Arrhenius Acids

The Arrhenius concept is the easiest one retained by majority of peelers, because most of peelings acids are ionic compounds, acting as a source of H₃O⁺ when dissolved in water.

The Swedish chemist Svante Arrhenius attributed the properties of acidity to hydrogen in 1884. An Arrhenius acid is a substance that increases the concentration of the hydronium ion, H₃O⁺, when dissolved in water. This definition stems from the equilibrium dissociation of water into hydronium and hydroxide (OH⁻) ions:

In pure water the majority of molecules exist as H₂O, but a small number of molecules are constantly dissociating and reassociating. Pure water is neutral with respect to acidity or basicity because the concentration of hydroxide ions is always equal to the concentration of hydronium ions. An Arrhenius base is a molecule which increases the concentration of the hydroxide ion when dissolved in water. Note that chemists often write H⁺(aq) and refer to the hydrogen ion when describing acid-base reactions but the free hydrogen nucleus, a proton, does not exist alone in water, it exists as the hydronium ion, H₃O⁺.

Brønsted Acids

While the Arrhenius concept is useful for describing many reactions, it is also quite limited in its scope. Brønsted acids act by donating a proton to water and at the difference of Arrhenius acids, can also be used to describe molecular compounds, whereas Arrhenius acids must be ionic compounds.

In 1923 chemists Johannes Nicolaus Brønsted and Thomas Martin Lowry independently recognized that acid–base reactions involve the transfer of a proton. A Brønsted–Lowry acid (or simply Brønsted acid) is a species that donates a proton to a Brønsted–Lowry base. Brønsted–Lowry acid–base theory has several advantages over Arrhenius theory. Consider the following reactions of acetic acid (CH₃COOH), (used as chemical peel for the décolleté by some great peelers like L. Wiest) the organic acid that gives vinegar its characteristic taste:

Both theories easily describe the first reaction: CH₃COOH acts as an Arrhenius acid because it acts as a source of H₃O⁺ when dissolved in water, and it acts as a Brønsted acid by donating a proton to water. In the second example CH₃COOH undergoes the same transformation, donating a proton to ammonia (NH3), but cannot be described using the Arrhenius definition of an acid because the reaction does not produce hydronium.

As with the acetic acid reactions, both definitions work for the first example, where water is the solvent and hydronium ion is formed. The next reaction does not involve the formation of ions but can still be viewed as proton transfer reaction.

Lewis Acids

The Brønsted–Lowry definition is the most widely used definition; unless otherwise specified acid–base reactions are assumed to involve the transfer of a proton (H⁺) from an acid to a base.

A third concept was proposed by Gilbert N. Lewis which includes reactions with acid-base characteristics that do not involve a proton transfer. A Lewis acid is a species that accepts a pair of electrons from another species; in other words, it is an electron pair acceptor. Brønsted acid–base reactions are proton transfer reactions while Lewis acid–base reactions are electron pair transfers. All Brønsted acids are also Lewis acids, but not all Lewis acids are Brønsted acids. Contrast the following reactions which could be described in terms of acid-base chemistry:

In the first reaction a fluoride ion, F⁻, gives up an electron pair to boron trifluoride to form the product tetrafluoroborate. Fluoride ‘loses’ a pair of valence electrons because the electrons shared in the B—F bond are located in the region of space between the two atomic nuclei and are therefore more distant from the fluoride nucleus than they are in the lone fluoride ion. BF3 is a Lewis acid because it accepts the electron pair from fluoride. This reaction cannot be described in terms of Brønsted theory because there is no proton transfer. The second reaction can be described using either theory. A proton is transferred from an unspecified Brønsted acid to ammonia, a Brønsted base; alternatively, ammonia acts as a Lewis base and transfers a lone pair of electrons to form a bond with a hydrogen ion. The species that gains the electron pair is the Lewis acid; for example, the oxygen atom in H₃O⁺ gains a pair of electrons when one of the H—O bonds is broken and the electrons shared in the bond become localized on oxygen. Depending on the context, Lewis acids may also be described as a reducing agent or an electrophile.

