Hydroquinone

Last updated
Hydroquinone
Hydrochinon2.svg
Trans-hydroquinone-from-xtal-3D-balls.png
Hydroquinone crystal.jpg
Names
Preferred IUPAC name
Benzene-1,4-diol [1]
Other names
Hydroquinone [1]
Idrochinone
Quinol
1,4-Dihydroxybenzene
p-dihydroxybenzene
p-hydroxyphenol
1,4-Hydroxy benzene
Identifiers
3D model (JSmol)
605970
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.004.199 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-617-8
2742
KEGG
PubChem CID
RTECS number
  • MX3500000
UNII
UN number 3077, 2662
  • InChI=1S/C6H6O2/c7-5-1-2-6(8)4-3-5/h1-4,7-8H Yes check.svgY
    Key: QIGBRXMKCJKVMJ-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C6H6O2/c7-5-1-2-6(8)4-3-5/h1-4,7-8H
    Key: QIGBRXMKCJKVMJ-UHFFFAOYAX
  • c1cc(ccc1O)O
Properties
C6H6O2
Molar mass 110.112 g·mol−1
AppearanceWhite solid
Density 1.3 g cm−3, solid
Melting point 172 °C (342 °F; 445 K)
Boiling point 287 °C (549 °F; 560 K)
5.9 g/100 mL (15 °C)
Vapor pressure 10−5 mmHg (20 °C) [2]
Acidity (pKa)9.9 [3]
−64.63×10−6 cm3/mol
Structure
1.4±0.1  D [4]
Pharmacology
D11AX11 ( WHO )
Hazards
GHS labelling:
GHS-pictogram-acid.svg GHS-pictogram-exclam.svg GHS-pictogram-silhouette.svg GHS-pictogram-pollu.svg
Danger
H302, H317, H318, H341, H351, H400
P201, P202, P261, P264, P270, P272, P273, P280, P281, P301+P312, P302+P352, P305+P351+P338, P308+P313, P310, P321, P330, P333+P313, P363, P391, P405, P501
NFPA 704 (fire diamond)
[5]
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability (yellow): no hazard codeSpecial hazards (white): no code
2
1
Flash point 165 °C (329 °F; 438 K)
Lethal dose or concentration (LD, LC):
490 mg/kg (mammal, oral)
245 mg/kg (mouse, oral)
200 mg/kg (rabbit, oral)
320 mg/kg (rat, oral)
550 mg/kg (guinea pig, oral)
200 mg/kg (dog, oral)
70 mg/kg (cat, oral) [6]
NIOSH (US health exposure limits):
PEL (Permissible)
TWA 2 mg/m3 [2]
REL (Recommended)
C 2 mg/m3 [15-minute] [2]
IDLH (Immediate danger)
50 mg/m3 [2]
Related compounds
Related benzenediols
Pyrocatechol
Resorcinol
Related compounds
 1,4-benzoquinone
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a para position. It is a white granular solid. Substituted derivatives of this parent compound are also referred to as hydroquinones. The name "hydroquinone" was coined by Friedrich Wöhler in 1843. [7]

Contents

Production

Hydroquinone is produced industrially in two main ways. [8]

Other, less common methods include:

Note that methods such as hydrolysis of chlorinated phenol and oxidation of phenols are much more polluting methods than some others. [16]

Reactions

The reactivity of hydroquinone's hydroxyl groups resembles that of other phenols, being weakly acidic. The resulting conjugate base undergoes easy O-alkylation to give mono- and diethers. Similarly, hydroquinone is highly susceptible to ring substitution by Friedel–Crafts reactions such as alkylation. This reaction is exploited en route to popular antioxidants such as 2-tert-butyl-4-methoxyphenol (BHA). The useful dye quinizarin is produced by diacylation of hydroquinone with phthalic anhydride. [8]

Redox

Hydroquinone undergoes oxidation under mild conditions to give benzoquinone. This process can be reversed. Some naturally occurring hydroquinone derivatives exhibit this sort of reactivity, one example being coenzyme Q. Industrially this reaction is exploited both with hydroquinone itself but more often with its derivatives where one OH has been replaced by an amine.

