Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
other information
Study period:
22.04. - 02.06.2005
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Type of study / information:
Type: In vitro penetration from three different Vehicles through pig skin
Test guideline
Qualifier:
according to
Guideline:
other: OECD 428
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Results and discussion

Applicant's summary and conclusion

Conclusions:
1. The vast majority of the applied A 130 in the cream formulations was removed after a contact period of 0.5h by gently washing the skin with a mild detergent solution (101%from the formulation with hydrogen peroxide, 96.6% from the formulation without hydrogen peroxide and 95.6% was washed off the skin from the aqueous solution).
2. Less than 0.6% of the A 130 applied remained in the stratum corneum at the end of the study from the cream applications and less than 0.5% was found in the stratum corneum following the aqueous application.
3. After washing and tape stripping, less than 1.4% of the A 130 applied was found in the remaining epidermis/dermis from the cream applications and less than 0.5% was found in the remaining epidermis/dermis following the aqueous application.
4. Less than 0.8% and less than 1.6% had penetrated through the skin into the receptor fluid from the cream formulations, with and without hydrogen peroxide respectively, at the end of the 48h sampling period. Less than 0.5% penetrated through the skin into the receptor fluid from the aqueous application at the end of the 48h sampling period.
5. The systemically available dose for the cream formulations with and without hydrogen peroxide and the aqueous solution would be approximately 1.72%, 2.94% and 0.881% of the applied dose, respectively. These respective amounts expressed in µg/cm2 are 3.87µg/cm2, 6.62µg/cm2 and 1.99µg/cm2. Therefore, these calculated amounts could be used for risk assessments.
6. The results obtained in this study demonstrate that the penetration of A 130, from these formulations, through dermatomed pig skin is considered to be very slow.
7. These data demonstrate that the systemic availability, after dermal exposure to A 130 from two realistic formulations, would be low especially under normal use conditions in combination with a hydrogen peroxide developer.







Executive summary:

1. Summary

1.1 Study design

The penetration of A 130 has been measured in vitro through dermatomed pig skin from a standard cream formulation (with and without hydrogen peroxide) and from a solution in water.  The aqueous solution and formulated material, all containing a nominal 1.13% w/w A 130, were applied to the dermatomed membranes at a nominal rate of 20mg/cm2 or 20µl/cm2 and left unoccluded.  The applications were rinsed off after a 0.5h contact period, with the penetration of A 130 through the membrane being assessed throughout the entire 48h exposure period.  At the end of the exposure period, the distribution of A 130 in the test system was assessed, which included a tape stripping technique to determine its distribution in the skin.

The applications and exposure conditions were designed to simulate potential human dermal exposure to the formulation during normal use and compare the penetration of A 130 from a standard formulation (with and without hydrogen peroxide) with the penetration from an aqueous solution.  

Samples collected during this study were analysed by liquid scintillation counting (LSC).

1.2 Results

1.2.1 A 130 cream formulation with hydrogen peroxide

The dermal penetration of A 130 from this application was low and the vast majority of the dose was recovered in the wash at 0.5h.  After 0.5h exposure, the amount which had penetrated the dermatomed pig skin was 0.316µg/cm² (≡0.140%) and after 48h the amount penetrated was 1.59µg/cm² (≡0.707%).  Most of the penetration occurred during the first 2 hours giving a penetration rate of 0.596µg/cm²/h.  After 2h, the penetration rate remained relatively constant at 0.007µg/cm²/h indicating that the penetration process was essentially complete.  The penetration rate over the 0–48h exposure period was 0.022µg/cm²/h.  A small proportion of the dose was found adsorbed to the stratum corneum and absorbed in the remaining epidermis/dermis.  The overall quantity found to be bioavailable (absorbed and penetrated) within 48 hours under the given study conditions was calculated to be 1.72% (≡ 3.87µg/cm²) of the topically applied amount.  The total recovery for this application was 105%.

1.2.2 A 130 cream formulation without hydrogen peroxide

The dermal penetration of A 130 from this application was low and the vast majority of the dose was recovered in the wash at 0.5h.  After 0.5h exposure, the amount which had penetrated the dermatomed pig skin was 0.730µg/cm² (≡0.324%) and after 48h the amount penetrated was 3.54µg/cm² (≡1.57%).  Most of the penetration occurred during the first 2 hours giving a penetration rate of 1.47µg/cm²/h.  After 2h, the penetration rate remained relatively constant at 0.009µg/cm²/h indicating that the penetration process was essentially complete.  The penetration rate over the 0–48h exposure period was 0.045µg/cm²/h.  A small proportion of the dose was found adsorbed to the stratum corneum and absorbed in the remaining epidermis/dermis.  The overall quantity found to be bioavailable (absorbed and penetrated) within 48 hours under the given study conditions was calculated to be 2.94% (≡ 6.62µg/cm²) of the topically applied amount.  The total recovery for this application was 101%.  

1.2.3 A 130 aqueous solution

The results for one diffusion cell have not been included in the results, as the data indicated that the skin membrane had been damaged during the 0.5h decontamination process.

The dermal penetration of A 130 from this application was low and the vast majority of the dose was recovered in the wash at 0.5h.  After 0.5h exposure, the amount which had penetrated the dermatomed pig skin was 0.149µg/cm² (≡0.066%) and after 48h the amount penetrated was 1.00µg/cm² (≡0.444%).  Most of the penetration occurred during the first 4 hours giving a penetration rate of 0.192µg/cm²/h. After 4h, the penetration rate remained relatively constant at 0.005µg/cm²/h indicating that the penetration process was essentially complete. The penetration rate over the 0–48h exposure period was 0.015µg/cm²/h. A small proportion of the dose was found adsorbed to the stratum corneum and absorbed in the remaining epidermis/dermis. The overall quantity found to be bioavailable (absorbed and penetrated) within 48 hours under the given study conditions was calculated to be 0.881% (≡ 1.99µg/cm²) of the topically applied amount. The total recovery for this application was 97.6%.