Dissociation and Equilibrium

Reactions of acids are often generalized in the form HA  H⁺ + A⁻, where HA represents the acid and A⁻ is the conjugate base. Acid–base conjugate pairs differ by one proton, and can be interconverted by the addition or removal of a proton (protonation and deprotonation, respectively). Note that the acid can be the charged species and the conjugate base can be neutral in which case the generalized reaction scheme could be written as HA  H⁺ + A. In solution there exists an equilibrium between the acid and its conjugate base. The equilibrium constant K is an expression of the equilibrium concentrations of the molecules or the ions in solution. Brackets indicate concentration, such that [H₂O] means the concentration of H₂O. The acid dissociation constant K_a is generally used in the context of acid-base reactions. The numerical value of K_a is equal to the concentration of the products divided by the concentration of the reactants, where the reactant is the acid (HA) and the products are the conjugate base and H⁺.

The stronger of two acids will have a higher K_a than the weaker acid; the ratio of hydrogen ions to acid will be higher for the stronger acid as the stronger acid has a greater tendency to lose its proton. Because the range of possible values for K_a spans many orders of magnitude, a more manageable constant, pK_a is more frequently used, where pK_a = −log₁₀K_a. Stronger acids have a smaller pK_a than weaker acids. Experimentally determined pK_a at 25°C in aqueous solution are often quoted in textbooks and reference material.

Acid Strength

For peelers, this notion is very important because stronger acids have a higher K_a and a lower pK_a than weaker acids.

For our classification, two parameters have to be taken in consideration for peelers:

For chemists, the strength of an acid refers to its ability or tendency to lose a proton. A strong acid is one that completely dissociates in water; in other words, one mole of a strong acid HA dissolves in water yielding one mole of H⁺ and one mole of the conjugate base, A⁻, and none of the protonated acid HA. In contrast a weak acid only partially dissociates and at equilibrium both the acid and the conjugate base are in solution. In water each of these essentially ionizes 100%. The stronger an acid is, the more easily it loses a proton, H⁺. Two key factors that contribute to the ease of deprotonation are the polarity of the H—A bond and the size of atom A, which determines the strength of the H—A bond. Acid strengths are also often discussed in terms of the stability of the conjugate base.

According to the classification of A. Tenenbaum, which is described later in this chapter, peelers should be careful with the dangerous distinction between so called ‘cosmetic’, peelings for acids with pK_a > 3 and ‘medical’, peelings for acids with pK_a < 3, because some acids like salicylic acid with a pK_a near 3, as the phenol, toxic substance with a pK_a > 3 need to be exclusively used by trained physicians.

Monoprotic Acids

Monoprotic acids are those acids that are able to donate one proton per molecule during the process of dissociation (sometimes called ionization) as shown below (symbolized by HA):

Common examples of monoprotic acids in organic acids indicate the presence of one carboxyl group and mostly these acids are known as monocarboxylic acid. Examples in organic acids include acetic acid (CH₃COOH), glycolic acid and lactic acid.

Polyprotic Acids

Polyprotic acids are able to donate more than one proton per acid molecule, in contrast to monoprotic acids that only donate one proton per molecule. Specific types of polyprotic acids have more specific names, such as diprotic acid (two potential protons to donate) and triprotic acid (three potential protons to donate).

A diprotic acid (here symbolized by H₂A) can undergo one or two dissociations depending on the pH. Each dissociation has its own dissociation constant, K_a1 and K_a2.

The first dissociation constant is typically greater than the second; i.e., K_a1 > K_a2. For example, the weak unstable carbonic acid (H₂CO₃) can lose one proton to form bicarbonate anion (HCO₃⁻) and lose a second to form carbonate anion (CO₃²⁻). Both Ka values are small, but K_a1 > K_a2.

Diprotic acids used for peelings are malic, tartaric and azelaic acids.

Two dissociations depending on the pH mean that such acids can generate two peelings with the second one less acidic than the first one, in case we consider one peeling reaction per one dissociation.

A triprotic acid (H₃A) can undergo one, two, or three dissociations and has three dissociation constants, where K_a1 > K_a2 > K_a3.

An organic example of a triprotic acid is citric acid, which can successively lose three protons to finally form the citrate ion. Even though the positions of the protons on the original molecule may be equivalent, the successive K_a values will differ since it is energetically less favorable to lose a proton if the conjugate base is more negatively charged.

