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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
March/April 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was conducted by means of Read Across approach. Further information was attached at section 13

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A LLNA study has not been conducted because adequate data from guinea pig Maximisation test study are already available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
albino Dunkin-Hartley guinea pigs
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, U.K.
- Weight at study initiation: 330 - 411g
- Age: six to ten weeks
- Housing: groups of up to 4
- Diet: Guinea Pig FD1 Diet, Special Diet Services Limited, Witham, Essex, U.K. ad libitum
- Water: tap water ad libitum
- Acclimatisation period: at least five days,

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25°C
- Humidity (%): 45 to 60%
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 17. March To: 1 May 1987

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
5% / 2 x 0.1 mL
5% / 2 x 0.1 mL in arachis oild : Freund's Complete Adjuvant (FCA) 1:1
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
50% (w/w) in petroleum jelly B.P. / 0.1 to 0.2 mL


Day(s)/duration:
on Day 8 for 48 hours
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:
petrolatum
Concentration / amount:
50% (w/w) in petroleum jelly B.P. / 0.1 to 0.2 mL
Day(s)/duration:
on Day 22 for 24 hours
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
25% (w/w) in petroleum jelly B.P.
10% (w/w) in petroleum jelly B.P.
Day(s)/duration:
Day 29 for 24 hours
No. of animals per dose:
Determination of primary not irritating concentration: 4
Determination of intradermal tolerability: 2
Control group: 10
Re-challenge control group; 10
Treatment group: 20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal + 1 epicutaneous
- Exposure period: intradermal: 24 hours; epicutaneous: 48 hours
- Test groups: 1
- Control group: 2
- Site: shoulder
- Frequency of applications: Day 1; Day 8
- Duration: 24 and 48 hours
- Concentrations: 5 and 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: Day 22 and Day 29
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1 + 1
- Site: flank
- Concentrations: 50%, 25%, 10%
- Evaluation (hr after challenge): Challenge 1: 24, 48, 72 hours Challenge 2: 24 and 48 hours after removal of patches
Positive control substance(s):
yes

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
yellow/green coloured staining of skin
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
yellow/green coloured staining of skin; one animal not evaluable due to skin alterations was counted as positive
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
25%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
yellow/green coloured staining of skin; one animal not evaluable due to skin alterations was counted as positive
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow/green coloured staining of skin
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow/green coloured staining of skin
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow/green coloured staining of skin

Any other information on results incl. tables

Yellow/green coloured staining of the skin was noted at all test sample sites but did not prevent assessment of the skin responses.

Initial Challenge - 50% (w/w)

Positive results were also observed in the negative control group. The sensitisation potential of the test sample could not be evaluated at this concentration. A re-challenge was performed at two lower concentrations.

Re-challenge - 25% and 10% (w/w)

Moderate and diffuse redness (score 2) and scattered mild redness (score 1) were noted at the 25% and 10% test sample re-challenge sites of test animalsat the 24-hour observation and at the 25% test sample re-challenge sites of test animals at the 48-hour observation. Scattered mild redness (score 1) continued to be noted at the 10% test sample re-challenge sites of the test animals at the 48-hour observation. Severe desquamation was noted at a number of 25% test sample re-challenge sites and at one 10% test sample re-challenge site at the 48-hour observation. The 25% and 10% test sample sites of control animals showed no erythema at the 24 or 48-hour observations.

The test sample, therefore, at re-challenge concentrations of 25% and 10%, produced a skin reaction in 85% (17/20) and 80% (16/20) animals, respectively after 24 hours. After 48 hours, a skin reaction was observed in 45% (9/20) and 15% (3/20) at concentrations of 25% and 10%, respectively.

Bodyweight gains of surviving guinea pigs in the test group, between day 0 and day 24, were comparable to those observed in the control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:
other: Category 1B (skin sensitising) based on CLP criteria
Conclusions:
Skin sensitizer
Executive summary:

A study was performed to assess the skin sensitisation potential of the test sample in the albino guinea pig. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 406 "skin Sensitisation" - Magnusson and Kligman Maximisation Test.

 

Twenty test and ten control animals were used for the main study.

Following sighting studies, the following concentrations were used in the induction and challenge phases:

Intradermal Induction       5% (w/v) in arachis oil

Topical Induction             50% (w/w) in petroleum jelly

Topical Challenge             50% (w/w) in petroleum jelly; re-challenge at 25% and 10%

 

 

Yellow/green coloured staining of the skin was noted at all test sample sites but did not prevent assessment of the skin responses.

 

 Initial Challenge - 50% (w/w)

Positive results were also observed in the negative control group. The sensitisation potential of the test sample could not be evaluated at this concentration. A re-challenge was performed at two lower concentrations.

Re-challenge - 25% and 10% (w/w)

Moderate and diffuse redness (score 2) and scattered mild redness (score 1) were noted at the 25% and 10% test sample re-challenge sites of test animalsat the 24-hour observation and at the 25% test sample re-challenge sites of test animals at the 48-hour observation. Scattered mild redness (score 1) continued to be noted at the 10% test sample re-challenge sites of the test animals at the 48-hour observation. Severe desquamation was noted at a number of 25% test sample re-challenge sites and at one 10% test sample re-challenge site at the 48-hour observation. The 25% and 10% test sample sites of control animals showed no erythema at the 24 or 48-hour observations.

The test sample, therefore, at re-challenge concentrations of 25% and 10%, produced a skin reaction in 85% (17/20) and 80% (16/20) animals, respectively after 24 hours. After 48 hours, a skin reaction was observed in 45% (9/20) and 15% (3/20) atconcentrations of 25% and 10%, respectively.

Bodyweight gains of surviving guinea pigs in the test group, between day 0 and day 24, were comparable to those observed in the control group animals over the same period.

 

The test substance caused positive reactions in more than 30% of animals after 24 hours after removal of the test substance at 10% and 25% test substance contentration. After 48 hours, only the 25% concentration caused skin reddening in more that 30% of test animals.

The test substance is hence considered to be a skin sensitiser at concentrations of 25% and above.