3-icosyl-4-henicosylidene-2-oxetanone

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 april 2004 - 8 may 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recent study performed according to OECD 428 and GLP principals.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

PMC D-532

IUPAC Name:

PMC D-532

Test material form:

other: waxy solid

Details on test material:

- Name of test material (as cited in study report): PMC D-532
- Physical state: waxy solid
- Analytical purity: 86.9% w/w
- Lot/batch No.: 30GT0982
- Expiration date of the lot/batch: 4.8.08
- Stability under test conditions: Stable
- Storage condition of test material: Ambient temperature in the dark

Radiolabelling:

yes

Test animals

Species:

human

Administration / exposure

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin:
human: Extraneous tissue was removed from human whole skin samples obtained from surgery or post mortem. The skin samples were immersed in water at 60°C for 40-45 seconds and the epidermis teased away from the dermis. Each epidermal membrane was given an identifying number and stored frozen on aluminium foil until required for use.
rat: Skin was used from male rats of the Wistar Crl:(WI) BR strain (supplied by Charles River UK Ltd, Margate, Kent, UK.) aged 28 days ± 2 days. Fur from the dorsal and flank region was carefully shaved using animal clippers, ensuring that the skin was not damaged. The clipped area was excised and any subcutaneous fat removed. The skins were soaked for approximately 20 hours in 1.5M sodium bromide then rinsed in distilled water. The epidermis was carefully peeled from the dermis. Each epidermal membrane was given an identifying number and stored frozen on aluminium foil until required for use.

- Membrane integrity check: yes


PRINCIPLES OF ASSAY
- Diffusion cell: exposed membrane area of 2.54cm2. Discs of approximately 3.3cm diameter of prepared skin membrane from at least three subjects/animals were mounted, dermal side down, in diffusion cells held together with individually numbered clamps and placed in a water bath maintained at 32 ± 1°C.
- Receptor fluid: physiological saline
- Solubility od test substance in receptor fluid: insoluble
- Static system: The receptor chambers were stirred continuously throughout the exposure period.

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

no effects

Absorption in different matrices:

Receptor fluid:
For the active ingredient, PMC D-532 absorption through human and rat epidermis into the receptor fluid was below the limit of quantitation (<0.175μg/cm2/h and <0.138μg/cm2/h respectively) for the entire 24 hour exposure period. For the 20% dispersion, PMC D-532 absorption through human and rat epidermis was also below the limit of quantitation (<0.033μg/cm2/h for both human and rat epidermis) for the entire 24 hour exposure period.

Epidermis:
The amount of PMC D-532 found in the tape strips was <0.037%, representing the stratum corneum, for human skin, from the active ingredient, with <0.125% being found in the strips from the 20% dispersion dose. For the active ingredient, the total PMC D-532 absorption into the remaining human and whole rat epidermis was 4.82μg/cm2 and 47.3μg/cm2 respectively, for the entire 24 hour exposure period. These respective amounts, expressed as percentages of the applied dose, were 0.048%, and 0.474%.

Applicant's summary and conclusion

Conclusions:

1. The majority of the applied dose (between 86.4 - 95.1%) could be removed from the surface of the skin by mild skin washing at 24 hours.
2. If the amount of PMC D-532 retained in the epidermis is considered to be potentially absorbed, then these data predict that the absorption through human skin of PMC D-532 from the active ingredient or its 20% dispersion would be extremely slow when compared with the absorption rates of other penetrants measured using this in vitro technique (Dugard et al, 1984; Dugard and Scott, 1984). These data would also predict that the human dermal absorption of PMC D-532 from potential exposure to the active ingredient or the 20% dispersion would be almost negligible.