Hydroquinone is an aromatic compound that functions in cosmetics as an antioxidant, fragrance, reducing agent, or polymerization inhibitor. Hydroquinone is also used as a skin bleaching agent. Safety and toxicity information indicate that hydroquinone is dermally absorbed in humans from both aqueous and alcoholic formulations and is excreted mainly as the glucuronide or sulfate conjugates. Hydroquinone is associated with altered immune function in vitro and in vivo in animals and an increased incidence of renal tubule cell tumors and leukemia in F344 rats, but the relevance to humans is uncertain. Quantitatively, however, the use of hydroquinone in cosmetics is unlikely to result in renal neoplasia through this mode of action. Thus, hydroquinone is safe at concentrations of ≤1% in hair dyes and is safe for use in nail adhesives. Hydroquinone should not be used in other leave-on cosmetics.
Final report on the safety assessment of hydroquinone and pyrocatechol . J Am Coll Toxicol. 1986:5(3):123-165.
2.
Andersen FAAddendum to the final report on the safety assessment of hydroquinone . J Am Coll Toxicol. 1994;13(3):167-230.
3.
Gottschalck TE , Bailey JEInternational Cosmetic Ingredient Dictionary and Handbook. 12th ed. Washington, DC: CTFA; 2008.
4.
Hudnall PMHydroquinone. 5th ed. New York : Wiley-VCH; 1994:(A13), 499-505.
5.
L’Oreal.Rate of disappearance of Hydroquinone during the oxidation of hair dyeing formulation in presence of hair. 1990.
6.
Scientific Committee on Cosmetic Products.The Use of Benzoyl Peroxide (BPO), Hydroquinone (HQ), Hydroquinone Methylether (MeHQ) in Artificial Nail Systems. Report No. 0486/01; 2009:1-15.
7.
FDA.Frequency of Use of Cosmetic Ingredients. Washington DC: FDA; 2007.
8.
FDA.Frequency of Use of Cosmetic Ingredients. Washington DC: FDA; 2009.
9.
Personal Care Products Council.Concentration of Use - Hydroquinone. 2008.
10.
FDA.VCRP Total Number of Products in Each Product Category; March 2008. Washington, DC: FDA; 2008.
11.
Steinberg DCSubmission: Letter from ESSTECH RE: Analysis of HQ/MEHQ content of Finished Nail Matrix, 2000. 2009.
12.
EU.Commission directive 2008/88/EC concerning cosmetic products. Official Journal of the European Union. 2008; L25612L25616.
13.
EU.Commission directive 2003/83/EC relating to cosmetic products. Official Journal of the European Union. 2003; L23823-L23827.
14.
FDA.Skin bleaching drug products for over-the-counter human use; Proposed rule. Federal Register. 2006;71(167):51146-51155.
15.
EU.Commission directive 2000/6/EC relating to cosmetic products. Official Journal of the European Union. 2000;L5642-L5646.
16.
EU.Council directive 76/768/EEC . Official Journal of the European Union. 2008;1-129.
Palumbo A., d’Ischia M., Misuraca G., Prota G.Mechanism of inhibition of melanogenesis by hydroquinone. Biochim Biophys Acta. 1991;1073(1):85-90.
19.
Parvez S., Kang M., Chung HS, et al. Survey and mechanism of skin depigmenting and lightening agents . Phytother Res. 2006; 20(11):921-934.
20.
Wester RC, Melendres J., Hui X., et al. Human in vivo and in vitro hydroquinone topical bioavailability, metabolism, and disposition. J Toxicol Environ Health A. 1998;54(4):301-317.
21.
Poet TS, Wu H., English JC, Corley RAMetabolic rate constants for hydroquinone in F344 rat and human liver isolated hepatocytes: application to a PBPK model. Toxicol Sci. 2004;82(1): 9-25.
22.
Lau SS, Peters MM, Kleiner HE, Canales PL, Monks TJLinking the metabolism of hydroquinone to its nephrotoxicity and nephrocarcinogenicity . Adv Exp Med Biol. 1996;387:267-273.
23.
DeCaprio APThe toxicology of hydroquinone-relevance to occupational and environmental exposure. Crit Rev Toxicol . 1999;29(3):283-330.
24.
