DIHYDROXYACETONE

Synonyms:
1,3-Dihydroxypropan-2-one; 1,3-Dihydroxypropanone; Dihydroxyacetone; DHA; Glycerone; Dihydroxyacetone; 1,3-dihydroxyacetone; 96-26-4; 1,3-Dihydroxypropan-2-one; Chromelin; 1,3-Dihydroxy-2-propanone; Otan; glycerone; Triulose; Viticolor; Dihyxal; Oxantin; Oxatone; Soleal; 2-Propanone, 1,3-dihydroxy-; 1,3-Dihydroxypropanone; 1,3-Dihydroxydimethyl ketone; NSC-24343; Ketochromin; Bis(hydroxymethyl) ketone; dihydroxy-acetone; UNII-O10DDW6JOO; 2-Propanone, 1,3-dihydroxy; BRN 1740268; CCRIS 4899; AI3-24477; Dihydroxyacetone [USP]; EINECS 202-494-5; O10DDW6JOO; CHEBI:16016; Dihydroxyacetone (USP); Vitadye; dihydroxyacetone (monomer); Protosol; Aliphatic ketone; HSDB 7513; Chromelin (TN); MFCD00004670; 1,3-Dihydroxyaceton; 1.3-dihydroxyacetone; a,a'-Dihydroxyacetone; PubChem4053; 1,3-dihyroxy-acetone; 1,3-dihydroxy-acetone; DIHYDROXY ACETONE; 1,3-Dihydroxy Acetone; 1,3-propanediol-2-one; 2-Propanone,3-dihydroxy-; bmse000144; EC 202-494-5; alpha,alpha'-dihydroxyacetone; Dibutyl(1-propyl)phosphonate; 1, 3-dihydroxypropan-2-one; 1,3-dihydroxy propan-2-one; 4-01-00-04119 (Beilstein Handbook Reference); KSC493Q7J; 1,3-Dihydroxyacetone (DHA); CHEMBL1229937; CTK3J3874; 1,3-Dihydroxyacetone 96-26-4; DI HYDROXYACETONE; DİHYDROXYACETONE; DI HİDROXYACETONE; DİHİDROXYACETONE; DI HYDROXYACETON; DİHYDROXYACETON;  dihidroksi aseton; dihidroksiaseton; di hidroksi aseton; dihidroxy aseton; di hidroksi aceton ; di hidroksi acetone
 

DIHYDROXYACETONE

Dihydroxyacetone
Dihydroxyacetone

Names
Preferred IUPAC name
1,3-Dihydroxypropan-2-one
Other names
1,3-Dihydroxypropanone
Dihydroxyacetone
DHA
Glycerone
Identifiers
CAS Number    
96-26-4 check
3D model (JSmol)    
Interactive image
ChEBI    
CHEBI:16016 check
ChEMBL    
ChEMBL1229937 ☒
ChemSpider    
650 check
DrugBank    
DB01775 check
ECHA InfoCard    100.002.268
EC Number    
202-494-5
KEGG    
D07841 check
PubChem CID    
670
UNII    
O10DDW6JOO check
CompTox Dashboard (EPA)    
DTXSID0025072 

Properties[1]
Chemical formula    C3H6O3
Molar mass    90.078 g·mol−1
Melting point    89 to 91 °C (192 to 196 °F; 362 to 364 K)
Hazards[2]
GHS pictograms    Eye Irrit. 2
GHS Signal word    Warning
GHS hazard statements    H319
GHS precautionary statements    P264, P280, P305+351+338, P337+313
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒ verify (what is check☒ ?)
Infobox references
Dihydroxyacetone /ˌdaɪhaɪˌdrɒksiˈæsɪtoʊn/ (About this soundlisten) (DHA), also known as glycerone, is a simple saccharide (a triose) with formula C
3H
6O
3.

Dihydroxyacetone is primarily used as an ingredient in sunless tanning products. It is often derived from plant sources such as sugar beets and sugar cane, and by the fermentation of glycerin.

Chemistry
Dihydroxyacetone is a hygroscopic white crystalline powder. It has a sweet cooling taste and a characteristic odor. It is the simplest of all ketoses and has no chiral center or optical activity. The normal form is a dimer (2,5-bis(hydroxymethyl)-1,4-dioxane-2,5-diol) which is slowly soluble in one part water and 15 parts ethanol.[3] When freshly prepared, it reverts rapidly to the monomer in solution.

Conversion of dihydroxyacetone dimer to monomer
The monomer is very soluble in water, ethanol, diethyl ether, acetone and toluene.

