Hydroquinone: Cure worse than complaint?

by Ralph Hill - Internet Technology Researcher and Writerby Ralph Hill - Internet Technology Researcher and Writer

Despite being banned for use in skin treatment products in over a dozen western and African countries, Hydroquinone is still used in the US and Canada for de-pigmentation (skin lightening) in formulations with concentrations of 2% over the counter and up to 4% by prescription.
Why is it still prescribed when it has largely been abandoned elsewhere due to reported adverse effects and detrimental health warnings?

Hydroquinone is still considered to be the gold standard of treatment for hyperpigmentation by many physicians in the US and Canada where it is still legal to useHydroquinone is still considered to be the gold standard of treatment for hyperpigmentation by many physicians in the US and Canada where it is still legal to useAlmost every skin treatment practitioner knows of Hydroquinone. Many have at one time used products containing it, but many may not know enough about this compound to make an informed judgement on its safe use.
The fact that its use as a skin-lightening agent is banned in so many countries raises questions of its suitability in current cross-ethnic society.
Hydroquinone is still considered to be the gold standard of treatment for hyperpigmentation by many physicians in the US and Canada, this despite its abandonment elsewhere.
So exactly what is Hydroquinone? What effects does it have on our cells and systems, and why has it been banned in some countries?

 What is Hydroquinone?
It is an aromatic organic compound which is a type of phenol. It is also known as alpha-hydroquinone, hydroquinol, quinol, benzoquinol, p-benzenediol, 1,4-benzenediol, p-dihydroxybenzene, p-hydroxyphenol, p-dioxobenzene, 1,4-dihydroxybenzene, dihydroquinone, pyrogentistic acid, quinnone, aida, arctuvin, eldoquin, eldopaque, phiaquin, tecquinol, tenox HQ, tequinol. 

The MSDS database listing for Hydroquinone displays this warning symbolThe MSDS database listing for Hydroquinone displays this warning symbolTypical industrial uses include Corrosion Inhibitors, Photochemical developers, Printing and process regulators during the manufacturing of polystyrene and latex products.
In human medicine, hydroquinone has been used since the 1930s as a topical application to selectively de-pigment or reduce the color of skin.
It is currently classified as a poison, and is listed on CAS (US) and MSDS (UK) chemical databases as possible carcinogen, severe skin irritant, and allergen, and was given Alert status by World Health Organization IPCS (International Programme on Chemical safety) in 1996.  

How does Hydroquinone work? 
Hydroquinone produces reversible depigmentation of the skin of humans by a complex mechanism of action. 
At the cellular level, hydroquinone and its derivatives are oxidized by tyrosinase to form highly toxic free radicals that cause selective damage to the lipoprotein membranes of the melanocyte, thereby reducing conversion of tyrosine to dopa and subsequently to melanin. It disrupts membranous cytoplasmic organelles, affecting formation, melanization, and degradation of melanosomes.

Hydroquinone produces reversible depigmentation by disrupting membranous cytoplasmic organelles,  affecting formation, melanization, and degradation of melanosomes.Hydroquinone produces reversible depigmentation by disrupting membranous cytoplasmic organelles, affecting formation, melanization, and degradation of melanosomes.Typical topical preparations of 2 - 5% hydroquinone have been proven effective in producing cutaneous depigmentation, although the 2% concentration is considered by many as safer while producing results equal to higher concentrations.
Long-term observation would suggest hydroquinone offers better results on lighter skins and on lighter lesions. In skins with higher melanin density, the response to hydroquinone depends on the amount of pigment present. The earlier it is used to treat minor skin blemishes, the more likely the results will be satisfactory.
On commencement of treatment, melanin excretion may briefly increase and when depigmentation does occur, melanin production is reduced by approximately 50%.

A decrease in skin colour usually becomes noticeable in approximately 4 weeks; however, the time of onset can vary from 3 weeks to 3 months.
Typically, depigmentation lasts for 2 - 6 months, but is reversible. Darker lesions generally re-pigment faster than lighter lesions, and ethnically darker skins (Fitzpatrick types 5 & 6) will re-pigment more readily due to the dendrites of the melanocyte being longer and reaching further in to the upper layers of the epidermis (Through and often above the granular layer) than lighter skins.
Because the ability of the sun to darken lesions is much greater than that of hydroquinone to lighten them, strict avoidance of sunlight during its use is critically important.

