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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:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
- Principle of test: study conducted according to Magnusson, B. and Kligman A.M.: The Identification of Contact Allergens by Animal Assay. The Guinea Pig Maximization Test. J. Invest. iDermatol. 52, 268 - 276 (1969)
- Short description of test conditions: intradermal and percutaneous (occlusive coverage; 1 week after intradermal induction) applikation of the test substance (induction); 3 percutaneous challenges (2, 3 and 4 weeks after the percutaneous induction);
- Parameters analysed / observed: body weight (recorded before each applikation and at the end of the observation period); clinical signs (assessed daily); sensitisation rate
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The LLNA method was not established yet by the time the study was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- No. of test material: 82/355-1
- Purity: ca. 99.5 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark
- Stability under test conditions: guaranteed for at least the study period
- Stability of the test substance in the solvent/vehicle: Since the test substance was prepared immediately before the application, stability was not tested.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: diluted in aqua dest.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, 4923 Extertal 1
- Microbiological status of animals, when known: SPF-LAC
- Age at study initiation: not specified
- Weight at study initiation: 250 - 309 g
- Housing: 5 animals per cage
- Diet: Saniff GK 4 mm, ad libitum
- Water: tap water ad libitum; twice a week tap water + ascorbic acid (0.2 g/L)
- Acclimation period: not specified
- Indication of any skin lesions: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 / 12
- IN-LIFE DATES: not specified

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
water
Concentration / amount:
1 % in aqua dest. or Freunds Adjuvant/Aqua dest. (1:1)
Day(s)/duration:
reading after 24 h
Adequacy of induction:
other: a higher concentration (5 %) caused mortality in a dose range finding study
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
approx. 0.3 g test substance (10 % in aqua dest.); sucked up by filter paper strips
Day(s)/duration:
48 h; reading ca. 48 h after application
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
approx. 0.15 g test substance (5 % in aqua dest.); sucked up by filter paper strips
Day(s)/duration:
approx. 2 weeks after last induction; 24 h; readings ca. 24 after patch removal as well as 48 and 72 h after application
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
approx. 0.15 g test substance (5 % in aqua dest.); sucked up by filter paper strips
Day(s)/duration:
24 h; readings ca. 24 after patch removal as well as 48 and 72 h after application
Adequacy of challenge:
highest non-irritant concentration
No.:
#3
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
approx. 0.15 g test substance (5 % in aqua dest.); sucked up by filter paper strips
Day(s)/duration:
24 h; readings ca. 24 after patch removal as well as 48 and 72 h after application
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (10 in control group)
Details on study design:
RANGE FINDING TESTS: In a preliminary experiment with percutaneous occlusive application of the test substance, a concentration of 10 % aqueous test substance caused minimal skin irritation, whereas a concentration of 5 % aqueous test substance was determined as the highest non-irritant concentration. The intradermal application of a 5 % aqueous test substance preparation resulted in mortality of 18/20 animals. The 2 survivors showed bad general conditions.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and percutaneous)
- Exposure period: 48 h (percutaneous induction)
- Control group: only for the intradermal injection; without test substance
- Site: shoulders (intradermal induction); flanks (percutaneous induction)
- Frequency of applications: 2 injections
- Duration: percutaneous induction was performed 1 week after the intradermal induction
- Concentrations: 1 % test substance in aqua dest. or Freunds Adjuvant/Aqua dest. (1:1) for the intradermal induction; approx. 0.3 g test substance (10 % in aqua dest.), sucked up by filter paper strips for the percutaneous induction

B. CHALLENGE EXPOSURE
- No. of exposures: 3
- Day(s) of challenge: 1st challenge approx. 2 weeks after the last induction; 2nd challenge 1 week later; 3rd challenge 2 weeks after the 1st challenge
- Exposure period: 48 h each
- Control group: same procedure as for the experimental groups
- Site: flanks
- Concentrations: approx. 0.15 g test substance (5 % in aqua dest.), sucked up by filter paper strips
- Evaluation (hr after challenge): ca. 24, 48 and 72 h after application
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: 1st challenge
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: 2nd challenge
Hours after challenge:
24
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: 2nd challenge
Hours after challenge:
48
Group:
test group
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 2nd challenge
Hours after challenge:
72
Group:
test group
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 3rd challenge
Hours after challenge:
24
Group:
test group
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 3rd challenge
Hours after challenge:
48
Group:
test group
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 3rd challenge
Hours after challenge:
72
Group:
test group
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria