MICE ... . [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. V15 168 (1977)]**PEER REVIEWED**
  • IN 2-YR FEEDING STUDY /UP TO 1% HYDROQUINONE/ IN RATS, NO EFFECT ON FINAL BODY WT ... /& NO/ HEMATOLOGICAL OR PATHOLOGICAL CHANGES ... WHEN 5% ... ADMIN, 46% LOSS OF BODY WT WAS OBSERVED WITHIN 9 WEEKS; THE ANIMALS ALSO DEVELOPED APLASTIC ANEMIA, DEPLETION OF BONE MARROW, LIVER AND CORD-CELL ATROPHY, SUPERFICIAL ULCERATION & HEMORRHAGE OF GASTRIC MUCOSA. [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. V15 168 (1977)]**PEER REVIEWED**
  • EXPOSURE OF EXPTL ANIMALS (UNSPECIFIED) TO LETHAL DOSES ... SIGNS OF INCR MOTOR ACTIVITY ... CONVULSIONS & METHEMOGLOBINEMIA. SUBACUTE POISONING ... CHARACTERIZED BY HEMOLYTIC ICTERUS, ANEMIA, LEUCOCYTOSIS, HYPOGLYCEMIA & LATER, CACHEXIA ... . [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. V15 168 (1977)]**PEER REVIEWED**
  • PUPPY ... CHEWED PACKET OF DEVELOPER CONTAINING HYDROQUINONE ... EXHIBITED INCOORDINATION & VOMITING, WITH PULSE OF 180, FAST, SHALLOW BREATHING & PHOTOSENSITIZATION ... . [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 105]**PEER REVIEWED**
  • ... CAUSES RENAL TUBULAR NECROSIS IN RATS WHEN ADMIN IV @ DOSE OF 198 MG/KG BODY WT. [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. V15 169 (1977)]**PEER REVIEWED**
  • ... INDUCED CHROMOSOME ABERRATIONS OR KARYOTYPIC EFFECTS IN ALLIUM CEPA, ... CHERA ZEYLANICA, ... VICIA FABA, ... CALLISIA FRAGRANS, ... TRIGONELLA FOENUM-GRAECUM, ... ALLIUM SATIVUM ... /PLANTS/. [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. V15 169 (1977)]**PEER REVIEWED**
  • EXPTL EXPOSURE OF RABBIT EYES TO HIGH CONCN OF ... VAPOR OR DIRECT CONTACT WITH ... /IT/ CAUSED ... CONJUNCTIVITIS, CORNEAL EDEMA, & NECROSIS. /BENZOQUINONE/ [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 499]**PEER REVIEWED**
  • UPTAKE & TURNOVER OF THE SC ADMIN HYDROQUINONE WAS QUITE RAPID IN MOST TISSUES & ORGANS OF CARASSIUS AURATUS. IT SHOWED NO SPECIFIC AFFINITY FOR MELANOSOMES, ALTHOUGH IT INDUCED CYTOPATHOLOGIC ALTERATION IN THESE PIGMENT CELLS. ONLY THE MELANOSOME-CONTAINING PIGMENT CELLS PRESENT AT THE TIME OF TREATMENT WERE DESTROYED. [CHAVIN W; VIRCHOWS ARCH B 9 (4): 343 (1971)]**PEER REVIEWED**
  • THE EFFECTS OF SOME PHENOLS & PHENOLCARBOXYLIC ACIDS, MOST OF WHICH ARE FOUND IN ROASTED COFFEE, ON BILE FLOW IN RATS & INTESTINAL MOTILITY IN MICE & GUINEA PIGS WERE STUDIED. HYDROQUINONE HAD GREATER CHOLERETIC EFFECTS THAN THE STANDARD DEHYDROCHOLIC ACID. HYDROQUINONE ALSO INHIBITED INTESTINAL PERISTALSIS IN MICE & GUINEA PIGS. [CZOK G ET AL; Z ERNAEHRUNGSWISS SUPPL 14: 68 (1972)]**PEER REVIEWED**
  • The coadministration of phenol and hydroquinone has been shown to produce myelotoxicity in mice similar to that observed following benzene exposure. One explanation of this phenomenon may be that phenol enhances the peroxidase-dependent metabolic activation of hydroquinone in the mouse bone marrow. The authors report that radiolabeled (14)C hydroquinone and (14)C phenol bind covalently to tissue macromolecules of blood, bone marrow, liver and kidney, when administered ip to the mouse in vivo. Substantially more radiolabeled hydroquinone was covalently bound 18 hr after administration as compared with that bound after 4 hr. [Subrahmanyam VV et al; Toxicol 62 (1): 107-16 (1990)]**PEER REVIEWED**
  • To obtain information on potential developmental toxicity, hydroquinone was administered to pregnant New Zealand White rabbits (18 mated per dose group) in aqueous solution (O, 25, 75, or 150 mg hydroquinone) by gavage on Gestation Days (GD) 6 to 18. Caesarean sections were performed on gestation day 30. Doses of 75 and 150 mg/kg/day adversely affected feed consumption and/or body weights of dams during the treatment period. At these doses, however, treatment-related effects were not evident from physical observations, liver and kidney weights, premature delivery incidence, and caesarean sectioning data. The NOEL for maternal toxicity was 25 mg/kg/day. In the 150 mg/kg/day dose group, total _ incidences of external, visceral, and skeletal findings for fetuses did not differ statistically from controls. Slight, statistically insignificant, increases were found, however, in the incidences of ocular and minor skeletal malformations (micro-ophthalmia, vertebral/rib defects, angulated hyoid arch) on both a per fetus and a per litter basis. Under the conditions of this study, hydroquinone at 150 mg/kg/day produced minimal developmental alterations in the presence of maternal toxicity. The NOEL for developmental toxicity was 75 mg/kg/day. [Murphy SJ et al; Fundam Appl Toxicol 19 (2): 214-21 (1992)]**PEER REVIEWED**
  • To determine the potentlal developmental toxicity of hydroquinone, pregnant rats were given 0, 30, 100, or 300 mg/kg hydroquinone by gavage on the 6th through the 15th days of gestation. Maternal effects included a slight, but significant (p less than or equal to 0.051, reduction in body weight gain and feed consumption for the 300 mg/kg hydroquinone dams. Reproductive indices, ie, pregnancy rate, numbers of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, fetal sex ratio, pre- and postimplantation losses, and gravid uterine weights, were not affected by treatment with hydroquinone. A slightly reduced (p less than or equal to 0.05) mean fetal body weight seen at the 300 mg/kg dose level was associated with the slightly reduced body weight gain seen for the dams at this dose level. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed no hydroquinone related malformations. The incidences of gross external variations (small hematomas) and internal soft tissue variations (dilated renal pelvis, hydronephrosis, and hydroureter) in the hydroquinone treated litters were not statistically different from the control incidences. Skeletal variations (delayed ossification of membranous skull bones, hyoid bone, thoracic centra 1-3, sacral arches 3 and 4, and bilobed thoracic centra 9-13 were seen with similar frequency in the control and hydroquinone treated groups. A statistically significant increase in the incidence of total common vertebral variations seen at the 300 mg/kg hydroquinone dose level was not considered toxicologically significant. The incidences of total skeletal variations were not statistically different between the control and the hydroquinone treated groups. [Krasavage WJ et al; Fundam Appl Toxicol 18 (3): 370-5 (1992)]**PEER REVIEWED**
  • Hydroquinone was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation. It induced trifluorothymidine resistance in mouse L5178Y/TK lymphoma cells in the presence or absence of metabolic activation. An equivocal response was obtained in tests for induction of sex-linked recessive lethal mutations in Drosophila administered hydroquinone by feeding. Hydroquinone induced sister chromatid exchanges in Chinese hamster ovary cells both with or without exogenous metabolic activation and caused chromosomal aberrations in the presence of activation. [NTP; Toxicology and Carcinogenesis Studies of Hydroquinone (Gavage Studies) p.5 Report #366 (1989) NIH Pub #90-2821]**PEER REVIEWED**
  • Acute neurotoxic effects reported in animals include activity increase; hyperactive reflexes; hypersensitivity; convulsions; paralysis. /From table/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 104]**PEER REVIEWED**
  • Acute neurotoxic effects reported in animals include convulsions; medullary paralysis. /From table/ /Quinones/ [O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume I. Boca Raton, FL: CRC Press, Inc., 1985., p. 129]**PEER REVIEWED**
  • Oral LD50 values for rats, mice, guinea pigs, cats, and dogs range from 70 to 550 g/kg of hydroquinone, with the cat having the greatest sensitivity. Hyperexcitability, tremors, convulsions, salivation, and emesis were observed in cats within 90 minutes of administration of lethal doses, and death occurred after several hours. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 789]**PEER REVIEWED**