In darker skins, it is reported that exogenous ochronosis is more widespread with prolonged useIn darker skins, it is reported that exogenous ochronosis is more widespread with prolonged useWhat can go wrong?
Typical side effects of topical hydroquinone are generally mild when used in low concentrations, however tingling or burning on application and subsequent erythema and inflammation can occur in over 30% of users with higher occurrences in formulations approaching a 5% concentration.
As well as frequently irritating the skin, these concentrations if used for prolonged periods can cause disfiguring effects including epidermal thickening, weak connective tissue, ochronosis-like pigmentation (a bluish black discoloration of tissue) and yellowish papules. The mechanism for the formation of the rare ochronosis-like pigments on the skin is thought to occur by the inhibition of hydroquinone on the epidermal homogentisic acid oxidase. This inhibition would lead to the accumulation of homogentisic acid, which then polymerises to form the ochronotic pigments. 



Without strict controls of use, disfigurement can occurWithout strict controls of use, disfigurement can occur

In darker skins, it is reported that exogenous ochronosis is more widespread with prolonged use. This disorder is characterized by progressive darkening of the treated area. Histologically, the degeneration of collagen and elastic fibres has occurred.

This degeneration is followed by the appearance of characteristic ochronotic deposits consisting of crescent-shaped, ochre-coloured fibres in the dermis.
It is these issues with darker skins that have forced many health authorities in countries with darker skin populations to take steps to limit the sale of, or ban the sale of hydroquinone for use on the skin. This however did not solve the problem as since the banning of the ingredient, the sales of products that contain hydroquinone have, to a large extent, been driven underground. Traders are known to supply these creams from under the counter and consumers are continuing to buy these products unwittingly.
In 1999, a South African epidemic of exogenous ochronosis due to black market hydroquinone products was reported more than a decade after they were banned for having disfigured thousands of darker skinned women. 


Hydroquinone warning on the Cosmetic Safety DatabaseHydroquinone warning on the Cosmetic Safety DatabaseOther concerns
Hydroquinone is known to irritate some skin and to make all skin more sensitive to sunlight, and by making the skin sensitive to the sun, hydroquinone can quickly render it more vulnerable to the very problems the chemicals are meant to get rid of when used incorrectly.

This along with consumers' concerns over those side effects and over reports that the chemical may be connected to more serious health problems in laboratory animal tests (Hydroquinone has been reported to induce mutations in Salmonella and at the hart locus of Chinese hamster V79 cells) have led many cosmetics companies to avoid using it in their skin lightening products.

Several respected scientists have written papers regarding the carcinogenic potential of hydroquinone, with one document from the European Academy of Dermatology & Venereology summarising with this: The risks of long-term effects (cancer) of topically applied hydroquinone may no longer be ignored. Based on recent evidence of the potential risks, which are higher than has been assumed up until now, we plead that the use of hydroquinone as a skin lightening agent will be stopped completely.

In 1997, the Swedish National Chemicals Inspectorate issued a paper concerning the Carcinogenicity and Mutagenicity of Hydroquinone, and discussed the classification of the compound as a class 2 mutagen and class 2 carceogen after hyperploid spermatocytes were observed in a number of in vivo studies conducted at the Rome Laboratory of Comparative Toxicology and Ecotoxicology. These studies were part of a coordinated research program sponsored by the Commission of the European Communities in to ten known and suspect spindle poisons. (These poisons disrupt cellular reproduction by affecting the protein threads that connect the centromere regions of chromosomes, known as spindles)

Interestingly, in the US and Canada where Hydroquinone is still sold and used in concentrations of up to 4%, there does not seem to be such concern.
In a US publication, Critical Reviews in Toxicology, May 1999, research indicated reactions are minor or a result of using extremely high concentrations. A leading professor of dermatology at a US university school of medicine was reported to have stated: To date there is no evidence of adverse systemic reactions following the use of hydroquinone", and "hydroquinone is undoubtedly the most active and safest skin-depigmenting substance... ."
With such polarised opinion on the use of Hydroquinone, it is easy to understand why there is such confusion.

