The Use and Safety of Hydroxy Acids in Cosmetics

Date: 16th February 2005

The Use and Safety of Hydroxy Acids (Alpha Hydroxy Acids, Beta Hydroxy Acids and Alpha Keto Acids) in Cosmetics.

R.J.E.Williams B.Sc., Dip.Env.St..

Abstract.

The use of Hydroxy Acids (Alpha Hydroxy Acids, Beta Hydroxy Acids and Alpha Keto Acids), represented one of the major breakthroughs in cosmetic technology and achievement towards truly functional “anti-aging” products. The popularity of Hydroxy Acid based products with the consumers, stimulated a significant growth in the personal care market. An understanding of Hydroxy Acids and specifics of formulating with them may assist in the development of safe and effective personal care formulations.

Preface

The original position paper was published in “Cosmetics, Aerosols and Toiletries in Australia” Vol 10, No1, p 23-26, 1996 - ISSN 0817-637X., and an updated form of this paper is included in the body of text below.

Since this publication other regulatory action has taken place and a brief synopsis of each of these is included in further sections below.

Introduction.

Hydroxy Acids are a class of organic chemical compounds which have an Hydroxyl or Keto group in close proximity to the Carboxyl group. In the case of Alpha Hydroxy Acids (AHAs) and Alpha Keto Acids (AKAs) the hydroxyl group (with AHAs) and the Keto group (with AKAs) is in the alpha position (one removed) and in the case of Beta Hydroxy Acids the hydroxy group in the beta position from the carboxyl group (two removed).

These Hydroxy Acids have been reported to act as common moisturising agents by absorbing moisture from the atmosphere, hence when applied topically; they help increase moisture content and plasticity of the stratum corneum.

It has also been reported that Hydroxy Acids stimulate cell desquamation by reducing corneocyte adhesion/cohesion and accelerate cell renewal within the basal layer by induction of epidermolysis, leading to the synthesis of new collagen, and hence their use as exfolients and skin smoothing agents. The danger is when, through high levels, low pH and excessive exposure times, more than the dead skin layers are removed, exposing immature skin cells, blood, nerve or lymphatic systems to harmful effects of the environment.

Table 1.

In his article “Technology Transfer – Alpha Hydroxy Acids (AHA): Borrowing from Dermatology”; Morris Herstein lists,

The Cosmetic Benefits of AHAs as                                    the Therapeutic Uses of AHAs as
Retexturising                                                                          Ichthyosis

Improved Skin Tone                                                               Actinic Keratosis

Softer, Smoother Skin                                                            Age Spots

Less lines and Wrinkles                                                         Skin Peeling

Fading of Age Spots                                                               Warts

                                                                                                Photoaging/Wrinkles

This paper discusses the chemical types available, the selection and concentration of Hydroxy Acids, the pH of products containing Hydroxy Acids, the selection of delivery systems, the selection of excipients and anti-irritants and the establishment of a skin irritation index through clinical testing.


Table 2.

Chemical Examples.

Single Alpha Hydroxy Acids                           eg Fruit Acids

Glycolic Acid                                        CH2 (OH)–COOH

Lactic Acid                                            CH3-CH(OH)-COOH

Malic Acid                                             CH3-CH2-CH(OH)-COOH

Poly-Alpha Hydroxy Acids

Tartaric Acid                                         COOH-CH(OH)-CH(OH)-COOH

Citric Acid                                             COOH-CH2-HOC(COOH)- CH2-COOH

Glyceric Acid                                        CH2(OH)-CH(OH)-COOH

Gluconic Acid                                       CH2(OH)-CH(OH)-CH(OH)-CH(OH)-CH(OH)-COOH

Discarboxylic Acid types

Tartronic Acid                                       HOCH(COOH)2

Aromatic Hydroxy Acids

Mandelic Acid                                       C6H5-CH(OH)-COOH

Benzylic Acid                                        C6H5-(HO)C(COOH)-C6H5

Beta Hydroxy Acids

Salicylic Acid

Note; these have been used as Kerotylic agents for many years in such products as medicated wipes.

