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Research Article

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

Pages 283-330 | Published online: 29 Sep 2008

References

  • International Programme on Chemical Safety (IPCS), Environmental Health Criteria 157: Hydro- quinone, Geneva: World Health Organization, 1994.
  • Hazardous Substance Data Bank (HSDB), Entry for Hydroquinone, Bethesda: National Library of Medicine, 1997.
  • Krumenacker, L., Constantini, M., Pontal, P., and Sentenac, J., Hydroquinone, resorcinol, and catechol. In: Howe-Grant, M. Ed. Encyclopedia of Chemical Technology, Vol. 13. John Wiley & Sons, New York. 1995, 996–1014.
  • National Institute of Occupational Safety and Health (NIOSH), National Occupational Exposure Survey (NOES), Cincinnati, NIOSH, 1982.
  • Deisinger, P. J., Hill, T. S., and English, J. C.,Human exposure to naturally occurring hydroquinone, J. Toxicol. Environ. Health 47, 101–116, 1996.
  • Leanderson, P. and Tagesson, C., Cigarette smoke- induced DNA-damage: role of hydroquinone and cat- echol in the formation of the oxidative DNA-adduct, 8-hydroxydeoxyguanosine, Chem.-Biol. Interact. 75, 71–81, 1990.
  • National Toxicology Program (NTP), Toxicology and Carcinogenesis Studies of Hydroquinone in F- 344/N Rats and B6C3F1 Mice, NTP Technical Report No. 366; Washington, U.S. Department of Health and Human Services, 1989.
  • International Agency for Research on Cancer (IARC), Monographs on the Evaluation of the Carci- nogenic Risk of Chemicals to Man; Overall Evalua- tions of Carcinogenicity: An Updating of IARC Mono- graphs Volumes 1 to 42, Lyon: IARC, 1987, 64.
  • American Conference of Governmental Industrial Hygienists (ACGIH), 1997–1998 Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents, Cincinnati: ACGIH, 1997.
  • Hard, G. C., Whysner, J., English, J. C., Zang, E., and Williams, G. M., Relationship of hydroquinone- associated rat renal tumors with spontaneous chronic progressive nephropathy, Toxicol. Pathol. 25, 132– 143, 1997.
  • Whysner, J., Verna, L., English, J. C., and Will- iams, G. M., Analysis of studies related to tumorige- nicity induced by hydroquinone, Regul. Toxicol. Pharmacol. 21, 158–176, 1995.
  • Cosmetic, Toiletry, and Fragrance Association (CTFA), Addendum to the final report on the safety assessment of hydroquinone, J. Am. Coll. Toxicol. 13: 167–230, 1994.
  • Cosmetic, Toiletry, and Fragrance Association (CTFA), Final report on the safety assessment of hydroquinone and pyrocatechol, J. Am. Coll. Toxicol. 5, 123–165, 1986.
  • Devillers, J., Boule, P., Vasseur, P., Prevot, P., Steiman, R., Seigle-Murandi, F., Benoit-Guyod,J. L., Nendza, M., Grionin, C., Dive, D., and Chambon, P., Environmental and health risks of hy- droquinone, Ecotoxicol. Environ. Safety 19, 327–354, 1990.
  • United States Environmental Protection Agency (USEPA), Health and Environmental Effects Docu- ment for p-Hydroquinone, Cincinnati, Environmental Criteria and Assessment Office, USEPA, 1987.
  • O’Donoghue, J. L., Richardson, D. P., and Dyer,W. M., Hydroquinone and hepatitis, Lancet 346, 1427– 1428, 1995.
  • Oglesby, F. L., Sterner, J. H., and Anderson, B., Quinone vapors and their harmful effects. II. Plant exposures associated with eye injuries, J. Ind. Hyg. Toxicol. 29, 74–84, 1947.
  • Friedlander, B. R., Hearne, F. T., and Newman,B. J., Mortality, cancer incidence, and sickness-ab- sence in photographic processors: an epidemiologic study, J. Occup. Med. 24, 605–613, 1982.
  • Barber, E. D., Hill, T., and Schum, D. B., The percutaneous absorption of hydroquinone (HQ) through rat and human skin in vitro, Toxicol. Lett. 80, 167–172, 1995.
  • O’Donoghue, J. L., Eastman Kodak Corp., Occupa- tional Medicine and Hygiene Laboratories, United Kingdom Health and Safety Executive, London, U.K., unpublished data, 1993.
  • Semenza, G., Bircher, J., Mulhaupt, E., Koide, T., Pfenninger, E., Marthaler, T., Gmunder, U., and Haemmerli, U. P., Arbutin absorption in human small intestine: a simple procedure for the determination of active sugar uptake in peroral biopsy specimens, Clin. Chim. Acta 25, 213–219, 1969.
  • Inoue, O., Seiji, K., Nakatsuka, H., Watanabe, T., Yin, S-N., Li, G-L., Cai, S-X., Jin, C., and Ikeda, M., Excretion of 1,2,4–benzenetriol in the urine of workers exposed to benzene, Br. J. Ind. Med. 46, 559– 565, 1989.
  • Bechtold, W. E., Sun, J. D., Birnbaum, L. S., Yin,S. N., Li, G. L., Kasicki, S., Lucier, G., and Henderson, R. F., S-Phenylcysteine formation inhemoglobin as a biological exposure index to ben- zene, Arch. Toxicol. 66, 303–309, 1992.
  • Sterner, J. H., Ames, S., and Fassett, D. W., Com- parison of acute toxicity of hydroquinone and some related di and trihydroxy benzenes, Fed. Proc. 8, 334(abstract), 1949.
  • Woodard, G. D. L., The Toxicity, Mechanism of Action, and Metabolism of Hydroquinone. Washing- ton, George Washington University, Dissertation the- sis, 1951.
  • Carlson, A. J. and Brewer, N. R., Toxicity studies on hydroquinone, Proc. Soc. Exp. Biol. Med. 84, 684– 688, 1953.
  • Christian, R. T., Clark, C. S., Cody, T. E., Whiterup, S., Gartside, P. S., Elia, V. J., Eller, P. M., Lingg, R., and Cooper, G. P., The Development of a Test for the Potability of Water Treated by a Direct Reuse System. University of Cincinnati, Cincinnati, Ohio, Washington: U.S. Army Medical Research and De- velopment Command, Contract No. DADA-17–73– C-3013, 1976.
  • Dutton, G. J. and Greig, C. G., Observations on the distribution of glucuronide synthesis in tissues, Biochem. J. 66: 52P(abstract), 1957.
  • Hartiala, K. J., Studies on detoxication mechanisms.III. Glucuronide synthesis of various organs with speacial reference to the detoxifying capacity of the mucous membrane of the alimentary canal, Ann. Med. Exp. Fenn. 33, 239–245, 1955.
  • Registry of Toxic Effects of Chemical Substances (RTECS), Entry for Hydroquinone, Cincinnati, Na- tional Institute of Occupational Safety and Health, 1998.
  • Nomiyama, K., Minai, S. T., and Kita, H., Studies on poisoning by benzene and its homologues: median lethal doses of benzene metabolites, Ind. Health 5, 143–148, 1967.
  • Brieger, L., On the knowledge of the physiological behavior of catechol, hydroquinone and resorcinol and their formation in the animal organism (German), Dubois Arch. Physiol. S61, 1879.
  • Topping, D. C., Subchronic Oral Toxicity Study of Hydroquinone in Rats Utilizing a Functional-Obser- vational Battery and Neuropathology to Detect Neu- rotoxicity, TSCATS Database, EPA/OTS Doc #40– 8869294, NTIS/OTS0516694, 1988.
  • Angel, A. and Rogers, K. J., Convulsant activity of polyphenols, Nature, 217, 84–85, 1968.
  • Angel, A. and Rogers, K. J., An analysis of the convulsant activity of substituted benzenes in the mouse, Toxicol. Appl. Pharmacol. 21, 214–229, 1972.
  • Otsuka, M. and Nonomura, Y., The action of phe- nolic substances on motor nerve endings, J. Pharmacol. Exp. Ther. 140, 41–45, 1963.
  • Mogey, G. A. and Young, P. A., The antagonism of curarizing activity by phenolic substances, Br. J. Pharmacol. 4, 359–365, 1949.
  • Chambers, P. L. and Rowan, M. J., An analysis of the toxicity of hydroquinone on central synaptic trans- mission, Toxicol. Appl. Pharmacol. 54, 238–243, 1980.
  • Mitchell, A. and Webster, J., Notes on a case of poisoning by hydroquinone, Br. Med. J. 21, 465, 1919.
  • Rémond, A. and Colombies, H., Intoxication with hydroquinone (French), Ann. Méd. Lég. 7, 79–81, 1927.
  • Guyot, H. J., Bchelier-Notter, J., and Tiffeneau, J., A case of fatal poisoning from hydroquinone (French), Ann. Méd. Lég. 46, 177–178, 1966.
  • Hooper, R. R. and Husted, S. R., A shipboard out- break of gastroenteritis: Toxin in the drinking water, Military Med. 144, 804–807, 1979.
  • Halbron, P., Bosquet, A., and Tiffeneau, J., Fatal poisoning from a photographic developer (French), Bull. Mem. Soc. Med. Hop. Paris 55, 1596–1601, 1931.
  • Busatto, S., Fatal poisoning from photographic de- veloper containing hydroquinone (German), Deutsch. Ztschr. Ges. Gerichtl. Med. 31, 285–297, 1939.
  • Zeidman, I. and Deutl, R., Poisoning by hydro- quinone and mono-methyl-paraminophenol sulfate, Am. J. Med. Sci. 210, 328–333, 1945.
  • Saito, T., Kojimahara, M., Aoki, K., and Takeichi, S., Detection of hydroquinone in a poisoning case, J. Forensic Sci. 39, 266–270, 1994.
  • DiVincenzo, G. D., Hamilton, M. L., Reynolds,R. C., and Ziegler, D. A., Fate and Disposition of [U- 14C]Hydroquinone in Rats, TSCATS Database, EPA/ OTS Doc #40–7969029, NTIS/OTS0517792, 1979.
  • DiVincenzo, G. D., Hamilton, M. L., Reynolds, R. C., and Ziegler, D. A., Metabolic fate and dispo- sition of [14C]hydroquinone given orally to Sprague- Dawley rats, Toxicology, 33, 9–18, 1984.
  • Lockhart, H. B., Fox, J. A., and DiVincenzo, G. D., The Metabolic Fate of [U-14C]Hydroquinone Admin- istered by Gavage to Male Fischer 344 Rats, TSCATS Database, EPA/OTS Doc #878214473, NTIS/ OTS206577, 1984.
  • Fox, J. A., English, J. C., and Lockhart, H. B., Blood Elimination Kinetics of [U-14C]Hydroquinone Administered by Intragastric Intubation, Intratracheal Instillation or Intravenous Injection to Male Fischer 344 Rats, Rochester, NY, Health and Environment Laboratories; Eastman Kodak Company, 1986, Re- port No. TX-86–1.
  • English, J. C., Deisinger, P. J., Perry, L. G., Schum,D. B., and Guest, D., Toxicokinetics Studies with Hydroquinone in Male and Female Fischer 344 Rats, TSCATS Database, EPA/OTS Doc #40–8869295, NTIS/OTS0516692, 1988.
  • Saito, T. and Takeichi, S., Experimental studies on the toxicity of lithographic developer solution, Clin. Toxicol. 33, 343–348, 1995.
  • Lockhart, H. B., The Metabolic Fate of [14C]Hydro- quinone Administered by Intratracheal Instillation to Male Fischer 344 Rats, Rochester, NY, Health and Environment Laboratories; Eastman Kodak Company, 1985, Report No. TX-85–76
  • Deisinger, P. J. and English, J. C., Bioavailability and Pulmonary Metabolism of Hydroquinone Follow- ing Intratrachael Instillation, Rochester, NY, Health and Environment Laboratories, Eastman Kodak Com- pany, 1997.