When colorless hydroquinone and benzoquinone, a bright yellow solid, are cocrystallized in a 1:1 ratio, a dark-green crystalline charge-transfer complex (melting point 171 °C) called quinhydrone (C6H6O2·C6H4O2) is formed. This complex dissolves in hot water, where the two molecules dissociate in solution. [18]

Amination

An important reaction is the conversion of hydroquinone to the mono- and diamine derivatives. Methylaminophenol, used in photography, is produced in this way: [8]

Diamines, useful in the rubber industry as antiozone agents, are similarly produced from aniline:

Uses

Hydroquinone has a variety of uses principally associated with its action as a reducing agent that is soluble in water. It is a major component in most black and white photographic developers for film and paper where, with the compound metol, it reduces silver halides to elemental silver.

There are various other uses associated with its reducing power. As a polymerisation inhibitor, exploiting its antioxidant properties, hydroquinone prevents polymerization of acrylic acid, methyl methacrylate, cyanoacrylate, and other monomers that are susceptible to radical-initiated polymerization. By acting as a free radical scavenger, hydroquinone serves to prolong the shelflife of light-sensitive resins such as preceramic polymers. [19]

Hydroquinone can lose a hydrogen cation from both hydroxyl groups to form a diphenolate ion. The disodium diphenolate salt of hydroquinone is used as an alternating comonomer unit in the production of the polymer PEEK.

Skin depigmentation

Hydroquinone is used as a topical application in skin whitening to reduce the color of skin. It does not have the same predisposition to cause dermatitis as metol does. This is a prescription-only ingredient in some countries, including the member states of the European Union under Directives 76/768/EEC:1976. [20] [21]

In 2006, the United States Food and Drug Administration revoked its previous approval of hydroquinone and proposed a ban on all over-the-counter preparations. [22] The FDA officially banned hydroquinone in 2020 as part of a larger reform of the over-the-counter drug review process. [23] The FDA stated that hydroquinone cannot be ruled out as a potential carcinogen. [24] This conclusion was reached based on the extent of absorption in humans and the incidence of neoplasms in rats in several studies where adult rats were found to have increased rates of tumours, including thyroid follicular cell hyperplasias, anisokaryosis (variation in nuclei sizes), mononuclear cell leukemia, hepatocellular adenomas and renal tubule cell adenomas. The Campaign for Safe Cosmetics has also highlighted concerns. [25]

Numerous studies have revealed that hydroquinone, if taken orally, can cause exogenous ochronosis, a disfiguring disease in which blue-black pigments are deposited onto the skin; however, skin preparations containing the ingredient are administered topically. The FDA had classified hydroquinone in 1982 as a safe product - generally recognized as safe and effective (GRASE), however additional studies under the National Toxicology Program (NTP) were suggested in order to determine whether there is a risk to humans from the use of hydroquinone. [22] [26] [24] NTP evaluation showed some evidence of long-term carcinogenic and genotoxic effects [27]

While hydroquinone remains widely prescribed for treatment of hyperpigmentation, questions raised about its safety profile by regulatory agencies in the EU, Japan, and USA encourage the search for other agents with comparable efficacy. [28] Several such agents are already available or under research, [29] including azelaic acid, [30] kojic acid, retinoids, cysteamine, [31] topical steroids, glycolic acid, and other substances. One of these, 4-butylresorcinol, has been proved to be more effective at treating melanin-related skin disorders by a wide margin, as well as safe enough to be made available over the counter. [32]

Natural occurrences

Hydroquinones are one of the two primary reagents in the defensive glands of bombardier beetles, along with hydrogen peroxide (and perhaps other compounds, depending on the species), which collect in a reservoir. The reservoir opens through a muscle-controlled valve onto a thick-walled reaction chamber. This chamber is lined with cells that secrete catalases and peroxidases. When the contents of the reservoir are forced into the reaction chamber, the catalases and peroxidases rapidly break down the hydrogen peroxide and catalyze the oxidation of the hydroquinones into p-quinones. These reactions release free oxygen and generate enough heat to bring the mixture to the boiling point and vaporize about a fifth of it, producing a hot spray from the beetle's abdomen. [33]

