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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other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2-hydroxyethyl)imidazolidin-2-one
EC Number:
223-032-9
EC Name:
1-(2-hydroxyethyl)imidazolidin-2-one
Cas Number:
3699-54-5
Molecular formula:
C5H10N2O2
IUPAC Name:
1-(2-hydroxyethyl)imidazolidin-2-one
Details on test material:
- Name of test material: N-(2-hydroxyethyl)imidazolidin-2-one, HOXI
- Lot/batch No.: 0029411150002
- Physical state: white crystalline solid
- Analytical purity: 98.6 ± 0.4% m/m. approx 15 organic byproducts, each ≤ 0.3% m/m

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: Approx. 6 weeks
- Weight at study initiation: 354 - 479 grams
- Housing: Group housing af 2 animals, except for 1 control animal, per labelled metal cage with wire-mesh flaors and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet (e.g. ad libitum): Free access to standard guinea pig diet, including ascorbic acid (1600 mg/kg); LC 23-8, pellet diameter 4 mm (Hope farms, Woerden, The Netherlands).
- Water (e.g. ad libitum): Free access to tap water, diluted with decalcified water.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
induction:
intradermal injection: 25%
epidermal application: 50%

challenge:
epidermal application: 50%, 25% and 10%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
induction:
intradermal injection: 25%
epidermal application: 50%

challenge:
epidermal application: 50%, 25% and 10%
No. of animals per dose:
10 (treatment group), 5 (control group)
Details on study design:
INDUCTION - EXPERIMENTAL ANIMALS
Day 1: Three pairs of intradermal injections (0.1 ml/site) were made in the clipped scapular region as follows:
A) Freunds' Complete Adjuvant (Difco, Detroit, U.S.A.), 50:50 with water for injection (Ferensius AG, Bad Homburg, Germany).
B) The test substance at a 25% concentration.
C) The test substance, at twice the concentration used in (B), emulsified in a 50:50 mixture of Freunds' Complete Adjuvant.
Note: One of each pair was on each side of the midline and from cranial A) to caudal C).

Day 3: The dermal reactions caused by the intradermal injections were recorded.
Day 7: The clipped scapular area was rubbed with 10% sodium-dodecyl-sulfate (SOS, Boom, Meppel, The Netherlands) in vaseline using a spatula. This concentration of SOS provokes a mild inflammatory reaction.
Day 8: The c1ipped area between the injection sites was treated with 0.5 ml of a 50% test substance concentration using a Scotchpak-non-woven patch (2 x 4 cm) mounted on Micropore tape and secured with Coban elastic bandage.
Day 10: After 48 hours, the dressings were removed and the skin cleaned of residual test substance. Subsequently, all dermal reactions caused by the epidermal exposure were recorded, according the scale presented before.

INDUCTION - CONTROL ANIMALS
Day 1: Intradermal injections were made similar to the method described above with the omission of the test substance.
Day 3: The dermal reactions caused by the intradermal injections were recorded.
Day 7: SOS 10% treatment, as described above.
Day 8: Epidermal treatment as described far the experimental animals, but with the vehicle only.
Day 10: After 48 hours, the dressings were removed and the skin cleaned. Subsequently, all dermal reactions caused by the epidermal exposure were recorded.

CHALLENGE
Day 22: All animals were treated epidermally with 0.05 ml of each of a the following test substance concentrations, 50%, 25% and 10% and the vehicle on a clipped flank, using Square chambers, attached to Micropore tape and secured with Coban elastic bandage.
Day 23: After approximate1y 24 hours, the dressings were removed and the skin cleaned of residual test substance and vehicle. The treated sites were assessed for erythema and swelling 24 and 48 hours after removal of the dressings, using the numerical grading system be1ow. After the first reading, the test sites were clipped with an electric clipper.
Challenge controls:
No
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

Induction phase

Since comparable reactians were noted in the experimental and contral animals after the epidermal induction exposure, the reactions were considered to be enhanced by the SOS treatment.

 

Challenge phase

No skin reactions were evident after the challenge exposure in the experimental and control animals.

No evidence was obtained that the substance had caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in the challenge phase. This result leads to a sensitisation rate of 0 per cent.

 

Toxicity Symptoms / Mortality

One experimental animal showed hyperpnoea and dark red coloured eyes on day 19. This animal was removed from the study and killed in extremis later that day. An enlarged spleen and dark red lungs were found at necropsy. These findings indicate acute pneumonia. Since no further mortality occurred and no symptoms of systemic toxicity were observed during the study period, it was considered that the study outcome, based on the surviving animals, was not adversely affected.

 

Body Weights

Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Applicant's summary and conclusion

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