Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No GLP study but equivalent to guideline study with acceptable restrictions. The highest concentration at which 1,1-dichloroethene was tested was 50% due to solubility issues. Despite the fact that the substance was not tested at the 100% concentration, the results of the study are considered to be acceptable because the stimulation index was < 1 for all tested concentrations i.e. 10%, 25% and 50%. Therefore there is no indication that a stimulation index higher than 3 could be expected by doubling the dose (100%).
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Preliminary assessment of the skin sensitizing activity of selected rodent carcinogens using the local lymph node assay
Author:
Warbrick E.V., Dearman R.J., Ashby J., Schmezer P. and Kimber I.
Year:
2001
Bibliographic source:
Toxicology 163(63):69

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
no Body Weights, substance not tested at 100% conc.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): vinylidene dichloride
- Purity cited in the report: 100 % pure
- Vehicle: Acetone: olive oil (AOO v/v 4:1)

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Seralab, Oxon, UK
- Age at study initiation: 8–12 weeks old
- Housing: 4/cage on flushing metal racks
- Diet ad libitum: SDS PCD pelleted diet; Special Diets Services, Witham, Essex, UK
- Water : ad libitum





Study design: in vivo (non-LLNA)

Induction
Concentration / amount:
no data
Challenge
Concentration / amount:
no data
No. of animals per dose:
no data
Details on study design:
no data
Challenge controls:
no data
Positive control substance(s):
not required

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
Exposure concentration (%):
0, 10, 25, 50
(dose = 25 µL)
No. of animals per dose:
4 mice per dose
Details on study design:
INITIATION OF EXPOSURE
- No. of exposures: 3 (daily)
- Day(s) of challenge: 3 consecutive days
- Exposure period: 3 days
- Site: the dorsum of both ears
- Concentrations: various concentrations see table 1
- Dose: 25 µl

- Five days following initiation of exposure all mice were injected via the tail vein with 250 µl of phosphate buffered saline (PBS) containing 20 µCi of [3H] methyl thymidine.

- Five hours later the mice were sacrificed and the draining auricular lymph nodes excised and pooled.
Single cell suspensions of LNC were prepared by mechanical disaggregation through 200-mesh stainless steel gauze.
Pooled LNC were washed twice with PBS and precipitated in 5% trichloroacetic acid (TCA) at 4°C overnight.
Pellets were then resuspended in 1 ml of TCA and transferred to 10 ml of scintillation fluid (Optiphase ‘Hisafe 3’, Wallac, Turku, Finland).
The incorporation of 3H-TdR was measuredby B-scintillation counting as disintegrations per minute (dpm) per node for each experimental
group.
- A stimulation index (SI) relative to the concurrent vehicle-treated control was derived; an SI of 3 or greater being indicative of a
chemical possessing the potential to cause contact sensitization.


Statistics:
EC3 is the estimated concentration required to induce an SI of 3 in the LLNA. The EC3 value was calculated by interpolating between two points on the SI axis, one immediately above, and the other immediately below, the SI value of three. Where the data points falling immediately above and below the SI value of three have the coordinates (a,b) and (c,d), respectively, then the EC3 value may be calculated using the following equation : EC3=c+[ (3−d)/(b−d)]×(a−c)

Results and discussion

Positive control results:
no data

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: see table 1
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see table 1

Any other information on results incl. tables

Table 1 : Local lymph node assay responses to test chemicals

Chemical  Chemical Vehicle  Exposure concentration (%)  dpm/node  SI  EC3 (%)
1,1 -dichloroethene  acetone:olive oil 0 631 1 >50
10 530 0.84 >50
25 476 0.75 >50
50 575 0.91 >50

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to this study, 1,1-dichloroethene is not a dermal sensitizer.
Executive summary:

The dermal sensitising potential of 1,1 -dichloroethene was tested using the Local Lymph Node Assay (Kimber and Basketter, 1992)

1,1 -dichloroethene failed to induce an increase of the stimulation index above 3 at all tested concentrations . A stimulation index for 1,1 -dichloroethene of 0.91 was observed at the highest tested concentration of 50 %.

Therefore, according to this study, 1,1-dichloroethene is not a dermal sensitizer.