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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
It is well documented, and was tested using neat Cinnamic Aldehyde and this makes the comparison to the data in Jimbo (1983) someway more straightfoward. The study follows some principles of the OECD Guideline 428 (skin absorption : in vitro method), but the total recovery did not meet the criteria in the OECD guideline.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study follows some principles of the OECD Guideline 428 (skin absorption : in vitro method)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):cinnamic aldehyde
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance):
- Substance type:
- Physical state:
- Analytical purity: >99%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other: purchased from Sigma-Aldrich Inc. (Gillingham, UK)
Radiolabelling:
no

Test animals

Species:
human
Sex:
female

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours or 2 hours
Doses:
10 µL of cinnamaldehyde (up to 78 µM) was used
No. of animals per group:
not applicable
Control animals:
no
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: reduction mammoplasty (breast) or apronectomy (abdomen) operation
- Ethical approval if human skin: all skin samples were obtained with ethical approval from the Local Research Ethics Committees of St. Mary's Hospital and Stephen Kirby Skin Bank, respectively.
- Type of skin: breast or abdomen
- Preparative technique: operation
- Thickness of skin (in mm): no information
- Membrane integrity check: no information
- Storage conditions:
- Justification of species, anatomical site and preparative technique:

PRINCIPLES OF ASSAY
- Diffusion cell: yes
- Receptor fluid: 0.025 M Hepes, Hank's balanced salts solution (9.8g/l), 4 mM sodium bicarbonate, 50 mg/l gentamycin, pH7.4; degassed; and filtered using a 65-um PEFE filter (Whatman, UK) prior to use
- Solubility od test substance in receptor fluid:
- Static system: nono information
- Flow-through system: yes (flowing at 2 mL/h)
- Test temperature: no information
- Humidity: no information
- Occlusion: all samples were occluded throughout the experiment
- Reference substance(s):
- Other: During 24-h experiments, each fraction was collected over 2 h; for 2-h experiments each fraction was collected over 15 min.

Results and discussion

Total recovery:
The total recovery of cinnamic compounds (adding together the percentage levels found to penetrate, evaporate, remain unabsorbed, or reside free within the skin) following application of 78 micro mol cinnamic aldehyde was 82.9%. The majority of the initial dose was recovered as cinnamaldehyde (62.2%); 2.8% was reduced to cinnamic alcohol and a total of 17.9% had been oxidatively metabolized to cinnamic acid.

Any other information on results incl. tables

During 24 h absorption of neat cinnamaldehyde, parent cinnamaldehyde was detected at low levels (80 -150 nmol/cm2 skin/h) in receptor fluid in the first three 2 -h fractions and began to penetrate the skin at an increasing rate after an approximately lag time of 6 h. Levels of cinnamaldehyde-derived cinnamic alcohol (321.4 +/- 250.3 nmol/cm2 skin/h) and cinnamic acid (238.0 +/- 164.0 nmol/cm2 skin/h) metabolites were higher than parent cinnamaldehyde (132.9 +/- 24.6 nmol/cm2 skin/h) in the first 2 -h receptor fluid fraction and maximal penetration for the two metabolites occurred between 4 and 8 h. After 8 h, the rates of penetration for cinnamic alcohol and cinnamic acid continually fell and cinnamic alcohol approached undetectable levels (limit of detection < 0.1 nmol) in the 22- to 24 -h fraction. After 12 h, the level of penetrated cinnamaldehyde became greater than the level of cinnamic alcohol metabolite and, after 18 h, parent cinnamaldehyde became the predominant cinnamic compound present in recceptor fluid.

Applicant's summary and conclusion

Conclusions:
The skin penetration of Cinnamic Aldehyde in this study was 16%. It is proposed to use this study in a weight of evidence approach with the Jimbo (1983) one and apply the relative penetration rates found in Jimbo (1983), i.e. 87.5-fold, to estimate the penetration rate of Hexylcinnamaldehyde. This would therefore be 0.183%.
Executive summary:

The in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic acid (78 micromol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography.

At the end of the 24 -h experiment for neat cinnamaldehyde application to human skin, a total of 9.4% of the initial applied dose of cinmamaldehyde had penetrated the skin as cinnamaldehyde, cinnamic alcohol, or cinnamic acid. Only cinnamaldehyde (1.0% of the initial dose) was seen to evaporate onto the occlusion cell cap after 24 h. The majority of parent cinnamaldehyde (~55%) had remained on the skin surface at the end of the experiment; ~10.6% of the initial dose had been converted to cinnamic acid and had remained on the skin surface; no cinnamic alcohol was found to be unabsorbed. Within the skin, a total of 6.6% of the initial cinnamaldehyde dose was found as either cinnamaldehyde (2.9%), cinnamic alcohol (0.4%), or cinnamic acid (3.3%). Therefore, the skin penetration of cinnamaldehyde in this study was 16% (9.4% + 6.6%).