Hydroquinone is thought to be the active toxin in Agaricus hondensis mushrooms. [34]

Hydroquinone has been shown to be one of the chemical constituents of the natural product propolis. [35]

It is also one of the chemical compounds found in castoreum. This compound is gathered from the beaver's castor sacs. [36]

Related Research Articles

<span class="mw-page-title-main">Phenol</span> Organic compound (C6H5OH)

Phenol, or Benzenol, is an aromatic organic compound with the molecular formula C6H5OH. It is a white crystalline solid that is volatile. The molecule consists of a phenyl group bonded to a hydroxy group. Mildly acidic, it requires careful handling because it can cause chemical burns.

<span class="mw-page-title-main">Phenyl group</span> Cyclic chemical group (–C₆H₅)

In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6H5, and is often represented by the symbol Ph. The phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen, which may be replaced by some other element or compound to serve as a functional group. A phenyl group has six carbon atoms bonded together in a hexagonal planar ring, five of which are bonded to individual hydrogen atoms, with the remaining carbon bonded to a substituent. Phenyl groups are commonplace in organic chemistry. Although often depicted with alternating double and single bonds, the phenyl group is chemically aromatic and has equal bond lengths between carbon atoms in the ring.

<span class="mw-page-title-main">Naphthalene</span> Chemical compound

Naphthalene is an organic compound with formula C
10H
8. It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromatic hydrocarbon, naphthalene's structure consists of a fused pair of benzene rings. It is the main ingredient of traditional mothballs.

<span class="mw-page-title-main">Cumene process</span> Industrial process

The cumene process is an industrial process for synthesizing phenol and acetone from benzene and propylene. The term stems from cumene, the intermediate material during the process. It was invented by R. Ūdris and P. Sergeyev in 1942 (USSR), and independently by Heinrich Hock in 1944.

<span class="mw-page-title-main">Aniline</span> Organic compound (C₆H₅NH₂); simplest aromatic amine

Aniline is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starting material for fine chemical synthesis. Its main use is in the manufacture of precursors to polyurethane, dyes, and other industrial chemicals. Like most volatile amines, it has the odor of rotten fish. It ignites readily, burning with a smoky flame characteristic of aromatic compounds. It is toxic to humans.

<span class="mw-page-title-main">Phthalic anhydride</span> Chemical compound

Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commercially. This white solid is an important industrial chemical, especially for the large-scale production of plasticizers for plastics. In 2000, the worldwide production volume was estimated to be about 3 million tonnes per year.

<i>p</i>-Phenylenediamine Chemical compound

p-Phenylenediamine (PPD) is an organic compound with the formula C6H4(NH2)2. This derivative of aniline is a white solid, but samples can darken due to air oxidation. It is mainly used as a component of engineering polymers and composites like kevlar. It is also an ingredient in hair dyes and is occasionally used as a substitute for henna.

In organic chemistry, an aryl halide is an aromatic compound in which one or more hydrogen atoms, directly bonded to an aromatic ring are replaced by a halide. The haloarene are different from haloalkanes because they exhibit many differences in methods of preparation and properties. The most important members are the aryl chlorides, but the class of compounds is so broad that there are many derivatives and applications.

<span class="mw-page-title-main">Resorcinol</span> Chemical compound

Resorcinol (or resorcin) is a phenolic compound. It is an organic compound with the formula C6H4(OH)2. It is one of three isomeric benzenediols, the 1,3-isomer (or meta-isomer). Resorcinol crystallizes from benzene as colorless needles that are readily soluble in water, alcohol, and ether, but insoluble in chloroform and carbon disulfide.

In organic chemistry, dihydroxybenzenes (benzenediols) are organic compounds in which two hydroxyl groups are substituted onto a benzene ring. These aromatic compounds are classed as phenols. There are three structural isomers: 1,2-dihydroxybenzene is commonly known as catechol, 1,3-dihydroxybenzene is commonly known as resorcinol, and 1,4-dihydroxybenzene is commonly known as hydroquinone.