Deisinger PJ , Hill TS, English JCHuman exposure to naturally occurring hydroquinone . J Toxicol Environ Health. 1996;47(1): 31-46.
25.
Li Q., Geiselhart L., Mittler JN, Mudzinski SP, Lawrence DA, Freed BMInhibition of human T lymphoblast proliferation by hydroquinone. Toxicol Appl Pharmacol. 1996;139(2):317-323.
26.
Lee JY, Kim JY, Lee YG, et al. Hydroquinone, a reactive metabolite of benzene, reduces macrophage-mediated immune responses. Mol Cells. 2007;23(2):198-206.
27.
Boatman RJ, English JC, Perry LG, Bialecki VEDifferences in the nephrotoxicity of hydroquinone among Fischer 344 and Sprague-Dawley rats and B6C3F1 mice. J Toxicol Environ Health. 1996;47(2):159-172.
28.
Topping DC, Bernard LG, O’Donoghue JL, English JCHydroquinone: acute and subchronic toxicity studies with emphasis on neurobehavioral and nephrotoxic effects. Food Chem Toxicol . 2007;45(1):70-78.
29.
David RM, English JC, Totman LC, Moyer C., O’Donoghue JLLack of nephrotoxicity and renal cell proliferation following subchronic dermal application of a hydroquinone cream. Food Chem Toxicol . 1998;36(7):609-616.
30.
Picardo M., Cannistraci C., Cristaudo A., DeLuca C., Santucci B.Study on cross-reactivity to the para group. Dermatologica . 1990;181:104-108.
31.
Andreoli C. , Rossi S., Leopardi P., Crebelli R.DNA damage by hydroquinone in human white blood cells: analysis by alkaline single-cell gel electrophoresis. Mutat Res. 1999;438(1):37-45.
32.
do Ceu Silva M., Gaspar J., Duarte Silva I., Leao D., Rueff J.Mechanisms of induction of chromosomal aberrations by hydroquinone in V79 cells. Mutagenesis. 2003;18(6):491-496.
33.
Silva Mdo C. , Gaspar J., Duarte Silva I., Faber A., Rueff J.GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human lymphocytes . Environ Mol Mutagen. 2004;43(4): 258-264.
34.
Luo L., Jiang L., Geng C., Cao J., Zhong L.Hydroquinone-induced genotoxicity and oxidative DNA damage in HepG2 cells . Chem Biol Interact. 2008;173(1):1-8.
35.
Jagetia GC, Aruna R.Hydroquinone increases the frequency of micronuclei in a dose-dependent manner in mouse bone marrow. Toxicol Lett. 1997;93(2-3):205-213.
36.
Jagetia GC, Menon KS, Jain V.Genotoxic effect of hydroquinone on the cultured mouse spleenocytes . Toxicol Lett. 2001;121(1):15-20.
37.
Olumide YM, Akinkugbe AO, Altraide D., et al. Complications of chronic use of skin lightening cosmetics. Int J Dermatol. 2008; 47(4):344-353.
38.
Lau SS, Monks TJ, Everitt JI, Kleymenova E., Walker CLCarcinogenicity of a nephrotoxic metabolite of the ‘‘nongenotoxic’’ carcinogen hydroquinone. Chem Res Toxicol. 2001;14(1):25-33.
39.
McGregor D.Hydroquinone: an evaluation of the human risks from its carcinogenic and mutagenic properties. Crit Rev Toxicol . 2007;37(10):887-914.
40.
English JC, Deisinger PJMetabolism and disposition of hydroquinone in Fischer 344 rats after oral or dermal administration. Food Chem Toxicol. 2005;43(3):483-493.
41.
English JC, Perry LG, Vlaovic M., Moyer C., O’Donoghue JLMeasurement of cell proliferation in the kidneys of Fischer 344 and Sprague-Dawley rats after gavage administration of hydroquinone. Fundam Appl Toxicol. 1994;23(3):397-406.
42.
English JC, Hill T., O’Donoghue JL, Reddy MVMeasurement of nuclear DNA modification by 32P-postlabeling in the kidneys of male and female Fischer 344 rats after multiple gavage doses of hydroquinone . Fundam Appl Toxicol. 1994;23(3):391-396.
43.