  • Marty, J. P., Trouvin, J. H., Jacquot, C., and Wepierre, J., Rate of percutaneous pharmacokinetics of 14C-hydroquinone, Compt. Rend. Cong. Eur. Biopharm. Pharmaco. 2, 221–228, 1981.
  • Marzulli, F. N., Brown, D. W. C., and Maibach,H. I., Techniques for studying skin penetration, Toxicol. Appl. Pharmacol. 3, 76–83, 1969.
  • Hamilton, M. L., Guest, D., and DiVincenzo, G. D., The Percutaneous Absorption of [U-14C]Hydroquinone in Beagle Dogs, TSCATS Database, EPA/OTS Doc #40–8569237, NTIS/OTS0518004, 1985.
  • Bucks, D. A., McMaster, J. R., Guy, R. H., and Maibach, H. I., Percutaneous absorption of hydro- quinone in humans: effect of 1–dodecylazacyclo-hep- tane-2–one (azone) and the 2–ethylhexyl ester of 4– (dimethylamino)benzoic acid (Escalol 507), J. Toxicol. Environ. Health 24, 249–289, 1988.
  • Lehman, P. A. and Franz, T. J., Percutaneous ab- sorption of hydroquinone in human, pig, monkey and baboon in vitro. Proceedings: Society for Investiga- tive Dermatology, Baltimore; 1992 (abstract).
  • Wester, R. C., Melendres, J., Hui, X. Y., Cox, R., Serranzana, S., Zhai, H. B., Quan, D. Y., and Maibach, H. I., Human in vivo and in vitro hydro- quinone topical bioavailability, metabolism, and dis- position, J. Toxicol. Environ. Health 54, 301–317, 1998.
  • Hill, T. S., Morgott, D. A., and English, J. C., Tissue-to-plasma partition coefficients (PCS) for hy- droquinone (HQ) in male Fischer and Sprague-Dawley rats, Fundam. Appl. Toxicol. 30, 39–40, 1996.
  • Greenlee, W. F., Gross, E. A., and Irons, R. D., Relationships between benzene toxicity and the dis- position of 14C-labeled benzene metabolites in the rat, Chem.-Biol. Interact. 33, 285–299, 1981.
  • Greenlee, W. F., Sun, J. D., and Bus, J. S., A proposed mechanism of benzene toxicity: Formation of reactive intermediates from polyphenol metabo- lites, Toxicol. Appl. Pharmacol. 59, 187–195, 1981.
  • Subrahmanyam, V. V., Doane-Setzer, P., Steinmetz, K. L., Ross, D., and Smith, M. T., Phenol-induced stimulation of hydroquinone bioactivation in mouse bone marrow in vivo: possible implications in ben- zene myelotoxicity, Toxicology 62, 107–116, 1990.
  • Legathe, A., Hoener, B., and Tozer, T. N., Pharma- cokinetic interaction between benzene metabolites, phenol and hydroquinone, in B6C3F1 mice, Toxicol. Appl. Pharmacol. 124, 131–138, 1994.
  • Garton, G. A. and Williams, R. T., Studies in detoxi- cation. XXI. The fates of quinol and resorcinol in the rabbit in relation to the metabolism of benzene, Biochem. J. 44, 234–238, 1949.
  • Nerland, D. E. and Pierce, W. M. J., Identification of N-acetyl-S-(2,5–dihydroxyphenyl)-L-cysteine as a urinary metabolite of benzene, phenol, and hydro- quinone, Drug Metab. Disp. 18, 958–961, 1990.
  • Hill, B. A., Kleiner, H. E., Ryan, E. A., Dulik,D. M., Monks, T. J., and Lau, S. S., Identification of multi-S-substituted conjugates of hydroquinone by HPLC-colorimetric electrode array analysis and mass spectroscopy, Chem. Res. Toxicol. 6, 459–469, 1993.
  • Gut, I., Nedelcheva, V., Soucek, P., Stopka, P., Vodicka, P., Gelboin, H. V., and Ingelman- Sundberg, M., The role of CYP2E1 and 2B1 in meta- bolic activation of benzene derivatives, Arch. Toxicol. 71, 45–56, 1996.
  • Lau, S. S., Sawalha, A. F., Halpert, J. R., Koop,D. R., and Monks, T. J., Cytochrome P450 catalyzed oxidation of hydroquinone in rodent and human mi- crosomes, Toxicologist 36, 23(abstract), 1997.
  • Corley, R. A., English, J. C., and Morgott, D. A., A physiologically based pharmacokinetic model for hy- droquinone, Toxicol. Sci. 1–S, 141(abstract), 1998.
  • Seaton, M. J., Schlosser, P. M., and Medinsky,M. A., In vitro conjugation of benzene metabolites by human liver: potential influence of interindividual variability on benzene toxicity, Carcinogenesis 16, 1519–1527, 1995.
  • Cappiello, M., Giuliani, L., and Pacifici, G. M., Differential distribution of phenol and catechol sulphotransferases in human liver and intestinal mu- cosa, Pharmacology 40, 69–76, 1990.
  • Cassidy, M. K. and Houston, J. B., In vivo capacity of hepatic and extrahepatic enzymes to conjugate phe- nol, Drug Metab. Disp. 12, 619–624, 1984.
  • Jeftic, L. and Manning, G., A survey on the electro- chemical reduction of quinones, J. Electroanal. Chem. 26, 195–200, 1970.
  • Finley, K. T., The addition and substitution chemistry of quinones. In: Patai, S., Ed., The Chemistry of the Quinoid Compounds, Part II. Wiley, London, 1974, 878–1144.
  • Peter, M. G., Chemical modifications of biopolymers by quinones and quinone methides, Angew. Chem. Int. Ed. 28, 555–570, 1989.
  • Monks, T. J., Hanzlik, R. P., Cohen, G. M., Ross, D., and Graham, D. G., Quinone chemistry and tox- icity, Toxicol. Appl. Pharmacol. 112, 2–16, 1992.
  • Smith, M. T., Evans, C. G., Thor, H., and Orrenius, S., Quinone induced oxidative injury to cells and tis- sues. In: Sies, H. Ed. Oxidative Stress, Academic Press, London, 1985, 91–113.
  • O’Brien, P. J., Molecular mechanisms of quinone cytotoxicity, Chem.-Biol. Interact. 80, 1–41, 1991.
  • Schlosser, M. J., Shurina, R. D., and Kalf, G. D., Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified pros- taglandin H synthase, Environ. Health Perspect. 82, 229–237, 1989.
  • Munday, R., Inhibition of naphthohydroquinone au- toxidation by DT-diaphorase (NAD(P)H:[quinone acceptor]oxidoreductase), Redox Report 3, 189–196, 1997.
  • Schlosser, M. J. and Kalf, G. F., Metabolic activa- tion of hydroquinone by macrophage peroxidase, Chem.-Biol. Interact. 72, 191–207, 1989.
  • Boatman, R. J., Perry, L. G., Fiorica, L. A., Polvino,J. M., and English, J. C., Quantification of covalentprotein adducts of hydroquinone in the blood and kidneys of rats, Toxicologist 14, 74(abstract), 1994.
  • Ekström, T., Warholm, M., Kronevi, T., and Högberg, J., Recovery of malondialdehyde in urine as a 2,4–dinitrophenylhydrazine derivative after ex- posure to chloroform or hydroquinone, Chem.-Biol. Interact. 67, 25–31, 1988.
  • Stenius, U. and Högberg, J., -Glutamyltranspepti-dase-conferred resistance to hydroquinone induced GSH depletion and toxicity in isolated hepatocytes, Carcinogenesis 9, 1223–1227, 1988.
  • Nakagawa, Y. and Moldeu, P., Cytotoxic effects of phenyl-hydroquinone and some hydroquinones on isolated rat hepatocytes, Biochem. Pharmacol. 44, 1059–1065, 1992.
  • English, J. C., Deisinger, P. J., Hill, T., and Perry,L. G., Measurement of glutathione and cysteine in the kidneys of rats after oral treatment with hydroquinone, Int. Toxicol. 11–PF-6(abstract), 1995.
  • Okazaki, S., Hoshiya, T., Takahashi, S., Futakuchi, M., Saito, K., and Hirose, M., Modification of hepato- and renal carcinogenesis by catechol and its isomers in rats pretreated with N-ethyl-N-hydroxyethylnitros- amine, Teratogen. Carcinogen. Mutagen. 13, 127– 137, 1993.
  • Ganousis, L. G., Goon, D., Zyglewska, T., Wu,K. K., and Ross, D., Cell-specific metabolism in mouse bone marrow stroma: studies of activation and detoxification of benzene metabolites, Mol. Pharma- col. 42, 1118–1125, 1992.
  • Epe, B., Harttig, U., Stopper, H., and Metzler, M., Covalent binding of reactive estrogen metabolites to microtubular protein as a possible mechanism of aneu- ploidy induction and neoplastic cell transformation, Environ. Health Perspect. 88, 123–127, 1990.
  • Fiorica, L. A., Hill, T. S., Morgott, D. A., and English, J. C., The plasma protein binding of hydro- quinone (HQ) in rats and humans, Toxicologist 30, 40(abstract), 1996.
  • McDonald, T. A., Waidyanatha, S., and Rappaport,S. M., Measurement of adducts of benzoquinone with hemoglobin and albumin, Carcinogenesis 14, 1927– 1932, 1993.
  • Waidyanatha, S., Yeowelloconnell, K., and Rappaport, S. M., A new assay for albumin and hemoglobin adducts of 1,2– and 1,4–benzoquinones, Chem.-Biol. Interact. 115, 117–139, 1998.
  • McDonald, T. A., Yeowell-O’Connell, K., and Rappaport, S. M., Comparison of protein adducts of benzene oxide and benzoquinone in the blood and bone marrow of rats and mice exposed to [14C/ 13C]benzene, Cancer Res. 54, 4907–4914, 1994.
  • Frantz, C. E., Chen, H., and Eastmond, D. A., Inhibition of human topoisomerase II in vitro by bioactive benzene metabolites, Environ. Health Perspect. 104, 1319–1323, 1996.
  • Schwartz, C. S., Snyder, R., and Kalf, G. F., The inhibition of mitochondrial DNA replication in vitro by the metabolites of benzene, hydroquinone andp-benzoquinone, Chem.-Biol. Interact. 53, 327–350,1985.
  • Soucek, P., Filipcova, B., and Gut, I., Cytochrome P450 destruction and radical scavenging by benzene and its metabolites, Biochem. Pharmacol. 47, 2233– 2242, 1994.
  • Gut, I., Nedelcheva, V., Soucek, P., Stopka, P., and Tichavská, B., Cytochromes P450 in benzene me- tabolism and involvement of their metabolites and reactive oxygen species in toxicity, Environ. Health Perspect. 104, 1211–1218, 1996.
  • Rushmore, T., Snyder, R., and Kalf, G., Covalent binding of benzene and its metabolites to DNA in rabbit bone marrow mitochondria in vitro, Chem.- Biol. Interact. 49, 133–154, 1984.
  • Kalf, G. F., Snyder, R., and Rushmore, T. H., Inhi- bition of RNA synthesis by benzene metabolites and their covalent binding to DNA in rabbit bone marrow mitochondria in vitro, Am. J. Ind. Med. 7, 485–492, 1985.
  • Jowa, L., Witz, G., Snyder, R., Winkle, S., and Kalf, G. F., Synthesis and characterization of deoxyguanosine-benzoquinone adducts, J. Appl. Toxicol. 10, 47–54, 1990.