Weak Acid/Weak Base Equilibria

In order to lose a proton, it is necessary that the pH of the system rise above the pK_a of the protonated acid. The decreased concentration of H⁺ in that basic solution shifts the equilibrium towards the conjugate base form (the deprotonated form of the acid). In lower-pH (more acidic) solutions, there is a high enough H⁺ concentration in the solution to cause the acid to remain in its protonated form, or to protonate its conjugate base (the deprotonated form).

Solutions of weak acids and salts of their conjugate bases form buffer solutions.

Le Chatelier’s Principle

In a solution there is an equilibrium between a weak acid, HA, and its conjugate base, A⁻:

Thus, in both cases, some of the added reagent is consumed in shifting the equilibrium in accordance with Le Chatelier’s principle and the pH changes by less than it would if the solution were not buffered.

Henderson–Hasselbach Equation

The acid dissociation constant for a weak acid, HA, is defined as:

Simple manipulation with logarithms gives the Henderson–Hasselbach equation, which describes pH in terms of pK_a:

In this equation [A⁻] is the concentration of the conjugate base and [HA] is the concentration of the acid. It follows that when the concentrations of acid and conjugate base are equal, often described as half-neutralization, pH = pK_a. In general, the pH of a buffer solution may be easily calculated, knowing the composition of the mixture, by means of an ICE table.

One should remember that the calculated pH may be different from measured pH.

Buffer Capacity

Figure 1.1 Buffer capacity for pK_a = 7 as percentage of maximum

Buffer capacity is a quantitative measure of the resistance of a buffer solution to pH change on addition of hydroxide ions. It can be defined as follows:

where dn is an infinitesimal amount of added base and d(pH) is the resulting infinitesimal change in pH. With this definition the buffer capacity can be expressed as:

where K_w is the self-ionization constant of water and C_A is the analytical concentration of the acid, equal to [HA]+[A⁻]. The term K_w/[H⁺] becomes significant at pH greater than about 11.5 and the second term becomes significant at pH less than about 2. Both these terms are properties of water and are independent of the weak acid. Considering the third term, it follows that:

Useful Buffer Mixtures

Neutralization

There is among physicians a big confusion between a buffered peel (see above) and a neutralized peel. In chemistry, neutralization is a chemical reaction whereby an acid and a base react to form water and a salt.

In an aqueous solution, solvated hydrogen ions (hydronium ions, H₃O⁺) react with hydroxide ions (OH⁻) formed from the alkali to make two molecules of water. A salt is also formed. In non-aqueous reactions, water is not always formed; however, there is always a donation of protons (see Brønsted–Lowry acid–base theory).

Often, neutralization reactions are exothermic, giving out heat to the surroundings (the enthalpy of neutralization). An example of an endothermic neutralization is the reaction between sodium bicarbonate (baking soda) and any weak acid, for example acetic acid (vinegar).

Neutralization of the chemical peeling agent is an important step, which is determined by either the frost or how much time has elapsed. Neutralization is achieved by a majority of peelers applying cold water or wet, cool towels to the face following the frost. According to physical chemistry, using water just after the frost provokes an exothermic reaction which can provoke a ‘cold’ burn. Other neutralizing agents that can be used include bicarbonate spray or soapless cleanser. Peeling agents for which this neutralization step is less important include salicylic acid, Jessner solution, TCA, and phenol.

In partially neutralized AHA solutions, the acid and a lesser amount of base are combined in a reversible chemical reaction that yields unneutralized acid and a salt.

The resulting solution has less free acid and a higher pH than a solution that has not been neutralized. In partially neutralized formulations, the salt functions as a reservoir of acid that is available for second-phase penetration. This means that partially neutralized formulas can deliver as much, if not more, alpha-hydroxy acid than free acid formulas, but in a safer, ‘time-released’ manner. Therefore, the use of partially neutralized glycolic acid solutions seems prudent, since they have a better safety profile than low-pH solutions containing only free glycolic acid.

Clinical studies have shown that a partially neutralized lactic acid preparation improves the skin, both in appearance and histologically. Other studies using skin tissue cultures showed that partially neutralized glycolic acid stimulates fibroblast proliferation – an index of tissue regeneration. Looking at electrical conductance of the skin (an indicator of water content or moisturization), higher pH products (those that have been partially neutralized) are better moisturizers than lower pH preparations.