  • In studies designed to evaluate the carcinogenicity of hydroquinone in the urinary bladder of mice, an unspecified number of mice were implanted with a 10 mg cholesterol/20% hydroquinone pellet (2 mg hydroquinone per mouse) and were observed for 25 weeks. At 25 weeks, the incidence of urinary bladder carcinomas in survivors of the dosed group (6 of 19) was significantly greater (p = 0.03) than the incidence of bladder carcinomas in mice receiving only the cholesterol pellet (5 of 57). [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 789]**PEER REVIEWED**
  • The mechanisms by which two quinone-forming compounds, hydroquinone and tert-butyl-hydroquinone, induce chromosomal loss and breakage in a prostaglandin H synthase-containing V79 cell line have been investigated using the cytokinesis-block micronucleus assay with CREST antibody staining. Increased frequencies of CREST-positive micronuclei (indicating chromosone loss) and CREST-negative micronuclei (indicating chromosome breakage) were observed following exposure of cells to HQ hydroquinone and tert-butyl-hydroquinone. The formation of micronuclei by hydroquinone, but not tert-butyl-hydroquinone, was dependent on arachidonic acid supplementation, indicating activation by prostaglandin H synthase. Since the oxidation of hydroquinones can result in the generation of oxygen radicals, the contribution of oxygen radicals to the formation of chromosomal alterations induced by hydroquinone and tert-butyl-hydroquinone was investigated. In the presence of a superoxide-generating system consisting of hypoxanthine and xanthine oxidase, a significant increase in micronucleated cells was observed. These induced micronuclei consisted exclusively of CREST-negative micronuclei and their formation was completely inhibited by pretreatment with catalase. Catalase also significantly inhibited the CREST-negative micronuclel induced by hydroquinone and tert-butyl-hydroquinone. In addition, glutathione treatment inhibited both CREST-positive and negative micronuclei induced by these phenolic compounds. ... Both chromosome loss and breakage are induced by these two quinone-forming agents. Reactive oxygen species contribute to the chromosomal breakage induced by hydroquinone and tert-butyl-hydroquinone but the observed chromosomal loss appears to result from other mechanisms such as an interference of quinone metabolites with spindle formation. [Dobo KL, Eastmond DA; Environ Mol Mutagen 24 (4): 293-300 (1994)]**PEER REVIEWED**
  • The occurrence of induced forestomach lesions was studied in rats fed butylated-hydroxyanisole and related compounds. Wistar-rats were fed diets containig 2% butylated-hydroxyanisole, 2% tert-butylhydroquinone, 2% 4-methoxyphenol, 2% 1,4-dimethoxybenzene, 2% hydroquinone, or 1% butylated-hydroxytoluene for periods of 4 or 8 weeks. Animals were sacrificed and forestomachs were examined. Butylated-hydroxyanisole caused severe diffuse hyperplasia, acanthosis, and hyperkeratosis in the forestomach. tert-butylhydroquinone caused mild hyperplasia of the forestomach with increased hyperplasia of basal cells. Butylated-hydroxytoluene treatment caused no visible forestomach lesions. Effects of 4-methoxyphenol resembled those of butylated-hydroxyanisole, but the structurally related 1,4-dimethoxybenzene produced no macroscopically visible lesions. Hydroquinone feeding resulted in only mild hyperplastic and hyperkeratotic areas. /It was/ concluded that compounds structurally related to butylated-hydroxyanisole also cause forestomach lesions, and that the methoxy group in the para position seems to be important in this respect. [Altmann H-J et al; Archives of Toxicol Suppl 8: 114-6 (1985)]**PEER REVIEWED**
  • Hydroquinone, catechol, duroquinone and resorcinol have been shown to induce single-strand breaks in DNA in isolated hepatocytes using the alkaline elution assay. The relative capacities of these agents to induce single-strand breaks were shown to be: duroquinone = hydroquinone much greater than catechol greater than resorcinol. Preincubation of hepatocytes with the Ca(2+)-chelator Quin-2 AM reduced the level of DNA damage to a great extent, as did treatment with duroquinone and resorcinol, and, to a lesser extent, treatment with hydroquinone and catechol. Preincubation with an inhibitor of poly(ADP-ribose) polymerase, 3-amino-benzamide, did not influence the extent of DNA damage caused by duroquinone and resorcinol, but increased the dan~age caused by hydroquinone and catechol. The dominating reaction of hydroquinone and catechol, with DNA is an arylation, whereas duroquinone and resorcinol induce DNA damage by oxidative stress. [Walles SA; Cancer Lett 63 (1): 47-52 (1992)]**PEER REVIEWED**
  • The relationship between in vivo aneuploidy and cell-cycle perturbation induced by potential aneugens was investigated in mouse bone marrow cells. The effects of colchicine and hydroquinone on cell-cycle progression, aneuploidy, polyploidy, micronucleus and sister chromatid exchange induction in mouse bone marrow cells after bromodeoxyuridine incorporation are reported. Hyperploidy and polyploidy were scored in metaphases of cells that had undergone only one division after treatment. Both chemicals induced cell-cycle lengthening, hyperploidy and micronuclei. The kinetics of hyperploidy induction by the two compounds differed in that colchicine was positive at 24 hr, whereas hydroquinone was positive 18 hr after treatment. Only colchicine was positive for polyploidy induction and neither chemical induced sister chromatid exchange. These results are compared with similar data obtained after vinblastine treatment. Vinblastine and colchicine induce chromosome malsegregation via a mechanism associated with perturbations in the cell-cycle, whereas hydroquinone induces aneuploidy independently of cell-cycle lengthening, possibly altering a chromosomal component of chromosome segregation rather than a spindle component. [Pacchierotti F et al; Mutagenesis 6 (4): 307-11 (1991)]**PEER REVIEWED**
  • The hematopoietic and carcinogenic effects of benzene may result from an interaction of various benzene metabolites. Following the co-administration of phenol and hydroquinone, a synergistic increase in myelotoxicity and genotoxicity has been observed in the bone marrow of mice. The origin of micronuclei formed in bone marrow erythrocytes was studied following the co-administration of these two metabolites. Phenol and hydroquinone were administered to male CD-1 mice by ip injection three times at 24 hr intervals. The frequency of micronuclei was evaluated in bone marrow cells harvested 24 hr following the final dose. A marked increase in micronuclei was observed in mice co-administered phelol and hydroquinone, which was significantly greater than that observed with the individual metabolites. Labeling with the CREST antibody and multicolor fluorescence in situ hybridization with the mouse major and minor satelite probes indicated that both chromosomal loss and breakage and occurred. The major increase in micronuclei induced by the phenol and hydroquinone combination originated from breakage in the euchromatic region of the mouse chromosomes. The origin of micronuclei in mice co-administered phenol and hydroquinone differed substantially from that induced by hydroquinone alone but was almost identical to that seen in micronuclei from benzene-treated mice. These results support the hypothesis that interactive effects among benzene metabolites play an important role in the genotoxic and carcinogenic effects of benzene. [Chen H, Eastmond DA; Carcinogenesis 16 (8): 1963-9 (1995)]**PEER REVIEWED**