  • Pathak, D. N., Lévay, G., and Bodell, W. J., DNA adduct formation in the bone marrow of B6C3F1 mice treated with benzene, Carcinogenesis 16, 1803–1808, 1995.
  • Reddy, M. V., Blackburn, G. R., Irwin, S. E., Kommineni, C., Mackerer, C. R., and Mehlman,M. A., A method for in vitro culture of rat zymbal gland: use in mechanistic studies of benzene carcino- genesis in combination with 32P-postlabeling, Environ. Health Perspect. 82, 239–247, 1989.
  • Levay, G., Pongracz, K., and Bodell, W. J., Detec- tion of DNA adducts in HL-60 cells treated with hydroquinone and p-benzoquinone by 32P-postlabeling, Carcinogenesis, 12, 1181–1186, 1991.
  • Levay, G. and Bodell, W. J., Potentiation of DNA adduct formation in HL-60 cells by combinations of benzene metabolites, Proc. Nat. Acad. Sci. U.S.A. 89, 7105–7109, 1992.
  • Bodell, W. J., Lévay, G., and Pongracz, K., Inves- tigation of benzene-DNA adducts and their detection in human bone marrow, Environ. Health Perspect. 99, 241–244, 1993.
  • Hedli, C. C., Rao, N. R., Reuhl, K. R., Witmer,C. M., and Snyder, R., Effects of benzene metabolite treatment on granulocytic differentiation and DNA adduct formation in HL-60 cells, Arch. Toxicol. 70, 135–144, 1996.
  • Levay, G. and Bodell, W. J., Role of hydrogen per- oxide in the formation of DNA adducts in HL-60 cells treated with benzene metabolites, Biochem. Biophys. Res. Comm. 222, 44–49, 1996.
  • Pongracz, K. and Bodel, W. J., Synthesis of N 2–(4- hydroxyphenyl)-2-deoxyguanosine 3-phosphate: comparison by 32P-postlabeling with the DNA adduct formed in HL-60 cells treated with hydroquinone, Chem. Res. Toxicol. 9, 593–598, 1996.
  • Kolachana, P., Subrahmanyam, V. V., Meyer, K. B., Zhang, L., and Smith, M. T., Benzene and its phe- nolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo, Cancer Res. 53, 1023–1026, 1993.
  • Schlosser, M. J., Shurina, R. D., and Kalf, G. D., Prostaglandin H synthase catalyzed oxidation of hyd- roquinone to a sulfhydryl-binding and DNA-damag- ing metabolite, Chem. Res. Toxicol. 3, 333–339, 1990.
  • Reddy, M. V., Bleicher, W. T., Blackburn, G. R., and Mackerer, C. R., DNA adduction by phenol, hydroquinone, or benzoquinone in vitro but not in vivo: nuclease P1–enhanced 32P-postlabeling of adducts as labeled nucleoside biphosphates, dinucleotides and nucleoside monophosphates, Carcinogenesis 11, 1349– 1357, 1990.
  • English, J. C., Perry, L. G., Vlaovic, M., Moyer, C., and O’Donoghue, J. L., Measurement of nuclear DNA modification by 32P-postlabeling in the kidney of male and female Fischer 344 rats after multiple gavage doses of hydroquinone, Fundam. Appl. Toxicol. 23, 391–396.
  • Reddy, M. V., Hill, T., O’Donoghue, J. L., and English, J. C., Lack of oxidative DNA damage by hydroquinone in the kidneys of rats after oral admin- istration, Proc. Am. Assoc. Cancer Res. 38, 78(ab- stract), 1997.
  • Cho, D. H., Hong, J. T., Chin, K., Cho, T. S., and Lee, B. M., Organotropic formation and disappear- ance of 8-hydroxydeoxyguanosine in the kidney of Sprague-Dawley rats exposed to Adriamycin and KBrO3, Cancer Lett. 74, 141–145, 1993.
  • Brusick, D., Mutagenic Evaluation of Compound 75–151 (HQ). LBI Project #2547, Kensington, Maryland: Litton Bionetics, Inc. 1975.
  • Cotruvo, J. A., Simmon, V. F., and Spanggord,R. J., Investigation of mutagenic effects of products of ozonation research in water, Ann. N.Y. Acad. Sci. 298, 124–140, 1978.
  • Epler, J. L., Larimer, F. W., Rao, T. K., Nix, C. E., and Ho, T., Energy-related pollutants in the environ- ment: use of short-term tests for mutagenicity in the isolation and identification of biohazards, Environ. Health Perspect. 27, 11–20, 1978.
  • Florin, I., Rutberg, L., Curvall, M., and Enzell,C. R., Screening of tobacco smoke constituents for mutagenicity using the Ames test, Toxicology 15, 219– 232, 1980.
  • Haworth, S., Lawlor, T., Mortelmans, K., Speck, W., and Zeiger, E., Salmonella mutagenicity test results for 250 chemicals, Environ. Mutagen. 5, 1– 142, 1983.
  • Sakai, M., Yoshida, D., and Mizusaki, S., Mutage- nicity of polycyclic aromatic hydrocarbons and quino- nes on Salmonella typhimurium TA97, Mutat. Res. 156, 61–67, 1985.
  • Rossman, T. G., Klein, C. B., and Snyder, C. A., Mutagenic metabolites of benzene detected in the microscreen assay, Environ. Health Perspect. 81, 77– 79, 1989.
  • Glatt, H., Padykula, R., Berchtold, G. A., Ludewig, G., Platt, K. L., Klein, J., and Oesch, F., Multiple activation pathways of benzene leading to products with varying genotoxic characteristics, Environ. Health Perspect. 82, 81–89, 1989.
  • Gocke, E., King, M.-T., Eckhardt, K., and Wild, D., Mutagenicity of cosmetics ingredients licensed by the European Community, Mutat. Res. 90, 91–109, 1981.
  • Murphy, S. and Serva, R., Lack of Mutagenicity of Hydroquinone (HQ), Tetramethylthiuram Monosulfide (TMTM), and Tetramethylthiuram Disulfide (TMTD), TSCATS Database, EPA/OTS Doc #88–920005216, NTIS/OTS0544190, 1992.
  • Gocke, E., Wild, D., Eckhardt, K., and King, M.- T., Mutagenicity studies with the mouse spot test, Mutat. Res. 117, 201–212, 1983.
  • Krasavage, W. J., Hydroquinone: A Dominant Le- thal Assay in Male Rats, TSCATS Database, EPA/ OTS Doc #878214709, NTIS/OTS206628, 1984.
  • Wild, D., King, M.-T., Eckhardt, K., and Gocke, E., Mutagenic activity of aminophenols and diphenols, and relations with chemical structure, Mutat. Res. 85, 456(abstract), 1981.
  • Lin, J. K. and Lee, S. F., Enhancement of the mu- tagenicity of polyphenols by chlorination and nitrosation in Salmonella typhimurium, Mutat. Res. 269, 217–224, 1992.
  • Koike, N., Haga, S., Ubukata, N., Sakurai, M., Shimizu, H., and Sato, A., Mutagenicity of benzene metabolites by fluctuation test, Jpn. J. Ind. Health 30, 475–480, 1988.
  • Tsutsui, T., Hayashi, N., Maizumi, H., Huff, J., and Barrett, J. C., Benzene-, catechol-, hydroquinone-, and phenol-induced cell transformation, gene muta- tions, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthe- sis in Syrian hamster embryo cells, Mutat. Res. 373, 113–123, 1997.
  • McGregor, D. B., Riach, C. G., Brown, A., Edwards, I., Reynolds, D., West, K., and Willington, S., Reactivity of catecholamines and related substances in the mouse lymphoma L5178Y cell assay for mu- tagens, Environ. Mol. Mutagen. 11, 523–544, 1988.
  • Adler, I.-D., Synopsis of the in vivo results obtained with the 10 known or suspected aneugens tested in the CEC collaborative study, Mutat. Res. 287, 131–137, 1993.
  • Parry, J. M. and Sors, A., The detection and assess- ment of the aneugenic potential of environmental chemicals: the European Community Aneuploidy Project, Mutat. Res. 287, 3–15, 1993.
  • Paramentier, R. and Dustin, P., Early effects of hydroquinone on mitosis, Nature 171, 527–528, 1948.
  • Rosin, A. and Doljanski, F., Effect of hydroquinone on mitosis, Nature 172, 1151, 1953.
  • Galloway, S. M., Armstrong, M. J., Reuben, C., Colman, S., Brown, B., Cannon, C., Bloom, A. D., Nakamura, F., Ahmed, M., Duk, S., Rimpo, J., Margolin, B. H., Resnick, M. A., Anderson, B., and Zeiger, E., Chromosome aberrations and sister chro- matid exchanges in Chinese hamster ovary cells: evalu- ations of 108 chemicals, Environ. Mol. Mutagen. 10, 1–175, 1987.
  • Morimoto, K. and Koizumi, A., Inhibition of rejoin- ing of radiation-induced chromosome lesions and in- duction of sister chromatid exchanges — effects of benzene or its metabolites in cultured human leuko- cytes, Jpn. J. Hum. Genet. 23, 279–281, 1978.
  • Morimoto, K. and Wolff, S., Increase of sister chro- matid exchanges and perturbations of cell division kinetics in human lymphocytes by benzene metabo- lites, Cancer Res. 40, 1189–1193, 1980.
  • Morimoto, K., Wolff, S., and Koizumi, A., Induc- tion of sister-chromatid exchanges in human lympho- cytes by microsomal activation of benzene metabo- lites, Mutat. Res. 119, 355–360, 1983.
  • Morimoto, K., Takeshita, T., Takeuchi, T., Maruyama, S., Ezoe, S., Mure, K., and Inoue, C., Chromosome alterations in peripheral lymphocytes as indices of lifestyle and genotoxicity, Int. Arch. Occup. Environ. Health 65, S37–S41, 1993.
  • Knadle, S., Synergistic interaction between hydro- quinone and acetaldehyde in the induction of sister chromatid exchange in human lymphocytes in vitro, Cancer Res. 45, 4853–4857, 1985.
  • Erexson, G. L., Wilmer, J. L., and Kligerman,A. D., Sister chromatid exchange induction in human lymphocytes exposed to benzene and its metabolites in vitro, Cancer Res. 45, 2471–2477, 1985.
  • Pacchierotti, F., Bassani, B., Leopardi, P., and Zijno, A., Origin of aneuploidy in relation to distur- bances of cell-cycle progression. II. Cytogenetic analy- sis of various parameters in mouse bone marrow cells after colchicine or hydroquinone treatment, Mutagen- esis 6, 307–311, 1991.
  • Yager, J. W., Eastmond, D. A., Robertson, M. L., Paradisin, W. M., and Smith, M. T., Characteriza- tion of micronuclei induced in human lymphocytes by benzene metabolites, Cancer Res. 50, 393–399, 1990.
  • Migliore, L. and Nieri, M., Evaluation of twelve potential aneuploidogenic chemicals by the in vitro human lymphocyte micronucleus assay, Toxicol. In Vitro 5, 325–336, 1991.
  • Robertson, M. L., Eastmond, D. A., and Smith,M. T., Two benzene metabolites, catechol and hydro- quinone, produce a synergistic induction of micronu- clei and toxicity in cultured human lymphocytes, Mutat. Res. 249, 201–209, 1991.
  • Vian, L., van Hummelen, P., Bichet, N., Gouy, D., and Kirsch-Volders, M., Evaluation of hydroquinone and chloral hydrate on the in vitro micronucleus test on isolated lymphocytes, Mutat. Res. 334, 1–7, 1995.
  • Ferguson, L. R., Morcombe, P., and Triggs, C. N., The size of cytokinesis-blocked micronuclei in hu- man peripheral blood lymphocytes as a measure of aneuploidy induction by Set A compounds in the EEC trial, Mutat. Res. 287, 101–112, 1993.