<span class="mw-page-title-main">Catechol</span> Organic compound (C6H4(OH)2); benzene with two adjacent –OH groups

Catechol, also known as pyrocatechol or 1,2-dihydroxybenzene, is an organic compound with the molecular formula C6H4(OH)2. It is the ortho isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amounts. It was first discovered by destructive distillation of the plant extract catechin. About 20,000 tonnes of catechol are now synthetically produced annually as a commodity organic chemical, mainly as a precursor to pesticides, flavors, and fragrances.

<span class="mw-page-title-main">Ochronosis</span> Medical condition

Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. Macroscopically, though, the affected tissues appear bluish-grey because of a light-scattering phenomenon known as the Tyndall effect. The condition is most often associated with alkaptonuria, but can occur from exogenous administration of phenol complexes such as hydroquinone. It was first described by Rudolf Virchow in 1865.

<span class="mw-page-title-main">1,4-Benzoquinone</span> Chemical compound

1,4-Benzoquinone, commonly known as para-quinone, is a chemical compound with the formula C6H4O2. In a pure state, it forms bright-yellow crystals with a characteristic irritating odor, resembling that of chlorine, bleach, and hot plastic or formaldehyde. This six-membered ring compound is the oxidized derivative of 1,4-hydroquinone. The molecule is multifunctional: it exhibits properties of a ketone, being able to form oximes; an oxidant, forming the dihydroxy derivative; and an alkene, undergoing addition reactions, especially those typical for α,β-unsaturated ketones. 1,4-Benzoquinone is sensitive toward both strong mineral acids and alkali, which cause condensation and decomposition of the compound.

Alpha hydroxy acids, or α-hydroxy acids, are a class of chemical compounds that consist of a carboxylic acid with a hydroxyl group substituent on the adjacent (alpha) carbon. Prominent examples are glycolic acid, lactic acid, mandelic acid and citric acid.

<span class="mw-page-title-main">Gentisic acid</span> Chemical compound

Gentisic acid is a dihydroxybenzoic acid. It is a derivative of benzoic acid and a minor (1%) product of the metabolic break down of aspirin, excreted by the kidneys.

<span class="mw-page-title-main">Diphenyl ether</span> Chemical compound

Diphenyl ether is the organic compound with the formula (C6H5)2O. It is a colorless, low-melting solid. This, the simplest diaryl ether, has a variety of niche applications.

<span class="mw-page-title-main">Benzene</span> Hydrocarbon compound consisting of a 6-sided ring

Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, benzene is classed as a hydrocarbon.

Butyl acrylate is an organic compound with the formula C4H9O2CCH=CH2. A colorless liquid, it is the butyl ester of acrylic acid. It is used commercially on a large scale as a precursor to poly(butyl acrylate). Especially as copolymers, such materials are used in paints, sealants, coatings, adhesives, fuel, textiles, plastics, and caulk.

<span class="mw-page-title-main">Mercaptobenzothiazole</span> Chemical compound

2-Mercaptobenzothiazole is an organosulfur compound with the formula C6H4(NH)SC=S. A white solid, it is used in the sulfur vulcanization of rubber.

<span class="mw-page-title-main">Alkoxide</span> Conjugate base of an alcohol

In chemistry, an alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They are written as RO−, where R is the organyl substituent. Alkoxides are strong bases and, when R is not bulky, good nucleophiles and good ligands. Alkoxides, although generally not stable in protic solvents such as water, occur widely as intermediates in various reactions, including the Williamson ether synthesis. Transition metal alkoxides are widely used for coatings and as catalysts.

