Glycollic acid

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

other: conclusion

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

There were no indications of skin sensitisation potential from the results of animal tests (guinea pig maximisation test – Buehler design). The use of glycolic acid in cosmetics necessitates confirmation that human sensitisation is unlikely to occur in all but the most sensitive cases. Human patch tests have been completed and are reviewed in the NICNAS document 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 Type:

other: conclusion

Title:

Unnamed

Year:

2007

Materials and methods

Study type:

other: Various animal and human models reviewed and evaluated

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

various tests for contact sensitisation evaluated using human and animal study results for various uses of glycolic acid.

GLP compliance:

not specified

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

Any other information on results incl. tables

Available studies provide information on the incidence of treatment-emergent adverse skin events during regular use of cosmetics with glycolic acid. These studies had a duration of 7 days to 6 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 42% and signs of skin irritation for 55% of the total. None of the use studies provided information on systemic tolerability.

 

The results of these tests indicate that cosmetic products containing glycolic acid do not induce contact sensitisation, phototoxicity or photosensitisation and are non-comedogenic. It can be presumed that the higher concentrations found in biocidal uses will be more irritant but have similar properties in relation to immunotoxic/allergenic response.   However, at concentrations of >2% glycolic acid does induce stinging in a dose- and pH-related manner, skin irritation to a degree that appears to depend more on pH than glycolic acid content, and dose-related follicular irritation. The frequency and severity of these effects also depend on the choice of excipients, in ways which are not well understood. However for biocidal use, the formulation is less complicated than that used in cosmetics where many more excipients may be included. The relevance of the test results is borne out by a high incidence of stinging (10%) and signs of skin irritation (13%) in a number of use studies involving 869 subjects. These effects were also frequent causes of spontaneous consumer complaints.

There were no indications of skin sensitisation potential from the results of animal tests (guinea pig maximisation test – Buehler design). The use of glycolic acid in cosmetics necessitates confirmation that human sensitisation is unlikely to occur in all but the most sensitive cases. Human patch tests have been completed and are reviewed in the NICNAS document. In summary, the conclusion of the NICNAS evaluation is presented below.

 

Contact sensitisation tests

The repeat insult patch test is a standard method for testing the potential of a substance to induce allergic contact dermatitis. Various protocols are used, but in general subjects are treated with 24-h, 48-h or 72-h occluded and/or semi-occluded patches containing 0.1-0.2 mL of the test formulation 2-3 days per week for a total of 5-10 applications. After a rest period of 10-14 days, subjects are challenged by re-patching on both treated and untreated sites and examined for the presence of erythema, papules and blisters at 1 and 24-48 h after removal of the challenge patches. A reaction to the challenge that exceeds the reactions during the treatment phase or spreads beyond the patch site indicates sensitisation. The guinea pig maximisation test (Magnusson and Kligman) is a variation in which the sensitivity is increased by pre-treatment of the test sites with the skin irritant sodium lauryl sulphate.

Repeat insult patch testing has been 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 sensitisation. The weight of evidence indicates the risk of sensitisation occurring in the general public following exposure to glycolic acid is very low.

 

Since glycolic acid is used cosmetically as a “leave-on” product the phototoxicity of the material was evaluated and the photosensitisation potential was also investigated. Results are presented in NICNAS and reproduced here for supporting evidential purposes. 

Tests for phototoxicity

Phototoxicity is defined as a non-immunological, light-induced dermatitis caused by a photoactive chemical. It is determined by applying the test product to 2 skin sites under occlusion for 24 h, irradiating one treated and an untreated control site with UV light and comparing the degree of erythema and oedema of all 3 sites at 15 min, 24 h and 48 h post-irradiation.

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.

 

Tests for photosensitisation

A chemical is a photosensitiser if it reacts with light to produce one or more substances that induce allergic contact dermatitis. The standard test for photosensitisation is similar to the repeat insult patch test described above. However, the test sites are irradiated with UV light immediately after patch removal during the induction as well as the challenge phase and non-irradiated treated and irradiated untreated sites are included in the test as negative controls.

 

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 photosensitising potential was observed.

 

Comedogenicity tests

Substances applied to the skin may induce the formation of comedones (blackheads). The standard test for comedogenicity involves applying the test substance and a negative control under occlusive or semi-occlusive patches to the upper back of healthy volunteers. The patches are changed 3 times per week for 4 weeks, providing 28 days of continuous exposure. At the end of the test period, a piece of stratum corneum with follicular extensions is lifted off from each site and examined for horny cylinders under a dissecting microscope. When so tested in 6 subjects, 5 commercial cosmetics (3 creams and 2 lotions) containing from 2-10% glycolic acid at pH 3.7-3.8 showed no potential to induce blackheads.

 

Applicant's summary and conclusion

Conclusions:

Cosmetic products containing glycolic acid do not induce contact sensitisation, phototoxicity or photosensitisation and are non-comedogenic. It can be presumed that the higher concentrations found in biocidal uses will be more irritant but have similar properties in relation to immunotoxic/allergenic response. Concentrations of >2% glycolic acid induce stinging and skin irritation.

Executive summary:

Available studies provide information on the incidence of treatment-emergent adverse skin events during regular use of cosmetics with glycolic acid. These studies had a duration of 7 days to 6 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 42% and signs of skin irritation for 55% of the total. None of the use studies provided information on systemic tolerability.

 

The results of these tests indicate that cosmetic products containing glycolic acid do not induce contact sensitisation, phototoxicity or photosensitisation and are non-comedogenic. It can be presumed that the higher concentrations found in biocidal uses will be more irritant but have similar properties in relation to immunotoxic/allergenic response.   However, at concentrations of >2% glycolic acid does induce stinging in a dose- and pH-related manner, skin irritation to a degree that appears to depend more on pH than glycolic acid content, and dose-related follicular irritation. The frequency and severity of these effects also depend on the choice of excipients, in ways which are not well understood. However for biocidal use, the formulation is less complicated than that used in cosmetics where many more excipients may be included. The relevance of the test results is borne out by a high incidence of stinging (10%) and signs of skin irritation (13%) in a number of use studies involving 869 subjects. These effects were also frequent causes of spontaneous consumer complaints.