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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
Study period:
1987-06-09 to 1987-07-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, but with restrictions (no details on test substance purity, no GLP)

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)
Version / remarks:
adopted May 12, 1981
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
(no data on test substance purity, more animals tested than necessary)
Qualifier:
according to
Guideline:
other: EEC directive 79/831
GLP compliance:
no
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-Geigy LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: 299-417 g
- Housing: individually in Macrolon cages (Type 3)
- Diet (ad libitum): guinea pig pellets - NAFAG No. 846, Gossau SG
- Water (ad libitum)
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline / sesame oil
Concentration / amount:
- Intradermal induction: Substance in sesame oil (1%)
- Epidermal induction: Approximately 0.4 g Paste of 30% substance in vaseline
- Challenge: 0.2 g Paste of 10% substance in vaseline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline / sesame oil
Concentration / amount:
- Intradermal induction: Substance in sesame oil (1%)
- Epidermal induction: Approximately 0.4 g Paste of 30% substance in vaseline
- Challenge: 0.2 g Paste of 10% substance in vaseline
No. of animals per dose:
10 males and 10 females
Details on study design:
RANGE FINDING TESTS: Animals were treated with test substance for the evaluation of the primary irritation treshold concentration. The tested concentrations of 10 and 30 % of the test substance in vaseline did not induce erythema reactions. 10 % was used as a subirritant concentration for the challenge application, to exclude nonspecific reactions in the adjuvant treated animals (s. Magnussen, 1980).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
- Exposure period: Day 1: 2 intradermal injections, one week later epidermal induction application for 48 h
- Test groups: Intradermal: Three pairs of injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
1) adjuvant and saline (1:1)
2) test compound in sesame oil
3) test compound in the adjuvant saline mixture
Epicutaneous: 0.4 g paste of 30 % substance in vaseline for 48 h (application sites were pretreated the day before with 10 % sodium lauryl sulfate - open application)
- Control group: Intradermal: Same injections as test group, but without test substance;
Epicutaneous: Animals treated analogously to the test group, but without test substance
- Site: neck region
- Frequency of applications: single intradermal injections, one week later single epidermal induction application (see above)
- Duration: Day 1: intradermal injections, one week later epidermal induction
- Concentrations: Intradermal injection: 1 % of the test substance; epidermal application: 30 % test substance in vaseline

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Two weeks after the epidermal induction
- Exposure period: 24 h
- Test groups: on one flank with test substance in vaseline and on the other flank the vehicle alone (patch 2 x 2 cm; occluded administration for 24 hours)
- Control group: Vehicle and test substance on seperate flanks
- Site: flank
- Concentrations: 10 % test substance in vaseline
- Evaluation (hr after challenge): 24 and 48 h after removing the dressings

OTHER:
Skin findings were assessed according to Draize.
Challenge controls:
- Vehicle group: 20 animals
- Test substance group: 10 animals
Positive control substance(s):
yes
Remarks:
Paraphenylene-diamine or Potassium-dichromate

Results and discussion

Positive control results:
The sensitivity of the strain is checked every six months with Paraphenylene-diamine or Potassium-dichromate. (s. Th. Maurer, R. Hess Toxicology 31, (1984) 217-222). The results were not given in the report.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: 1st negative control (vehicle)
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 1st negative control (vehicle)
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: 2nd negative control (test substance)
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:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 2nd negative control (test substance)
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:
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
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: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
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: 20.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information