1,1-dichloroethylene

Skin sensitisation

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

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

Test material information

Constituent 1

Reference substance name:

1,1-dichloroethylene

EC Number:

200-864-0

EC Name:

1,1-dichloroethylene

Cas Number:

75-35-4

Molecular formula:

C2H2Cl2

IUPAC Name:

1,1-dichloroethene

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 (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)

Results

Results 1

Parameter:

other: disintegrations per minute (DPM)

Value:

631

Test group / Remarks:

Negative control

Results 2

Parameter:

other: disintegrations per minute (DPM)

Value:

530

Test group / Remarks:

10 (w/v)%

Results 3

Parameter:

other: disintegrations per minute (DPM)

Value:

476

Test group / Remarks:

25 (w/v)%

Results 4

Parameter:

other: disintegrations per minute (DPM)

Value:

575

Test group / Remarks:

50 (w/v)%

Results 5

Parameter:

SI

Value:

1

Test group / Remarks:

Negative control

Results 6

Parameter:

SI

Value:

0.84

Test group / Remarks:

10 (w/v)%

Results 7

Parameter:

SI

Value:

0.75

Test group / Remarks:

25 (w/v)%

Results 8

Parameter:

SI

Value:

0.91

Test group / Remarks:

50 (w/v)%

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.