Alpha Keto Acids

Pyruvic Acid                                          CH3-CO-COOH

                                                              Note; Alpha Keto Acids (AKAs) are likely to have two                                                                    modes of action in that;
                                                             a)   they exhibit specific effects as AKAs (similar to                                                                        AHAs) in the upper layers of skin, and
                                                             b)   in their reduced form (eg after conversion of Pyruvic                                                               Acid to Lactic Acid by Lactic Dehydrogenase) act as                                                                    AHAs in the lower levels of skin.

Ascorbic Acid (Vitamin C)

Please note that the compounds found in Table 2. are by no means a complete list of possible compounds and there are many Hydroxy Acids which may prove effective and non-irritant in commercial use.


Formulating

When formulating with Hydroxy Acids standard product development should be employed.

That is;

1.      Select the type and concentration of the Hydroxy Acid

        Selection of the type and concentration of the Hydroxy Acid should be based on the end            usage of the product (see tables 1. 2. and 3.)


It seems that there has been an almost direct transfer of technology from Dermatology to Cosmetics (ie. the use of high levels of short chain AHAs or Fruit Acids) without sometimes considering the consequences. That is, some formulators have used materials which have a very high efficacy but leading to potential skin problems sometimes experienced when not formulated correctly, not formulated with safety in the forefront of consideration or not used under strict clinical supervision. These potential skin problems can be simple skin irritations, to short term skin damage (chemical burns) and possible long term detrimental effects.

It goes without saying that there should be a balance between efficacy and irritation. Products intended for Dermatologists and Salon use, where the patient is under constant supervision, stronger levels of Hydroxy Acids may be used, however where the cosmetic customer buys a product and uses it at home where little or no supervision is available then the formulator must take the potential for simple skin irritations, to short term skin damage (chemical burns) and possible long term detrimental effects, into consideration.

2.      Select the pH of the Product


In his article “Technology Transfer – Alpha Hydroxy Acids (AHA): Borrowing from Dermatology”; Morris Herstein states the “optimal pH is between 3.0 and 5.5 … the lower the level the greater the efficacy … there is a need for the free acid form for maximum efficacy, as 100% salt form of an AHA is not as effective as the acid form.. However a mixture of acid and salt form can be effective too.”

The relationship between pH, cellular renewal and irritation has been proven utilising varying concentrations of different hydroxy and non-hydroxy acids at different pHs (see table 3. below).

Table 3.

“Relationship Between Cell Renewal, Irritation and pH”

W.Smith, Advance Technology Conference, March 1994.

Cell renewal - a higher value indicates greater skin renewal and,

Irritation results are based on standard tests where the lower value indicates a lower irritation potential.

​​​​Test material

pH

​​​​Cell Renewal

Irritation

4% Lactic Acid

4% Glycolic Acid

4% Salicylic Acid

5% Citric Acid

4% Pyruvic Acid

3
5
3
5
3
5
3
5
3
5

35
24
34
23
42
28
18
14
23
16

2.8
2.1
2.9
2.1
3.0
2.3
2.3
2.1
2.4
2.0

Other studies have also shown that at a pH 3.0 all acids significantly stimulated the skin and produced some degree of irritation. At pH 7.0 little or no irritation was observed, however there was no stimulation either. Pure 70% Glycolic Acid has been used and with a pH of less than 2 the irritation potential is so high that some chemical burns have been reported with excessive exposure, hence should be avoided.

The early Van Scott patents stressed the importance of neutralising AHAs with specific bases. Smith’s studies demonstrated no marked changes if neutralisation was achieved with Sodium Hydroxide, Triethanolamine or Ammonium bases.

3.      Choose the appropriate delivery system for the hydroxy Acid


Research indicates formulation design is of key importance to ensure optimal delivery of the skin condition benefits. The performance of particular Hydroxy Acids can be affected by the delivery system, such as a lotion, cream or gel, etc. whether it is to be buffered or unbuffered and the incorporation of percutaneous penetration enhancers.