  • Benzene metabolism to phenolic intermediates appears to be an important factor in bone marrow toxicity. The authors compared the effects of benzene and several of its metabolites on nitric oxide production by murine bone marrow leukocytes. Bone marrow cells readily produced nitric oxide in response to the inflammatory mediators lipopolysaccharide and interferon-gamma. Treatment of mice with benzene (80 mg/kg) or its metabolites hydroquinone (100 mg/kg), 1,2,4-benzenetriol (25 mg/kg) or p-benzoquinone (2 mg/kg) at doses that impair hematopoiesis sensitized bone marrow leukocytes to produce increased amounts of nitric oxide in response to lipopolysaccharide and interferon-gamma. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor augmented bone marrow leukocyte production of nitric oxide induced by inflammatory mediators. Benzene as well as its metabolites markedly increased the sensitivity of the cells to both granulocyte-macrophage colony-stimulating factor and macrophages-stimulating factor. Cells from hydroquinone- or 1,2,4-benzenetriol-treated mice were significantly more responsive to the inflammatory cytokines and growth factors than cells isolated from benzene- or p-benzoquinone-treated mice, suggesting that the phenolic metabolites of benzene are important biological reactive intermediates. [Laskin JD et al; J Leukoc Biol 57 (3): 422-6 (1995)]**PEER REVIEWED**
  • Copper(II) strongly induces the oxidation of hydroquinone, producing benzoquinone and hydrogen peroxide through a copper(II)/copper(I) redox cycle mechanism. The oxidation of hydroquinone by copper(II) also results in plasmid DNA cleavage. Mixing 100 uM hydroquinone with 10 uM copper(II) in phosphate-buffered saline resulted in a marked consumption of oxygen and the concomitant generation of hydrogen peroxide, and extensive DNA degradation in chi X-174 RF I DNA. The presence of superoxide dismutase or mannitol did not affect either the oxygen consumption, hydrogen peroxide generation or DNA damage. In contrast, the copper(I) chelators, bathocuproinedisulfonic acid and glutathione, extensively inhibited the hydroquinone/copper(II)-mediated oxygen consumption and DNA damage. The presence of catalase also prevented the DNA damage. Although the hydroquinone/copper(II)-mediated oxygen consumption increased in the presence of azide, azide markedly inhibited the hydroquinone/copper(II)-induced DNA degradation. ESR spectroscopy showed that copper(II) strongly mediated the formation of semiquinone anion radicals from hydroquinone in phosphate-buffered saline, which could be blocked by bathocuproinedisulfonic acid. Spin trapping experiments suggest that hydroxyl radical or an equivalent reactive intermediate is generated from the hydroquinone/copper(II) system. [Li Y et al; Chem Biol Interact 94 (2): 101-20 (1995)]**PEER REVIEWED**
  • TGF-beta-treated normal fibroblasts are able to induce apoptosis of transformed fibroblasts leading to their elimination. A test system allows the quantitative analysis of the elimination of G418-resistant transformed cells by TGF-beta-treated normal cells. Catechol and hydroquinone but not resorcinol were found to represent potent antagonists of TGF-beta-induced elimination of transformed cells by normal cells. [Schaefer D et al; Int J Cancer 60 (4): 520-6 (1995)]**PEER REVIEWED**
  • Benzene and several of its metabolites were investigated for dysmorphogenic and embryotoxic effects after direct exposures of cultured whole rat conceptuses. Benzene produced no statistically significant effects at concentrations up to 1.6 mM inclusion with 1.6 mM benzene of an hepatic xenobiotic-biotransforming system (S9) resulted in only minor decreases in embryonic growth parameters and no detectable dysmorphogenesis. Phenol, a major benzene metabolite, also elicited only minimal embryotoxicity at 1.6 mM concentrations. However, inclusion of an S9 system with phenol resulted in significant dysmorphogenic and embryotoxic effects at concentrations as low as 0.01 mM. For phenol bioactivation, S9 from phenobarbital-induced rats was the most effective, with induction by pregnenolone-16 alpha-carbonitrile, isopropanol, Aroclor 1254, no inducer, and 3-methylcholanthrene following in order of effectiveness. Bioactivating activity resided solely in the microsomal fraction. Metabolites coeluting on HPLC with hydroquinone and catechol were the major metabolites generated from phenol by each S9 system, but no significant correlation between specific metabolite generation and embryotoxicity was apparent. Of the benzene metabolites studied, trans, trans-muconaldehyde exhibited the highest embryotoxic potency but was not detectably generated by any of the S9 systems. Hydroquinone, catechol, and benzoquinone were approximately equipotent, each producing 100% lethality at 0.1 mM. Combined additions to the culture medium of hydroquinone together with phenol resulted in greater than additlve effects, indicating a possible synergistic interaction between these metabolites and suggesting that peroxidase activity may be important to the mechanism of phenol-elicited embryotoxicity. [Chapman DE et al; Toxicol Appl Pharmacol 128 (1): 129-37 (1994)]**PEER REVIEWED**
  • The induction of hyperdiploidy in human lymphocytes following in-vitro exposure to hydroquinone was investigated using fluorescence in-situ hybridization techniques. ... Hydroquinone exposure resulted in a significant increase in hyperdoploid nuclei, but also indicated that the different frequency of nuclei containing three or more hybridization regions observed using the chromosome 1 and 7 probes was due to breakage within the chromosomal region targeted -by the chromosome 1 classical satellite probe. The use of multicolor fluorescence in situ hybridization with chromosome specific DNA probes following the in-vitro exposure of human lymphocytes to hydroquinone indicates that hydroquinone is able to induce both hyperdiploidy and chromosomal breakage. [Eastmond DA et al; Mutation Research 322 (1): 9-20 (1994)]**PEER REVIEWED**
  • Male and female F344 rats were administered 2.5, 25, or 50 mg/kg hydroquinone by gavage once daily, 5 days/week for 6 weeks. Nuclear DNA isolated from kidneys was analyzed by the phosphorus-32 postlabeling assay. At 50 mg/kg, male rats demonstrated an increase in the rate of excretion of N-acetyl-beta-D-glucosaminidase demonstrating proximal tubular damage. Analysis of nuclear DNA preparations by the postlabeling assay demonstrated that hydroquinone did not produce covalent DNA adducts in the kidneys of male and female rats. No treatment related increases were noted in background radioactivity levels on the chromatograms at locations corresponding to the major in-vitro adducts of hydroquinone and p-benzoquinone. Hydroquinone treatment resulted in the reduction of the levels of certain endogenous adducts. Mild kidney toxicity was seen in treated male rats. Hydroquinone does not produce covalent DNA adducts in the kidneys of male and female rats following repeated oral administration at nephrotoxic dose levels. [English JC et al; Fundam Appl Toxicol 23 (3): 391-6 (1994)]**PEER REVIEWED**
  • Oral administration of hydroquinone over 2 years to male Fischer 344 (F344) rats results in a dose-related nephropathy and an increase in the incidence of renal tubule adenomas. Female F344 rats B6C3F1 mice and Sprague-Dawley (SD) rats are resistant to the chronic renal toxicity of hydroquinone and nephrotoxicity was not seen in dogs or humans following subchronic exposure. To characterize the early development of renal toxicity in rats cell proliferation was quantitated within the proximal (P1, P2, and P3) and distal tubule segments of the kidney in rats given O, 2.5, 25, or 50 mg/kg hydroquinone by gavage. Male and female F344 rats were treated for 1, 3, or 6 wk and male SD rats were treated for 6 wk. Cell proliferation was quantitated by incorporation of bromodeoxyuridine detected immunohistochemically, into newly synthesized DNA. At 6 wk renal cell proliferation was increased over vehicle-controls in male F344 rats dosed at 50 mg/kg. Significant elevations (p < 0.001) occurred in the P1 segments (87%) and in the P2 segments (50%) but the elevation in the P3 segment (34%) was not statistically significant. Urinalyses revealed increases in the rate of excretion of enzymes indicative of proximal tubular damage. Histopathologic evaluation of the kidneys was consistent with a dose-related tubular degeneration in the male F344 rat. No chemical-related effects were observed in the kidneys of female F344 and male SD rats. These data parallel the findings of sex- and strain-specific kidney adenomas in the 2 yr bioassays and suggest that chemically induced cell proliferation secondary to toxicity may be important in the pathogenesis of benign renal tumors in male F344 rats treated with hydroquinone. [English JC et al; Fundam Appl Toxicol 23 (3): 397-406 (1994)]**PEER REVIEWED**