  • Bonatti, S., Cavalieri, Z., Viaggi, S., and Abbondandolo, A., The analysis of 10 potential spindle poisons for their ability to induce CREST- positive micronuclei in human diploid fibroblasts, Mutagenesis 7, 111–114, 1992.
  • Glatt, H., Gemperlein, I., Setiabudi, F., Platt, K. L., and Oesch, F., Expression of xenobiotic-metaboliz- ing enzymes in propagatable cell cultures and induc- tion of micronuclei by 13 compounds, Mutagenesis 5, 241–249, 1990.
  • Antoccia, A., Degrassi, F., Battistoni, A., Ciliutti, P., and Tanzarella, C., In vitro micronucleus test with kinetochore staining: evaluation of test perfor- mance, Mutagenesis 6, 319–324, 1991.
  • Ellard, S. and Parry, E. M., Induction of micronu- clei in V79 Chinese hamster cells by hydroquinone and econazol nitrate, Mutat. Res. 287, 87–91, 1993.
  • Seelbach, A., Fissler, B., and Madle, S., Further evaluation of a modified micronucleus assay with V79 cells for detection of aneugenic effects, Mutat. Res. 303, 163–169, 1993.
  • Dobo, K. I. and Eastmond, D. A., Role of oxygen radicals in the chromosomal loss and breakage in- duced by the quinone-forming compounds, hydro- quinone and tert-butylhydroquinone, Environ. Mol. Mutagen. 24, 293–300, 1994.
  • Tunek, A., Hogstedt, B., and Olofsson, T., Mecha- nism of benzene toxicity, effects of benzene and ben- zene metabolites on bone marrow cellularity, number of granulopoietic stem cells and frequency of micro- nuclei in mice, Chem.-Biol. Interact. 39, 129–138, 1982.
  • Gad-El-Karim, M. M., Ramanujam, V. S., Ahmed,A. E., and Legator, M. S., Benzene myeloclasto- genicity: a function of its metabolism, Am. J. Ind. Med. 7, 475–484, 1985.
  • Gad-El-Karim, M. M., Sadagopa Ramanujam,V. M., and Legator, M. S., trans, trans-Muconic acid, an open-chain urinary metabolite of benzene in mice. Quantification by high-pressure liquid chroma- tography, Xenobiotica 15, 211–220, 1985.
  • Ciranni, R., Barale, R., Marrazzini, A., and Loprieno, N., Benzene and the genotoxicity of its metabolites. II. The effect of the route of administra- tion on the micronuclei and bone marrow depression in mouse bone marrow cells, Mutat. Res. 209, 23–28, 1988.
  • Adler, I. and Kleisch, U., Comparison of single and multiple treatment regimens in the mouse bone mar- row micronucleus assay for hydroquinone (HQ) and cyclophosphamide (CP), Mutat. Res. 234, 115–123, 1990.
  • Barale, R., Marrazzini, A., Betti, C., Vangelisti, V., Loprieno, N., and Barrai, I., Genotoxicity of two metabolites of benzene: phenol and hydroquinone show strong synergistic effects in vivo, Mutat. Res. 244, 15– 20, 1990.
  • Adler, I.-D., Kliesch, U., van Hummelen, P., and Kirsch-Volders, M., Mouse micronucleus tests with known and suspected spindle poisons: results from two laboratories, Mutagenesis 6, 47–53, 1991.
  • Gudi, R., Xu, J., and Thilagar, A., Assessment of the in vivo aneuploidy/micronucleus assay in mouse bone marrow cells with 16 chemicals, Environ. Mol. Mutagen. 20, 106–116, 1992.
  • van Hummelen, P., Deleener, A., Vanparys, P. H., and Kirsch-Volders, M., Discrimination of aneup- loidogens from clastogens by C-banding, DNA and area measurements of micronuclei from mouse bone marrow, Mutat. Res. 271, 13–28, 1992.
  • Chen, H. W., Tomar, R., and Eastmond, D. A., Detection of hydroquinone-induced nonrandom break- age in the centromeric heterochromatin of mouse bone marrow cells using multicolor fluorescence in situ hybridization with the mouse major and minor satel- lite probes, Mutagenesis 9, 563–569, 1994.
  • Marrazzini, A., Betti, C., Bernacchi, F., Barrai, I., and Barale, R., Micronucleus test and metaphase analyses in mice exposed to known and suspected spindle poisons, Mutagenesis 9, 505–515, 1994.
  • Marrazzini, A., Chelotti, L., Barrai, I., Loprieno, N., and Barale, R., In vivo genotoxic interactions among three phenolic benzene metabolites, Mutat. Res. 341, 29–46, 1994.
  • Grawe, J., Nusse, M., and Adler, I. D., Quantitative and qualitative studies of micronucleus induction in mouse erythrocytes using flow cytometry. I. Mea- surement of micronucleus induction in peripheral blood polychromatic erythrocytes by chemicals with known and suspected genotoxicity, Mutagenesis 12, 1–8, 1997.
  • Grawe, J., Adler, I. D., and Nusse, M., Quantitative and qualitative studies of micronucleus induction in mouse erythrocytes using flow cytometry. II. Analy- sis of micronuclei of aneugenic and clastogenic origin by dual-colour FISH on populations of bone marrow PCEs flow sorted on the basis of their relative DNA content, Mutagenesis 12, 9–16, 1997.
  • Ciranni, R., Barale, R., Marrazzini, A., and Loprieno, N., Benzene and the genotoxicity of its metabolites. I. Transplacental activity in mouse fe- tuses and in their dams, Mutat. Res. 208, 61–67, 1988.
  • Rupa, D. S., Schuler, M., and Eastmond, D. A., Detection of hyperdiploidy and breakage affecting the 1cen-1q12 region of cultured interphase human lym- phocytes treated with various genotoxic agents, Environ. Mol. Mutagen. 29, 161–167, 1997.
  • Miller, B.-M. and Adler, I.-D., Aneuploidy induc- tion in mouse spermatocytes, Mutagenesis, 7, 69–76, 1992.
  • Leopardi, P., Zijno, A., Bassani, B., and Pacchierotti, F., In vivo studies on chemically in- duced aneuploidy in mouse somatic and germinal cells, Mutat. Res. 287, 119–130, 1993.
  • Marrazzini, A., Betti, C., Barale, R., Bernacchi, F., and Loprieno, N., Cytogenetic effects of possible aneuploidizing agents, Mutat. Res. 252, 195–196, 1991.
  • Eastmond, D. A., Rupa, D. S., and Hasegawa, L. S.,Detection of hyperdiploidy and chromosome break-age in interphase human lymphocytes following ex- posure to the benzene metabolite hydroquinone using multicolor fluorescence in situ hybridization with DNA probes, Mutat. Res. 322, 9–20, 1994.
  • Albertini, S., Analysis of nine known or suspected spindle poisons for mitotic chromosome malsegre- gation using Saccharomyces cerevisiae D61. M, Mu- tagenesis 5, 453–459, 1990.
  • Xu, W. and Adler, I.-D., Clastogenic effects of known and suspected spindle poisons studied by chromo- some analysis in mouse bone marrow cells, Mutagen- esis 5, 371–374, 1990.
  • Ciranni, R. and Adler, I., Clastogenic effects of hydroquinone: induction of chromosomal aberrations in mouse germ cells, Mutat. Res. 263, 223–229, 1991.
  • Crebelli, R., Conti, G., and Carere, A., On the mechanism of mitotic segregation induction in As- pergillus nidulans by benzene hydroxy metabolites, Mutagenesis 2, 235–238, 1987.
  • Crebelli, R., Conti, G., Conti, L., and Carere, A., In vitro studies with nine known or suspected spindle poisons: results in tests for chromosome malsegrega- tion in Aspergillus nidulans, Mutagenesis 6, 131–136, 1991.
  • Bilimoria, M., Detection of mutagenic activity of chemicals and tobacco smoke in a bacterial system, Mutat. Res. 31, 328(abstract), 1975.
  • Painter, R. B. and Howard, R., The HeLa DNA- synthesis inhibition test as a rapid screen for mu- tagenic carcinogens, Mutat. Res. 92, 427–437, 1982.
  • Lewis, J. G., Stewart, W., and Adams, D. O., Role of oxygen radicals in induction of DNA damage by metabolites of benzene, Cancer Res. 48, 4762–4765, 1988.
  • Lewis, J. G., Odom, B., and Adams, D. O., Toxic effects of benzene and benzene metabolites on mono- nuclear phagocytes, Toxicol. Appl. Pharmacol. 92, 246–254, 1988.
  • Maeda, M., Yamada, K., Ikeda, I., Nakajima, H., Tajima, M., and Murakami, H., Effects of phenyl compounds on proliferation and IgM production of human-human hybridoma HB4C5 cells cultured in serum-free medium, Agric. Biol. Chem. 54, 1093– 1096, 1990.
  • Stenius, U., Warholm, M., Rannug, A., Walles, S., Lundberg, I., and Högberg, J., The role of GSH depletion and toxicity in hydroquinone-induced de- velopment of enzyme-altered foci, Carcinogenesis 10, 593–599, 1989.
  • Walles, S., Mechanisms of DNA damage induced in rat hepatocytes by quinones, Cancer Lett. 63, 47–52, 1992.
  • Pellack-Walker, P. and Blumer, J. L., DNA dam- age in L5178Y cells following exposure to benzene metabolites, Mol. Pharmacol. 30, 42–47, 1986.
  • Shimada, H., Sato, T., Hattori, C., Satake, S., and Itoh, S., Induction of micronuclei by benzene and its metabolites, Mutat. Res. 216, 377(abstract), 1989.
  • Sze, C. C., Shi, C. Y., and Ong, C. N., Cytotoxicity and DNA strand breaks induced by benzene and its metabolites in Chinese hamster ovary cells, J. Appl. Toxicol. 16, 259–264, 1996.
  • Anderson, D., Yu, T. W., and Schmezer, P., An investigation of the DNA-damaging ability of ben- zene and its metabolites in human lymphocytes, using the comet assay, Environ. Mol. Mutagen. 26, 305– 314, 1995.
  • Leanderson, P. and Tagesson, C., Cigarette smoke- induced DNA damage in cultured human lung cells: role of hydroxyl radicals and endonuclease activation, Chem.-Biol. Interact. 81, 197–208, 1992.
  • Andreoli, C., Leopardi, P., and Crebelli, R., Detec- tion of DNA damage in human lymphocytes by alka- line single cell gel electrophoresis after exposure to benzene or benzene metabolites, Mutat. Res. 377, 95– 104, 1997.
  • Zhang, L. P., Wang, Y. X., Shang, N., and Smith,M. T., Benzene metabolites induce the loss and long arm deletion of chromosomes 5 and 7 in human lym- phocytes, Leuk. Res. 22, 105–113, 1998.
  • Smith, M. T. and Zhang, L. P., Biomarkers of leu- kemia risk: benzene as a model, Environ. Health Perspect. 106, 937–946, 1996.
  • Kappas, A., On the mechanism of induced aneup- loidy in Aspergillus nidulans and validation of tests for genomic mutations. In: Resnick, M. A. and Vig, B. K., Eds., Mechanisms of Chromosome Distribution and Aneuploidy. Alan R. Liss, Inc., New York, 1989, 377–384.
  • Miller, B. M. and Adler, I. D., Suspect spindle poi- sons: analysis of c-mitotic effects in mouse bone marrow cells, Mutagenesis 4, 208–215, 1989.
  • Warr, T. J., Parry, E. M., and Parry, J. M., A comparison of two in vitro mammalian cell cytoge- netic assays for the detection of mitotic aneuploidy using 10 known or suspected aneugens, Mutat. Res. 287, 29–46, 1993.