The popularity of the "lighter look" in African countries brought about the misuse epedemicThe popularity of the "lighter look" in African countries brought about the misuse epedemicHydroquinone prohibition
Because of the potential mutagenic and carcinogenic properties that produce mid-term effects such as leukomelanoderma , along with ongoing problems with darker skins, France and most of Europe banned cosmetic creams or treatments containing hydroquinone in 1999, with the UK, Australia and New Zealand following in 2001. As mentioned previously, South Africa banned its use as early as 1989, with other African countries such as Kenya and Uganda enforcing bans in 1998.
The UK has taken the ban one step further by making it illegal to supply, offer to supply or posess to supply. This is due to the embarrassment of the discovery that British companies were smuggling their contraband hydroquinone creams and lotions to agents in South Africa, Zimbabwe, Zambia, Angola, Zaire, Botswana and Kenya.
In those countries where skin bleaching using hydroquinone was popular, reports of severe adverse effects including individuals with such bad skin disease that they are unable to safely go out in the sun, and doctors experiencing cases in which they cannot apply stitches to the skin because it has weakened to the point where it falls apart. 

Lack of control or guidance of use caused many of the problems associated with hypopigmentation and ochronosis. Users of skin lightening products who misused the formulations in an effort to get a faster result unwittingly hastened the ban. 
The only exception to the bans on hydroquinone are its use in hair dyes, where in most countries products are permitted to contain a maximum level of 0.3%. This is over five times less than the levels typically found in skin lightening creams sold on the internet and in the US and Canada at the time of writing this article.

While alternative ingredients may not provide the quick fix depigmentation that hydroquinone offers, there are other options that may sit easier on your concience for treatment of pigmentation issues. 

Azelaic Acid is another popular alternative found naturally in wheat, rye, and barley. It is saturated dicarboxylic acid with antibacterial properties that also lends itself to the treatment of acne. In treating pigmentation, it is less effective as a tyrosinase inhibitor, and when used in conjunction with other ingredients its role is that of an exfoliant, helping desquamate the pigmented keratinocytes in the treatment area.

Paper Mulberry is also a tyrosinase inhibitor isolated from a plant herbal extract. In one study, a comparison of the tyrosinase inhibition of a paper mulberry/ kojic acid mixture revealed similar results to that of hydroquinone without significant irritation after 24 hours.

Glabridin (liquorice extract) has been reported to inhibit tyrosinase activity of melanocytes without cytotoxicity, and has showed promise treating UV-Binduced pigmentation and erythema with topical applications of just 0.5% glabridin. The anti-inflammatory properties of glabridin are attributed to inhibition of superoxide anion production and cyclooxygenase activity.



Michael P Tabibian, MD, Consulting Staff, Department of Dermatology, Daniel Freedman Hospital, Marina Hospital

Craig G Burkhart, MD, MPH, Clinical Professor, Department of Medicine, Section of Dermatology, Medical College of Ohio at Toledo, Clinical Assistant Professor, Department of Dermatology, Ohio University School of Medicine

Mutagenesis. 1992 Jan;7(1):69-76. Miller BM, Adler ID.

Associate Professor Mohd Isa Abdul Majid Ph.D

Skin Lightening and Depigmenting Agents. Alaina J James, MD, PhD, Staff Physician, Department of Dermatology, University of Pennsylvania Medical Center

Journal of the European Academy of Dermatology and Venereology, December 2004

Toxicology and health risks of hydroquinone in skin lightening formulations. TJ Kooyers, W Westerhof

Johannesburg Sunday Times, 12 December 1999

The Village Voice, January 23 - 29, 2002

CNN.com/World of August 14, 2001

About the Author:


Ralph Hill is the technology writer, illustrator and editor for Virtual Beauty Corporation. He has a background in science, electronics and electro-mechanical devices, but enjoys researching and writing on a myriad of skin care related topics including cosmetic chemistry and anatomy & physiology.




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