Glycollic acid

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: Review

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: See "Remarks".

Remarks:

Extensive review cases are available in the public domain relating to human exposure to glycolic acid or derivatives, primarily from its use in the cosmetic sector. Therefore, further studies are unnecessary.The combined data provide evidence for the hazard endpoint that is sufficient for the purpose of classification and labelling and risk assessment.

Data source

Reference

Reference 1

Reference Type:

other: conclusion

Title:

Unnamed

Year:

2007

Reference 2

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Study type:

other: Various study and published literature source reviews

Principles of method if other than guideline:

Various test designs utilised and reviewed in the NICNAS summary

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycollic acid

EC Number:

201-180-5

EC Name:

Glycollic acid

Cas Number:

79-14-1

Molecular formula:

C2H4O3

IUPAC Name:

2-hydroxyacetic acid

Details on test material:

Glycolic acid

Results and discussion

Results:

No specific epidemiological studies on the general population are available for glycolic acid. However, extensive review cases are available in the public domain relating to human exposure to glycolic acid or derivatives, primarily from its use in the cosmetic sector. Cases have been investigated by NICNAS in their evaluation of the safety of glycolic acid, specifically in relation to cosmetic use.

Glycolic acid as 15, 25, and 50% in cosmetic products (pH 4.5) was a non-irritant when tested on rabbit skin.

Repeat insult patch testing was performed on a total of 23 products containing from 0.5-50% glycolic acid at pH values ranging from 2.2-5.5, in groups comprising from 25-198 healthy volunteers per product. All results were negative, except in the case of a 1.25% solution of a glycolic acid-cyclodextrin complex at pH 2.2, which induced strong irritation in most subjects and challenge reactions suggestive of sensitization.

Volunteers had tested a topical solution which contained 7000 mg of glycolic acid crystals, 50% water, 15% propylene glycol, and ethanol to 100 mL. This patented solution was applied to improve signs of skin, nail, and hair changes associated with intrinsic or extrinsic aging.

Full strength glycolic acid with a pH of 0.5 should not be applied to the skin except under special conditions such as the removal of keratoses; this must only be done by trained and experienced dermatologists. Commercially available peels for the physician do not exceed 70% glycolic acid. In this case, the material is adjusted for both concentration and pH to allow application without burning of the skin for the treatment of acne and photoaging. When glycolic acid is esterified with an alcohol, it is neutralized and will no longer have an acidic effect. If products contain esters of glycolic acid, the skin must supply esterases to split the esters back to the acid and alcohol for activity or must hydrolyze part of the molecule for the acid to become active for any biologic activity to occur. It is also possible that the product could be partially esterified having some free acid present.

Two experimental oil-in-water emulsions containing 5% glycolic acid at pH 3 or 7, and two commercial products containing 5% or 10% glycolic acid at pH 2.5 and 3.5, respectively, were compared for their effects on the barrier properties of hairless guinea pig skin. Steady-state3H-water absorption through the skin was measured in vitro following a 24-hour in vivo exposure to the test substances, and the permeability constant was calculated. The average permeability constant for all formulations was determined at 7.5x10-4cm/h, which was significantly higher than the permeability constant of 4.6x10-4cm/h in untreated controls.

Three commercial products containing 0.5-4% glycolic acid at pH 3.6-4.1 were tested in separate groups of 10 healthy volunteers. No evidence of phototoxicity was observed.

Five commercial products containing 0.5-6% glycolic acid at pH 3.6-4.2 were tested in separate groups of 25-27 healthy volunteers. No evidence of photosensitizing potential was observed.

In tests of commercial creams and lotions containing two to 10% glycolic acid at pH 3.25-5.5, approximately 42% of the products were classified as mildly and 18% as moderately stinging.

The potential of a commercial gel containing two or four percent glycolic acid at pH 3.9 to cause folliculitis (inflammation of the hair follicles) was tested by applying the products or a vehicle control to the chest of groups of healthy subjects once or twice daily for 7-14 days. Throughout the test period, the treated sites were examined visually for the presence of bumps, papules, or pustules. The gel caused follicular irritation in 3/30 and 10/30 subjects treated with the two and four percent strength, respectively. No follicular reactions were observed in 20 subjects treated with the vehicle only.