  • Hader, C., Hadnagy, W., and Seemayer, N. H., A rapid method for detection of nongenotoxic carcino- gens of environmental pollutants using synchronized V79 cells and flow cytometry, Toxicol. Lett. 88, 99– 108, 1996.
  • Seiler, J. P., Inhibition of testicular DNA synthesis by chemical mutagens and carcinogens. Preliminary re- sults in the validation of a novel short-term test, Mutat. Res. 46, 305–310, 1977.
  • Post, G. B., Snyder, R., and Kalf, G. F., Inhibition of mRNA synthesis in rabbit bone marrow nuclei in vitro by quinone metabolites of benzene, Chem.-Biol. Interact. 50, 203–211, 1984.
  • Post, G. B., Snyder, R., and Kalf, G. F., Inhibition of RNA synthesis and interleukin-2 production in lym- phocytes in vitro by benzene and its metabolites, hy- droquinone and p-benzoquinone, Toxicol. Lett. 29, 161–167, 1985.
  • Pellack-Walker, P., Walker, J. K., Evans, H. H., and Blumer, J. L., Relationship between the oxidation potential of benzene metabolites and their inhibi- tory effect on DNA synthesis in L517YS cells, Mol. Pharmacol. 28, 560–566, 1985.
  • Lee, E. W., Johnson, J. T., and Garner, C. D., Inhibitory effect of benzene metabolites on nuclear DNA synthesis in bone marrow cells, J. Toxicol. Environ. Health 26: 277–291, 1989.
  • International Programme on Chemical Safety (IPCS), Hydroquinone Health and Safety Guide, World Health Organization, Geneva, 1996.
  • Irons, R. D., Neptun, D. A., and Pfeifer, R. W., Inhibition of lymphocyte transformation and microtu- bule assembly by quinone metabolites of benzene: evidence for a common mechanism, J. Reticulo- endothel. Soc. 30, 359–372, 1981.
  • Brunner, M., Albertini, S., and Wurgler, F. E., Effects of 10 known or suspected spindle poisons in the in vitro porcine brain tubulin assembly assay, Mutagenesis 6, 65–70, 1991.
  • Wallin, M. and Hartley-Asp, B., Effects of potential aneuploidy inducing agents on microtubule assembly in vitro, Mutat. Res. 287, 17–22, 1993.
  • Li, Y. and Trush, M. A., DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation, Carcinogenesis 14, 1303–1311, 1993.
  • Li, Y., Kuppusamy, P., Zweier, J. L., and Trush,M. A., ESR evidence for the generation of reactive oxygen species from the copper-mediated oxidation of the benzene metabolite, hydroquinone: role in DNA damage, Chem.-Biol. Interact. 94, 101–120, 1995.
  • Hiraku, Y. and Kawanishi, S., Oxidative DNA dam- age and apoptosis induced by benzene metabolites, Cancer Res. 56, 5172–5178, 1996.
  • Yu, T. W. and Anderson, D., Reactive oxygen spe- cies-induced DNA damage and its modification: A chemical investigation, Mutat. Res. 379, 201–210, 1997.
  • Lee, E. W. and Gardner, C. D., Effects of benzene on DNA strand breaks in vivo versus benzene me- tabolite-induced DNA strand breads in vitro in mouse bone marrow cells, Toxicol. Appl. Pharmacol. 108, 497–508, 1991.
  • Hutt, A. M. and Kalf, G. F., Inhibition of human DNA topoisomerase II by hydroquinone and p-benzo- quinone, reactive metabolites of benzene, Environ. Health Perspect. 104(Suppl. 6), 1265–1269, 1996.
  • Mozhaev, E. A., Osintseva, V. P., and Arzamastsev,E. V., Hydroquinone toxicity in chronic poisoning (Russian), Farmikol. Toksikol. 29, 238–240, 1966.
  • Rao, G. S., Siddiqui, S. M., Pandya, K. P., and Shanker, R., Relative toxicity of metabolites of ben- zene in mice, Vet. Hum. Toxicol. 30, 517–520, 1988.
  • Kari, F. W., Bucher, J., Eustis, S. L., Haseman, J. K., and Huff, J. E., Toxicity and carcinogenicity of hydroquinone in F344/N rats and B6C3F1 mice, Food Chem. Toxicol. 30, 737–747, 1992.
  • Boatman, R. J., English, J. C., Perry, L. G., and Bialecki, V. E., Differences in the nephrotoxicity of hydroquinone among Fischer 344 and Sprague-Dawley Rats and B6C3F1 mice, J. Toxicol. Environ. Health 47, 159–172, 1996.
  • Shibata, M.-A., Hirose, M., Tanaka, H., Asakawa, E., Shirai, T., and Nobuyuki, I., Induction of renal cell tumors in rats and mice, and enhancement of hepatocellular tumor development in mice after long- term hydroquinone treatment, Jpn. J. Cancer Res. 82, 1211–1219, 1991.
  • David, R. M., English, J. C., Totman, L. C., Moyer, C., and O’Donoghue, J. L., Lack of nephrotoxicity and renal cell proliferation following subchronic der- mal application of a hydroquinone cream, Food Chem. Toxicol. 36, 609–616, 1998.
  • Perry, L. G., English, J. C., Vlaovic, M., Moyer, C., and Edna, J. L., Measurement of cell proliferation in the kidneys of rats after oral administration of hydro- quinone, Toxicologist 13, 394(abstract), 1993.
  • Lau, S. S., Hill, B. A., Highet, R. J., and Monks,T. J., Sequential oxidation and glutathione addition to 1,4–benzoquinone: correlation of toxicity with in- creased glutathione substitution, Mol. Pharmacol. 34, 829–836, 1988.
  • Hill, B. A., Monks, T. J., and Lau, S., The effects of 2,3,5–(triglutathion-S-yl)hydroquinone on renal mito- chondrial respiratory function in vivo and in vitro: possible role in cytotoxicity, Toxicol. Appl. Pharmacol. 117, 165–171, 1992.
  • Hill, B. A., Davidson, K. L., Dulik, D. M., Monks,T. J., and Lau, S. S., Metabolism of 2–(glutathion-S- yl)hydroquinone and 2,3,5–(triglutathion-S-yl)hydro- quinone in the in situ perfused rat kidney: Relation- ship to nephrotoxicity, Toxicol. Appl. Pharmacol. 129, 121–132, 1994.
  • Eckert, K-G., Eyer, P., Sonnenbichler, J., and Zetl, I., Activation and detoxication of aminophenols. III. Synthesis and structural elucidation of various glu- tathione addition products to 1,4–benzoquinone, Xenobiotica 20, 351–361, 1990.
  • Barber, E. D., Polvino, J. M., and English, J. C., Acetylation of (L-cystein-S-yl)hydroquinone in the liver and kidney of male and female Fischer (F344) rats and male Sprague-Dawley (SD) rats, Int. Toxicol. 69, 12(abstract), 1995.
  • Lau, S. S., Kleiner, H. E., and Monks, T. J., Me- tabolism as a determinant of species susceptibility to 2,3,5–(triglutathion-S-yl)hydroquinone-mediated nephrotoxicity, Drug Metab. Disp. 23, 1136–1142, 1995.
  • English, J. C., Perry, L. G., Vlaovic, M., Moyer, C., and O’Donoghue, J. L., Measurement of cell prolif- eration in the kidneys of Fischer 344 and Sprague- Dawley rats after gavage administration of hydro- quinone, Fundam. Appl. Toxicol. 23, 297–406, 1994.
  • O’Donoghue, J. L. and English, J. C., Some com- ments on the potential effects of hydroquinone expo- sure, Food Chem. Toxicol. 32, 863–864, 1994.
  • Konishi, N. and Ward, J. M., Increased levels of DNA synthesis in hyperplastic renal tubules of aging nephropathy in female F344/NCR rats, Vet. Pathol. 26, 6–10, 1989.
  • Hirose, M., Inoue, T., Asamoto, M., Tagawa, Y., and Ito, N., Comparison of the effects of 13 phenolic compounds in induction of proliferative lesions of the forestomach and increase in the labelling indices of the glandular stomach and urinary bladder epithelium of Syrian golden hamsters, Carcinogenesis 7, 1285– 1289, 1986.
  • Hirose, M., Yamaguchi, S., Fukushima, S., Hasegawa, R., Takahashu, S., and Ito, N., Promo- tion by dihydroxybenzene derivatives of N-methyl- N-nitro-N-nitrosoguanidine-induced F344 rat fore- stomach and glandular stomach carcinogenesis, Cancer Res. 49, 5143–5147, 1989.
  • Yamaguchi, S., Hirose, M., Fukushima, S., Hasegawa, R., and Ito, N., Modification by catechol and resorcinol of upper digestive tract carcinogenesis in rats treated with methyl-N-amylnitrosamine, Can- cer Res. 49, 6015–6018, 1989.
  • Shibata, M.-A., Yamada, M., Hirose, M., Asakawa, A., Tatematsu, M., and Ito, N., Early proliferative responses of forestomach and glandular stomach of rats treated with five different phenolic antioxidants, Carcinogenesis 11, 425–429, 1990.
  • Altmann, H. J., Grunow, W., Wester, P. W., and Mohr, U., Induction of forestomach lesions by butylhydroxyanisole and structurally related sub- stances, Arch. Toxicol. 114–116, 1985.
  • National Toxicology Program (NTP), Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71– 43–2) in F344/N Rats and B6C3F1 Mice (Gavage Studies), NTP Technical Report No. 289; Washing- ton: U.S. Department of Health and Human Services, 1986.
  • Stromberg, P. C., Large granular lymphocyte leuke- mia in F344 rats. Model for human T lymphoma, malignant histiocytosis, and T-cell chronic lympho- cytic leukemia, Am. J. Pathol. 119, 517–519, 1985.
  • Rao, G. N., Haseman, J. K., Grumbein, S., Crawford, D. D., and Eustis, S. L., Growth, body weight, survival, and tumor trends in F344/N rats during an eleven-year period, Toxicol. Pathol. 18, 61– 70, 1990.
  • Roe, F. J. C. and Salaman, M. H., Further studies on incomplete carcinogenesis: Triethylene melamine (T.E. M.), 1,2–benzanthracene and β-propiolactone, as ini- tiators of skin tumor formation in the mouse, Br. J. Cancer 9, 177–203, 1955.
  • Boutwell, R. K. and Bosch, D. K., The tumor-pro- moting activity of phenol and related compounds for mouse skin, Cancer Res. 19, 413–424, 1959.
  • Van Duuren, B. L. and Goldschmidt, B. M., Cocarcinogenic and tumor-promoting agents in to- bacco carcinogenesis, J. Natl. Cancer Inst. 56, 1237– 1242, 1976.
  • Maruyama, H., Amanuma, T., Nakae, D., Tsutsumi, M., Kondo, S., Tsujiuchi, T., Denda, A., and Konishi, Y., Effects of catechol and its analogs on pancreatic carcinogenesis initiated by N-nitrosobis(2– oxopropyl)amine in Syrian hamsters, Carcinogenesis 12, 1331–1334, 1991.
  • Kurata, Y., Fukushima, S., Hasegawa, R., Hirose, M., Shibata, M.-A., Shirai, T., and Ito, N., Struc- ture-activity relations in promotion of rat urinary blad- der carcinogenesis by phenolic antioxidants, Jpn. J. Cancer Res. 81, 754–759, 1990.
  • Miyata, Y., Fukushima, S., Hirose, M., Masui, T., and Ito, N., Short-term screening of promoters of bladder carcinogenesis in N-butyl-N-(4-hydroxy- butyl)nitrosamine-initiated, unilaterally ureter-ligated rats, Jpn. J. Cancer Res. 76, 828–834, 1985.
