Registration Dossier

Toxicological information

Dermal absorption

Currently viewing:

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Qualifier:
according to
Guideline:
other: Official recommendation of the European Scientific Committee on Consumer Products (SCCP)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Radiolabelled Ammonium thioglycolate, ATGA (SAT 060260)[Carboxyl-14C] Ammonium Mercaptoacetate ([14C]-ATGA)
Source: PerkinElmer Life and Analytical Sciences, 549 Albany Street, Boston, MA 02118, USA.
Batch no.3574086A
The test item, supplied as a solution in water, was stored at ca -20°C in the dark
Concentration: 1 mCi/mL
Specific activity: 42.27 mCi/mmol
Radiochemical purity: 98.00%

Non-Radiolabelled Ammonium thioglycolate, ATGA
Source: Bruno Bock
Batch no. 16612
Purity: 71.3% in water
Radiolabelling:
yes

Test animals

Species:
pig
Strain:
other: Landrace large white cross
Sex:
male/female

Administration / exposure

Type of coverage:
open
Vehicle:
other: hair waving formulation
Duration of exposure:
30 min
Doses:
ca 20 mg of the hair waving formulation/cm2, the resulting dose of ATG was approx. 2.63 mg/cm² skin.
Details on in vitro test system (if applicable):
The dermal absorption/percutaneous penetration of [14C]-radiolabelled Ammonium Thioglycolate out of a representative permanent hair waiving formulation was studied on the clipped excised skin of four Landrace large white cross pigs (two male, two female). The pig skin, dermatomed to a mean thickness of 0.80 mm, was used because it shares essential penetration characteristics with human skin . Pigs were control/spare animals from separate studies at the test institute.

The skin integrity of frozen (at -20 °C) skin discs was checked by measuring the trans-dermal electrical resistance. The intact, clipped excised pig skin of the cosmetic formulation without occlusion for a representative exposure time (see below).

Before topical application to skin the respective [14C]-radiolabelled ammonium thioglycolate salt was added to the hair waving formulation.
The dermal absorption/percutaneous penetration of the test substance was investigated for the open application of about 20 mg formulation per cm² pig skin. Therefore the resulting dose of ATGA was approx. 2.63 mg/cm² skin. Skin discs of about 3.14 cm² were exposed to the formulation for 30 min, terminated by gently rinsing with a commercial shampoo solution diluted with water and drying the skin surface with tissue paper (tissue swabs). At 24 h post dose, the washing procedure was repeated. The skin was then removed from the static diffusion cells, dried and the stratum corneum was removed with 20 successive tape strips. The remaining skin was divided into exposed and unexposed skin and solubilised with Solvable® tissue solubiliser. The receptor fluid in the receptor chamber was removed and split into fractions for analysis. All samples were analysed by liquid scintillation counting. The formulation was analysed with nine replicates obtained from three different animals per experiment for absorbed and penetrated amount of the test substance. The receptor fluid used was phosphate buffered saline. Samples of the receptor fluid were drawn before the application of the test substance formulation and 0.5, 1, 2, 4, 6, and 24 hours after application. The removed volume was replaced by fresh receptor fluid.

Results and discussion

Absorption in different matrices:
For [14C]-ammonium thioglycolate in permanent hair waving formulation (13%, w/w) applied to dermatomed pig skin in vitro, most of the applied dose (98.69%) was removed by washing at 30 min post dose. At 24 h post dose, the total dislodgeable dose was 98.98% of the applied dose. The total unabsorbed dose was 99.04% of the applied dose. The stratum corneum (Dermal Adsorption) retained 0.17% of the applied dose. The percutaneous penetration and dermal bioavailability were 0.22% (5.23 µg equiv./cm2) and 0.77% (19.83 µg equiv./cm2) of the applied dose, respectively. The mass balance was complete with 99.97% of the applied dose recovered. Both the amounts absorbed and penetrated were taken as systemically available.
Total recovery:
99.97%
Percutaneous absorption
Dose:
2.63 mg/cm² skin
Parameter:
percentage
Absorption:
0.8 %
Remarks on result:
other: 24h
Remarks:
The amount of test item penetrating and /or remaining in the exposed skin after removing the stratum corneum

Any other information on results incl. tables

ANALYSED SAMPLE 13% ATG (or 11% TGA) in a permanent hair waving formulation

Exposure time : 30 min

[% of dose] [µg/cm²]

Unadsorbed Dose* 99.04 2610.93

Adsorption (stratum corneum) 0.17 4.58

Not Bioavailable 99.21 2615.51

Absorption (epidermis/dermis) 0.55 14.60

Penetration (receptor fluid) 0.22 5.23

Bioavailable 0.77 19.83

Total recovery / mass balance 99.97 2635.34

* Unadsorbed dose: skin washes + tissue swabs + pipette tips + donor chamber wash + unexposed skin

Applicant's summary and conclusion

Conclusions:
In this in vitro dermal penetration study the amount of Ammonium Thioglycolate systemically available from a representative permanent hair waving formulation was found to be 19.83 µg/cm² (0.77%), corresponding to 16.74 µg/cm² when calculated for Thioglycolic Acid.
Executive summary:

The dermal absorption/percutaneous penetration of [14C]-radiolabelled ammonium thioglycolate out of a representative permanent hair waiving formulation (13% in the formulation, pH 9.5) was studied on the clipped excised skin of four Landrace large white cross pigs. The pig skin, dermatomed to a mean thickness of 0.80 mm, was used because it shares essential penetration characteristics with human skin. The dermal absorption/percutaneous penetration of the test substance was investigated for the open application of about 20 mg formulation per cm² pig skin. Therefore the resulting dose of ammonium thioglycolate was approximately 2.63 mg/cm² skin (equivalent to 2.1 mg thioglycolic acid/cm²). Skin discs of about 3.14 cm² were exposed to the formulations for 30 min., terminated by gently rinsing with a commercial shampoo solution diluted with water. The amount of ammonium thioglycolate systemically available (epidermis/dermis plus receptor fluid) was found to be 19.83 µg/cm² (0.77%), corresponding to 16.74 µg/cm² when calculated for thioglycolic acid.