Glycollic acid

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Experiments were conducted using methods similar to OECD guideline 428 "Skin Absorption: in-vitro method" and were repeated multiple times. The integrity of skin was not checked and the total recovery of radioactivity was not calculated. Not GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Remarks:

The integrity of the skin was not tested. Total recovery not calculated

Principles of method if other than guideline:

Percutaneous absorption studies using a flow-through diffusion cell system with skin specimens from 24 healthy women to assess the penetration of glycolic acid (GA). Followed background on the use of an in vitro method reported in "In vitro Percutaneous Absorption: Principles, Fundamentals and Applications" by Bronaugh RL and Maibach HI. (1991)

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:

- Name of test material (as cited in study report): glycolic acid (GA)
- Source: [1,2-14C]GA was obtained from ICN biomedicals, CA, USA.
- Specific activity (if radiolabelling): 44 mCi/mmol
- Other: The concentration of [1,2-14C]GA was 250 μCi/ml.

Radiolabelled, 14C-glycolic acid was used as
- 4% glycolic acid at pH 2.0 or pH 3.8 or
- 4 to 60% glycolic acid at native pH values.
(1,2-14C)Glycolic acid was obtained from ICN Biomedicals, CA, USA).

Radiolabelling:

yes

Remarks:

[1,2-14C] glycolic acid

Test animals

Species:

other: human skin samples obtained from24 volunteers - Age at study initiation: 19-48 years (35 ± 10 years) - Other: The participants were judged to be healthy based on medical history and physical evaluation

Strain:

other: human volunteers

Sex:

female

Details on test animals or test system and environmental conditions:

Not applicable.

Administration / exposure

Type of coverage:

open

Duration of exposure:

6-24 hr.

Doses:

100 μL of 4% GA solution

No. of animals per group:

N represents the numbers of human volunteers, and n represents the numbers of experimental repeats.
N = 3-4
n= 10-31

Control animals:

no

Details on study design:

Twenty-four healthy women participated in the study by providing the skin tissue. The skin specimens were collected from the hospital after plastic surgery. The skin tissue was transferred in the sterilized culture media to maintain the tissue's viability. The skin sample was prepared and used within 4 hours after surgery. Experiments were also conducted using frozen skin sections (frozen at -20°C in HHBSS and the storage duration was no longer than 2 months). The percutaneous absorption experiments were conducted using a Diffusion Cell System (Crown Glass, PA, USA).

Details on in vitro test system (if applicable):

One hundred micro litres of glycolic acid solution spiked with (14C) glycolic acid (0.25 µCi/µl) was applied on the SC side of the skin section. Experiments were conducted for 6-24hours. A single fraction of effluent from each individual cell was collected for the 6-hour duration. For a 24-hour experiment, a total of four fractions of the 6-hour duration were obtained. At the end of the incubation time, skin surface was washed with 1% soap solution and water using a Q-tip cotton swab to remove unabsorbed material. The Q-tips from the individual cell were combined in a vial and 10ml of scintillation liquid was added to enable measuring the radioactivity. The results obtained were analysed using SAS software.

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Dose:

100µl of a 4% GA solution

Parameter:

percentage

Absorption:

>= 1.5 - <= 2.6 %

Remarks on result:

other: 24 hours

Remarks:

pH 3.8

Percutaneous absorption 2

Dose:

100µl of a 10% GA solution

Parameter:

percentage

Absorption:

>= 0.6 - <= 1.2 %

Remarks on result:

other: 24 hours

Remarks:

pH 3.8

Percutaneous absorption 3

Dose:

100µl of a 20% GA solution

Parameter:

percentage

Absorption:

>= 0.2 - <= 0.9 %

Remarks on result:

other: 24 hours

Remarks:

pH 3.8

Conversion factor human vs. animal skin:

Not applicable.

Any other information on results incl. tables

After 24 hr exposure, the percentage of radio-labelled GA found in the skin after application of 4% GA at pH 2.0 or pH 3.8 were as follows (p less than 0.05 in each case):

 - stratum corneum (SC) = 2.65 ±1.80 and 1.13 ± 1.14

 - viable skin (VS) = 13.46 ± 7.44 and 2.23 ±1.15 and

 - effluent fraction (EF) = 12.22 ± 9.03 and 1.42 ± 0.77

 

An increased penetration of GA through the skin was observed after application of 4-60% GA at their native pH. The percent of GA in the skin after application of 20% GA for 24 hrs at pH 1.9 were as follows: SC = 2.69 ± 2.26; VS = 4.07 ±1.78 and EF=6.12 ±4.95.

 

Exposure duration after affected the extent of penetration. Application of 20% GA at pH 1.9 for 6 hr resulted in the following levels: SC = 1.16 ± 0.80 (p0.05); VS = 4.07 ± 1.78; and EF = 6.12 ±4.95. The results of this study indicated that under the conditions of low concentration and partially neutral pH (3.0-4.2), most of the GA appeared to stay in SC and VS layers with very limited penetration through the skin. Due to the similarity of absorption through the viable and the dead tissue, the absorption of GA might be a passive process rather than an active one.

Applicant's summary and conclusion

Conclusions:

As there are no differences in absorption between fresh (live) and frozen (dead) skin specimens, it is considered that dermal absorption of glycolic acid is a passive diffusion process. The absorption process is influenced by time, pH, concentration, type and composition of the formulation, and by the degree of occlusion of the site of application. The estimated permeability coefficient ranges from 3 x 10-5 to 2 x 10-4 cm/h, which is in reasonable agreement with the experimentally determined permeability coefficient of 3 x 10-4 cm/h.

Executive summary:

Penetration of dermis by glycolic acid (GA) was investigated using a flow-through cell system with skin specimens from 24 healthy women. Radio-labelled 14C-glycolic acid was applied to the skin for 24 hours as a 4% glycolic acid preparation at pH 2.0 or pH 3.8 or as 4 to 60% glycolic acid preparations at native pH values. The percent radio-labelled GA appearing in the stratum corneum was 2.65 at pH 2.0 and 1.13 at pH 3.8; in viable skin the values were 13.46 at pH 2.0 and 2.23 at pH 3.8 and in the effluent fraction 12.22 at pH 2.0 and 1.42 at pH 3.8. At higher concentrations, the penetration was greater, e.g. for 20% GA (pH 1.9) the percentages were 2.69%, 4.88% and 30.69% for stratum corneum, viable skin and effluent fraction respectively. The duration of exposure also affected skin penetration – application of the 20% GA (pH 1.9) for only 6 hours resulted in stratum corneum radioactivity of 1.16%, viable skin levels of 4.07% and effluent fraction levels of 6.12%. Absorption of glycolic acid through human skin was found to be pH, concentration and time-dependent. The in vitro human skin model is considered a suitable model for estimation of in vivo human absorption.The pH factor is most critical to dermal penetration. Absorption across a range of glycolic acid concentrations is enhanced with decreased pH. Glycolic acid is a weak acid, with a pKa value of 3.83, at pH values of less than 3 most of the GA is in the uncharged acid form which facilitates penetration through the lipid layer in the stratum corneum enhancing dermal absorption. This is important, particularly in human cosmetic usages, since high absorption of GA at low pH causes severe skin irritation. As there are no differences in absorption between fresh (live) and frozen (dead) skin specimens, it is considered that dermal absorption of glycolic acid is a passive diffusion process. The absorption process is influenced by time, pH, concentration, type and composition of the formulation, and by the degree of occlusion of the site of application.

 

Absorption of GA in human skin is pH-, concentration-, and time-dependent. The in vitro method appeared to provide an appropriate model to reflect in vivo absorption of GA through human skin.