  • Hasegawa, R., Furukawa, F., Toyoda, K., Taka- hashi, M., Hayashi, Y., Hirose, M., and Ito, N., Inhibitory effects of antioxidants on N-bis(2- hydroxypropyl)nitrosamine-induced lung carcinogen- esis in rats, Jpn. J. Cancer Res. 81, 871–877, 1990.
  • Boyland, E., Busby, E. R., Dukes, C. R., Grover, P. L., and Manson, D., Further experiments on im- plantation of materials into the urinary bladder of mice, Br. J. Cancer 18, 575–581, 1964.
  • Hasegawa, R. and Ito, N., Liver medium-term bioas- say in rats for screening of carcinogens and modifying factors in hepatocarcinogenesis, Food Chem. Toxicol. 30, 979–992, 1992.
  • Stenius, U., Warholm, M., and Högberg, J., Selec- tive toxicity in putative preneoplastic hepatocytes: a comparison of hydroquinone and duroquinone, Can- cer Lett. 68, 149–157, 1993.
  • Hagiwara, A., Kokubo, Y., Takesada, Y., Tanaka, H., Tamano, S., Hirose, M., Shirai, T., and Ito, N., Inhibitory effects of phenolic compounds on develop- ment of naturally occurring preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats, Teratogen. Carcinogen. Mutagen. 16, 317–325, 1996.
  • Delcambre, J., Weber, B., and Baron, C., Toxicity of hydroquinone (French), Revue Agressologie 3, 311– 315, 1962.
  • Nakamura, S., The effects of oral administration of resorcin, hydroquinone and phenol on the hematopoi- etic system in mice (Japanese), Osaka-Furitsu Koshu Eisei Kenkyusho 20, 45–49, 1982.
  • Mitchell, J. R., Mechanism of benzene-induced aplas- tic anemia, Fed. Proc. 30, 561(abstract), 1971.
  • Snyder, R. and Kalf, G. F., A perspective on ben- zene leukemogenesis, Crit. Rev. Toxicol. 24, 177– 209, 1994.
  • Smith, M. T., Overview of benzene-induced aplastic anaemia, Eur. J. Haematol. 57(Suppl.), 107–110, 1996.
  • Tunek, A., Olofsson, T., and Berlin, M., Toxic ef- fects of benzene and benzene metabolites on granulopoietic stem cells and bone marrow cellularity in mice, Toxicol. Appl. Pharmacol. 59, 149–156, 1981.
  • Wierda, D. and Irons, R. D., Hydroquinone and catechol reduce the frequency of progenitor B lym- phocytes in mouse spleen and bone marrow, Immunopharmacology 4, 41–54, 1982.
  • Eastmond, D. A., Smith, M. T., and Irons, R. D., An interaction of benzene metabolites reproduces the myelotoxicity observed with benzene exposure, Toxicol. Appl. Pharmacol. 91, 85–95, 1987.
  • Henschler, R., Glatt, H. R., and Heyworth, C. M., Hydroquinone stimulates granulocyte-macrophage progenitor cells in vitro and in vivo, Environ. Health Perspect. 104, 1271–1274, 1996.
  • Hazel, B. A. and Kalf, G. F., Induction of granulo- cytic differentiation in myeloblasts by hydroquinone, a metabolite of benzene, involves the leukotriene D4 receptor, Receptor Signal Transduction 6, 1–12, 1996.
  • Boyd, R., Griffiths, J., Kindt, V., Snyder, R., Caro, J., and Ersley, A., Relative toxicity of five benzene metabolites on CFU-GM cultures, Toxicologist 2, 121– 122(abstract), 1982.
  • Colinas, R. J., Burkart, P. T., and Lawrence, D. A., In vitro effects of hydroquinone, benzoquinone, and doxorubicin on mouse and human bone marrow cells at physiological oxygen partial pressure, Toxicol. Appl. Pharmacol. 129, 95–102, 1994.
  • Irons, R. D., Stillman, W. S., Colagiovanni, D. B., and Henry, V. A., Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulat- ing factor in vitro, Proc .Natl. Acad. Sci. U.S.A. 89, 3691–3695, 1992.
  • Irons, R. D. and Stillman, W. S., The effects of benzene and other leukaemogenic agents on haematopoietic stem and progenitor cell differentia- tion, Eur. J. Haematol. 57(Suppl.), 119–124, 1996.
  • Oliveira, N. L. and Kalf, G. F., Induced differentia- tion of HL-60 promyelocytic leukemia cells to mono- cyte/macrophages is inhibited by hydroquinone, a hematotoxic metabolite of benzene, Blood 79, 627– 633, 1992.
  • Hazel, B. A., O’Connor, A., Niculescu, R., and Kalf, G. F., Benzene and its metabolite, hydroquinone, induce granulocytic differentiation in myeloblasts by interacting with cellular signaling pathways activated by granulocyte colony-stimulating factor, Stem Cells 13, 295–310, 1995.
  • Moran, J. L., Siegel, D., Sun, X. M., and Ross, D., Induction of apoptosis by benzene metabolites in HL60 and CD34+ human bone marrow progenitor cells, Mol. Pharmacol. 50, 610–615, 1996.
  • Hazel, B. A., Baum, C., and Kalf, G. F., Hydro- quinone, a bioreactive metabolite of benzene, inhibits apoptosis in myeloblasts, Stem Cells 14, 730–742, 1996.
  • Bolcsak, L. E. and Nerland, D. E., Inhibition of erythropoiesis by benzene and benzene metabolites, Toxicol. Appl. Pharmacol. 69, 363–368, 1983.
  • Snyder, R., Dimitriadis, E., Guy, R., Hu, P., Coo- per, K., Bauer, H., Witz, G. and Goldstein, B. D., Studies on the mechanism of benzene toxicity, Environ. Health Perspect. 82, 31–35, 1989.
  • Guy, R. L., Dimitriadis, E. A., Hu, P., Cooper,K. R., and Snyder, R., Interactive inhibition of erythroid 59Fe utilization by benzene metabolites in female mice, Chem.-Biol. Interact. 74, 55–62, 1990.
  • Guy, R. L., Hu, P., Witz, G., Goldstein, B. D., and Snyder, R., Depression of iron uptake into erythro- cytes in mice by treatment with the combined benzene metabolites p-benzoquinone, muconaldehyde and hy- droquinone, J. Appl. Toxicol. 11, 443–446, 1991.
  • Seidel, H. J., Barthel, E., Schafer, F., Scad, H., and Weber, L., Action of benzene metabolites on murine hematopoietic colony-forming cells in vitro, Toxicol. Appl. Pharmacol. 111, 128–131, 1991.
  • Brown, A., Lutton, J. D., Nelson, J., Abraham,N. G., and Levere, R. D., Microenvironmental cytokines and expression of erythroid heme metabolic enzymes, Blood Cells 13, 123–136, 1987.
  • Neun, D. J., Penn, A., and Snyder, C. A., Evidence for strain-specific differences in benzene toxicity as a function of host target cell susceptibility, Arch. Toxicol. 66, 11–17, 1992.
  • Gross, S., Gruntmeir, J., Helm, K., Stillman, W., and Irons, R., The benzene metabolite, hydroquinone, alters phenotypic expression of human CD34+ cells in liquid culture, Toxicologist 36, 163(abstract), 1997.
  • Greenberger, J. S., The hematopoietic microenvi- ronment, Crit. Rev. Oncol. Hematol. 11, 65–84, 1991.
  • Morrison, S. J., Uchida, N., and Weissman, I. L., The biology of hematopoietic stem cells, Annu. Rev. Cell Dev. Biol. 11, 35–71, 1995.
  • Gaido, K. and Wierda, D., In vitro effects of ben- zene metabolites on mouse bone marrow stromal cells, Toxicol. Appl. Pharmacol. 76, 45–55, 1984.
  • Gaido, K. W. and Wierda, D., Suppression of bone marrow stromal cell function by benzene and hydro- quinone is ameliorated by indomethacin, Toxicol. Appl. Pharmacol. 89, 378–390, 1987.
  • Thomas, D. J., Reasor, M. J., and Wierda, D., Macrophage regulation of myelopoiesis is altered by exposure to the benzene metabolite hydroquinone, Toxicol. Appl. Pharmacol. 97, 440–453, 1989.
  • Renz, J. F. and Kalf, G. F., Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1, Blood 78, 938–944, 1991.
  • Miller, A. C., Schattenberg, D. G., Malkinson, A. M., and Ross, D., Decreased content of the IL-1 processing enzyme calpain in murine bone marrow- derived macrophages after treatment with the benzene metabolite hydroquinone, Toxicol. Lett. 74, 177–184, 1994.
  • Niculescu, R., Bradford, H. N., Colman, R. W., and Kalf, G. F., Inhibition of the conversion of pre- interleukins-1 and -1β to mature cytokines by p-benzoquinone, a metabolite of benzene, Chem.-Biol. Interact. 98, 211–222, 1995.
  • Kalf, G. F., Renz, J. F., and Niculescu, R., p-Ben- zoquinone, a reactive metabolite of benzene, prevents the processing of pre-interleukins-1 and -β to active cytokines by inhibition of the processing enzymes,calpain, and interleukin-1β converting enzyme, Environ. Health Perspect. 104: 1251–1256, 1996.
  • Carbonnelle, P., Lison, D., LeRoy, J-Y. and Lauwerys, R., Effect of the benzene metabolite, hy- droquinone, on interleukin-1 secretion by human monocytes in vitro, Toxicol. Appl. Pharmacol. 132, 220–226, 1995.
  • Post, G., Snyder, R., and Kalf, G. F., Metabolism of benzene and phenol in macrophages in vitro and the inhibition of RNA synthesis by benzene metabolites, Cell Biol. Toxicol. 2, 231–246, 1986.
  • Smart, R. C. and Zannoni, V. G., DT-diaphorase and peroxidase influence the covalent binding of the metabolites of phenol, the major metabolite of ben- zene, Mol. Pharmacol. 26, 105–111, 1984.
  • Schattenberg, D. G., Stillman, W. S., Gruntmeir, J. J., Helm, K. M., Irons, R. D., and Ross, D., Peroxidase activity in murine and human hematopoi- etic progenitor cells: potential relevance to benzene- induced toxicity, Mol. Pharmacol. 46, 346–351, 1994.
  • Wever, R., Plat, H., and Hamers, M. N., Suppres- sion of bone marrow stromal cell function by benzene and hydroquinone is ameliorated by indomethacin, FEBS Lett. 123: 327–331.
  • Pirozzi, S. J., Schlosser, M. J., and Kalf, G. F., Prevention of benzene-induced myelotoxicity and pros- taglandin synthesis in bone marrow of mice by inhibi- tors of prostaglandin H synthase, Immunopharma- cology 18, 39–55, 1989.
  • Thomas, D. J., Sadler, A., Subrahmanyam, V. V., Siegel, D., Reasor, M. J., Wierda, D., and Ross, D., Bone marrow stromal cell bioactivation and detoxifi- cation of the benzene metabolite hydroquinone: com- parison of macrophages and fibroblastoid cells, Mol. Pharmacol. 37, 255–262, 1990.
  • London, S. J., Lehman, T. A., and Taylor, J. A., Myeloperoxidase genetic polymorphism and lung can- cer risk, Cancer Res. 57, 5001–5003, 1997.
  • Meyer, K. B., Subrahmanyam, V. V., Kolachana, P., and Smith, M. T., Bioactivation and cytotoxicity of hydroquinone in human promyelocytic leukemia (HL60) cells, Toxicologist 11, 180(abstract), 1991.
  • Bratton, S. B., Lau, S. S., and Monks, T. J., Iden- tification of quinol thioethers in bone marrow of hy- droquinone/phenol-treated rats and mice and their po- tential role in benzene-mediated hematotoxicity, Chem. Res. Toxicol. 10, 859–865, 1997.