Dihydroxyacetone may be prepared, along with glyceraldehyde, by the mild oxidation of glycerol, for example with hydrogen peroxide and a ferrous salt as catalyst. It can also be prepared in high yield and selectivity at room temperature from glycerol using cationic palladium-based catalysts with oxygen, air or benzoquinone acting as co-oxidants.[4][5][6] Glyceraldehyde is a structural isomer of dihydroxyacetone.

Biology
Its phosphorylated form, dihydroxyacetone phosphate (DHAP), takes part in glycolysis, and it is an intermediate product of fructose metabolism.

Uses
Dihydroxyacetone was first recognized as a skin coloring agent by German scientists in the 1920s. Through its use in the X-ray process, it was noted as causing the skin surface to turn brown when spilled.

In the 1950s, Eva Wittgenstein at the University of Cincinnati did further research with dihydroxyacetone.[7][8][9][10] Her studies involved using Dihydroxyacetone as an oral drug for assisting children with glycogen storage disease. The children received large doses of Dihydroxyacetone by mouth, and sometimes spat or spilled the substance onto their skin. Healthcare workers noticed that the skin turned brown after a few hours of Dihydroxyacetone exposure.

Eva Wittgenstein continued to experiment with DHA, painting liquid solutions of it onto her own skin. She was able to consistently reproduce the pigmentation effect, and noted that Dihydroxyacetone did not appear to penetrate beyond the stratum corneum, or dead skin surface layer (the FDA eventually concluded this is not entirely true[11]). Research then continued on DHA's skin coloring effect in relation to treatment for patients suffering from vitiligo.

This skin browning effect is non-toxic[citation needed], and is a result of a Maillard reaction. Dihydroxyacetone reacts chemically with the amino acids in the protein keratin, the major component of the skin surface. Different amino acids react to Dihydroxyacetone in different ways, producing different tones of coloration from yellow to brown. The resulting pigments are called melanoidins. These are similar in coloration to melanin, the natural substance in the deeper skin layers which brown or "tan", from exposure to UV rays.

Winemaking
Both acetic acid bacteria Acetobacter aceti and Gluconobacter oxydans use glycerol as a carbon source to form dihydroxyacetone. Dihydroxyacetone is formed by ketogenesis of glycerol.[12] It can affect the sensory quality of the wine with sweet/etherish properties. Dihydroxyacetone can also react with proline to produce a "crust-like" aroma.[12][13][14] Dihydroxyacetone can affect the anti-microbial activity in wine, as it has the ability to bind SO2.[15]

Sunless tanning
Coppertone introduced the first consumer sunless tanning lotion into the marketplace in the 1960s. This product was called “Quick Tan” or “QT”. It was sold as an overnight tanning agent, and other companies followed suit with similar products. Consumers soon tired of this product due to unattractive results such as orange palms, streaking and poor coloration. Because of the QT experience, many people still associate sunless tanning with fake-looking orange tans.[citation needed]

In the 1970s the United States Food and Drug Administration (FDA) added Dihydroxyacetone permanently to their list of approved cosmetic ingredients.[16]

By the 1980s, new sunless tanning formulations appeared on the market and refinements in the Dihydroxyacetone manufacturing process created products that produced a more natural looking color and better fading. Consumer concerns surrounding damage associated with UV tanning options spurred further popularity of sunless tanning products as an alternative to UV tanning. Dozens of brands appeared on drugstore shelves, in numerous formulations.[citation needed]

Today, Dihydroxyacetone is the main active ingredient in many sunless tanning skincare preparations. Lotion manufacturers also produce a wide variety of sunless tanning preparations that replace Dihydroxyacetone with natural bronzing agents such as black walnut shell. Dihydroxyacetone may be used alone or combined with other tanning components such as erythrulose. Dihydroxyacetone is considered the most effective sun-free tanning additive.[citation needed]

Sunless tanning products contain Dihydroxyacetone in concentrations ranging from 1% to 20%. Most drugstore products range from 3% to 5%, with professional products ranging from 5% to 20%. The percentages correspond with the product coloration levels from light to dark. Lighter products are more beginner-friendly, but may require multiple coats to produce the desired color depth. Darker products produce a dark tan in one coat, but are also more prone to streaking, unevenness, or off-color tones. The artificial tan takes 2 to 4 hours to begin appearing on the skin surface, and will continue to darken for 24 to 72 hours, depending on formulation type.[citation needed]

