(2-hydroxyethyl)ammonium mercaptoacetate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

Department of Health, United Kingdom

Test material

Test material information

Constituent 1

Reference substance name:

(2-hydroxyethyl)ammonium mercaptoacetate

EC Number:

204-815-4

EC Name:

(2-hydroxyethyl)ammonium mercaptoacetate

Cas Number:

126-97-6

Molecular formula:

C2H7NO.C2H4O2S

IUPAC Name:

2-hydroxyethan-1-aminium 2-sulfanylacetate

Details on test material:

- Name of test material: Monoethanolamine Thioglycolate 83,7%
- Content of active ingredient: 83.7%
All test concentrations were corrected for active ingredient content.
- Lot/batch No.: 9787
- Physical state: colourless liquid
- Description: aqueous solution
- Storage condition of test material: room temperature in the dark, under nitrogen in a glass bottle

Specific details on test material used for the study:

permanent hair waving formulation (18%, w/w)

Radiolabelling:

yes

Remarks:

MeaTG, [Carboxyl-14C]

Test animals

Species:

pig

Strain:

other: Landrace large white cross

Sex:

male/female

Details on test animals or test system and environmental conditions:

Four samples of full-thickness pig skin were obtained from the back and flank regions of four Landrace large white cross pigs (2 female, 2 male). These animals were control/spare animals from separate studies at Charles River Laboratories.

Administration / exposure

Type of coverage:

open

Vehicle:

other: depilary formulation

Duration of exposure:

30 min

Doses:

The test substance concentration (10% w/w) corresponds to the concentration in a depilary formulation.

Details on in vitro test system (if applicable):

The dermal absorption/percutaneous penetration of [14C]-radiolabelled CaTG of a representative depilatry formulation was studied on 9 samples of pig skin, obtained from 3 different animals.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Applicant's summary and conclusion

Conclusions:

For [14C]-MEATG in a permanent hair waving formulation (18%, w/w) applied to dermatomed pig skin in vitro, the percutaneous penetration and dermal bioavailability were 0.17% (5.83 µg equiv./cm2 ) and 0.38% (13.64 µg equiv./cm2) of the applied dose, respectively. The mass balance was complete with 98.87% of the applied dose recovered.

Executive summary:

The three [C]-radiolabelled test items (Ammonium thioglycolic acid (ATG), Calcium thioglycolic acid (CaTG) and Monoethanolamine thioglycolic acid (MeaTG)) are used in basic formulations (test preparations). The formulations are typical for a permanent hair waving formulation, a depilatory formulation and a hair straightening formulation.

As part of a safety evaluation of each test item, this study was required to assess their extent of dermal bioavailability, following topical application of ATG in a permanent hair waving formulation (13%, w/w), CaTG in a depilatory formulation (10%, w/w) and MeaTG in a hair straightening formulation (18%, w/w) to excised pig skin. The skin surface was washed at 30, 15 and 45 min, respectively, for each formulation to reflect the in use conditions. The skin was again washed at 24 h post dose for all groups as a final wash off before test run termination.

Previously frozen dermatomed pig skin was mounted into static diffusion cells containing receptor fluid (phosphate buffered saline, ca 10 mL) in the receptor chamber. The skin surface temperature was maintained at ca 32°C throughout the experiment. An electrical resistance barrier integrity test was performed and any pig skin sample exhibiting a resistance <4 kΩ was excluded from subsequent dermal bioavailability measurements.

The permanent hair waving formulation, depilatory formulation and hair straightening formulation containing [¹⁴C]-ATG, [¹⁴C]-CaTG and [¹⁴C]-MEATG, respectively, were applied, at an application volume of ca 20 mg/cm² , to dermatomed pig skin mounted into static diffusion cells in vitro.

Dermal Bioavailability was assessed by collecting receptor fluid aliquots (250 µL) at 0.5, 1, 2, 4, 6 and 24 h post dose. At 30, 15 and 45 min post dose, respectively, for ATG in a permanent hair waving formulation, CaTG in a depilatory formulation and MEATG in a hair straightening formulation, exposure was terminated by washing the skin surface with a dilute shampoo solution 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.

A summary of the mean results are provided in the tables overleaf:

 

Test Preparation	ATG in Permanent Hair Waving Formulation	CaTG in Depilatory Formulation	MeaTG in Hair Straightening Formulation
Test Item Concentration (w/w)	13	10	18
Mean Application Rate of Formulation (mg/cm^2)	20.28	20.11	20.12
Mean Application Rate of Test Item (µg equiv./cm^2)	2636.13	2010.74	3621.78
Dislodgeable Dose at 30, 15, 45 min, respectively (% Applied Dose)	98.69	104.70	98.14
Total Dislodgeable Dose* (% Applied Dose)	98.98	105.07	98.36
Unabsorbed Dose** (% Applied Dose)	99.04	105.08	98.41
Dermal Adsorption (% Applied Dose)	0.17	0.07	0.09
Percutaneous Penetration (% Applied Dose)	0.22	0.02	0.17
Dermal Bioavailability (% Applied Dose)	0.77	0.20	0.38
Mass Balance (% Applied Dose)	99.97	105.36	98.87
Dislodgeable Dose at 30, 15, 45 min, respectively (µg equiv./cm^2)	2601.66	2105.30	3554.39
Total Dislodgeable Dose* (µg equiv./cm^2)	2609.26	2112.73	3562.29
Unabsorbed Dose** (µg equiv./cm^2)	2610.93	2112.94	3564.05
Dermal Adsorption (µg equiv./cm^2)	4.58	1.48	3.15
Percutaneous Penetration (µg equiv./cm^2)	5.23	0.41	5.83
Dermal Bioavailability (µg equiv./cm^2)	19.83	4.09	13.64
Mass Balance (µg equiv./cm^2)	2635.34	2118.52	3580.85

* Total dislodgeable dose = skin washes + tissue swabs + pipette tips + donor chamber wash

** Unabsorbed dose = total dislogeable Dose + unexposed skin

 

For [¹⁴C]-ATG 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.

For [¹⁴C]-CaTG in depilatory formulation (10%, w/w) applied to dermatomed pig skin in vitro, most of the applied dose (104.70%) was removed by washing at 15 min post dose. At 24 h post dose, the total dislodgeable dose was 105.07% of the applied dose. The total unabsorbed dose was 105.08% of the applied dose. The stratum corneum retained 0.07% of the applied dose. The percutaneous penetration and dermal bioavailability were 0.02% (0.41 µg equiv./cm² ) and 0.20% (4.09 µg equiv./cm² ) of the applied dose, respectively. The mass balance was complete with 105.36% of the applied dose recovered.

For [¹⁴C]-MEATG in a permanent hair waving formulation (18%, w/w) applied to dermatomed pig skin in vitro, most of the applied dose (98.14%) was removed by washing at 45 min post dose. At 24 h post dose, the total dislodgeable dose was 98.36% of the applied dose. The total unabsorbed dose was 98.41% of the applied dose. The stratum corneum (Dermal Adsorption) retained 0.09% of the applied dose. The percutaneous penetration and dermal bioavailability were 0.17% (5.83 µg equiv./cm² ) and 0.38% (13.64 µg equiv./cm²) of the applied dose, respectively. The mass balance was complete with 98.87% of the applied dose recovered.