  • Twerdok, L. E. and Trush, M. A., Differences in quinone reductase activity in primary bone marrow stromal cells derived from C57BL/6 and DBA/2 mice, Res. Commun. Chem. Pathol. Pharmacol. 67, 375– 386, 1990.
  • Zhu, H., Li, Y., and Trush, M.A., Differences in xenobiotic detoxifying activities between bone mar- row stromal cells from mice and rats: implications for benzene-induced hematotoxicity, J. Toxicol. Environ. Health 46, 183–201, 1995.
  • Twerdok, L. E., Rambish, S. J., and Trush, M. A.,Induction of quinone reductase and glutathione in bone marrow cells by 1,2–dithiole-3–thione: effect on hydroquinone-induced cytotoxicity, Toxicol. Appl. Pharmacol. 112, 273–281, 1992.
  • Twerdok, L. E., Rambish, S. J., and Trush, M. A., Studies with 1,2–dithiole-3–thione as a chemoprotector of hydroquinone-induced toxicity to DBA/2–derived bone marrow stromal cells, Environ. Health Perspect. 101, 172–177, 1993.
  • Li, Y., Lafuente, A., and Trush, M. A., Character- ization of quinone reductase, glutathione and glu- tathione S-transferase in human myeloid cell lines: induction by 1,2–dithiole-3–thione and effects on hy- droquinone-induced cytotoxicity, Life Sci. 54, 901– 916, 1994.
  • Rothman, N., Smith, M. T., Hayes, R. B., Traver,R. D., Hoener, B., Campleman, S., Li, G. L., Dosemeci, M., Linet, M., Zhang, L., Xi, L., Wacholder, S., Lu, W., Meyer, K. B., Titenko- Holland, N., Stewart, J. T., Yin, S., and Ross, D., Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609CT mutation and rapid fractional excretion of chlorzox- azone, Cancer Res. 57, 2839–2842, 1997.
  • Laskin, J. D., Rao, N. R., Punjabi, C. J., Laskin, D. L., and Synder, R., Distinct actions of benzene and its metabolites on nitric oxide production by bone marrow leukocytes, J. Leukocyte Biol. 57, 422–426, 1995.
  • Rao, N. R. and Snyder, R., Oxidative modifications produced in HL-60 cells on exposure to benzene metabolites, J. Appl. Toxicol. 15, 403–409, 1995.
  • Pfeifer, R. W. and Irons, R. D., Inhibition of lectin- stimulated lymphocyte agglutination and mitogenesis by hydroquinone: reactivity with intracellular sulfhy- dryl groups, Exp. Mol. Pathol. 35, 189–198, 1981.
  • Pfeifer, R. W. and Irons, R. D., Alteration of lym- phocyte function by quinones through a sulfhydryl- dependent distribution of microtubule assembly, Int.J. Immunopharmacol. 5, 463–470, 1983.
  • King, A. G., Landreth, K. S., and Wierda, D., Hy- droquinone inhibits bone marrow pre-B cell matura- tion in vitro, Mol. Pharmacol. 32, 807–812, 1987.
  • King, A. G., Landreth, K. S., and Wierda, D., Bone marrow stromal cell regulation of B-lymphopoiesis. II. Mechanisms of hydroquinone inhibition of pre-B cell maturation, J. Pharmacol. Exp. Ther. 250, 582– 590, 1989.
  • Lang, D. S., Meier, K. L., and Luster, M. I., Com- parative effects of immunotoxic chemicals on in vitro proliferative responses of human and rodent lympho- cytes, Fundam. Appl. Toxicol. 21, 535–545, 1993.
  • Li, Q., Geiselhart, L., Mittler, J. N., Mudzinski,S. P., Lawrence, D. A., and Freed, B. M., Inhibition of human T lymphoblast proliferation for hydro- quinone, Toxicol. Appl. Pharmacol. 139, 317–323, 1996.
  • Li, Q. and Freed, B. M., HQ inhibits lymphoblast proliferation by two different mechanisms, Toxicolo- gist 36, 200(abstract), 1997.
  • Li, Q. and Freed, B. M., Role of iron in hydro- quinone- and catechol-induced inhibition of IL-2–de- pendent lymphoblast proliferation, Fundam. Appl. Toxicol. 30, 4(abstract), 1996.
  • Li, Q., Aubrey, M. T., Christian, T., and Freed,B. M., Differential inhibition of DNA synthesis in human T cells by the cigarette tar components hydro- quinone and catechol, Fundam. Appl. Toxicol. 38, 158–165, 1997.
  • Li, Q., Kasten-Jolly, J., Yen, Y., and Freed, B. M., Reversal of hydroquinone-mediated suppression of T cell proliferation by transfection of the M2 subunit of ribonucleotide reductase, Toxicol. Appl. Pharmacol. 150, 154–157, 1988.
  • Updyke, L. W., Wilson, P. S., and Wierda, D., Decreased IL-7 production by long term bone marrow cultures following exposure to quinones, Toxicologist 11, 203(abstract), 1991.
  • Cheung, S. C., Newland, D. E., and Sonnenfeld, G., Inhibition of interferon gamma production by ben- zene and benzene metabolites, J. Natl. Cancer Inst. 80, 1069–1072, 1988.
  • Cheung, S. C., Nerland, D. E., and Sonnenfeld, G., Inhibition of interferon-/β induction in L-929 cells by benzene and benzene metabolites, Oncology 46, 335–338, 1989.
  • Pyatt, D. W., Stillman, W. S., and Irons, R. D., Hydroquinone, a reactive metabolite of benzene, in- hibits NF-B in primary human CD4+ T lymphocytes, Toxicol. Appl. Pharmacol. 149, 178–184, 1998.
  • Fan, X., Hirata, Y., and Minami, M., Effect of benzene and its metabolites on natural killer activity of mouse spleen cells in vitro, Jpn. J. Ind. Health, 31, 330–334, 1989.
  • Manning, B. W., Adams, D. O., and Lewis, J. G., Effects of benzene metabolites on receptor-mediated phagocytosis and cytoskeletal integrity in mouse peri- toneal macrophages, Toxicol. Appl. Pharmacol. 126, 214–223, 1994.
  • Medinsky, M. A., Kenyon, E. M., Seaton, M. J., and Schlosser, P. M., Mechanistic considerations in benzene physiological model development, Environ. Health Perspect. 104, 1399–1404, 1996.
  • Burgaz, S., Ozcan, M., Ozkul, A., and Karakaya,A. E., Effect of hydroquinone (HQ) on the develop- ment of chick embryos, Drug Chem. Toxicol. 17, 163–174, 1994.
  • Chapman, D. E., Namkung, M. J., and Juchau,M. R., Benzene and benzene metabolites as embryo- toxic agents: effects on cultured rat embryos, Toxicol. Appl. Pharmacol. 128: 129–137, 1994.
  • Oglesby, L. A., Ebron-McCoy, M. T., Logsdon,T. R., Copeland, F., Beyer, P. E., and Kavlock,R. J., In vitro embryotoxicity of a series of para- substituted phenols: structure, activity, and correla- tion with in vivo data, Teratology 45, 11–33, 1992.
  • Telford, I. R., Woodruff, C. S., and Linford, R. H., Fetal resorption in the rat as influenced by certain antioxidants, Am. J. Anat. 26, 195–200, 1962.
  • Racz, G., Fuzi, J., Kemeny, G., and Kisgyorgy, Z., The effect of hydroquinone and phlorizin on the sexual cycle of white rats (Russian), Orvosi Szemle, 5, 65– 67, 1958.
  • Rosen, F. and Millman, N., Anti-gonadotropic ac- tivities of quinones and related compounds, Endocri- nology 57, 466–471, 1955.
  • Skalka, P., Influence of hydroquinone on the fertility of male rats (Czech), Sb. Vys. Sk. Zemed. B, 12, 491– 494, 1964.
  • Ames, S. R., Ludwig, M. I., Swanson, W. J., and Harris, P. L., Effect of DPPD, methylene blue, BHT, and hydroquinone on reproductive process in the rat, Proc. Soc. Exp. Biol. Med. 93, 39–42, 1956.
  • Kavlock, R. J., Oglesby, L. A., Hall, L. L., Fisher,H. L., Copeland, F., Logsdon, T., and Ebron- McCoy, M., In vivo and in vitro structure-dosimetry- activity relationships of substituted phenols in devel- opmental toxicity assays, Fundam. Appl. Toxicol. 16, 225229, 1990.
  • Cosmetic, Toiletry, and Fragrance Association (CTFA), Dermal Teratology Study in Albino Female Sprague-Dawley Rats, Washington: Cosmetics, Toi- letry, and Fragrance Manufacturers, 1980; Study Project TR-01–80.
  • Murphy, S. J., Schroeder, R. E., Blacker, A. M., Krasavage, W. J., and English, J. C., A study of developmental toxicity of hydroquinone in the rabbit, Fundam. Appl. Toxicol. 19, 214–221, 1992.
  • Blacker, A. M., Schroeder, R. E., English, J. C., Murphy, S. J., Krasavage, W. J., and Simon, G. S., A two-generation reproduction study with hydro- quinone in rats, Fundam. Appl. Toxicol. 21, 420–424, 1993.
  • Nowak, A. K., Shilkin, K. B., and Jeffrey, G. P., Darkroom hepatitis after exposure to hydroquinone, Lancet 345, 1187, 1995.
  • Care, G. L., Darkroom exposure to hydroquinone, Lancet 347, 121, 1996.
  • Sterner, J. H., Oglesby, F. L., and Anderson, B., Quinone vapors and their harmful effects. I. Corneal and conjunctival injury, J. Ind. Hyg. Toxicol. 29, 60– 73, 1947.
  • Pifer, J. W., Hearne, F. T., Friedlander, B. R., and McDonough, J. R., Mortality study of men employed at a large chemical plant, 1972 through 1982, J. Occup. Med. 28, 438–444, 1986.
  • Pifer, J. W., Hearne, F. T., Swanson, F. A., and O’Donoghue, J. L., Mortality study of employees engaged in the manufacture and use of hydroquinone, Int. Arch. Occup. Environ. Health, 67, 267–280, 1995.
  • Choudat, D., Neukirch, F., Brochard, P., Barrat, G., Marsac, J., Conso, F., and Philbert, M., Allergy and occupational exposure to hydroquinone and to methionine, Br. J. Ind. Med. 45, 376–380, 1988.
  • Nielsen, H., Henriksen, L., and Olsen, J. H., Malig- nant melanoma among lithographers, Scand. J. Work Environ. Health, 22, 108–111, 1996.
  • Austin, D. F. and Reynolds, P., Investigation of an excess of melanoma among employees of the lawrenc livermore national laboratory, Am. J. Epidemiol., 145, 524–531, 1997.
  • Von Oettingen, W. F., Hydroquinone, in Phenol and Its Derivatives: The Relation Between Their Chemi- cal Constitution and Their Effect on the Organism, Washington: U.S. Public Health Service, 1949, 145– 166.
  • Grant, W. M. and Schuman, J. S., Toxicology of the Eye, Springfield, 4th ed., Charles C Thomas, 1993, 801–804.
  • Oglesby, F. L. and Raleigh, R. L., Eye Injury Asso- ciated with Exposure to Hydroquinone and Quinone, 2nd ed., Tennessee Eastman Company, Kingsport, 1973.
  • Anderson, B., Corneal and conjunctival pigmenta- tion among workers engaged in manufacture of hyd- roquinone, Arch. Ophthalmol. 38, 812–826, 1947.
  • Naumann, G., Corneal damage in hydroquinone work- ers, Arch. Ophthalmol. 76, 189–194, 1966.
  • Anderson, B., Corneal changes from quinone-hydro- quinone exposure, Arch. Ophthalmol. 59, 495–501, 1958.