4.             Select Excipients and Anti-Irritants


Firstly the emulsifying system and excipients must be selected from those which are stable at the chosen pH and compatible with the Hydroxy Acid. It should also be noted that performance of particular Hydroxy Acids can be affected by the presence of various emulsifiers and excipients. The product is then formulated around the Hydroxy Acid and compatible emulsion system.

If required anti-irritants can be selected from the following chemical groups;

Table 4.

Anti-Irritants

Thickeners                        by reducing diffusion on the skin and into the eyes.
Complexing agents           by reacting with the skin before the Hydroxy Acid can irritate.
High Molecular Weight
Molecules eg. Proteins,
Botanicals and Sterols.
                                   by reducing the ability of the Hydroxy Acid to penetrate the skin.
Compounds with high levels of Hydroxy groups eg Ethoxylated compounds and Glucose derivatives.



5.      Establish a Skin Irritation Index through clinical testing

Below is a list of Australian companies who are registered to conduct skin irritation testing.

Australian Photobiology Testing Facility Pty. Ltd.
 University of Sydney.

Dermatest Pty Ltd
Rockdale

Note; the ASCC in no way endorses any clinical testing facility and the above list is provided as a guide to available services only.

6.      Optimise the formulation

Repeat from step 1. if necessary

7.      Repeat Clinical and User Testing

Repeat from step 1. if necessary ensuring that if any changes are made step 5 is definitely repeated.


Further Regulatory Action

Cosmetic Ingredient Review (CIR) -1997

The Cosmetic Ingredient Review (CIR) published their findings, with respect to the “Safety Assessment of Glycolic Acid, Ammonium, Calcium, Potassium and Sodium Glycolate, Methyl, Ethyl, Propyl, and Butyl Glycolate, and Lactic Acid, Ammonium, Calcium, Potassium, Sodium, and TEA-Lactate, Methyl Ethyl, Isopropyl, and Butyl Lactate, and Lauryl, Myristyl, and Cetyl Lactate.”  June 6, 1997”. The essence of their findings were that there is some concern when using these materials, particularly when the concentration is above 10%w/w and the pH is below 3.0.


The CIR recommendation was that :

cosmetic products should have a concentration of Glycolic Acid, Lactic Acid and their derivatives no greater than 10.0%w/w and the pH of any product should be greater than 3.5.

and,
salon products should have a concentration of Glycolic Acid, Lactic Acid and their derivatives no greater than 30.0%w/w and the pH of any product should be greater than 3.0.


It is assumed that this would leave the medical profession (dermatologists) to use higher concentrations and lower pH products.

NICNAS (1999-2000)

The NICNAS “Existing Chemicals” Committee (now a division of the Therapeutic Goods Administration) investigated Glycolic Acid as a “Priority Existing Chemical”. See “Glycolic Acid in Cosmetic Products” Priority Existing Chemical No.18 - Draft Preliminary Assessment Report (NICNAS – September 1999).

The ASCC actively worked with the representative of this government body. The approach has been to get a balanced view to any regulatory controls on Glycolic Acid.

The major area of concern to the ASCC is the recommendation that the use of glycolic Acid, AT ANY LEVEL IN A COSMETIC PRODUCT, should be considered for listing in the Standard for the Uniform Scheduling of Drugs and Poisons. The Australian Society of Cosmetic Chemist’s view is that there is a case that glycolic acid at low levels should be EXEMPT from listing in the Standard for the Uniform Scheduling of Drugs and Poisons. That is, if glycolic acid is incorporated into a cosmetic product, at a level less than 20%w/w in skin care and less than 10%w/w for products used around the eye, at a pH greater than 3.5, then we believe this should not be considered a poison.

We have also argued that Glycolic Acid (above 5%w/w) should not be considered a R63(3) Classification ie. “Possible risk of harm to the unborn child (Category 3)”, without supporting evidence. This was contained in the NICNAS Draft Report. We argued that the consequences, we see, are that if this is left in the draft, which goes out in the 2nd round of review (to a much more widely spread audience), without qualification, then the press/media may sensationalise and create unnecessary concerns. This would make it extremely difficult, in the future, for anyone to produce products, with higher than 5%w/w glycolic acid, based on what will be the market perception. Past cases of Urocanic Acid, Lanolin, Hexachlorophene and Formaldehyde are examples of what the media can do to market perception.

