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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Buehler/Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Himalayan, albino
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd, Basel, SWITZERLAND
- Age at study initiation: 5 wk
- Weight at study initiation: <500 g
- Housing: 5/metal cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (unspecified deviations from this value said not to affect findings)
- Humidity (%): 50 (unspecified deviations from this value said not to affect findings)
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
Concentrations:
INDUCTION
Intradermal - test group: 1:1 FCA saline; 100% TS; 1:1 Test substance in FCA
Intradermal - control group: identical but Test substance replaced by corn oil
Topical - test group: 100% Test substance
Topical - control group: corn oil
CHALLENGE:
1ST - 100% test substance
2ND - 20% and 50% test substance
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
Concentrations:
INDUCTION
Intradermal - test group: 1:1 FCA saline; 100% TS; 1:1 Test substance in FCA
Intradermal - control group: identical but Test substance replaced by corn oil
Topical - test group: 100% Test substance
Topical - control group: corn oil
CHALLENGE:
1ST - 100% test substance
2ND - 20% and 50% test substance
No. of animals per dose:
test = 10
control = 5
Details on study design:
RANGE FINDING TESTS:
primary irritation phase: intradermal (2 animals) 10, 20, 50, 100% tested in corn oil ; topical (4 animals) 10, 20, 50, 100% tested in corn oil

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal-3 paired injections, topical)
- Exposure period: topical 48h
- Test groups: 10
- Control group: +ve 10; -ve 5
- Site: two rows of 3 sites, one row either side of dorsal mid-line
- Frequency of applications: intradermal treatment day 0; topical induction day 7
- Duration: induction period continues to day 21
- Concentrations:
Intradermal - test group: 1:1 FCA saline; 100% TS ; 1:1 TS in FCA
Intradermal - control group: identical with TS replaced by corn oil
24 h before topical induction 10% sodium dodecyl sulfate was applied to induce mild inflammation
Topical - test group: 100% TS
Topical - control group: corn oil

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: day 22
- Exposure period: 24h
- Test groups: 10
- Control group: +ve 10; -ve 5
- Site: flank
- Concentrations: 100% TS; corn oil
- Evaluation (hr after challenge): 24 and 48 h following patch removal

C. RECHALLENGE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: day 29
- Exposure period: 24h
- Test groups: 10
- Control group: +ve 10; -ve 5
- Site: flank
- Concentrations: 59% and 20% TS in corn oil
- Evaluation (hr after challenge): 24 and 48 h following patch removal
Challenge controls:
see above
Positive control substance(s):
yes
Remarks:
alpha hexylcinnamic aldehyde (10% aqueous)

Results and discussion

Positive control results:
See table 1, below.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
other: Negative control
Hours after challenge:
24
Group:
negative control
Dose level:
-
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other:
Hours after challenge:
48
Group:
negative control
Dose level:
-
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
20% and 50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other:
Hours after challenge:
24
Group:
positive control
Dose level:
10% in water alpha-cinnamic aldehyde
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
other: Positive control
Hours after challenge:
48
Group:
positive control
Dose level:
10% in water alpha-cinnamic aldehyde
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
other: Positive control
Hours after challenge:
72
Group:
positive control
Dose level:
10% in water alpha-cinnamic aldehyde
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing

GROUP

MATERIAL

INTERVAL (AFTER 6h CHALLENGE)

SKIN REACTIONS NUMBERS OF ANIMALS (SCORE)

 

NO. ANIMALS

Challenge – test group

TS (100%)

24h

2(1)

10

48h

3(1)

10

Vehicle (corn oil)

24h

0

10

48h

0

10

Challenge – control group

TS (100%)

24h

1(1)

5

48h

1(1)

5

Vehicle (corn oil)

24h

0

5

48h

0

5

Re-challenge – test group

TS (50%)

24h

0

10

48h

0

10

TS (20%)

24h

0

10

48h

0

10

Re-challenge – control group

TS (50%)

24h

0

5

48h

0

5

TS (20%)

24h

1

5

48h

0

5

Positive control (alpha-cinnamic aldehyde)*

10% in water

24h

8(2); 2(1)

10

48h

9(2); 1(1)

10

72 h

7(2); 3(1)

10

Vehicle (water)

24h

0

10

48h

0

10

72 h

0

10

* The control group of 5 animals for the positive control test producted the following reactions at 24, 48 and 72 h: 4(1), 3(1), 1(1).

No conclusion regarding sensitization could be drawn from the first challenge which produced responses in both the control and test group that were believed to indicate an irritation response. There was no indication of sensitization from the second challenge.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
A well conducted, well reported guinea-pig maximization test found no indication of sensitization potential from challenge applications of 20% and 50% of the test material in corn oil. An earlier challenge using the neat material was discounted as responses believed to indicate irritation were seen in the control and test groups.