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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The aim of the study was to investigate the influence of the pH (pH 6, 7, 8) on the percutaneous absorption of thioglycolic acid
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Thioglycolic acid titrated with ammonia to give solutions of pH 6, 7 and 8.
A solution of 14C-thioglycolic acid (Batch: 2675-291, radiochemical purity: 97.55 %) was gradually neutralized with a 25 % solution of ammonia resulting in three final solutions of 11 % ammonium 14C-thioglycolate with pH 6, pH 7 and pH 8, respectively (concentration calculated as thioglycolic acid).
Radioactive test substance:
Labelling: 14C
Preparation: synthesis by NEN, 549 Albany Street, Boston, USA
Supplier: NEN-DU PONT WIEN, A-1020, Lasallestr. 2/20, Austria
Radiochemical purity: 97.69 %
Storage: in the freezer at about -25 °C under nitrogen
Radiolabelling:
yes
Remarks:
14C-labelled thioglycolic acid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
ANIMALS:
Supplier: Forschnugsinstitut für Versuchstierzucht, A-2325 Himberg, Austria.
Weight: approx. 200 g
Age: male ca. 6-7weeks, females ca. 9-10 weeks
Housing: Single caging in metabolism cages (UNO B.V., Zevenaar, Holland)
Diet: ad libitum Altromin 1321ff
Water: ad libitum tap water
Acclimatization: 1 week

CONDITIONS:
Temperature: average 23°C
Relative humidity: average 75%
Air changes: 12/hour
Light-Dark cycle: 12/12

Administration / exposure

Type of coverage:
open
Vehicle:
water
Duration of exposure:
30 min
Doses:
165 mg/kg bw
No. of animals per group:
5
Control animals:
no
Details on study design:
Groups of 5 male and 5 female Sprague-Dawley rats were used to investigate the dermal bioavailability and excretion of ammonium thioglycolate.

Approx. 300 mg of the solutions (equivalent to 165 mg/kg bw) were applied to the clipped dorsal skin of the rats for 30 min and then washed off. The treatment was followed by a neutralization step where 0.3 ml of a "Natural styling solution" containing 2.1 % hydrogen peroxide was applied for 10 min and then washed off. The treated area was then covered with 4 layers of gauze fixed by adhesive tape and the animals were subsequently placed into metabolism cages for 72 hours.

The concentration of the test material (11 %), the time of exposure (30 min), the area of exposure (ratio application site to body surface: 0.026) and the neutralization step were chosen to mimic human exposure during the application of hair waiving products.
Solutions from the two rinsings were united. Urine and faeces were collected daily.
The animals were killed after 72 hours.
The application area plus some surrounding skin was excised and dissolved in Soluene-350 for analysis of radioactivity.
The radioactivity of the carcass was determined after removal of the remaining skin to avoid false 14C concentrations in the carcass due to skin, possibly contaminated e.g. by urine.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
yes
Remarks:
small focal redness appeared on the treated skin during application and remained at least until the area was covered
Absorption in different matrices:
Most of the 14C was removed from the rat skin during washing of the test material and neutralization solution (mean 96.1 - 96.8%). The mean 14C recovered in urine and faeces in the pH 6, pH 7, and pH 8 exposure groups was 0.139%, 0.119%, and 0.137%, respectively. The mean 14C-content of the skin at the application site for the pH 6, pH 7, and pH 8 exposure groups was 0.82%, 0.57%, and 0.60%, respectively. The mean cutaneous absorption for 11% Ammonium 14C-thioglycolate at pH 6, pH 7, and pH 8 was 1.09%, 0.81%, and 0.86%, respectively. Cutaneous absorption and 14C concentrations in urine, feces, and carcasses were higher in males than females, but it was determined that this was not statistically significant
Total recovery:
Total mean (sd) recovery was 97.9% (1.1), 97.5% (2.1) and 97.0% (1.5) at pH 6, 7 and 8, respectively.
Percutaneous absorption
Dose:
165 mg/kg bw
Parameter:
percentage
Absorption:
ca. 1 %
Remarks on result:
other: rinsing after 30 min

Any other information on results incl. tables

Recovery of the radioactivity after dermal administration of ammonium14C-thioglycolate to rats

Analysed sample

14C-activity in % of applied dose,
mean (SD)

pH 6

pH 7

pH 8

Rinsings

96.8 (1.2)

96.7 (2.1)

96.1 (1.4)

Adsorption
(application site)

0.82 (0.43)

0.57 (0.24)

0.60 (0.34)

Urine (0-72 h)

0.11 (0.12)

0.091 (0.073)

0.11 (0.11)

Faeces (0-72 h)

0.029 (0.032)

0.028 (0.025)

0.027 (0.025)

Carcass

0.126 (0.087)

0.116 (0.076)

0.121 (0.089)

Total recovery*

97.9 (1.1)

97.5 (2.1)

97.0 (1.5)

Cutaneous absorption

1.09

0.81

0.86

*Total of urine, faeces, adsorption at the application site and carcass14C recovery.

Applicant's summary and conclusion

Conclusions:
The mean cutaneous absorption20for 11% Ammonium14C-thioglycolate at pH 6, pH 7, and pH 8 was 1.09%, 0.81%, and 0.86%, respectively.
Executive summary:

Three groups of rats (5/sex; ~200 g) received on the clipped dorsal skin approximately 300 mg of ammonium14C-thioglycolate (radiochemical purity 97.6%) as an 11% solution (equivalent to 165 mg a.i./kg bw or 133 mg/kg bw as thioglycolic acid) at pH 6, pH 7, and pH 8 for 30 minutes followed by a washing of the site. The test site was then neutralized with 0.3 ml of a “natural styling solution” containing 2.1% hydrogen peroxide for 10 minutes followed by a washing of the site. These applications were to mimic human exposure to hair waving products. After the second wash, the test sites were covered with four layers of gauze and the rats were placed into metabolism cages for 72 hours. Following the observation period, the animals were sacrificed. The test sites and surrounding skin were excised and dissolved in Soluene-350 for radioactivity analysis. The radioactivity of the waste wash water, urine, and feces as well as the carcasses was also measured.

Most of the14C was removed from the rat skin during washing of the test material and neutralization solution (mean 96.1 - 96.8%). The mean14C recovered in urine and faeces in the pH 6, pH 7, and pH 8 exposure groups was 0.139%, 0.119%, and 0.137%, respectively. The mean14C-content of the skin at the application site for the pH 6, pH 7, and pH 8 exposure groups was 0.82%, 0.57%, and 0.60%, respectively. The mean cutaneous absorption20for 11% Ammonium14C-thioglycolate at pH 6, pH 7, and pH 8 was 1.09%, 0.81%, and 0.86%, respectively. Cutaneous absorption and14C concentrations in urine, feces, and carcasses were higher in males than females, but it was determined that this was not statistically significant.