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Toxicological information

Skin sensitisation

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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: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Remarks:
Centre International de Toxicologie, France
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): 2,6 DCPTFMA
- Physical state: solid
- Storage condition of test material: 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: Lebeau breeding centre, 78950 Gambais, France
- Weight at study initiation: mean: 365 ± 20 g for the males and 357 ± 23 g for the females
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 10% test substance in corn oil
cuntaneous induction: 500mg test substance (unchanged)
cuntaneous challenge: 20% test substance in corn oil
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 10% test substance in corn oil
cuntaneous induction: 500mg test substance (unchanged)
cuntaneous challenge: 20% test substance in corn oil
No. of animals per dose:
5 male and 5 female in control group
10 male and 10 female in test group
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (first intradermal, second on day 8: cutaneous)
- Exposure period: cutaneous exposure: 48 hours
- Test groups: test substance
- Control group: vehicle
- Site: scapular
- Frequency of applications: d1: intradermal injection, d8 cutaneous application
- Duration: d1 - d10
- Concentrations: intradermal: 10% in corn oil


B. CHALLENGE EXPOSURE
- No. of exposures: 1 cutaneous
- Day(s) of challenge: day 22
- Exposure period: 24 hours
- Test groups: test substance
- Control group: vehicle
- Site: each flank
- Concentrations: 20% in corn oil
- Evaluation (hr after challenge): 24, 48 hours

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle only
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle only. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle only
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle only. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20%. No with. + reactions: 13.0. Total no. in groups: 20.0. Clinical observations: erythema.

Any other information on results incl. tables

After the challenge application of the test substance, a very slight erythema (score of 1) was observed after 24 and 48 hours in one animal of the control group. No cutaneous reactions were noted in 9/10 animals. In the treated group and on the right flank a very slight erythema (score of 1) was observed after 24 hours in 5/20 animals. This very slight erythema was reversible after 48 hours in 4 animals or remained very slight in 1 animal. This slight macroscopic reaction was considered to be due to a slightly irritant primary effect of the test substance. After the challenge application of the test substance in the treated group a positive response characterised by a well-defined, moderate and severe erythema (scores of 2 to 4) was observed on the right flank of 15/20 animals after 24 hours. No oedema was noted. After 48 hours well-defined and moderate to severe erythema (scores of 2 or 3) persisted in 8/20 animals.

The reactions noted in 15 animals were considered to be due to a sensitization effect of the test substance in 75% of the animals. In addition after 48 hours, a dryness of the skin was noted in 17/20 animals of the treated group.

Erythema:

Group Sex Erythema score Scoring of the cutaneous parameters
24 hours 48 hours
LF RF LF RF
control male 0 5/5 4/5 5/5 4/5
1 1/5 1/5
treated male 0 10/10 10/10 5/10
1 4/10 4/10
2 6/10 1/10
3
4
control female 0 5/5 5/5 5/5 5/5
treated female 0 10/10 10/10 2/10
1 1/10 1/10
2 5/10 3/10
3 3/10 4/10
4 1/10

LF: left flank; RF: right flank

0 = No erythema

1 = Very slight erythema (barely perceptible)

2 = Well-defined erythema

3 = Moderate to severe erythema

4 = Severe erythema (beet redness) to slight eschar formation (injuries in depth)

No clinical signs or mortality were observed throughout the study. Between days 8 and 15 a loss in body weight was noted in 3 females of the treated group without consequence thereafter. The body weight gain of the other animals of the treated group was normal when compared to that of the control group .

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information