Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Recent study conducted according to OECD/US EPA guidelines but the test substance evaporated in the experimental conditions (although occluded conditions were used) and skin integrity was deteriorated by the test substance in Kp determination experiment. Incomplete access to the data.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): vinylidene chloride
- Physical state: liquid
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Epidermal membranes from the abdominal skin of human cadavers
Static diffusion cell maintained at 32 °C using 0.9 % saline as receptor fluid

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
Permeability coefficient (Kp) determination: 2 h
Short term dermal absorption rates: 10 and 60 min
Doses:
Kp determination (infinite dose): 1200 µL/cm²
Short term dermal absorption rates: 30 µL/cm²
No. of animals per group:
For each experiment, six skin experiments representing three human subjects
Control animals:
no
Details on study design:
Due to the low boiling point of vinylidene chloride, the experiments were conducted in occluded conditions
Washing procedures and type of cleaning agent: mild soap solution

Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human cadavers
- Type of skin: abdominal
- Thickness of skin (in mm): 0.2 - 0.5
- Membrane integrity check: electrical impedance

PRINCIPLES OF ASSAY
- Diffusion cell system
- Receptor fluid: 0.9 % saline
- Test temperature: 32 °C
- Occlusion: yes

Results and discussion

Signs and symptoms of toxicity:
yes
Remarks:
For the Kp determination, there was a loss in skin integrity over the course of the testing. The ratio of post-electrical impedance values to pre-electrical impedance values was 0.39.
Dermal irritation:
not specified
Absorption in different matrices:
No data
Total recovery:
Percent recovery of applied doses:
73.2 % for the Kp determination
80.2 % for the 10 min absorption rate
78.2 % for the 60 min absorption rate
Conversion factor human vs. animal skin:
No

Any other information on results incl. tables

The penetration rates were calculated to be 2173, 800.7 and 144.7 µg equiv/cm²/h for the Kp determination, 10- and 60- minute time periods, respectively.

The mean permeability coefficient (Kp) was 0.00178 ± 0.000796 cm/h and the measured absorption values (skin plus receptor fluid) at 10 and 60 min were 89.9 and 92.2 µg, respectively.

Table 1: Pre and post-dose electrical impedance (EI) values

 Pre EI (k-ohms) Post  EI (k-ohms) Post/Pre
Kp determination  41.5  16.1  0.39
10 min absorption rate  44.8  45.1  1.01
60 min absorption rate   37.3  36.1  0.97

Table 2: Percentage of chemical in donor solution (wash), skin and receptor solution (RF)

Wash (%)  Skin (%)  RF (%) 
Kp determination  66.5  0.35  0.33 
10 min absorption rate  0.65  0.25  0.14 
60 min absorption rate  0.55  0.27  0.13 

The sum of wash, skin and receptor fluid suggests a low recovery of the applied chemical, primarily for the 10 and 60 min experiments: a significant portion of the applied chemical evaporated from the skin surface and was retained in a solid matrix synthetic sorbent trap (Anasorb 747, SKC Inc., USA)

Applicant's summary and conclusion

Conclusions:
Vinylidene chloride could potentially be well absorbed by dermal route.
Executive summary:

In vitro dermal absorption testing of vinylidene chloride was undertaken using epidermal membranes from the abdominal skin of human cadavers mounted in a static diffusion cell maintained at 32 °C with 0.9 % saline as receptor fluid. Radiolabeled [14C] vinylidene chloride was applied under infinite dose (1200 µL/cm²) and occluded conditions. The mean Kp was evaluated at 1.78 x 10-3 ± 7.96 x 10-4 cm/h. There was a moderate loss in skin integrity over the course of the testing: the ratio of post-EI values to pre-EI values was 0.39.

Short-term dermal penetration experiments with [14C] vinylidene chloride using the in vitro diffusion cell method were also conducted under finite dosing (i.e.30 gL/cm²) and occluded conditions. The short-term penetration rates were calculated to be 800.7 and 144.7 pg equiv/cm²/h for the 10- and 60- minute time periods, respectively. There was no loss in skin barrier function in these experimental conditions (ratio of post-El to pre-El values: 0.97 and 1 .01 for 10 and 60 minutes, respectively).

These results suggest that vinylidene chloride could potentially be well absorbed by dermal route but these results must be carefully considered as skin integrity was deteriorated during the evaluation of permeability coefficient.