Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 5 February 1998 to 27 May 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Study was completed in 1998 prior to widespread regulatory acceptance of LLNA

Test material

Reference
Name:
Unnamed
Type:
Constituent

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: breeder Charles River (France)
- Age at study initiation: approximately 3 months old
- Weight at study initiation: mean body weight +/- standard deviation of 329 g +/- 17 g for males and 342 g +/- 11 g for females
- Housing: polycarbonate cages
- Diet (e.g. ad libitum): 106 pelleted diet
- Water (e.g. ad libitum): drinking water filtered by a F.G Muillipore membrane (0.22 microns)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C +/- 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles per hour
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From 10 February 1998 to 13 March 1998

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test item administered undiluted.
Challengeopen allclose all
Route:
other: epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test item administered undiluted.
No. of animals per dose:
10 males and 10 females for treated group, 5 males and 5 females for control group
Details on study design:
RANGE FINDING TESTS:
Yes, to determine the concentrations to be used:
- the maximal practicable concentration or concentration causing weak to moderate skin reactions for induction
- the highest concentration which does not cause irritant effect.
The test item was used undiluted during the inductions and challenge phases.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours for each application
- Test groups: treated with the test substance (0.5 mL)
- Control group: treated with purified water (0.5 mL)
- Site: anterior flank
- Frequency of applications: days 1, 8 and 15
- Concentrations: substance used undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 29
- Exposure period: 6 hours
- Test groups: treated with the test substance (0.5 mL) on the right flank and with purified water (0.5 mL) on the left flank
- Control group: treated with the test substance (0.5 mL) on the right flank and with purified water (0.5 mL) on the left flank
- Site: posterior right and left flank
- Concentrations: substance used undiluted
- Evaluation (hr after challenge):

OTHER:
Positive control substance(s):
yes
Remarks:
2,4-dinitro chlorobenzene (DNCB)

Results and discussion

Positive control results:
33% of the animals (3/10) showed a positive reaction with the DNCB.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs and no death were noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No clinical signs and no death were noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No clinical signs and no death were noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No clinical signs and no death were noted.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5% w/w
No. with + reactions:
6
Total no. in group:
9
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5% w/w
No. with + reactions:
3
Total no. in group:
9
Clinical observations:
Dryness of skin in 3 animals

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the experimental conditions of the study and according to the Buehler method, the test substance 2-ETHYLHEXYLE NITRATE does not induce delayed contact hypersensitivity in guinea-pigs.