Boatman RJ, English JC, Perry LG, Fiorica LACovalent protein adducts of hydroquinone in tissues from rats: quantitation of sulfhydryl-bound forms following single gavage or intraperitoneal administration or repetitive gavage administration. Chem Res Toxicol. 2000;13(9):861-872.
44.
Boatman RJ, English JC, Perry LG, Fiorica LACovalent protein adducts of hydroquinone in tissues from rats: identification and quantitation of sulfhydryl-bound forms. Chem Res Toxicol . 2000;13(9):853-860.
45.
Hard GC, Whysner J., English JC, Zang E., Williams GMRelationship of hydroquinone-associated rat renal tumors with spontaneous chronic progressive nephropathy. Toxicol Pathol. 1997; 25(2):132-143.
46.
The Kidney.1998. Fundamentals of Toxicologic Pathology. New York, NY: Academic Press.
47.
Seely JC, Haseman JK, Nyska A., Wolf DC, Everitt JI, Hailey JRThe effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control male F344 rats. Toxicol Pathol. 2002;30(6):681-686.
48.
Hard GCMechanisms of chemically induced renal carcinogenesis in the laboratory rodent . Toxicol Pathol. 1998;26(1):104-112.
49.
Abrass CKThe nature of chronic progressive nephropathy in aging rats. Adv Ren Replace Ther. 2000;7(1):4-10.
50.
Clark B.Biology of renal aging in humans. Adv Ren Replace Ther. 2000;7(1):11-21.
51.
Subrahmanyam VV, Doane-Setzer P., Steinmetz KL, Ross D., Smith MTPhenol-induced stimulation of hydroquinone bioactivation in mouse bone marrow in vivo: possible implications in benzene myelotoxicity. Toxicology. 1990;62(1):107-116.
52.
Kalf G., Shurina R., Renz J., Schlosser M.The role of hepatic metabolites of benzene in bone marrow peroxidase-mediated myelo- and genotoxicity. Adv Exp Med Biol. 1991;283: 443-455.
53.
Smith MT, Yager JW, Steinmetz KL, Eastmond DAPeroxidase-dependent metabolism of benzene’s phenolic metabolites and its potential role in benzene toxicity and carcinogenicity. Environ Health Perspect. 1989;82:23-29.
54.
Barale R., Marrazzini A., Betti C., Vangelisti V., Loprieno N., Barrai I.Genotoxicity of two metabolites of benzene: phenol and hydroquinone show strong synergistic effects in vivo. Mutat Res. 1990 ;244(1):15-20.
55.
Robertson ML , Eastmond DA, Smith MTTwo benzene metabolites, catechol and hydroquinone, produce a synergistic induction of micronuclei and toxicity in cultured human lymphocytes. Mutat Res. 1991;249(1):201-209.
56.
NTP Toxicology and Carcinogenesis Studies of Hydroquinone(CAS No. 123-31-9) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Natl Toxicol Program Tech Rep Ser. 1989;366:1-248.
57.
Tan SK, Sim CS, Goh CLHydroquinone-induced exogenous ochronosis in Chinese-two case reports and a review. Int J Dermatol. 2008;47(6):639-640.
Charlin R., Barcaui CB, Kac BK, Soares DB, Rabello-Fonseca R., Azulay-Abulafia L.Hydroquinone-induced exogenous ochronosis: a report of four cases and usefulness of dermoscopy. Int J Dermatol. 2008;47(1):19-23.
60.
Lisi P., Hansel K.Is benzoquinone the prohapten in cross-sensitivity among aminobenzene compounds ? Contact Dermatitis. 1998;39(6):304-306.
61.
IARC working group on the evaluation of carcinogenic risks to humans: occupational exposures of hairdressers and barbers and personal use of hair colourants; some hair dyes, cosmetic colourants, industrial dyestuffs and aromatic amines. Proceedings . Lyon, France, 6-13 October 1992 . IARC Monogr Eval Carcinog Risks Hum. 1993 ;57:7-398.
62.
Rollison DE , Helzlsouer KJ, Pinney SMPersonal hair dye use and cancer: a systematic literature review and evaluation of exposure assessment in studies published since 1992. J Toxicol Environ Health B Crit Rev.2006;9(5):413-439.
63.
Baan R., Straif K., Grosse Y., et al. Carcinogenicity of some aromatic amines, organic dyes, and related exposures. Lancet Oncol. 2008;9(4):322-323.
