Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Available Data

Data source

Reference
Reference Type:
secondary source
Title:
OPINION ON 4-Chlororesorcinol, SCCS/1224/09 Revision of 12 July 2010
Author:
European Commission Directorate General for Health & Consumers
Year:
2010
Bibliographic source:
Scientific Committee on Consumer Safety (SCCS),

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
Dermal absorption study has been used to estimate the toxico-kinetic potential of the chemical 4-chlororesorcinol
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlororesorcinol
EC Number:
202-462-0
EC Name:
4-chlororesorcinol
Cas Number:
95-88-5
Molecular formula:
C6H5ClO2
IUPAC Name:
4-chlorobenzene-1,3-diol
Details on test material:
CAS NO: 95-88-5
Chemical Name: 4-chlororesorcinol
Nature of the chemical: Organic

Test animals

Species:
other: dermatomed pig skin, 380 μm thickness
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
dermal
Vehicle:
other: hydrogen peroxide & water
Details on exposure:
The aqueous solution and formulated material all containing 2.5% w/w of [14C] 4-chlororesorcinol were applied to the dermatomed membranes at a rate of 10mg/cm² and left unoccluded. The
applications were rinsed off after a 0.5h contact period, with the penetration of [14C] 4-chlororesorcinol through the membrane being assessed throughout the entire 48h exposure period. At the end of the exposure period, the distribution of [14C] 4-chlororesorcinol in the test system was assessed, which included a
tape stripping technique to determine its distribution in the skin.
Samples collected during this study were analysed by liquid scintillation counting (LSC).
Duration and frequency of treatment / exposure:
48h exposure period
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mg/cm²
No. of animals per sex per dose / concentration:
Not applicable

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The dermal penetration of [14C] 4-chlororesorcinol from the cream formulation with and without hydrogen peroxide was low and the vast majority of the dose was recovered in the wash at 0.5h.

After the 0.5h exposure period, the amount which had penetrated was 0.062 μg/cm² (~0.024%) (with hydrogen peroxide) and 0.022 μg/cm² (~0.008%)
(without hydrogen peroxide) and after 48h, the amount penetrated was 1.17 μg/cm² (~0.448%) (with hydrogen peroxide) and 1.69 μg/cm² (~0.651%) (without
hydrogen peroxide). A small proportion of the dose was found adsorbed to the stratum corneum (0.855%) (with hydrogen peroxide) and (0.533%) (without hydrogen peroxide).

For the aqueous solution of [14C] 4-chlororesorcinol, penetration occurred during the whole 48 hour test period giving a penetration rate of 2.03μg/cm²/h during the first 4 hours (for comparison with the cream formulations) and the penetration rate between the 4 and 48h time period was 0.623μg/cm²/h.
At 48h the amount penetrated was 35.8 μg/cm² (~14.2%). 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 20.8% (~52.6μg/cm²) of the topically applied amount.
Details on distribution in tissues:
Details not available
Details on excretion:
Not applicable

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

This data demonstrate that the systemic availability, after dermal exposure to[14C] 4-chlororesorcinolfrom formulations would be low especially under normal use conditions in combination with a hydrogen peroxide developer and would be significantly less than that available from a solution of[14C] 4-chlororesorcinolin water. The total recovery of radioactivity was 103% (with hydrogen peroxide) and 107% (without hydrogen peroxide).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
This data demonstrate that the systemic availability, after dermal exposure to [14C] 4-chlororesorcinol from formulations would be low especially under normal use conditions in combination with a hydrogen peroxide developer and would be significantly less than that available from a solution of [14C] 4-chlororesorcinol in water. The total recovery of radioactivity was 103% (with hydrogen peroxide) and 107% (without hydrogen peroxide).
Executive summary:

The in-vitro study conducted on dermatomed pig skinwith the test chemical[14C] 4-chlororesorcinol dissolved in the vehicle hydrogen peroxide and water indicates low dermal penetration of the test substance. Low absorption of the test chemical by the dermal route can be an indication of low bio-accumulation potential; though and in-vitro study result is insufficient to prove the same.