  • The authors have characterized quinone reductase, glutathione, glutathione S-transferase and their induction by a chemoprotector, 1,2-dithiole-3-thione, in the human myeloid cell lines ML-1 and HL-60. In addition, the toxicity of hydroquinone a benzene metabolite to these two cell lines. Treatment with hydroquinone caused both inhibition of cell proliferation and loss of cell viability in these two myeloid cell lines. Hydroquinone treatment also resulted in a significant depletion of cellular glutathione, which preceded the loss of cell viability. Pretreatment of both cell lines with buthionine sulfoximine an inhibitor of glutathione biosynthesis markedly increased hydroquinone-induced toxicity. In contrast the presence of dicumarol, a quinone reductase inhibitor failed to potentiate hydroquinone-induced toxicity in ML-1 cells. On the other hand pretreatment of these two myeloid cell lines with 1,2-dithiole-3-thione significantly protected against hydroquinone-induced inhibition of cell proliferation and cell death. Glutathione but not quinone reductase is an important factor involved in the toxicodynamics of hydroquinone these myeloid cells. [Li Y et al; Life Sci 54 (13): 901-16 (1994)]**PEER REVIEWED**
  • The effects of benzene metabolites on receptor mediated phagocytosis and cytoskeletal integrity in murine peritoneal macrophages were investigated. Peritoneal macrophages harvested from female C57BL/6-mice were incubated with 25, 50, 75, or 100 uM catechol, hydroquinone, 1,2,4-benzenetriol, or 1,4-benzoquinone, for 10 minutes at 37 deg C. The effects on Fc receptor mediated phagocytosis were assessed by measuring the ability of the cells to ingest immunoglobulin-G coated sheep red blood cells. Hydroquinone, 1,2,4-benzenetriol, and 1,4-benzenequinone significantly inhibited the ability of the macrophages to phagocytize immunoglobulin-G coated sheep red blood cells. 1,4-benzoquinone was the most potent. [Manning BW et al; Toxicol and Appl Pharmacol 126 (2): 214-23 (1994)]**PEER REVIEWED**
  • Micronucleus and metaphase chromosome analyses were performed in mouse bone marrow cells with two known and eight suspected mitotic spindle poisons. Polychromatic and normochromatic erythrocytes were scored for presence of micronucleus while structural and numerical chromosome aberrations, ie hyperploid cells, were evaluated by metaphase analysis. Hydroquinone induced micronucleus, numerical chromosome aberrations and structural. [Marrazzini A et al; Mutagenesis 9 (6): 505-15 (1994)]**PEER REVIEWED**
  • The effects of hydroquinone, on the production of the interleukin-1-alpha processing enzyme, calpain, by mouse bone marrow macrophages was investigated. Bone marrow macrophages were obtained from femurs of male B6C3F1-mice and incubated for 4 to 6 hours with hydroquinone concentrations of 0, 1, 10, and 100 uM hydroquinone. Calpain-II contents of both cytosol and particulate fractions decreased by about 50 after 4 hr hydroquinone exposure. Calpain-I levels were unchanged. The hydroquinone effects are specific for calpain-II in bone marrow macrophages and this represents a potential mechanism for decreased preIL-1a to IL-1a processing after exposure to benzene or hydroquinone. [Miller ACK et al; Toxicol Letters 74 (2): 177-84 (1994)]**PEER REVIEWED**
  • The effects of hydroquinone exposure on reproductive performance were studied over two generations in rats. Sprague-Dawley-rats were divided into three groups of 30 animals each, and dosed with 15, 50, or 100 mg/kg hydroquinone, respectlvely, per day by gavage (F0 group). The F1 and F2 litters were evaluated for number, sex, weight and gross abnormalities in pups on days 0, 4, 7, 14, and 21 of lactation. All parents and pups were examined for internal abnormalities at the end of the study. Results showed slight parental toxicity as evidenced by transient tremors in some F0 and F1 animals at the 150 mg/kg dose. Food consumption and body weights were unaffected in the treated females, but statistically significant differences in body weights were noted for the F1 parental males. Reproductive performance was not adversely affected over the two generations. The mean numbers of pups and their viability were similar among all groups for F1 and F2 litters. The total number of dead pups at birth or during lactation were 13, 13, nine, and ten for the F1 litters, and 17, 13, 26, and 23 for the F2 litters, at doses of 0, 15, 50 and 150 mg/kg/day, respectively. Significant increases in pup weights were noted for F2 pups at 15 and 50 mg/kg on postnatal day 0. At subsequent time points weights were comparable to those of controls. Hydroquinone is not a selective reproductive toxicant, and that 15 and 150 mg/kg/day are the no observed effect levels for general and reproductive toxicity, respectively. [Blacker AM et al; Fundam and Appl Toxicol 21 (4): 420-4 (1993)]**PEER REVIEWED**
  • DNA adduct formation was examined in HL-60 cells and human bone marrow treated with either hydroquinone or p-benzoquinone and have found that these treatments produce the same DNA adduct in both cell types. The DNA adduct level from these treatments varied from 0.05 to 7.5 adducts per 10(7) nucleotldes as a function of treatment time and concentration for both compounds. Reaction of calf thymus DNA with p-benzoquinone produced three adducts as detected by 32P-postlabeling. These adducts have been identified. The DNA adduct formed in HL-60 cells did not correspond to any of the principal adducts formed in DNA reacted with p-benzoquinone, suggesting that cellular enviromnemt modifies DNA adduct production by p-benzoquinone. DNA adduct formation occurs in human bone marrow treated with benzene metabolites. [Bodell WJ et al; Environ Health Perspect 99: 241-4 (1993)]**PEER REVIEWED**
  • Hydroquinone was examined for ability to induce micronuclei in a number of V79 Chinese hamster cell lines which express rat cytochrome p450 cDNAs. Hydroquinone elevated micronucleated cell frequencies in a dose-dependent manner in cell lines V79, XEM2 (expresses CYP1A1) and SD1 (expresses CYP2Bl). The different cell lines showed similar responses to the test agent, indicating that hydroquinone is not a substrate for biotransformation by rat CYP1A1 or CYP2B1. [Ellard S, EM Parry; Mutat Res 287 (1): 87-91 (1993)]**PEER REVIEWED**
  • The ability of benzene and its phenolic metabolites to cause oxidative DNA damage was studied in vitro and in vivo. Human HL-60 cell cultures were incubated with 10 uM hydroquinone, 100 uM phenol, catechol, or 10 uM 1,2,4-benzenetriol for 30 minutes. The DNA was extracted and analyzed for 8-hydroxy-2'-deoxyguanosine as a marker of oxidative DNA damage. Male B6C3F1 mice were injected intraperitoneally with 0 to 880 mg/kg benzene. They were killed 0 to 12 hr later and the femoral bone marrow was collected. The DNA was extracted and the extent of oxidative DNA was determined. Other mice were injected with 751 mg/kg phenol, hydroquinone, or catechol or 25, 50, or 75 mg/kg 1,2,4-benzenetriol alone or in combination. They were killed 1 hour later and the extent of oxidative DNA damage in the bone marrow was determined. Hydroquinone, phenol, and 1,2,4-benzenetriol caused significant increases in formation of 8-hydroxy-2'deoxyguanosine in HL-60 DNA. 1,2,4-Benzenetriol was the nost potent, followed by phenol and hydroquinone. Benzene at 880 mg/kg caused a significant increase in 8-hydroxy-2'-deoxyguanosine concentration in bone marrow DNA 0 to 6 hr post injection. The maximum increase occurred at 1 hr. In bone marrow DNA samples analyzed 1 hr post exposure, benzene concentrations of 501 mg/kg or higher caused significant increases in 8-hydroxy-2'-deoxyguanosine formation. The maximun increase was induced by 200 mg/kg benzene. Phenol, catechol, and hydroquinone did not significantly increase the concentration of 8-hydroxy-'-deoxyguanosine when given alone. When administered together, the metabolites significantly increased the level of 8-hydroxy-2'-deoxyguanosine formation. The combinations of hydroquinone with phenol or catechol were the most effective. 1,2,4-Benzenetriol alone caused a dose related increase in bone marrow 8-hydroxy-2'-deoxyguanosine formation. The largest response was obtained with 25 mg/kg 1,2,4-benzenetriol. Benzene causes oxidative DNA damage in mouse bone marrow. 1,2,4-Benzenetriol, a minor benzene metabolite alone can cause oxidative DNA damage. The results obtained with combinations of phenol, hydroquinone, and catechol support the hypothesis that benzene bone marrow toxicity is caused by multiple metabolites. [Kolachana P et al; Cancer Research 53 (5): 1023-26 (1993)]**PEER REVIEWED**
  • Metabolism of benzene results in the formation of multiple metabolites, including hydroquinone. Hydroquinone is a reducing co-substrate for peroxidase enzymes, and the resultant semiquinone and para-benzoquinone may bind to DNA. The authors investigated the role of peroxidase activation in the formation of DNA adducts by hydroquinone and p-benzoquinone in HL-60 cells, human bone marrow cells, mouse bone marrow macrophages and the U-937 and Raji leukemia cell lines. Adduct formation was measured by P1-enhanced 32P-postlabelinq. Treatment with hydroquinone produced one DNA adduct in HL-60 cells, human bone marrow and mouse bone marrow macrophages no adducts were detected in U-937 or Raji cells. The hydroquinone-DNA adducts in the three cell lines were identical. The adduct level was highest in the HL-60 cells, followed by human bone marrow and mouse bone marrow macrophages. There was a statistically significant correlation between peroxidase activity and the formation of hydroquinone-DNA adducts. Peroxidase-mediated metabolism is involved in the activation of hydroquinone to form DNA adducts in mouse bone marrow and human bone marrow. [L'evay G et al; Carcinogenesis 14 (11): 2329-34 (1993)]**PEER REVIEWED**
  • The effects of immunotoxic chemicals on in-vitro proliferative responses were studied in human and rodent lymphocytes. Splenocytes obtained from female B6C3F1-mice and Fisher-344-rats and human peripheral blood lymphocytes were stimulated with monoclonal antibodies directed at the T-lymphocyte CD3 complex (antiCD3 antibodies), phytohemagglutinin, or the B-lymphocyte mitogens Staphylococcus-aureus cells, Eschericilia-coli lipopolysaccharide, or Salmonella-typhimurium mitogen. They were incubated with O to 10(-5) molar hydroquinone for 20 hr. The effects on cellular proliferation were assessed by measuring uptake of tritiated thymidine. Dose response curves, plots of the change in degree of cell proliferation relative to the control values versus concentration, were constructed. Hydroquinone caused a biphasic response in mouse and human lymphocytes: stimulation followed by inhibition. The response was most pronounced in lymphocytes stimulated by the antiCD3 antibodies. Only an inhibitory effect was seen in rat lymphocytes. [Lang DS et al; Fundam and Appl Toxicol 21 (4): 535-45 (1993)]**PEER REVIEWED**
  • The ability of hydroquinone to induce aneuploidy in bone marrow cells and germinal cells was studied in mice. Male (C57B1/CnexC3H/Cne)F1-mice were injected intraperitoneally with O to 400 mg/kg hydroquinone. They were killed 6, 8, 18, or 24 hr after injection, the femurs and testes removed, hydroquinone at 80 mg/kg spermatocytic hyperploidy. [Leopardi P et al; Mutation Research 287 (1): 119-30 (1993)]**PEER REVIEWED**
  • In-vitro tests used for testing known or suspected aneugens were described. The endpoints included micronuclei kinetochore positive micronuclei in binucleated cells changes in the number of chromosomes or aberrations of mitosis and division. Target cells were human lymphocytes human diploid fibroblasts and Chinese-hamster transformed cells. In human cells, hydroquinone was positive for inducing kinetochore containing micronuclei, but was negative in Chinese-hamster LUC2 cells. [Natarajan AT; Mutation Research 287 (1): 113-8 (1993)]**PEER REVIEWED**
  • Human lymphocyte cultures were exposed to colchicine, hydroquinone, and vinblastine to validate suitable assays for chemically induced genomic mutations, chromosomal aberrations and spindle effects. Treatment was carried on for 48 to 72 hr after which chromosome number assays were determined. Spindle effects were analyzed in cultures treated 5 hr prior to fixation. Colchicine and vinblastine produced dose related numerical chromosomal aberrations and were the only two chemicals which also produced C-mitotic effects over a wide range of dose levels. Hydroquinone induced tetraploid and/or endoreduplicated cells without a dose effect relationship. [Sbrana I et al; Mutation Research 287 (1): 57-70 (1993)]**PEER REVIEWED**
  • Toxicology and carcinogenesis studies were conducted by administering hydroquinone (more than 99% pure) by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 wk or 2 yr. 14 Day studies were conducted by administering hydroquinone in corn oil to rats at doses ranging from 63 to 1000 mg/kg body weight and to mice at doses ranging from 31 to 500 mg/kg, 5 days/wk. In the 13-wk studies, doses for rats and mice ranged from 25 to 400 mg/kg. At those doses showing some indication of toxicity in the 14 day and 13 wk studies, the central nervous system, forestomach and liver were identified as target organs in both species and renal toxicity was observed in rats. Based on these results, 2 yr studies were conducted by administering 0, 25 or 50 mg hydroquinone/kg in deionized water by gavage to groups of 65 rats of each sex, 5 days/wk. Groups of 65 mice of each sex were given 0, 50 or 100 mg/kg on the same schedule. 10 rats and 10 mice from each group were killed and evaluated after 15 months. Mean body weights of high-dose male rats and high-dose mice were approx 5-14% lower than those of controls during the second half of the study. No differences in survival were observed between dosed and control groups of rats or mice. Nearly all male rats and most female rats in all vehicle control and exposed groups had nephropathy, which was judged to be more severe in high-dose male rats. Hyperplasia of the renal pelvic transitional epithelium and renal cortical cysts were increased in male rats. Tubular cell hyperplasia of the kidney was seen in two high-dose male rats, and renal tubular adenomas were seen in 4/55 low-dose and 8/55 high-dose male rats; none was seen in vehicle controls or in female rats. Mononuclear cell leukaemia in female rats occurred with increased incidences in the dosed groups (vehicle control, 9/55; low dose, 15/55; high dose, 22/55). Compound-related lesions observed in the liver of high-dose male mice included anisokaryosis, syncytial alteration and Basophilic foci. The incidences of hepatocellular neoplasms, primarily adenomas, were increased in dosed female mice (3/55; 16/55; 13/55). Follicular cell hyperplasia of the thyroid gland was increased in dosed mice. [Kari FW et al Food Chem Toxicol 30 (9): 737-47 (1992)]**PEER REVIEWED**