References

  1. 1 2 "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 691. doi:10.1039/9781849733069-FP001. ISBN   978-0-85404-182-4.
  2. 1 2 3 4 NIOSH Pocket Guide to Chemical Hazards. "#0338". National Institute for Occupational Safety and Health (NIOSH).
  3. ↑ "Hydroquinone" (PDF). OECD SIDS . UNEP Publications. Archived from the original (PDF) on 2016-10-20. Retrieved 2018-09-17.
  4. ↑ Lander, John J.; Svirbely, John J. Lander, W. J. (1945). "The Dipole Moments of Catechol, Resorcinol and Hydroquinone". Journal of the American Chemical Society. 67 (2): 322–324. doi:10.1021/ja01218a051.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ "Archived copy" (PDF). Archived (PDF) from the original on 2014-02-02. Retrieved 2014-01-25.{{cite web}}: CS1 maint: archived copy as title (link)
  6. ↑ "Hydroquinone". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  7. ↑ F. Wöhler (1844) "Untersuchungen über das Chinon" (Investigations of quinone), Annalen der Chemie und Pharmacie, 51 : 145-163. From page 146: "Das so erhaltene Destillat … enthält … einen neuen, krystallisierenden Körper, den ich unter dem Namen farbloses Hydrochinon weiter unten näher beschreiben werde." (The distillate so obtained … contains … a new, crystallizable substance, that I will describe, under the name of colorless hydroquinone, further below in more detail.) [Note: Wöhler's empirical formula for hydroquinone (p. 152) is incorrect because (1) he attributed 25 (instead of 24) carbon atoms to the molecule, and (2) as many chemists at the time did, he used the wrong atomic masses for carbon (6 instead of 12) and oxygen (8 instead of 16). With these corrections, his empirical formula becomes: C12H12O4. Dividing the subscripts by 2, the result is: C6H6O2, which is correct.]
  8. 1 2 3 Phillip M. Hudnall "Hydroquinone" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. 2005 Wiley-VCH, Weinheim. doi : 10.1002/14356007.a13_499.
  9. ↑ Gerhard Franz, Roger A. Sheldon "Oxidation" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2000 doi : 10.1002/14356007.a18_261
  10. 1 2 Reppe, Walter; Kutepow, N; Magin, A (1969). "Cyclization of Acetylenic Compounds". Angewandte Chemie International Edition in English. 8 (10): 727–733. doi:10.1002/anie.196907271.
  11. ↑ Hubel, Karl; Braye, Henri (1960). Process for the preparation of substituted cyclic compounds and products resulting therefrom US3149138 A (PDF). Union Carbide Corp.
  12. ↑ Pino, Piero; Braca, Giuseppe; Sbrana, Glauco (1964). Preparation of hydroquinone US3355503 A (PDF). Lonza Ag.
  13. ↑ Walter, Reppe; Magin, August (1966). Production of hydroquinones US3394193 A (PDF). Basf Ag.
  14. ↑ Piero, Pino; Giuseppe, Braca; Frediano, Settimo; Glauco, Sbrana (1967). Preparation of hydroquinone US3459812 A (PDF). Lonza Ag.
  15. ↑ Holmes, J.; Hagemeyer, H. (1971). Process for the production of hydroquinone US 3742071 A (PDF). Eastman Kodak Co.
  16. 1 2 3 Shi Y, Xia Y, Xu G, Wen L, Gao G, Zong B (28 October 2021). "Hydrogen peroxide and applications in green hydrocarbon nitridation and oxidation". Chinese Journal of Chemical Engineering (Review article). 41: 145–161. doi:10.1016/j.cjche.2021.09.030. S2CID   240248911.
  17. ↑ See:
    • Pelletier and Caventou (1820) "Recherches chimiques sur les quinquinas" (Chemical investigations of quinquinas [i.e., the bark of various Cinchona trees]), Annales de Chimie et de Physique, 2nd series, 15 : 289-318, 337-364. On pages 341-342, the preparation and properties of l'acide pyro-kinique (pyroquinic acid or hydroquinone) are discussed.