Once the darkening effect has occurred, the tan will not sweat off or wash away with soap or water. It will fade gradually over 3 to 10 days. Exfoliation, prolonged water submersion, or heavy sweating can lighten the tan, as these all contribute to rapid dead skin cell exfoliation (the dead skin cells are the tinted portion of the sunless tan).[citation needed]

Current sunless tanners are formulated into sprays, lotions, gels, mousses, and cosmetic wipes. Professional applied products include spray tanning booths, airbrush tan applications, and hand applied lotions, gels, mousses and wipes.[citation needed]

Dihydroxyacetone safety considerations
For the 24 hours after self-tanner (containing high Dihydroxyacetone levels, ~5%) is applied, the skin is especially susceptible to free-radical damage from sunlight, according to a 2007 study led by Katinka Jung of the Gematria Test Lab in Berlin.[17] Forty minutes after the researchers treated skin samples with high levels of Dihydroxyacetone they found that more than 180 percent additional free radicals formed during sun exposure compared with untreated skin. Another self-tanner ingredient, erythrulose, produced a similar response at high levels. For a day after self-tanner application, excessive sun exposure should be avoided and sunscreen should be worn outdoors, they say; an antioxidant cream could also minimize free radical production. Although some self-tanners contain sunscreen, its effect will not last long after application, and a fake tan itself will not protect the skin from UV exposure.[citation needed]

The study by Jung et al. further confirms earlier results demonstrating that dihydroxyacetone in combination with dimethylisosorbide enhances the process of (sun-based) tanning. This earlier study also found that dihydroxyacetone also has an effect on the amino acids and nucleic acids which is bad for the skin.[18]

The free radicals are in part due to the action of UV light on AGE (advanced glycation end products)[citation needed] such as Amadori products (a type of AGE) as a result of the reaction of Dihydroxyacetone with the skin. AGEs are behind the damage to the skin that occurs with high blood sugar in diabetes where similar glycation occurs. Some of the damage from AGE is independent of UV light. A study showed glycation of a protein increases its free-radical production rate nearly fifty-fold.[19]

Although some self-tanners contain sunscreen, its effect will not last as long as the tan. The skin browning of a sunless tan may provide some UV protection (up to SPF 3),[20][21] but this low-level protection should be supplemented with additional protection. The stated SPF for the product is only applicable for a few hours after application of the self-tanner. Despite darkening of the skin, an individual is just as susceptible to harmful UV rays, therefore an overall sun protection is still very necessary.[22] There may also be some inhibition of vitamin D production in DHA-treated skin.[23]

Contact dermatitis is occasionally reported,[24] and a recent study showed that Dihydroxyacetone causes severe contact dermatitis in Mexican hairless dogs.[25]

DHA-based sunless tanning has been recommended by the Skin Cancer Foundation, American Academy of Dermatology Association, Canadian Dermatology Association and the American Medical Association as a safer alternative to sun-bathing.[citation needed]

The use of Dihydroxyacetone in 'tanning' booths as an all-over spray has not been approved by the FDA, since safety data to support this use has not been submitted to the agency for review and evaluation.[26] A June 2012 FDA report claims the main chemical found inside that spray - Dihydroxyacetone - is potentially hazardous when inhaled. Some of the Dihydroxyacetone if inhaled can cause damage to cells and possibly lead to cancer according to physicians.[27]

An opinion[28] issued by the European Commission's Scientific Committee on Consumer Safety, concluding spray tanning with Dihydroxyacetone did not pose risk, has been heavily criticized by specialists.[29] This is because the cosmetics industry in Europe chose the evidence to review, according to the commission itself. Thus, nearly every report the commission's eventual opinion referenced came from studies that were never published or peer-reviewed and, in the majority of cases, were performed by companies or industry groups linked to the manufacturing of DHA. The industry left out nearly all of the peer-reviewed studies published in publicly available scientific journals that identified Dihydroxyacetone as a potential mutagen. A study by scientists from the Department of Dermatology, Bispebjerg Hospital, published in Mutation Research has concluded Dihydroxyacetone 'induces DNA damage, cell-cycle block and apoptosis' in cultured cells.[30] More recent research has shown that Dihydroxyacetone induces stress response gene expression and signaling in reconstructed human epidermis and cultured keratinocytes, as obvious from rapid activation of phospho-protein signal transduction [p-p38, p-Hsp27(S15/S78), p-eIF2α] and gene expression changes (HSPA6, HMOX1, CRYAB, CCL3). [31]