A test for comedogenicity was performed by applying the test substance and a negative control under occlusive or semi-occlusive patches to the upper back of healthy volunteers. The patches were changed three times/week for four weeks, providing 28 days of continuous exposure. At the end of the test period, a piece of stratum corneum with follicular extensions was lifted off from each site and examined for horny cylinders under a dissecting microscope. When tested in six subjects, five commercial cosmetics (three creams and two lotions) containing two to 20% glycolic acid at pH 3.7-3.8 showed no potential to induce blackheads.

A double blind study of the efficacy and adverse effects of creams and lotions containing glycolic acid at different concentrations and pH values (3.2-5) was conducted on 75 patients with various skin diseases. Increases in pH did not lead to improved effectiveness for any skin condition or formulation. Glycolic acid effectiveness was enhanced by increasing the acidification of the skin-penetrating hydroxy molecule, occurring with a lower pH. Reduction of the pH of 5% glycolic acid oil/water creams led to enhanced effectiveness, peaking at pH 3.5. Further pH reduction caused a decrease in effectiveness and an increase in the sensory irritation experienced by patients. These inhibitory effects were even more pronounced for higher glycolic acid concentrations.

A glycolic acid cream was applied to 20 volunteers aged 50-60 years to show better skin conditioning and wrinkling preventing effects than a control cream without it.

A 14-day test on two commercial face lotions of identical glycolic acid concentration (8.4%) and similar pH (3.3 and 4.0) was conducted. One was an oil in-water suspension whereas the other used a non-phospholipid liposome delivery system. Both products were found to be possibly mild in normal use and there was little difference between them.

In a mini-cumulative test in 19-20 subjects of 41 commercial creams and lotions containing 2-10% glycolic acid at pH 3.7-4.0, about 12% of the products were rated as slightly irritating, 22% as mildly irritating, 29% as moderately irritating, and 5% as severely irritating. There appeared to be no correlation between irritation scores and glycolic acid concentration or type of formulation.

In a 14-day test, in which semi-occluded patches were used throughout, the irritation score of a 10% glycolic acid formulation was shown to be inversely correlated with the pH of the formulation, whereas the scores of three formulations containing 10, 15, or 20% glycolic acid at pH 3.8 were very low with little difference between them. Of 12 commercial creams and lotions, five products containing 5-10% glycolic acid at pH 2.4-3.6 were classified as probably or possibly mild in normal use, whereas seven products containing 8-13% glycolic acid at pH 3.8-4.4 were classified as non-irritant/mild.

Three separate 21-day tests were conducted on various creams and lotions containing 4% (four products) or 8% (10 products) glycolic acid (pH not specified). All 4% products were classified as probably mild in normal use. Three 8% products were classified as probably mild, and the remaining seven as possibly mild in normal use.

Glycolic acid has become important and popular for treating acne. To evaluate the efficacy and safety of serial glycolic acid peels with glycolic acid home care products on facial acne lesions and other associated skin problems, 40 Asian patients with moderate to moderately severe acne were studied. They were divided in two groups according to the degree of greasiness of their facial skin. The two groups’ members were treated with four series of 35 and 50% glycolic acid peels, respectively. They also used 15% glycolic acid home care products during this study period. The improvement of acne as well as other associated problems was assessed by both physicians and the patient themselves. Significant resolution of comedones, papules, and pustules was found. The skin texture of each candidate was dramatically rejuvenated. Consistent and repetitive treatment with glycolic acid was needed for the apparent improvement of acne scars and cystic lesions. The follicular pores also became comparatively smaller. Furthermore, most of the patients had much brighter and lighter looking skin. Only a small percentage of patients (5.6%) developed side effects.

Application of 70% glycolic acid to acne lesions resulted in blanching papules, pustules, and comedones within three to five minutes. The authors suggested that spontaneous “unroofing” of the pustules is due to subcorneal epidermolysis secondary to more rapid penetration of glycolic acid through the epidermis and stratum corneum overlying the pustule. Prompt washing avoided deeper interfollicular penetration, which can cause epitheliolysis of follicular ostia, leaving perifollicular erythema that can persist for several weeks.

Various alpha-hydroxy acids were evaluated for their effects on skin properties at concentrations of 0.5 to 1.5 M; the acids were evaluated for their stinging potential on sensitive skin, the ability to increase skin cell renewal, and their ability to improve moisture content and reduce lines and wrinkles after application to skin of human volunteers over a six-week period. L(+)-lactic acid and glycolic acid were the most effective acids when tested at equimolar concentrations. Both materials were less irritating than the D(-)-lactic acid form and the other acids tested. Even though with long-term use of both D(-)- and L(+)-lactic acid and glycolic acid produced comparative improvements in skin hydration and lines with wrinkle improvement, the L(+)-form did so with fewer consumer complaints than any of the other acids tested. When the concentration of lactic and glycolic acids was increased to more than 1.5 M a greater difference in irritation potential was observed.

