Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Triethylene glycol divinyl ether
- Physical state:light yellow liquid
- Analytical purity: ABOUT 98.8 %
- Lot/batch No.: 87/1 - 87/2 - 87/3
- Stability under test conditions: not determined
- Storage condition of test material: ambient temperature.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England.
- Age at study initiation: No data
- Mean weight at study initiation: 434 g (range: 371 - 468 g)
- Housing: not given
- Diet (e.g. ad libitum): Vitamin C-enriched Guinea-Pig Diet F.D.1 (Special Diets Services Limited).
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: animals were acclimated to the laboratory environment, duration was not given.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intradermal injection
Vehicle:
water
Concentration / amount:
Concentration of test material and vehicle used at induction:
A) intradermal injection:
1) Freund's adjuvant / water (1:1)
2) Substance 30 % (v/v) in Alembicol D.
3) Substance 30 % (v/v) in Freund's adjuvant / Alembicol D. (1:1)
B) per cutan
Undiluted test substance

Concentration of test material and vehicle used for each challenge:
anterior: undiluted test substance
posterior: test substance 50% (v/v) in Alembicol D
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Concentration of test material and vehicle used at induction:
A) intradermal injection:
1) Freund's adjuvant / water (1:1)
2) Substance 30 % (v/v) in Alembicol D.
3) Substance 30 % (v/v) in Freund's adjuvant / Alembicol D. (1:1)
B) per cutan
Undiluted test substance

Concentration of test material and vehicle used for each challenge:
anterior: undiluted test substance
posterior: test substance 50% (v/v) in Alembicol D
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 10
Details on study design:
RANGE FINDING TESTS:
The intradermal and topical irritancy of a range of dilutions of triethylene glycol divinyl ether was investigated to identify (a) irritant test substance concentrations suitable for the induction phase of the main study and (b) non-irritant concentrations by the topical route of administration for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: intradermal injection and 48 hours topical application
- Test groups:
A) Injectables were prepared as follows:
1. Freund's complete adjuvant was diluted with an equal volume of water for irrigation.
2. Triethylene qlycol divinyl ether, 30% v/v in Alembicol D.
3. Triethylene glycol divinyl ether, 30% v/v in a 50 : 50 mixture of Freund's complete adjuvant and Alembicol D.
B) One week after the injections, the same 4 x 6 cm interscapular area was clipped and shaved free of hair.
A 2 x 4 cm patch of Whatman No 3 paper was saturated with triethylene glycol divinyl ether. The patch was placed on the skin and covered by a length of impermeable plastic adhesive tape (5 cm width "Blenderm") and firmly secured by elastic adhesive bandage ("Elastoplast" 5 cm width) wound round the torso af the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 hours.
- Control group:
During the induction period the control animals were treated similarly to the test animals with the exception that the test compound was omitted from the intradermal injections and topical application.
- Site: A 4 x 6 cm area of dorsal skin on the scapular region of the guinea-pig was clipped free of hair with electric clippers. Three pairs of intradermal injections were made simultaneously into this area.
- Frequency of applications: 2
- Duration:
- Concentrations: Triethylene qlycol divinyl ether, 30% v/v in Alembicol D

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: two weeks after the induction period using triethylene glycol divinyl ether, as supplied and as 50% v/v in Alembical D.
- Exposure period:
- Test groups:
- Control group:
- Site: topically, a 2 x 2 cm patch of Whatman No. 3 paper was saturated with approximately 0.2 ml of triethylene glycol divinyl ether, as supplied and applied to an anterior site an the flank. Triethylene glycol divinyl ether, 50% v/v in Alembicol D was applied in a similar manner to a posterior site. The
patches were sealed to the flank for 24 hours under strips af "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".
- Concentrations: as supplied and 50% v/v in Alembicol D
- Evaluation (hr after challenge): 24, 48 and 72 hours after removal af the patches.


SCORING
Reactions were scored according to the following arbitrary scale:
Erythema and eschar formation:
No erythema: 0
Slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation:
No oedema: 0
Slight oedema (barely perceptible): 1
Well-defined oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

INTERPRETATION OF RESULTS
Dermal reactions in the test animals elicited by the challenge applicatian were compared with the findings simultaneously obtained in the control animals.
A test animal was considered to show positive evidence of delayed contact hypersensitivity if the observed dermal reaction at challenge was definitely more marked and/or persistent than the maximum reaction seen in animals of the control group.

If the dermal reaction seen in a test animal at challenge was slightly more marked and/or persistent than (but not clearly distinguishable from) the maximum reaction seen in control animals, the result for that test animal was classified as inconclusive.

A test animal was considered to show no evidence of delayed contact hypersensitivity if the dermal reaction resulting from the challenge application was the same as, or less marked and/or persistent than the maximum reaction seen in animals of the control group.



Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 %
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
slight to well-defined erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: slight to well-defined erythema.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
50 %
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
slight to well-defined erythema, dryness and sloughing of the epidermis.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: slight to well-defined erythema, dryness and sloughing of the epidermis..
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
50 %
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
slight to well-defined erythema, dryness and sloughing of the epidermis.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 50 %. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: slight to well-defined erythema, dryness and sloughing of the epidermis..

Any other information on results incl. tables

In this screening test, performed in 20 albino guinea pigs, the substance produced evidence of delayed contact hypersensitivity in 4 animals. 
There was no evidence of delayed contact hypersensitivity seen in 16 animals. No rechallenge was performed.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

For the assessment of the skin sensitising potential of Triethylenglycoldivinylether a Guinea Pig Maximization test was performed. The test substance produced evidence of delayed contact hypersensitivity in four animals. There was no evidence of delayed contact hypersensitivity in sixteen animals. A positive skin response in at least 30% of the animals in an adjuvant test should be expected for mild/moderate sensitisers. In this study a positive result was only observed in 20 % of the animals, therefore the test substance was considered not to be sensitising.