In the report released to ABC News, FDA scientists concluded that Dihydroxyacetone does not stop at the outer dead layers of skin. They wrote: "The fate of Dihydroxyacetone remaining in skin is an important issue, since high Dihydroxyacetone skin levels were found." They added that tests they performed revealed that much of the Dihydroxyacetone applied to skin actually ended up in the living layers of skin. They concluded: "This leaves about 11 percent of the applied Dihydroxyacetone dose absorbed remaining in the [living] epidermis and dermis."[11] A toxicologist and lung specialist at the University of Pennsylvania's Perelman School of Medicine (Dr. Rey Panettieri) has commented, "The reason I'm concerned is the deposition of the tanning agents into the lungs could really facilitate or aid systemic absorption -- that is, getting into the bloodstream. These compounds in some cells could actually promote the development of cancers or malignancies, and if that's the case then we need to be wary of them.

Why use fake tan?
Fake tanners, sunless tanners or preparations used to imitate a tan are becoming much more popular as people are becoming more aware of the dangers of long-term sun exposure and sunburn. There are now several ways of achieving a tan without having to expose your skin to the sun, these include:

Stainers (dihydroxyacetone)
Bronzers (dyes)
Tan accelerators (tyrosine and psoralens)
Solaria (sunbeds and sunlamps)
The unlicensed injectable synthetic melanotropic peptide Melanotan II.
What is dihydroxyacetone? 
The sunless tanner dihydroxyacetone (DHA) is currently the most popular way of gaining a tan-like appearance without sun exposure as it carries fewer health risks than any of the other available methods. To date, it is the only active ingredient approved by the US Food and Drug Administration (FDA) for sunless tanning.

How does dihydroxyacetone work?
All effective sunless tanners contain DHA. It is a colourless 3-carbon sugar that when applied to the skin causes a chemical reaction with amino acids in the surface cells of the skin producing a darkening effect Dihidroksiaseton does not damage skin as it only affects the outermost cells of the epidermis (stratum corneum).

What formulations of DHA are available?
There are many self-tanning preparations containing DHA on the market and many will claim to be the best formulation available. Consider the following points when deciding upon the preparation most suitable for you.

Concentrations of DHA can range from 2.5 to 10% or more (mostly 3-5%). This may coincide with product ranges that list shades as light, medium, or dark. A lower concentration (lighter shade) product may be better for new users as it is more forgiving of uneven application or rough surfaces.
Some formulations will also contain moisturisers. Users with dry skin will benefit from this.
Alcohol-based preparations will be more suitable for oily-skinned users.
DHA provides some protection against UV rays (UVA). To increase UV protection some products also include a sunscreen.
Alpha hydroxy acids promote the sloughing off of excess dead skin cells so should improve the evenness of colouration.
Other ingredients may be added to facilitate application or to make the colour last longer. Consult your pharmacist for advice.
Who should use DHA-containing preparations?
Anyone wanting a tanned appearance without having to expose himself or herself to UV light can use these preparations. However, the final look will depend on the formulation used, an individual's application technique, and the user's complexion type.

Clinical uses may be for vitiligo and as camouflage of some skin irregularities such as spider veins.

It may provide some protection for individuals with certain photosensitivity disorders such as polymorphic light eruption, erythropoietic protoporphyria or drug-induced photosensitivity.

How do you use DHA-containing preparations?
The final result obtained from DHA self-tanning preparations is highly dependent upon the individual's application technique. Care, skill and experience are necessary when using these products. The following are some self-application tips to achieving a smooth and even look.

Prepare skin by cleansing then by exfoliation using a loofah; this will avoid uneven application of colour.
Wipe skin down with hydroalcoholic, acidic toner, as this will remove any alkaline residues from soaps or detergents that may interfere with the reaction between DHA and amino acids.
Moisturise the area first, being careful to include the bony parts of the ankles, heels and knees.
Apply to skin in thin layers wherever you want colour, less to thicker skin, as the colour is maintained longer in these areas.
To avoid uneven darkening on areas such as the elbows, ankles and knees, remove excess cream over bony prominences with a wet cotton pad or damp flannel.
Wash hands immediately after application to avoid tanned palms. Alternatively, wear gloves to apply.
To avoid staining of clothes, wait 30 minutes for the product to dry before putting on clothes.
Don't shave, bathe, or swim for at least an hour after applying the product.
Reapply regularly to maintain colour.
Tanning salons, spas and gyms may offer professional application of sunless tanning products.

