Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
The dermal absorption factor is reported from a regulatory opinion document from the Scientific Committee on Consumer Products (SCCP). The dermal absorption factor considered in this opinion is used to determine the Margin of Safety (MoS) of 4-methylbenzylidene camphor in sunscreens.

Data source

Reference
Reference Type:
review article or handbook
Title:
OPINION ON 4-Methylbenzylidene camphor (4-MBC) (COLIPA no S60)
Author:
Scientific Committee on Consumer Products (SCCP)
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Version / remarks:
1994, draft
Qualifier:
according to
Guideline:
other: COLIPA Guideline for Percutaneous Absorption/Penetration
Version / remarks:
1995
GLP compliance:
not specified
Remarks:
Study is summarised in a regulatory opinion document; full study details are not available

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
pig
Sex:
female

Administration / exposure

Type of coverage:
not specified
Duration of exposure:
24 hours
Doses:
167 to 200 μg test item/cm², corresponding to 4.5 mg formulation/cm² of a 4% test item formulation
No. of animals per group:
8 experiments, performed in triplicate
Details on study design:
SAMPLE COLLECTION
- Skin surface: Gentle scraping with a spatula and/or threefold wiping with cotton wool (corresponds to non-absorbed sample)
- Horny layer: About 15-20 fold stripping with self-adhesive "tesa-film" tape
- Epidermis: Heating of the skin disc (epidermal side for 45 seconds on a 80°C hot plate (Ceram), separation epidermis from dermis with forceps)
- Dermis: 3 punched samples or total dermis
- Receptor fluid: 2 aliquots

ANALYSIS
- Method type(s) for identification: HPLC-DAD
- Limits of detection and quantification: LOD: approximately 0.03 μg/mL, LOQ: approximately 0.1 μg/mL
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Pig
- Type of skin: Unboiled back skin
- Preparative technique: Skin discs (gently dry-shaved surface, diameter 5 cm)
- Thickness of skin: 3-4 mm

PRINCIPLES OF ASSAY
- Diffusion cell: Glass penetration cell
- Receptor fluid: 0.9% sodium chloride, 1% bovine serum albumin and 0.02% gentamycine sulphate in water
- Solubility of test substance in receptor fluid: Receptor fluid suitable for hydrophilic and lipophilic samples
- Test temperature: 32°C

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
No test item was detected in the receptor fluid.
Total recovery:
Mean total recovery was 91.8% (range 86.8 to 95.6%).
Percutaneous absorption
Key result
Time point:
24 h
Dose:
178 μg/cm²
Parameter:
percentage
Remarks:
1.96 μg/cm² (epidermis+dermis)
Absorption:
1.1 %
Remarks on result:
other: mean of 8 experiments

Any other information on results incl. tables

Table 1. Summary of dermal absorption rates

 Test  Applied substance (μg/cm²)  Surface (μg/cm²)  Horny layer (μg/cm²)  Epidermis (μg/cm²)  Dermis (μg/cm²)  Recovery (%)
 1  182  125  38.2  2.0  0.34  90.9
 2  200  159  26.2  1.3  0.50  93.8
 3  172  132  27.6  2.4  0.72  94.7
 4  175  119  31.0  1.7  0.90  87.2
 5  171  138  23.5  0.7  0.34  95.0
 6  167  132  16.2  1.4  0.88  90.0
 7  187  144  17.1  0.4  not detectable  86.8
 8  173  140  23.5  2.2  not detectable  95.6
 Mean  178  136  25.4  1.5  0.46  91.8
 Standard deviation  11  12.5  7.2  0.7  0.36  3.5

Applicant's summary and conclusion

Conclusions:
Taking into account the values obtained in eight separate experiments, the SCCP consider a mean dermal absorption value of 1.96 μg/cm² as the basis to determine safe use for 4-methylbenzylidene camphor in sunscreen formulations. Based on a mean applied amount of 178 μg/cm², the dermal absorption factor is calculated to be 1.10% (epidermis+dermis).
Executive summary:

Data on the dermal absorption of 4 -methylbenzylidene camphor is available in a regulatory opinion document from the Scientific Committee on Consumer Products (SCCP). Taking into account the values obtained in eight separate in vitro experiments using pig skin, the SCCP consider a mean dermal absorption value of 1.96 μg/cm² as the basis to determine safe use for 4-methylbenzylidene camphor in sunscreen formulations. Based on a mean applied amount of 178 μg/cm², the dermal absorption factor is calculated to be 1.10% (epidermis+dermis). The reliability of this data source cannot be assigned (Klimisch 4) as it is a secondary source reporting from a summary of eight individual experiments. The original studies were not obtained for reliability and relevance assessment, however as the data is used in a regulatory opinion, it is assumed to be sufficiently reliable.