Comparison of Their pH to Their pK_a, the cosmetic actions of the ahas are interesting

Their antiaging action can be compared to retinoids but their mechanism of action is different. They interfere with certain kinds of enzymes (sulfotransferases, phosphotransferases, kinases) whose function is to fix the sulfate and phosphate groups to the surface of the corneocytes. The reduction of these groups involves a decrease in electronegativity and corneocyte cohesion, which leads to a breaking away of the cells from each other, creating exfoliation and flaking. This activity can be characterized as a metabolic action. However, when used in strong concentrations of 30–70% free acid in aqueous solution for peeling, their effect is based on their acidity and results in destruction.

Glycolic Acid (pK_a = 3.83) and Its Different Concentrations

Abbreviation: GA

Properties:

Glycolic acid (or hydroxyacetic acid) is the smallest α-hydroxy acid (AHA). This colorless, odorless, and hygroscopic crystalline solid is highly soluble in water. It is used in various skin care products.

Glycolic acid: Formulated from sugar cane, this acid creates a mild exfoliating action. Glycolic acid peels work by loosening up the horny layer and exfoliating the superficial top layer. This peel also stimulates collagen growth.

Once applied, glycolic acid reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together. This allows the outer skin to ‘dissolve’ revealing the underlying skin.

In low concentrations, 5–10%, glycolic acid reduces cell adhesion in the top layer of the skin. This action promotes exfoliation of the outermost layer of the skin accounting for smoother texture following regular use of topical GA. This relatively low concentration of glycolic acid lends itself to daily use as a monotherapy or a part of a broader skin care management for such conditions as acne, photo-damage, wrinkling. Care needs to be taken to avoid irritation as this may result in worsening of any pigmentary problems. Newer formulations combine glycolic acid with an amino acid such as arginine and form a time-release system that reduces the risk of irritation without affecting glycolic acid efficacy. The use of an anti-irritant like allantoin is also helpful. Because of its safety, glycolic acid at the concentrations below 10% can be used daily by most people except those with very sensitive skin.

In medium concentrations, between 10 and 50%, its benefits are more pronounced but are limited to temporary skin smoothing without much long lasting results. This is still a useful concentration to use as it can prepare the skin for more efficacious glycolic acid at higher concentrations (50–70%) as well as prime the skin for deeper chemical peels such as TCA peel (trichloroacetic acid).

At higher concentrations (called here high concentrations), 50–70% applied for 3 to 8 minutes (usually done by a physician), glycolic acid promotes splitting between the cells and can be used to treat acne or photo-damage (such as mottled dyspigmentation, or fine wrinkles). The benefits from such short contact application (chemical peels) depend on the pH of the solution (the more acidic the product, or lower pH, the more pronounced the results), the concentration of GA (higher concentrations produce more vigorous response), the length of application and prior skin conditioning such as prior use of topical vitamin A products. Although single application of 50–70% GA will produce beneficial results, multiple treatments every 2 to 4 weeks are required for optimal results. It is important to understand that glycolic acid peels are chemical peels with similar risks and side effects as other peels.

Lactic Acid (pK_a = 3.86)

This acid is derived from either sour milk or bilberries. This peel will remove dead skin cells, and promote healthier, softer and more radiant skin.

Properties:

In our opinion, glycolic and lactic peel solutions must have a pH of between 1.5 and 2.5 in order to combine a source of inflammation and stimulation, with their metabolic effects being, essentially, the replacement of corneocytes.

Malic Acid (pK_a1 = 3.4, pK_a2 = 5.13)

This peel is the same type of mildly invasive peel derived from the extracts of apples. It can open up the pores, allow the pores to expel their sebum and reduce acne.

Tartaric Acid (pK_a1 = 3.04, pK_a2 = 4.37)

This is derived from grape extract and is able of delivering the same benefits as the above peels.

Citric Acid (pK_a1 = 3.15, pK_a2 = 4.77, pK_a3 = 6.40)

Usually derived from lemons, oranges, limes and pineapples. These peels are simple and effective, although not incredibly invasive or capable of significant improvement with one treatment.

The citric acid is triprotic, having three pK_a values. It is quite interesting because the first pK_a is lower than the pK_a of the monoprotic glycolic acid on one hand, and the three reactions are made of two peelings (pK_a1 = 3.15, pK_a2 = 4.77) that end with a buffer (third reaction) of a pK_a3 = 6.40.

We can easily understand that citric acid used for peelings does not need any neutralization nor a buffer.

Mandelic Acid: An Aromatic Alpha Hydroxy Acid (pK_a = 3.37)

Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C₈H₈O₃. It is a white crystalline solid that is soluble in water and most common organic solvents.

Mandelic acid has a long history of use in the medical community as an antibacterial, particularly in the treatment of urinary tract infections. It has also been used as an oral antibiotic. Lately, Mandelic acid has gained popularity as a topical skin care treatment for adult acne. It is also used as an alternative to glycolic acid in skin care products. Mandelic acid is a larger molecule than glycolic acid which makes it better tolerated on the skin. Mandelic acid is also advantageous in that it possesses antibacterial properties, whereas glycolic acid does not.

Its use as a skin care modality was pioneered by James E. Fulton, who developed vitamin A acid (tretinoin, Retin A) in 1969 with his mentor, Albert Kligman, at the University of Pennsylvania. On the basis of this research, dermatologists now suggest mandelic acid as an appropriate treatment for a wide variety of skin pathologies, from acne to wrinkles; it is especially good in the treatment of adult acne as it addresses both of these concerns. Mandelic acid is also recommended as a pre- and post-laser resurfacing treatment, reducing the amount and length of irritation.

Mandelic acid peels are commercialized nowadays as gels with a specific viscosity which make them user-friendly for beginners.

Pyruvic Acid: An Alpha Keto Acid (pK_a = 2.49)

A solution of 40–50% pyruvic acid in ethanol is the most used pyruvate in current practice.

Pyruvic acid is a ketone as well as the simplest alpha-keto acid. The carboxylate (COOH) ion (anion) of pyruvic acid, CH₃COCOO⁻, is known as pyruvate, and is a key intersection in several metabolic pathways.

It is often used to treat mild to moderate papulo-pustular acne with concentrations between 40–50% every 2 weeks for a total of 3–4 months, It reduces the sebum levels and does not affect the cutaneous hydratation.

Azelaic Acid (pK_a1 = 4.550, pK_a2 = 5.598)

Azelaic acid or 1,7-heptanedicarboxylic acid is a saturated dicarboxylic acid naturally found in wheat, barley, and rye. It is active in a concentration of 20% in topical products used in a number of skin conditions, mainly acne. Azelaic acid is used to treat mild to moderate acne, i.e., both comedonal acne and inflammatory acne. It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores clear

It has some interesting properties:

Azelaic acid does not result in bacterial resistance to antibiotics, reduction in sebum production, photosensitivity (easy sunburn), staining of skin or clothing, or bleaching of normal skin or clothing; however, 20% azelaic acid can be a skin irritant.

The azelaic acid is diprotic, having two pK_a values. It is quite interesting because its second pK_a is almost equal to the pH of the skin (5.5).

We can easily understand that azelaic acid used for peelings may need to be neutralized but does not need any buffer. In S. DiBlasi’s formula, azelaic acid is not buffered, nor neutralized.

In vitro, the azelaic acid works as a scavenger (captor) of free radicals and inhibits a number of oxidoreductase enzymes including 5-alpha reductase, the enzyme responsible of turning testosterone into dihydrotestosterone. It normalizes keratinization and leads to a reduction in the content of free oily acids in lipids on the skin surface.

Apart from that, azelaic acid has antiviral and antimitotic properties. Finally, it can also act as an antiproliferant and a cytotoxin via the blockage of mitochondrial respiration and DNA synthesis.

Salicylic Acid (pK_a = 2.97)

30% salicylic acid in ethanol is the most used peeling nowadays.

Salicylic acid is lipid soluble; therefore, it is a good peeling agent for comedonal acne. The salicylic acid is able to penetrate the comedones better than other acids. The anti-inflammatory and anesthetic effects of the salicylate result in a decrease in the amount of erythema and discomfort that generally is associated with chemical peels.

Salicylic acid is a key ingredient in many skin care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. It works as both a keratolytic and comedolytic agent by causing the cells of the epidermis to shed more readily, opening clogged pores and neutralizing bacteria within, preventing pores from clogging up again by constricting pore diameter, and allowing room for new cell growth.Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Use of concentrated solutions of salicylic acid may cause hyperpigmentation in patients with unconditioned skin, those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as in patients who do not regularly use a broad spectrum sunblock.

Also known as 2-hydroxybenzoic acid, it is a crystalline carboxylic acid and classified as a beta-hydroxy acid. Salicylic acid is slightly soluble in water but very soluble in ethanol and ether (like phenol and resorcinol). It is made from sodium phenolate and this explains its direct relationship with phenol with which it shares certain toxic properties that become apparent when used in great quantity and on large surface areas.

Salicylic acid is found naturally in certain plants (Spiraea ulmaria, Andromeda leschenaultii), particularly fruits.

Jessner’s Peel

Jessner’s peel solution, formerly known as the Coombe’s formula,was pioneered by Max Jessner, a dermatologist. Jessner combined 14% salicylic acid, 14% lactic acid, and 14% resorcinol in an ethanol base. It is thought to break intracellular bridges between keratinocytes.

Retinoic Acid Peel

Retinoic acid or vitamin A acid is not soluble in water but is soluble in fat.

Therefore retinyl palmitate or vitamin A palmitate is the elected retinoic agent for chemical peels.

Retinyl palmitate, or vitamin A palmitate is the ester of retinol and palmitic acid.

Tretinoin is the acid form of vitamin A and so also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris.

Tretinoin is the best studied retinoid in the treatment of photoaging. It is used as a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles

The terpene family, to which retinoic acid belongs, includes numerous compounds whose common feature is that they are formed by a chain of isoprene units CH₂=C(CH₃)—CH=CH₂ terpenes have a raw formula type (C₅H_x)_n, x being dependant on the amount of insaturation. Their names depend on n:

The main representative of the family of diterpenes is vitamin A or retinol. Retinol is present in food (beta carotene) and converts completely in the skin into retinaldehyde (retinal). Subsequently, 95% of this is converted into retinyl ester and 5% into all-trans and 9-cis retinoic acids.

Retinoids have multiple properties in embriogenesis, growth control and differentiation of adult tissues, reproduction, and sight. In dermatology their use is well established for psoriasis, hereditary disorders of keratinization, acne, and skin aging. The most commonly used retinoids are all-trans retinoic acid (tretinoin; used topically), 13-cis retinoic acid (isotretinoin; used both orally and topically), retinaldehyde/retinal and retinol (both of which are used topically). In addition there are the synthetic retinoids: etretinate, acitretin, adapalene, tazarotene, etc.

When considering chemical peelings we are only interested in the natural retinoids – retinol, all-trans retinal and retinoic acid – the last two of which are useful in strong concentrations as peeling agents used under medical supervision.

Trichloroacetic Acid (TCA) (pK_a = 0.54)

UN 1839 is required to transport it because of its corrosive activity.

TCA is also called trichloroethanoic acid. It is obtained through distillation of the product from nitric acid steam on chloral acid. It is found as anhydrous (very hygroscopic), white crystals.

TCA can be found directly in the environment because it is used as a herbicide (as sodium salt) and indirectly as metabolite derived from chlorination reactions for water treatment. At the same time, it is a major metabolite of perchlorethylene (PCE), which is used mainly in the field of dry cleaning. Its general toxicity when taken in low dose is almost nonexistent. Its molecular structure is very close to glycolic acid. The carbon in the alpha position has a hydroxyl group and two hydrogens in the case of glycolic acid, as opposed to three chlorines in TCA. TCA is a much stronger acid than any other current acids used for peelings; its pKa is the lowest of any current acids used for chemical peels. Like glycolic acid, TCA does not have general toxicity, even when applied in concentrated form on the skin. When applied to the skin, it is not transported into the blood circulation. TCA’s destructive activity is a consequence of its acidity in aqueous solutions, but in peels the acid is rapidly ‘neutralized’ as it progresses through the different skin layers, leading to a coagulation of skin proteins.

As TCA becomes more concentrated, it becomes more acidic and can penetrate deeper. The greater the amount of solution placed on the skin the more intense the destructive effect. TCA action is simple, reproducible, proportional to the concentration and to the amount applied. Unique to TCA, visual changes (light speckling to white frost)in the skin following application indicate degree of coagulation of protein molecules.