  • Fluorescence in situ hybridization with a mouse major satellite probe and CREST staining were used to characterize the origin of micronuclei occurring in mouse bone marrow erythrocytes following administration of the benzene metabolite hydroquinone. Hydroquinone was administered to male CD-l mice by ip injection on three consecutive days and the bone marrow cells were harvested 24 hr later. A pronounced difference in the results was observed using the two approaches: 63% of the micronuclei induced by hydroquinone labeled with the major satellite probe whereas only 25% labeled with the CREST antibody. To determine whether the observed difference was due to a disruption of the kinetochore or a result of breakage within centromeric heterochromatin, we developed a tandem label multicolor hybridization assay which requires the presence of both the mouse major and minor satellite probes in a micronucleus for a classification of chromosomal loss. The minor probe targets a centromeric region physically linked to the short arm of mouse chromosomes whereas the major probe hybridizes to the centromeric heterochromatin adjacent to the long arm. Using this approach 29% of the micronuclei induced by hydroquinone hybridized with both the major and minor satellite probes indicating chromosome loss; an additional 37% labeled with only the major satellite probe indicating breakage within the centromeric heterochromatin. Although the region targeted by the major satellite probe comprises only 5-10% of the mouse genome, these major-probe containing micronuclei represent 53% of the micronuclei formed as the result of chromosome breakage. [Chen HW et al; Mutagenesis 9 (6): 563-9 (1994)]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rat oral 320 mg/kg [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 763]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • ... ABSORBED FROM GI TRACT & POSSIBLY THROUGH SKIN. ... HYDROQUINONES ... ARE PARTIALLY EXCRETED IN URINE AS SUCH & IN CONJUGATION WITH HEXURONIC, SULFURIC & OTHER ACIDS ... . [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. V15 169 (1977)]**PEER REVIEWED**
  • Benzene myelotoxicity reproduced by coadministering phenol and hydroquinone but not when these benzene metabolites were administered alone has been postulated to be induced by phenol stimulating the myeloperoxidase-mediated oxidation of hydroquinone to the toxic 1 4-benzoquinone in bone marrow. A pharmacokinetic interaction between phenol and hydroquinone is also hypothesized. Both metabolites are sulfoconjugated and glucuronoconjugated. Sulfoconjugation of phenolic substrates has been shown to approach saturation at high concentrations in rats. Thus more phenol may be converted to hydroquinone and hydroquinone conjugatlon may be diminished. These effects would increase the amounts of phenol and hydroquinone present and result (by further oxidation) in the formation of more 1,4-benzoquinone. To test this hypothesis, The authors investigated the pharmacokinetics in blood and the recovery of hydroquinone and phenol in urine when the metabolites were administered intraperitoneally alone or in combination at 75 mg/kg each to B6C3F1 mice. The combination resulted in a 2.6-fold increase in the area under the blood concentration-time curve of hydroquinone compared to the sum of concentration-time curve values observed after administration of each compound alone. The half-life of hydroquinone was also increased from 9 + or - 2 to 15 + or - 3 min. The concentration-time curve of phenol was increased by a factor of 1.4. The clearance of phenol decreased from 89 + or - 13 ml/min per kilogram when injected alone to 62 + or - 7 ml/min/kg after coadministration. A decreased clearance of formation of each conjugate demonstrated that both conjugation pathways were diminished. [Legathe A et al; Toxicol Appl Pharmacol 124 (1): 131-8 (1994)]**PEER REVIEWED**
  • A fatality due to the ingestion of photographic developer solution containing hydroquinone is described. Hydroquinone was extracted from autopsy materials and identified using gas chromatography-mass spectrometry. The concentration of hydroquinone in the urine, liver, and kidney were 3.4 ug/ml, 0.5 and 0.2 ug/g, respectively. [Saito T et al; J Forensic Sci 39 (1): 266-70 (1994)]**PEER REVIEWED**

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Metabolism/Metabolites

  • ABSOLUTE RECOVERY OF APPROXIMATELY 45 NG (18%) OF HYDROQUINONE AS MICROSOMAL METABOLITE OF BENZENE WAS DETERMINED. [ROSTON DA, KISSINGER PT; ANAL CHEM 54 (11): 1798 (1982)]**PEER REVIEWED**
  • QUINOL YIELDS ARBUTIN IN LOCUST /SRP: PLANT/, IN BEAN, PRIDHAM & SALTMARCH, IN WHEAT. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-4]**PEER REVIEWED**
  • YIELDS ARBUTIN IN FERN; GLASS & BOHM, IN ANGIOSPERMS & GYMNOSPERMS. PARA-BENZOSEMIQUINONE IN HORSERADISH. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-4]**PEER REVIEWED**
  • YIELDS P-HYDROXYPHENYL-BETA-D-GENTIOBIOSIDE IN WHEAT. P-HYDROXYPHENYL-ALPHA-D-GLUCOSIDE IN ASPERGILLUS. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-4]**PEER REVIEWED**
  • YIELDS GAMMA-HYDROXYMUCONIC SEMIALDEHYDE IN PSEUDOMONAS. P-HYDROXYPHENYL-BETA-D-GLUCURONIDE IN RABBIT, IN CAT. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-4]**PEER REVIEWED**
  • YIELDS P-HYDROXYPHENOL SULFATE IN RABBIT, IN CAT. HYDROXYQUINOL IN RABBIT, METHOXYPHENOL IN STREPTOMYCES. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-4]**PEER REVIEWED**
  • YIELDS P-QUINONE IN MUSHROOM. IN POLYPORUS & RHUS. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-4]**PEER REVIEWED**
  • This study: investigated the metaolism of hydroquinone in naive and hydroquinone pretreated male Sprague-Dawley rats. (14)C hydroquinone was administered by gavage in single doses of 5, 30, or 200 mg/kg to naive rats. Hydroquinone was given repeatedly by gavage to male rats at 200 mg/kg for 4 consecutive days followed by a single dose with 200 mg/kg of (14)C hydroquinone. In separate studies rats were fed 5.6% unlabeled hydroquinone in the diet for 2 days or were dosed by gavage with 311 mg/kg (14)C hydroquinone. The excretion patterns of (14)C hydroquinone and its metabolites were similar for rats dosed singly or repeatedly. Rats given a single dose of 200 mg/kg of (14)C hydroquinone excreted 91.9% of the dose in the urine within 2-4 days; 3.8% was excreted in the feces, about 0.4% was excreted in expired air, and 1.2% remained in the carcass. Radioactivity was widely distributed throughout the tissues with higher concentrations in the liver and kidneys. A decrease in (14)C tissue concentrations occurred from 48 to 96 hr. The only radiolabeled compounds in the urine were hydroquinone (1.1-8.6% of the dose), hydroquinone monosulfate (25-42%), and hydroquinone monoglucuronide (56-66%). Similar findings were observed for rats given hydroquinone in the feed. There were no significant increases from controls for absolute or relative liver weights, liver microsomal protein concentrations, cytochrome b-5, cytochrome p450 or cytochrome c reductase activity in rats dosed repeatedly with 200 mg/kg hydroquinone. Cytochrome p450 values were slightly but significantly decreased in rats dosed repeatedly with hydroquinone compared with controls. [Divincenzo GD et al; Toxicol 33 (1): 9-18 (1984)]**PEER REVIEWED**