National Drugs and Poisons Schedule Committee (NDPSC) (1999-2000)

The TGA made submission for Glycolic Acid to be considered in the November 1999 meeting of the NDPSC. The TGA submission, prompted by the NICNAS Report above, is that Glycolic Acid be exempt below 20.0%w/w concentration and with a pH above 3.5 and Schedule 5 classification outside of these limits.

The ASCC made a submission to the NDPSC on behalf of the ASCC members, supporting the TGA. That is Glycolic Acid being exempt below 20.0%w/w concentration and with a pH above 3.5 and Schedule 5 classification outside of these limits. If, however, the product is likely to come into contact with the eyes, the Australian Society of Cosmetic Chemists would feel much more comfortable with a maximum level of Glycolic / Lactic Acids (and their derivatives) being 10.0%w/w and with a pH greater than 3.5.

We have also argued that Glycolic Acid (above 5%w/w) should not be considered a R63(3) Classification ie. “Possible risk of harm to the unborn child (Category 3)”. It is the opinion of the committee that this recommendation was proposed without sufficient supporting evidence. That is, the recommendation is made based on data for the concentrated raw material and just because there was no data within the report which declared as safe lower levels than the raw material, all levels above 5%w/w have been included in the recommendations. Even the CIR does not support this and left the lower limit at 10%w/w glycolic acid and derivatives.

These recommendations were agreed to at a NSPSC meeting (No. 27/3.1) 16-18 May 2000.


Conclusion (or) Position Statement.

Whilst cosmetic products containing Hydroxy Acids generally possess the least potential for harm to the consumer, forulators should be aware of the potential pitfalls when developing such products. The ASCC is not in a position to recommend the precise way you should formulate your product, however, we recommend that formlators carry out the appropriate development, clinical and dermatological tests to determine efficacy and potential irritatancyof formulations containing Hydroxy Acids. By following rigorous protocols of testing we may be able to bring the consumer, Hydroxy Acid based products which are effective and safe to use.

In essence, the Australian Society of Cosmetic Chemists believes that any regulatory control should be consistent (generally agree) with the CIR findings.

We suggested that cosmetic limits for a composite of Glycolic Acid (and derivatives), in "skin renewal products", should be no more than 20.0%w/w and with a pH greater than 3.5. If, however, the product is likely to come into contact with the eyes, the Australian Society of Cosmetic Chemists  would recommend a maximum level of Glycolic Acid (and derivatives) being 10.0%w/w and with a pH greater than 3.5. This stand is based on evidence as found in the Cosmetic Ingredient Review (CIR) Final Report of June 6, 1997 (noted above).


Higher levels of Glycolic Acid (and derivatives) and possibly lower pH’s may be encountered in specialist areas. A possible overview of this should be determined by the Therapeutic Goods Administration.


Other chemical forms of Hydroxy Acids, as previously listed, should be exempt from any regulation, as their action is generally milder than Glycolic Acid (and derivatives) and they have been used for many years without reported problems. Also new Hydroxy Acids being developed for the cosmetic industry have sufficient safety and efficacy data provided to ensure safe use of these chemicals.


All this should also be dependent on the final product (for cosmetic and salon use, containing Alpha Hydroxy Acids) having undergone some form of safety testing and, as a result, include appropriate label recommendations as to warnings, contact time and removal.

Note :
ASCC believes that up to 5.0%w/w Glycolic Acid, Lactic Acid (and their derivatives) should be exempt from any regulations as these AHA’s have been used, for many years, as pH adjusters / neutralisers in cosmetic products (notably hair care products, skin creams & lotions), and at these levels or at the normal pH encountered in cosmetic creams (4.5 - 7.0) there has been no adverse problems experienced.
That is, we do not wish to see traditional uses for such chemicals be caught up in any regulatory net designed for control of alternative uses.

While the Australian Society of Cosmetic Chemists supports appropriate regulatory controls for dangerous and hazardous chemicals we do believe that any drafting of legislation should be done in direct consultation with the industry (that is the Cosmetic Chemists themselves and not product sponsors). This then gives the regulator a “hands on” approach and insight which may not be easily apparent or forthcoming from academic and government fields.

References.

“Relationship Between Cell Renewal, Irritation and pH”,

W.Smith,
Advance Technology Conference, March 1994

2.      “The Great AHA Debate”,
SPC, June 1994, pp 32-35

3.      “Technology Transfer – Alpha Hydroxy Acids (AHA): Borrowing from Dermatology”;
          Morris Herstein

4.      “Viewpoint – The AHA Phenomenon: the Beauty or the Beast”,
         Galina Clare,
         Cosmetics, Aerosols and toiletries in Australia, Vol 9, No.4, pp 9-12

5.      “Formulating with Alpha Hydroxy Acids”,
          Robert W. Seigfried,
          DCI, may 1995, pp 32-112

6.      “Hydroxy Acids and Skin Aging”,
         Walter Smith Consultants (reprint)

7.      “Treatment Cosmetics – Retinoids and AHAs”,
         Bernard Idson,
        DCI, May 1995, pp 24-28

8.      “Antioxidant Activity’,
        N.Perricone,
       SPC, June 1994, p37

9.      “Use of AHAs Add New\Dimensions to Chemical peeling”,
        W.F.Dial,
        Cosmetic Dermatology, May 1990

10.    “Alpha Hydroxy Acids: Therapeutic Potentials”,
        E.J.Van Scott & R.J.Yu,
       The Canadian Journal of dermatology, Vol 1; No.5, Nov/Dec 1989, pp108-112

“Alpha Hydroxy Acids: Procedures for Use in Clinical Practice”,
E.J.Van Scott & R.J.Yu,
Cutis, Vol 43, March 1989, pp 222-228

“Treatment of Pseudofolliculitis barbae with Topical Glycolic Acid: A Report of Two Studies”,
N.V.Perricone,
Cutis, Vol 52, October 1993, pp 232-235

“Glycolic Acid Therapy; Evaluation of Efficacy and Techniques in Treatment of Photodamage Lesions”,
L.S.Moy, H.Murad and R.L.Moy,
The American journal of Cosmeti Surgery, Vol 10, No.1, 1993, pp 9-12

“”The Utilisation of Glycolic Acid in Photoaging”,
M.L.Elston,
reprint from Cosmetic Dermatology, January 1992

“Different Effects of Glycolic Acid and Tretinoin in Acne vulgaris”,
M.L.Elston,
reprint from Cosmetic Dermatology, January 1992

“Aged Skin, Retinoids and Alpha Hydroxy Acids”,
R.Hermitte,
Cosmetics and toiletries, Vol 107, July 1992, pp 63-67

‘The Skin Plasticization Effect of Medium Chain 2-Hydroxy Acid and the Use of Potentiators”,
J.C.Hill, R.H.White, M.D.Barratt & E. Mignini,
Journal of Applied Cosmeticoogy, 6, April – June 1988, pp 53-69

“Safety Assessment of Glycolic Acid, Ammonium, Calcium, Potassium and Sodium Glycolate, Methyl, Ethyl, Propyl, and Butyl Glycolate, and Lactic Acid, Ammonium, Calcium, Potassium, Sodium, and TEA-Lactate, Methyl Ethyl, Isopropyl, and Butyl Lactate, and Lauryl, Myristyl, and Cetyl Lactate.” ,
Cosmetic Ingredient Review (CIR)
June 6, 1997

“Glycolic Acid in Cosmetic Products” Priority Existing Chemical No.18 - Draft Preliminary Assessment Report,
Steen Kristensen,  NICNAS
September 1999.

“Glycolic Acid in Cosmetic Products”
Australian Society of Cosmetic Chemists Submission to the National Drugs and Poisons Schedule Committee (NDPSC),
27 October 1999

various personal communications between the author (R.Williams) and National Drugs and Poisons Schedule Committee (NDPSC) (1999-2000)