    • Roscoe, Henry (1891). A Treatise on Chemistry, Volume 3, Part 3. London: Macmillan & Co. p. 165.
  18. ↑ Streitwieser, Andrew (1992). Introduction to organic chemistry. Heathcock, Clayton H., 1936-, Kosower, Edward M. (4th ed.). Upper Saddle River, N.J.: Prentice Hall. ISBN   978-0139738500. OCLC   52836313.
  19. ↑ Additive manufacturing of ceramics from preceramic polymers Additive manufacturing 2019 vol. 27. pp 80-90
  20. ↑ Council Directive 76/768/EEC of 27 July 1976 on the approximation of the laws of the Member States relating to cosmetic products
  21. ↑ "Clear N Smooth Skin Toning Cream recalled". 2011-10-04. Retrieved 4 April 2018.
  22. 1 2 United States Food and Drug Administration (2006). Skin Bleaching Drug Products for Over-the-Counter Product Use; Proposed Rule (PDF) (Report). 1978N-0065. Archived (PDF) from the original on 2011-05-16.
  23. ↑ "Congress Enacts OTC Monograph Reform". JD Supra. Retrieved 2021-12-19.
  24. 1 2 Research, Center for Drug Evaluation and. "About the Center for Drug Evaluation and Research - Hydroquinone Studies Under The National Toxicology Program (NTP)". www.fda.gov. Archived from the original on 2017-01-22. Retrieved 2017-02-12.
  25. ↑ Campaign For Safe Cosmetics - Hydroquinone Archived 2010-11-27 at the Wayback Machine
  26. ↑ Olumide, YM; Akinkugbe, AO; Altraide, D; Mohammed, T; Ahamefule, N; Ayanlowo, S; Onyekonwu, C; Essen, N (April 2008). "Complications of chronic use of skin lightening cosmetics". International Journal of Dermatology. 47 (4): 344–53. doi:10.1111/j.1365-4632.2008.02719.x. PMID   18377596. S2CID   8159382.
  27. ↑ "Hydroquinone 10022-H". ntp.niehs.nih.gov. Archived from the original on 2017-10-01. Retrieved 2023-08-18.
  28. ↑ Draelos, Zoe Diana (2007-09-01). "Skin lightening preparations and the hydroquinone controversy". Dermatologic Therapy. 20 (5): 308–313. doi: 10.1111/j.1529-8019.2007.00144.x . ISSN   1529-8019. PMID   18045355. S2CID   24913995.
  29. ↑ Bandyopadhyay, Debabrata (2009-01-01). "Topical treatment of melasma". Indian Journal of Dermatology. 54 (4): 303–309. doi: 10.4103/0019-5154.57602 . ISSN   0019-5154. PMC   2807702 . PMID   20101327.
  30. ↑ Mazurek, Klaudia; Pierzchała, Ewa (2016-09-01). "Comparison of efficacy of products containing azelaic acid in melasma treatment". Journal of Cosmetic Dermatology. 15 (3): 269–282. doi:10.1111/jocd.12217. ISSN   1473-2165. PMID   27028014. S2CID   25303091.
  31. ↑ Mansouri, P.; Farshi, S.; Hashemi, Z.; Kasraee, B. (2015-07-01). "Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial". The British Journal of Dermatology. 173 (1): 209–217. doi:10.1111/bjd.13424. ISSN   1365-2133. PMID   25251767. S2CID   21618233.
  32. ↑ "Hydroquinones". Phenols—Advances in Research and Application: 2013 Edition. Scholastic. 2013. p. 76.
  33. ↑ Organic Chemistry, Solomon and Fryhle, 10th edition, Wiley Publishing, 2010.[ page needed ]
  34. ↑ Joval, E; Kroeger, P; N (April 1996). "Hydroquinone: the toxic compound of Agaricus hondensis". Planta Medica. 62 (2): 185. doi:10.1055/s-2006-957852. PMID   17252436. S2CID   260249338.
  35. ↑ Burdock, G.A. (1998). "Review of the biological properties and toxicity of bee propolis (propolis)". Food and Chemical Toxicology. 36 (4): 347–363. doi:10.1016/S0278-6915(97)00145-2. PMID   9651052.
  36. ↑ The Beaver: Its Life and Impact. Dietland Muller-Schwarze, 2003, page 43 (book at google books)
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