  • Hughes, W., The tolerance of rabbit cornea for vari- ous chemical substances, Bull. Johns Hopkins Hosp. 82, 338–349, 1948.
  • Ferraris de Gaspare, P. F., Experimental studies on keratoconjunctivitis from hydroquinone (Italian), Boll. Oculist. 28, 361–367, 1949.
  • Oettel, H., The toxicology of hydroquinone (Ger- man), Arch. Exp. Pathol. Pharmakol. 183, 319–362, 1936.
  • Martin, G. J. and Ansbacher, S., Confirmatory evi- dence of the chromotrichial activity of p-aminoben- zoic acid, J. Biol. Chem. 138, 441, 1941.
  • Chavin, W., Effects of hydroquinone and of hypo- physectomy upon the pigment cells of black goldfish, J. Pharmacol. Exp. Ther. 142, 275–290, 1963.
  • Chavin, W. and Schlesinger, W., Some potent mela- nin depigmentary agents in the black goldfish, Naturwissenschaftten 53, 413–414, 1966.
  • Bleehen, S. S., Pathak, M. A., Hori, Y., and Fitzpatrick, T. B., Depigmentation of skin with 4–isopropylcatechol, mercaptoamines, and other com- ponents, J. Invest. Dermatol. 50, 103–117, 1968.
  • Jimbow, K., Obata, K., Pathak, M. A., and Fitzpatrick, T. B., Mechanism of depigmentation by hydroquinone, J. Invest. Dermatol. 62, 436–449, 1974.
  • Lerner, A. B., Fitzpatrick, T. B., Calkins, E., and Summerson, W. H., Mammalian tyrosinase action of substances structurally related to tyrosine, J. Biol. Chem. 178, 185–195, 1951.
  • Denton, C., Lerner, A. B., and Fitzpatrick, T. B., Inhibition of melanin formation by chemical agents, J. Invest. Dermatol. 18, 119–135, 1952.
  • Iijima, S. and Watanabe, K., Studies on Dopa reac- tion. II. Effect of chemicals on the reaction, J. Invest. Dermatol. 28, 1–4, 1959.
  • Chen, Y. M. and Chavin, W., Hydroquinone activa- tion and inhibition of skin tyrosinase, Pigment Cell, 3, 105–112, 1976.
  • Passi, S. and Nazzaro-Porro, M., Molecular basis of substrate and inhibitory specificity of tyrosinase: phe- nolic compounds, Br. J. Dermatol. 104, 659–665, 1981.
  • Bolognia, J. L., Sodi, S. A., Osber, M. P., and Pawelek, J. M., Enhancement of the depigmenting effect of hydroquinone by cystamine and buthionine sulfoximine, Br. J. Dermatol. 133, 349–357, 1995.
  • Hu, F., The influence of certain hormones and chemi- cals on mammalian pigment cells, J. Invest. Dermatol. 46, 117–124, 1966.
  • Abramowitz, J. and Chavin, W., Acute effects of two melanocytolytic agents, hydroquinone and β- mercaptoethanolamine, upon tyrosinase activity and cyclic nucleotide levels in murine melanomas, Chem.- Biol. Interact. 32, 195–208, 1980.
  • Penney, K. B., Smith, C. J., and Allen, J. C., Depigmenting action of hydroquinone depends on disruption of fundamental cell processes, J. Invest. Dermatol. 82: 308–310, 1984.
  • Smith, C. J., O’Hare, K. B., and Allen, J. C., Selec- tive cytotoxicity of hydroquinone for melanocyte-de- rived cells is mediated by tyrosinase activity but inde- pendent of melanin content, Pigment Cell Res. 1, 386–389, 1988.
  • Passi, S., Picardo, M., and Nazzaro-Porro, M., Com- parative cytotoxicity of phenols in vitro, Biochem. J. 245, 537–542, 1987.
  • Picardo, M., Cannistraci, C., De Luca, C., Zompetta, C., and Santucci, B., Effect of para group substances on human keratinocytes in culture, Con- tact Dermatitis 23, 236, 1990.
  • Chavin, W., Jelonek, E. J., Reed, A. H., and Binder,L. R., Survival of mice receiving melanoma trans- plants is promoted by hydroquinone, Science 208, 408–410, 1980.
  • Fitzpatrick, T. B., Arndt, K. A., El Mofty, A. M., and Pathak, M. A., Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo, Arch. Dermatol. 93, 589–600, 1966.
  • Spencer, M., Hydroquinone bleaching, Arch. Dermatol. 84, 131–134, 1961.
  • Spencer, M. C., Topical use of hydroquinone for depigmentation, JAMA 194, 114–116, 1965.
  • Arndt, K. A. and Fitzpatrick, T. B., Topical use of hydroquinone as a depigmenting agent, JAMA 194, 117–119, 1965.
  • Bentley-Phillips, B. and Bayles, M. A. H., Cutane- ous reactions to topical application of hydroquinone, South African Med. J. 49, 1391–1395, 1975.
  • Kligman, A. M. and Willis, I., A new formula for depigmenting human skin, Arch. Dermatol. 111, 40–hypomelanosis: hyperpigmentation following reactions to hydroquinones, Br. J. Dermatol. 90, 232–233, 1974.
  • Findlay, G. H., Morrison, J. G. L., and Simson,I. W., Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams, Br. J. Dermatol. 93, 613–622, 1975.
  • Findlay, G. H. and De Beer, H. A., Chronic hydro- quinone poisoning of the skin from skin-lightening cosmetics, South African Med. J. 57, 187–190, 1980.
  • Burke, P. A. and Maibach, H. I., Exogenous ochro- nosis: an overview, J. Dermatol. Treat. 8, 21–26, 1997.
  • Hardwick, N., Van Gelder, J. W., Van der Merwe,C. A., and Van der Merwe, M. P., Exogenous ochro- nosis: an epidemiological study, Br. J. Dermatol. 120, 229–238, 1989.
  • Findlay, G. H., Ochronosis following skin bleaching with hydroquinone, J. Am. Acad. Dermatol. 6, 1092– 1093, 1982.
  • Godlee, F., Skin lighteners cause permanent damage, Br. Med. J. 305, 333, 1992.
  • Williams, H., Skin lightening creams containing hy- droquinone, Br. Med. J. 305, 903–904, 1992.
  • Cullison, D., Abele, D. C., and O’Quinn, J. L., Localized exogenous ochronosis, J. Am. Acad. Dermatol. 8, 882–889, 1983.
  • Hoshaw, R. A., Zimmerman, K. G., and Menter, A., Ochronosislike pigmentation from hydroquinone bleaching creams in American blacks, Arch. Dermatol. 121, 105–108, 1985.
  • Penneys, N. S., Ochronosislike pigmentation from hydroquinone bleaching creams, Arch. Dermatol. 121: 1239–1240, 1985.
  • Connor, T. and Braunstein, B., Hyperpigmentation following the use of bleaching creams, Arch. Dermatol. 123, 105–106, 1987.
  • Lawrence, N., Bligard, C. A., Reed, R., and Perret,W. J., Exogenous ochronosis in the United States, J. Am. Acad. Dermatol. 18, 1207–1212, 1988.
  • Mahe, A., Blanc, L., Halna, J. M., Keita, S., Sanogo, T., and Bobin, P., An epidemiologic survey on the cosmetic use of bleaching agents by the women of Bamako (Mali) (French), Ann. Dermatol. Venereol. 120, 870–873, 1993.
  • Sylla, R., Diouf, A., Niane, B., Ndiaye, B., Guisse,M. B., Diop, A., Ciss, M., and Ba, D., Artificial depigmentation practice of the skin in women of Dakar and analytical study of the cosmetic products used (French), Dakar Med. 39, 223–226, 1994.
  • Garcia, R. L., White, J. W., and Willis, W. F., Hydroquinone nail pigmentation, Arch. Dermatol. 114, 1402–1403, 1978.
  • Mann, R. J. and Harman, R. R. M., Nail staining due to hydroquinone skin-lightening creams, Br. J. Dermatol. 108, 363–365, 1983.
  • Duffield, J., Depigmentation of skin by quinol and its monobenzyl ether, Lancet I, 1164, 1952.
  • Frenk, E. and Loi-Zedda, P., Occupational depig- mentation due to a hydroquinone-containing photo- graphic developer, Contact Dermatitis 6, 238–239, 1980.
  • Kersey, P. and Stevenson, C. J., Vitiligo and occu- pational exposure to hydroquinone from servicing self- photographing machines, Contact Dermatitis 7, 285– 287, 1981.
  • Fisher, A. A., Can bleaching creams containing 2% hydroquinone produce leukoderma? J. Am. Acad. Dermatol. 7, 134, 1982.
  • Liden, C., Occupational dermatoses at a film labora- tory, Contact Dermatitis 10, 77–87, 1984.
  • Liden, C., Occupational dermatoses at a film labora- tory. Follow-up after modernization, Contact Derma- titis 20, 191–200, 1989.
  • Hull, P. R. and Procter, P. R., The melanocyte: an essential link in hydroquinone-induced ochronosis, J. Am. Acad. Dermatol. 22, 529–531, 1990.
  • Engasser, P. G., Ochronosis caused by bleaching creams, J. Am. Acad. Dermatol. 10, 1073, 1984.
  • Phillips, J. I., Isaacson, C., and Carman, H., Ochro- nosis in black South Africans who used skin lighten- ers, Am. J. Dermatopathol. 8, 14–21, 1986.
  • O’Donoghue, M. N., Lynfield, Y. L., and Derbes, V., Ochronosis due to hydroquinone, J. Am. Acad. Dermatol. 8, 123, 1983.
  • Brauer, E. W., Safety of over-the-counter hydro- quinone bleaching creams, Arch. Dermatol. 121, 1239, 1985.
  • Medinsky, M. A., Schlosser, P. M., and Bond, J. A.,Critical issues in benzene toxicity and metabolism the effects of interactions with other organic chemi- cals on risk assessment, Environ. Health Perspect. 102, 119–124, 1994.
  • Trush, M. A., Twerdok, L. E., Rembish, S. J., Zhu, H., and Li, Y., Analysis of target cell susceptibility as a basis for the development of a chemoprotective strategy against benzene-induced hematotoxicities, Environ. Health Perspect. 104, 1227–1234, 1996.
  • Rickert, D. F., Baker, T. S., Bus, J. S., Barrow, C. S., and Irons, R. D., Benzene disposition in the rat after exposure by inhalation, Toxicol. Appl. Pharmacol. 49, 417–423, 1979.
  • Hedli, C. C., Snyder, R., and Witmer, C. M., Bone marrow DNA adducts and bone marrow cellularity following treatment with benzene metabolites in vivo. In: Witmer, C. M., Ed., Biological Reactive Interme- diates. Plenum Press, New York, 1990, 745–748.
  • Laskin, D. L., MacEachern, L., and Snyder, R., Activation of bone marrow phagocytes following ben- zene treatment of mice, Environ. Health Perspect. 82, 75–79, 1989.
  • Kettle, A. J. and Winterbourn, C. C., Oxidation of hydroquinone by myeloperoxidase, J. Biol. Chem. 267, 8319–8324, 1992.
  • Subrahmanyam, V. V., Kolachana, P., and Smith,M. T., Metabolism of hydroquinone by human myeloperoxidase: Mechanisms of stimulation by other phenolic compounds, Arch. Biochem. Biophys. 286, 76–84, 1991.
  • Medinsky, M. A., Kenyon, E. M., and Schlosser,P. M., Benzene: a case study in parent chemical and metabolite interactions, Toxicology 105, 225–233, 1995.
  • Organisation for Economic Cooperation and De- velopment (OECD), Final SIAR (SIDS Initial As- sessment Report): Hydroquinone, Paris: OECD, 1997.

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