Lotion can be applied by an experienced technician.
A solution can be airbrushed onto the body.
Step into a sunless tanning booth for a uniform full-body application.
Be careful to cover eyes, lips and mucous membranes to prevent swallowing or inhaling the DHA-containing mist.

Is the tan instantaneous and how long does it last?
A colour change is usually apparent within an hour of application. Maximal darkening may take 8-24 hours to develop. If a darker colour is desired, several successive applications every few hours may be done to achieve this.

An artificial tan produced by DHA will last until the dead skin cells rub off, usually 5-7 days with a single application. Depending on the area, the same colour can be maintained with repeat applications every 1 to 4 days.

What precautions are there when using DHA self-tanning preparations?
The most important thing to remember when using DHA self-tanners is that they do not protect your skin against the sun. Although DHA does provide some UV protection and many products contain additional sunscreen, the UV protection provided is much more short-lived than the skin colour change. The stated SPF for the product is only applicable for a few hours after application of the self-tanner.

Despite darkening of the skin, an individual is just as susceptible to harmful UV rays, therefore it must be stressed that an overall sun protection program is still very necessary.

Are there any side effects of using DHA self-tanning preparations?
DHA reacts quickly in the stratum corneum, minimising systemic absorption. Contact dermatitis caused by DHA has rarely been reported. Most causes of sensitivity are due to other ingredients such as preservatives in the preparation.

Dihydroxyacetone is a ketotriose consisting of acetone bearing hydroxy substituents at positions 1 and 3. The simplest member of the class of ketoses and the parent of the class of glycerones. It has a role as a metabolite, an antifungal agent, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a ketotriose and a primary alpha-hydroxy ketone.

A ketotriose compound. Its addition to blood preservation solutions results in better maintenance of 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by triokinase in erythrocytes. In combination with naphthoquinones it acts as a sunscreening agent.

Molecular Weight of Dihydroxyacetone    90.08 g/mol    Computed by PubChem 2.1 (PubChem release 2019.06.18)
XLogP3-AA of Dihydroxyacetone    -1.4    Computed by XLogP3 3.0 (PubChem release 2019.06.18)
Hydrogen Bond Donor Count of Dihydroxyacetone    2    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Hydrogen Bond Acceptor Count of Dihydroxyacetone    3    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Rotatable Bond Count of Dihydroxyacetone    2    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Exact Mass of Dihydroxyacetone    90.031694 g/mol    Computed by PubChem 2.1 (PubChem release 2019.06.18)
Monoisotopic Mass of Dihydroxyacetone    90.031694 g/mol    Computed by PubChem 2.1 (PubChem release 2019.06.18)
Topological Polar Surface Area of Dihydroxyacetone    57.5 Ų    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Heavy Atom Count of Dihydroxyacetone    6    Computed by PubChem
Formal Charge of Dihydroxyacetone    0    Computed by PubChem
Complexity of Dihydroxyacetone    44    Computed by Cactvs 3.4.6.11 (PubChem release 2019.06.18)
Isotope Atom Count of Dihydroxyacetone    0    Computed by PubChem
Defined Atom Stereocenter Count of Dihydroxyacetone    0    Computed by PubChem
Undefined Atom Stereocenter Count of Dihydroxyacetone    0    Computed by PubChem
Defined Bond Stereocenter Count of Dihydroxyacetone    0    Computed by PubChem
Undefined Bond Stereocenter Count of Dihydroxyacetone    0    Computed by PubChem
Covalently-Bonded Unit Count of Dihydroxyacetone    1    Computed by PubChem
Compound  of Dihydroxyacetone Is Canonicalized    Yes

Currently obtained from glycerol through microbial fermentation, the demand of 1,3‐dihydroxyacetone (DHA) has significantly grown during the course of the last decade, driven by the consumer passion for a tan and increasing awareness of UV photodamage to the skin caused by prolonged exposure to the sun. We provide an updated bioeconomy perspective into a valued bioproduct (DHA), whose supply and production from glycerol, we argue in this study, will rapidly expand and diversify, with important global health benefits.
Commercially obtained from glycerol through microbial fermentation, over the acetic acid bacteria, 1,3‐dihydroxyacetone (DHA; 1,3‐dihydroxy‐2‐propanone) is the simplest ketone form of sugars (ketoses) and an important intermediate in carbohydrate metabolism in higher plants and animals formed during glycolysis.1 In the solid‐state, DHA exists as a dimer with a dioxan structure, which, upon dissolution, readily dissociates into a mixture of free carbonyl and hydrated monomers.