  • The metabolite 2-(S-glutathionyl)hydroquinone is formed when a microsomal incubation mixture containing either benzene or phenol is supplemented with glutathione. This metabolite is derived from the conjugation of benzoquinone, an oxidation product of hydroquinone. However, neither the glutathione conjugate or its mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine, have been identified as metabolites resulting from in vivo metabolism of benzene, phenol, or hydroquinone. To determine if a hydroxylated mercapturate is produced in vivo, we treated male Sprague-Dawley rats with either benzene (600 mg/kg), phenol (75 mg/kg), or hydroquinone (75 mg/kg) and collected the urine for 24 hr. HPLC coupled with electrochemical detection confirmed the presence of a metabolite that was chromatographically and electrochemically identical to N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine. The metabolite was isolated from the urine samples and treated with diazomethane to form the N-acetyl-S-(2,5-dimethoxyphenyl)-L-cysteine methyl ester derivative. The mass spectra obtained from these samples were identical to that of an authentic sample of the derivative. The results of these experiments indicate that benzene, phenol, and hydroquinone are metabolized in vivo to benzoquinone and excreted as the mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L- cysteine. [Nerland DE, Pierce WM Jr; Drug Metab Dispos 18 (6): 958-61 (1990)]**PEER REVIEWED**
  • Macrophage peroxidases were found to catalyze the metabolic oxidation of hydroquinones to macro-molecular binding metabolites. [Dean, J.H., M.I. Luster, A.E. Munson, I. Kimber. Immunotoxicology and Immunopharmacology. 2nd ed. New York, NY: Raven Press, Ltd., 1994., p. 130]**PEER REVIEWED**
  • Hepatic microsomal biotransformation of phenol to hydroquinone and catechol was investigated with special reference to the covalent binding to microsomal protein of reactive metabolites formed during microsomal metabolism of phenol. Incubation of (14)C phenol with microsomes from phenobarbital-treated rat liver in the presence of the reduced form of nicotinamide-adenine dinucleotide phosphate generating system resulted in the formation of hydroquinone and catechol in the ratio of 20:1. No significant formation of 1,2,4-benzenetriol was observed. The biotransformation of phenol to hydroquinione and catechol required the reduced form of nicotinamide-adenine dinucleotide phosphate and molecular oxygen nicotinamide adenine dinucleotide was much less effective than the reduced form of nicotinamide-adenine dinucleotide phosphate as an electron donor and exhibited no significant synergistic effect when used together with the reduced form of nicotinamide-adenine dinucleotide phosphate. The biotransformation was inhibited by typical cytochrome p450 (p450) inhibitors such as CO, SKF 525-A, and metyrapone. These results indicate the involvement of p450 in the microsomal hydroxylation of phenol at the ortho- and para-positions. Covalent binding of radioactivity to microsomal protein was observed when (14)C phenol was incubated with rat liver microsomes in the presence of an the reduced form of nicotinamide-adenine dinucleotide phosphate generating system. The covalent binding also require the reduced form of nicotinamide-adenine dinucleotide phosphate and molecular oxygen. Inclusion of p450 inhibitors in the incubation mixture resulted in a decrease in the covalent binding. At least 1 step in the metabolic activation of phenol to the metabolites responsible for covalent binding to microsomal protein was mediated by p450. Inclusion of N-acetylcysteine in the incubation mixture resulted in the complete inhibition of the covalent binding of radioactivity derived from (14)C phenol to microsomal protein, and there was a concomitant formation of N-acetylcysteine adducts of hydroquinone and catechol. Thus, hydroquinone and catechol were both precursors to reactive metabolites responsible for the covalent binding. [Sawahata T, Neal RA; Mol Phramacol 23 (2): 453-60 (1983)]**PEER REVIEWED**
  • Aspergillus fumigatus, a thermotolerant fungus, has been shown to be capable of growth on phenol as the sole carbon and energy source. During growth of the organism on phenol, catechol and hydroquinone accumulated transiently in the medium. Two different routes operating simultaneously leading to different ring-fission substrates are proposed for the metabolism of phenol. In one route phenol undergoes ortho-hydroxylation to give catechol which is then cleaved by an intradiol mechanism leading to 3-oxoadipate. In the other route phenol is hydroxylated in the para-position to produce hydroquinone which is then converted into 1,2,4-trihydroxybenzene for ring fission by ortho-cleavage to give maleylacetate. Cell-free extracts of phenol-grown mycelia were found to contain enzymic activities for the proposed steps. Two ring-fission dioxygenases one active towards 1,2,4-trihydroxybenzene but not catechol and one active towards both ring-fission substrates were separated. Succinate-grown mycelia did not oxidize any of the intermediates until a clear lag period had elapsed and did not contain any of the enzymic activities for phenol metabolism. [Jones KH et al; Archives Of Microbiology 163 (3): 176-81 (1995)]**PEER REVIEWED**
  • Toxicity of benzene most likely results from oxidative metabolism of benzene to reactive products. However, susceptibility to these toxic effects may be related to a balance between activation (phase I) and detoxication (phase II) reactions. The authors estimated kinetic parameters of the two major detoxication reactions for benzene metabolites--phenol sulfation and hydroquinone glucuronidation--in liver subcellular fractions from 10 humans and single samples from mice and rats. Initial rates of phenol sulfation varied 3-fold (range 0.309-0.919 nmol/mg protein/min) among human samples. Measured rates were faster in rats (1.195 nmol/mg protein/min) than in mice 10.458 nmol/mg protein/min). Initial rates of hydroquinone glucuronidation by human samples also varied 3-fold (range 0.101-0.281 nmol/mg protein/min). Hydroquinone glucuronidation was more rapid by mouse microsomes (0.218 nmol/mg protein/min) than by rat microsomes 10.077 nmol/mg protein/min). A physiological compartmental model was developed that incorporates rates of both conjugation reactions and oxidation reactions. Model equations were solved for steady-state concentrations of phenol and hydroquinone attained in human mouse and rat blood during continuous exposure to benzene (0.01 uM in blood). Among the 10 human subjects steady-state concentrations of phenol varied 6-fold (range 0.38-2.17 nM) and steady-state concentrations of hydroquinone varied 5-fold (range 6.66-31.44 nM). ... Higher steady-state concentrations of hydroquinone were predicted in mice than in rats (42.44 and 17.99 nM respectively). [Seaton MJ et al; Carcinogenesis 16 (7) 1519-27 (1995)]**PEER REVIEWED**
  • The In-vitro metabolism of benzene by rat and mouse liver was described. Microsomes prepared from the livers of Fischer-344-rats and B6C3Fl-mice were incubated with radiolabeled benzene or phenol. Twenty percent of the benzene was converted to phenol, 31% to hydroquinone and 2% to catechol after 45 minutes of incubation with mouse microsomes while 23% was converted to phenol, 8% to hydroquinone, and 0.5% to catechol by rat microsomes. The production of hydroquinone and catechol continued up to 90 minutes by mouse liver microsomes but had ceased by this time in rat microsomes. Less than 0.2% muconic-acid was produced from benzene by mouse liver microsomes. [Schlosser PM et al; Carcinogenesis 14 (12): 2477-86 (1993)]**PEER REVIEWED**
  • Benzene metabolism by reconstituted cytochrome-p450-2Bl and cytochrome-p450-2E1 and its inodulation by cytochrome-b5, microsomal epoxide-hydrolase and glutathione-transferase were investigated, and evidence of an important role of microsomal epoxide hydrolase in the formation of hydroquinone was presented. When benzene was metabolized by cytochrome-p450-2B1 and cytochrome-p450-2E1, phenol and hydroquinone were the only metabolites detected. Increasing substrate concentration resulted in increased total benzene metabolism and in levels of each metabolite. Cytochrome-p450-2E1 was more effective over a lower substrate concentration range than cytochrome-p450-2B1. The b5 increased benzene metabolism by both enzymes. Phenol metabolism by cytochrome-p450-2E1 yielded hydroquinone as the major metabolite. In the presence of increasing levels of microsomal epoxide-hydrolase, total benzene metabolized increased, but while phenol levels increased only 17%, hydroquinone levels increased fourfold. In the presence of glutathione and several glutathione, benzene metabolism did not yield any GSH adducts. When phenol was added, a new peak, probably a monoGSH adduct was formed. Microsomal epoxide-hydrolase leads to an increase rather than a decrease of hydroquinone formation from benzene. [Snyder R et al; Toxicol and Appl Pharmacol 122 (2): 172-81 (1993)]**PEER REVIEWED**

