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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: OECD guideline study + GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(3-hydroxypropyl)oxazolidin-2-one
EC Number:
431-840-1
EC Name:
3-(3-hydroxypropyl)oxazolidin-2-one
Cas Number:
87010-29-5
Molecular formula:
C6 H11 N O3
IUPAC Name:
3-(3-hydroxypropyl)oxazolidin-2-one
Details on test material:
- Name of test material (as cited in study report): Oxypropazone
- Physical state: Clear, colorless to slightly yellowish and viscous liquid
- Analytical purity: 97.2%
- Lot/batch No.: 108598
- Stability under test conditions: According to information from the sponsor, the test substance was stable throughout the experimental period of the study
- Storage condition of test material: The test substance was kept in a closed container at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan.Winkelmann GmbH, Borchen
- Age at study initiation: 8 weeks
- Weight at study initiation: Males 405.6-467.1 g, females 388.7-447.2 g
- Housing: Macrolon cages type IV, individual housing
- Diet: Standard diet ad libitum
- Water: ad libitum
- Acclimation period: Animals were kept at least five days under test conditions before test substance application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-22.5
- Humidity (%): 46-65%
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intracutaneous
Vehicle:
other: Physiological saline solution
Concentration / amount:
Concentration of test material and vehicle used at induction:
5 % in physiological saline solution (0,9 %); application volume 0.01 ml


Concentration of test material and vehicle used for each challenge:
30 % in deionized water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Physiological saline solution
Concentration / amount:
Concentration of test material and vehicle used at induction:
5 % in physiological saline solution (0,9 %); application volume 0.01 ml


Concentration of test material and vehicle used for each challenge:
30 % in deionized water
No. of animals per dose:
Tretament group: 10
Control group 1: 6
Control group 2: 6
Details on study design:
PRE-LIMINARY TESTS:
The folowing concentrations were identified in the preliminary test to be non-irritating and slightly irritating following intracutaneous or epidermal application:
intracutaneous, non-irritatin (induction)g: 5%
epidermal, slightly irritating (induction): 100%
epidermal, non-irritatlng (challenge): 50%

MAIN STUDY
A. INDUCTION EXPOSURE
- Day of application: 1
- Route of application: Intracutaneous injection
- No. of applications: 6 in total (2 x FCA/physiological saline solution (1:1), 2 x test substance, 2 x test substance/FCA (1:1); i.c. injections were made in two parallel lines in an area of 4x6 cm on day 1)
- Site: Scapular area
- Concentration: 5%
- Controls: treated accordingly, only vehicle was applied instead of test substance


Epidermal application:
- Day of Application: 8
- Route of application: occlusive patch
- Concentration of test substance: 100%
- Application site: Scapular area
- Number of applications: 1
- Duration of application: 48 h
- Control animals: Identical treatment with water instead of test substance

B. CHALLENGE EXPOSURE
- Day(s) of challenge: 22
- No. of applications: 2
- Duration of application: 24 h
- Route of administration: Epidermal (occusive patch)
- Concentration: 30%
- Application site: right flank (vehicle), left flank (test substance)

- Evaluation (hr after challenge): on day 24 and 25 (24 and 48h after last challenge)

A substance is classified as skin-sensitizing if at least 30% of the treated animals show a skin reaction

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:
30 %
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: 30 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30 %
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: 30 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
vehicle
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: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: vehicle. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30 %
No. with + reactions:
1
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 30 %. No with. + reactions: 1.0. Total no. in groups: 6.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30 %
No. with + reactions:
1
Total no. in group:
6
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30 %. No with. + reactions: 1.0. Total no. in groups: 6.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 6.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 6.0.

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 50 %

Signs of irritation during induction:
without findings

Evidence of sensitisation of each challenge concentration:
without findings

Other observations:
Forty-eight hours after the end of exposure of epidermal challenge one animal of the test substance group showed a discrete or patchy erythema at the vehicle treated site (right flank).

Twenty-four and 48 hours after the end of exposure of epidermal challenge one male animal of the control group exhibited a discrete or patchy erythema at the test substance treated site (left flank).

Applicant's summary and conclusion