Trichloroacetic acid is used as an intermediate to deep peeling agent in concentrations ranging from 20–50%. Depth of penetration is increased as concentration increases, with 50% TCA penetrating into the reticular dermis.

The quality of manufacture of a particular TCA depends of 14 parameters linked to the raw material itself and one parameter linked to the manufacturer (material of protection if necessary like dustmask, eyeshield, faceshield, full face particle respirator, gloves, respirator cartridge, respirator filter):

The storage of TCA peel has to be separated from food and foodstuffs; it should be stored in a secure cool, dry area in a well-ventilated room.

The packaging has to be unbreakable, if breakable put into closed unbreakable container.

It is preferable to keep the TCA peels solutions in opaque glass bottles.

In addition to this detailed chemistry data, we will also present some clinical scenarios to highlight the action of TCA on the skin. TCA is the most aggressive acid (lowest pK_a of all acids used for peels) and the depth of penetration is correlated with its pH.

The TCA application is linked to the pressure of application, the time, the number of coats, the total quantity used and the neutralization.

We do prefer special creams called ‘frosting stoppers’ instead of water to neutralize the TCA, avoiding then an exothermic reaction, which would provoke a ‘cold’ burn.

In our view, the unbuffered TCA prepared with pure crystals and completed with bi-distilled water added with rose oil mosqueta is less likely to provoke pigmentary rebound or postinflammatory hyperpigmentation versus the buffered TCA.

Figure 1.3 The schematic shows the difference of skin reactivity to the coating with TCA. The darker the area, the higher the number of coats to be applied at the same concentration to achieve the same level of frosting

It is recommended not to use water or primary or secondary alcohols before and after the application of an unbuffered TCA to avoid any exothermic reaction as a reversible reaction of esterification.

Phenol ((pK_aphoh₂⁺/phoh) – 6.4 (pK_aphoh/pho⁻) 9.95)

Phenol is also named phenic acid, or hydroxybenzene. It is a colorless, crystalline solid that melts at 41°C and boils at 182°C, is soluble in ethanol and ether and sometimes soluble in water.

Alcohols are organic compounds that have a functional hydroxyl group attached to a carbon atom of an alkyl chain. Benzene hydroxyl derivatives and aromatic hydrocarbons are called phenols, and the hydroxyl group is directly attached to a carbon atom in the benzene ring. In this case, phenol is an alcohol but not an alkyl alcohol: the group C₆H₅– is named phenyl but the C₆H₅OH compound is called phenol and not phenylic alcohol.

Phenol is an aromatic alcohol with the properties of a weak acid (it has a labile H, which accounts for its acid character). Its three-dimensional structure tends to retain the H+ ion from the hydroxyl group through a so-called mesomeric effect. It is sometimes called carbolic acid when in water solution. It reacts with strong bases to form the salts called phenolates. Its pK_a is high, at 9.95. Phenol has antiseptic, antifungal, and anesthetic pharmacological properties.

Carbolic acid is more acidic than phenol and it exists 3 differences between phenol and carbolic acid.

Resorcinol (pK_a = 11.27)

Resorcinol is a phenol substitued by an hydroxyl in position meta. (Also hydroquinone is a phenol substituted by an hydroxyl in position para; pyrocatechol is a phenol substituted by an hydroxyl in position otho).

Resorcinol is also named resorcin, m-dihydroxybenzene, 1,3-dihydroxybenzene or benzenediol-1,3. It is a crystalline powder that melts at 111°C, boils at 281°C, and is soluble.

Like phenol, resorcinol is a protoplasmatic poison that works through enzymatic inactivation and proteic denaturation with production of insoluble proteinates. Apart from that, both phenol and resorcinol act on the cellular membrane, modifying its selective permeability by changing its physical properties. This change in permeability then leads to cell death.

Phenol alone is a more powerful poison, with an anesthetic secondary action of paralysis of sensory nerve endings.

Phenol and (to a lesser extent) resorcinol are cardiac, renal, and hepatic toxins that are eliminated from the body at 80% concentration either unchanged or conjugated with glucuronic or sulfuric acid.