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TSCA Test Submissions

  • Teratogenicity was evaluated in pregnant female Crl: COBS CD(SD)BR rats (30/group) orally exposed by gavage to hydroquinone at dose levels of 0, 30, 100 or 300 mg/kg on gestation days (GD) 6-15. Surviving rats were sacrificed on GD 20. Significant differences were observed between treated and control animals in the following: decreased combined and female mean fetal body weight (high-dose group). No significant differences were observed between treated and control animals in the following: maternal mortality, body weight and weight gain, histologic examinations of livers and kidneys of high-dose group animals (other groups not examined), liver and kidney weights, pregnancy rates, number of litters with resorptions, corpora lutea, implantation sites, viable fetuses, resorptions/dam, pre- and post-implantation losses, mean gravid uterine weights, fetal ratio, male mean fetal body weight, and external, and internal soft tissue and skeletal examinations of the fetuses.[Eastman Kodak Co., Toxicological Sciences Section; Hydroquinone: A Developmental Toxicity Study in Rats. (1985), EPA Document No. FYI-AX-1285-0468, Fiche No. OTS0000468-0 ]**UNREVIEWED**
  • The mutagenicity of hydroquinone was evaluated in Salmonella tester strains TA98, TA100, TA1535 and TA1537 (Ames Test), both in presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Hydroquinone was tested at concentrations up 1000ug/plate using the plate incorporation technique. Toxicity of the treatments was not reported. Hydroquinone did not cause a positive response in any tester strain with or without metabolic activation.[Goodyear Health, Safety & Environmental Laboratory; Mutagenicity Evaluation of Hydroquinone, (1979), EPA Document No. 878210375, Fiche No. OTS0205939 ]**UNREVIEWED**
  • The mutagenicity of hydroquinone was evaluated in Salmonella tester strains TA98, TA100, TA1535 and TA1537 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Hydroquinone, diluted with DMSO, was tested up to concentrations up to 1000ug/plate without metabolic activation and up to 320ug/plate with metabolic activation using the plate incorporation technique. Toxicity was observed at 1000ug/plate. Hydroquinone did not cause a positive response in any tester strain with or without metabolic activation.[Goodyear Health, Safety and Environmental Laboratory; Salmonella typhimurium/Microsome Bioassay, (1982), EPA Document No. 878210376, Fiche No. OTS0205939 ]**UNREVIEWED**
  • The mutagenic potential of hydroquinone was evaluated in the germ cells (Sex-Linked Recessive Lethal Assay) of Drosophila melanogaster males. Based on preliminary toxicity determinations, hydroquinone, was fed to 100 males at a nominal concentration of 1000ug/ml. After treatment, each male was mated with three virgin females and offspring were analyzed. The treatment did not cause an statistically significant increase in the mutation frequency relative to the negative controls (sucrose/distilled water).[Goodyear Fiber and Polymer Products Research Division; Evaluation of Hydroquinone Using the Drosophila melanogaster/Sex-Linked Recessive Lethal Test, (1981), EPA Document No. 878210377, Fiche No. OTS0205939 ]**UNREVIEWED**
  • The mutagenicity of hydroquinone was evaluated in a dominant lethal assay using 4 groups of 25 male Charles River rats orally exposed by gavage to dose levels of 0, 30, 100 or 300 mg/kg/day (as a 5% water solutions) for 5 days/week over a 10 week period. Following exposure, each male was mated for 7 days/week with 1 untreated female/week for 2 consecutive weeks. Females were sacrificed on the 14th day of gestation. The mean body weights of the high-dose level males were significantly lower than controls from the 4th week to the end of the treatment period. Clinical signs of toxicity included brown colored urine for all treated animals and swollen eyelids, porphyrin-like tears, sialorrhea, spastic gait, tremors, convulsions, and spontaneous deaths (2 apparently treatment-related deaths) in the high-dose group. No statistically significant differences were observed between treated and control animals with respect to insemination rate, pregnancy rate, mean numbers of implantation sites, viable implants, early and late deaths, and pre- and post-implantation loss. Statistically greater mean numbers of corpora lutea and implantations/dam were observed in the high-dose group relative to the controls in the first mating period.[Eastman Kodak Co.; Hydroquinone: A Dominant Lethal Assay in Male Rats. (1984), EPA Document No. 878214709, Fiche No. OTS0206628 ]**UNREVIEWED**
  • The effects of hydroquinone were examined in the DNA repair test in E. coli tester strains W3110 (Pol A+, repair proficient) and P3478 (Pol A1-, repair proficient) in the absence of metabolic activation. Hydroquinone was tested at concentrations of 0, 0.1, 0.32, 1.0, 3.2, 10 or 100 ug/plate (solvent not reported). The 2 highest dose levels were extremely cytotoxic to both tester strains. Concentrations of 1.0 and 3.2 ug/plate induced preferential inhibition of the repair deficient strain as compared to the solvent control and to the repair proficient strain.[The Goodyear Tire and Rubber Co.; DNA Damage by Hydroquinone (Sublimed) in the E. Coli Pol A- Assay. (1980), EPA Document No. 878210373, Fiche No. OTS0205939 ]**UNREVIEWED**
  • The effects of hydroquinone were examined in the DNA repair test in E. coli tester strains W3110 (Pol A+, repair proficient) and P3478 (Pol A1-, repair deficient) in the absence of metabolic activation. Hydroquinone was tested at concentrations of 0, 0.001, 0.01, 0.1, 0.32 or 1.0 ug/plate (solvent not reported). Concentrations of 0.1, 0.32 and 1.0 ug/plate induced preferential inhibition of the repair deficient strain as compared to the solvent control and to the repair proficient strain.[The Goodyear Tire and Rubber Co.; DNA Damage by Hydroquinone Lot 07319A in the E. Coli Pol A1- Assay. (1980), EPA Document No. 878210374, Fiche No. OTS0205939 ]**UNREVIEWED**
  • Hydroquinone Administered By Gavage To Male Fischer 344 Rats, (1984), EPA Document No. 878214473, Fiche No. OTS0206577 ] The fate of hydroquinone was evaluated in male Fischer 344 rats (5/dose level) receiving a single dose of [U-14C] hydroquinone orally by gavage at 5, 25 or 50mg/kg. Animals were placed in metabolic cages and urine, feces and expired air were collected at 8 and 24 hours. Animals were sacrificed after the 24 hour collection period and selected tissue were excised. Animals at all dose levels rapidly absorbed and eliminated the compound. The primary route of elimination of the dose was as urinary metabolites. After 8 hours, 61.8 - 63.9% of the dose was excreted as hydroquinone glucuronide, 19.1 - 26.2% as hydroquinone sulfate (ethereal) and 0.6 - 1.4% as unchanged hydroquinone. There was no dose-related differences in the ratio of urinary metabolites formed over the dose range tested. Greater than 93% of the dose was recovered in the urine, 1.2 - 3.5% recovered in feces and 0.12 - 0.16% recovered as expired 14-CO2 after 24 hours. Small amounts of radioactivity were found in selective tissue and the carcass. The average recovery of radioactivity for each dose level was greater than 97% of the administered dose.[Kodak Health & Environmental Laboratories; The Metabolic Fate of [U-14C]]**UNREVIEWED**

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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