A total of 22 studies provided information on the incidence of treatment-emergent adverse skin events during regular use of cosmetics with glycolic acid. These studies had durations of seven days to six months, and monitored the use of various formulations and commercial products containing 0.5-50% glycolic acid at pH 1.2-5.5 by 770 healthy subjects, 59 subjects with photoaged skin, and 40 patients with acne. Adverse events were recorded in 24% of the subjects, with stinging accounting for 45% and signs of irritation for 55% of the total. None of the use studies provided information on systemic tolerability.

References:

AMA Laboratories (1993) Fifty human subject repeat insult patch test skin irritation/sensitization evaluation. Dated 19 May 1993. Unpublished data submitted by CTFA (95-AHA-0002). Washington, DC, Cosmetic Ingredient Review.

AMA Laboratories (1993) Fifty human subject repeat insult patch test skin irritation/sensitization evaluation. Dated 27 August 1993. Unpublished data submitted by CTFA (95-AHA-0005). Washington, DC, Cosmetic Ingredient Review.

AMA Laboratories (1993) Fifty human subject repeat insult patch test skin irritation/sensitization evaluation. Dated 27 August 1993. Unpublished data submitted by CTFA (95-AHA-0003). Washington, DC, Cosmetic Ingredient Review.

AMA Laboratories (1994) Fifty human subject repeat insult patch test skin irritation/sensitization evaluation. Dated 22 July 1994. Unpublished data submitted by CTFA (95-AHA-0004). Washington, DC, Cosmetic Ingredient Review.

Consumer Product Testing Co. (1993) Final report (repeated insult patch test of PEX Lotion 585901). Experiment Ref. No. C-439-93. Unpublished data submitted by CTFA (95-AHA-0105). Washington, DC, Cosmetic Ingredient Review.

CTFA (1991) Two-week use test results – AHA extremity lotion. Unpublished data submitted by CTFA (95-AHA-0030). Washington, DC, Cosmetic Ingredient Review.

CTFA (1995) Effect of alpha hydroxy acids on stratum corneum barrier function. A report of in vivo effects of glycolic and lactic acids on improved resistance to SLS challenge. Unpublished data submitted by industry. Washington, DC, Cosmetic Ingredient Review. Cited in: CIR (1998).

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer cream #C94-2596-1614G. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0089). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer cream #C94-2596-1614H. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0090). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer cream #C94-2596-1614I. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0091). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer cream #C94-2596-1614J. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0092). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer lotion #C94-2596-1614A Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0085). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer lotion #C94-2596-1614C. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0087). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer lotion #C94-2596-1614B. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0086). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of moisturizer lotion #C94-2596-1614D. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0088). Washington, DC, Cosmetic Ingredient Review.

Essex Testing Clinic (1994) Final report – clinical safety evaluation of PXL cream 536543-221165. Repeated insult patch test. Unpublished data submitted by CTFA (95-AHA-0098). Washington, DC, Cosmetic Ingredient Review.

FDA (1996) Memo on summary of glycolic acid studies dated March 3 from Chief, Skin Absorption and Metabolism Section, HFS-128, to Acting Director, Office of Cosmetics and Colors. Washington, DC, Cosmetic Ingredient Review.

Kanengiser BE, Morris WE, Katz SN, Muscatiello MJ (1994) Final report: Repeat insult patch testing (CRL37594-5). Washington, DC, Cosmetic Ingredient Review.

Kanengiser BE, Morris WE, Katz SN, Muscatiello MJ (1994) Final report: Repeat insult patch testing (CRL37594-6). Washington, DC, Cosmetic Ingredient Review.

Applicant's summary and conclusion

Conclusions:

Extensive review cases are available in the public domain relating to human exposure to glycolic acid or derivatives, primarily from its use in the cosmetic sector. Therefore, further studies are unnecessary.

Executive summary:

No specific epidemiological studies on the general population are available for glycolic acid. However, extensive review cases are available in the public domain relating to human exposure to glycolic acid or derivatives, primarily from its use in the cosmetic sector. Cases have been investigated by NICNAS in their evaluation of the safety of glycolic acid, specifically in relation to cosmetic use.