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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:
from 19 September 2000 to 21 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP. The test substance contained a mixture of the registered substance and the related S3 and S4 isomers, but the relative proportions of each are not known. The original study and the read-across are considered to be reliability 2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
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 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
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Hartley [Crl:(HA)BR]
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Labs, Raleigh, NC, USA
- Age at study initiation: young adults
- Weight at study initiation: 291-339 g (males); 285-315 g (females)
- Housing: 1/suspended wire-mesh cage
- Diet: standard ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67-73 deg F
- Humidity (%): 34-69
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 2000-09-19 To: 2000-10-21

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: ethanol
Concentration / amount:
intradermal induction: 5% in ethanol; 5% in 1:1 FCA:saline
topical induction: neat (100%)
topical challenge: 25% in ethanol
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
intradermal induction: 5% in ethanol; 5% in 1:1 FCA:saline
topical induction: neat (100%)
topical challenge: 25% in ethanol
No. of animals per dose:
test: 10/sex
+ve control: 5/sex
-ve control: 5/sex
Details on study design:
RANGE FINDING TESTS:
primary irritation phase: intradermal (2/sex) 1, 3, 5% tested in mineral oil and 1:1 FCA:saline; topical (4/sex) 2.5, 5, 10, 25, 50% in ethanol and 100%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal-3 paired injections, topical)
- Exposure period: topical 48h
- Test groups: 10/sex
- Control group: +ve 5/sex; -ve 5/sex
- 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: 1:1 FCA saline; 5% TS in ethanol; 5% TS in 1:1 FCA:saline
topical: 100% TS

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/sex
- Control group: +ve 5/sex; -ve 5/sex
- Site: flank
- Concentrations: 25% TS in ethanol
- Evaluation (hr after challenge): 24 and 48 h following patch removal
Challenge controls:
-ve control: 25% TS in ethanol
+ve control: 10% HCA (alpha-hexylcinnamaldeyde) in acetone
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldeyde

Results and discussion

Positive control results:
See table 1.
Based on the incidence index of 100%, the positive control material (HCA) was judged to be a sensitizing agent under the conditions of this study.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25% TS
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
Dermal scores of 1 were reported in the negative control group. Scores >1 in the test group were judged to indicate sensitization.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25% TS
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
Dermal scores of 1 were reported in the negative control group. Scores >1 in the test group were judged to indicate sensitization.
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing

GROUP

MATERIAL

INTERVAL

DERMAL SCORES*

NO. ANIMALS

SENSITIZATION INCIDENCE INDEX**

SEVERITY INDEX***

0

1

2

3

Test

TS

24h

3

16

1

0

20

1/20=5%

18/20=0.9

48h

7

12

1

0

20

14/20=0.7

vehicle

24h

20

0

0

0

20

0/20=0%

0

48h

20

0

0

0

20

0

Positive control

HCA in vehicle

24h

0

7

3

0

10

10/10=100%

13/10=1.3

48h

3

6

1

0

10

8/10=0.8

vehicle

24h

10

0

0

0

10

0/10=0%

0

48h

10

0

0

0

10

0

Negative control

TS

24h

5

5

0

0

10

n/a

5/10=0.5

48h

9

1

0

0

10

1/10=0.1

vehicle

24h

10

0

0

0

10

n/a

0

48h

10

0

0

0

10

0

*Skin reactions were graded:

0 no reaction or very slight dispersed redness. No swelling.

1 slight patchy or confluent erythema

2 moderate and confluent erythema and/or slight swelling

3 severe erythema and/or moderate to severe swelling

** Sensitization incidence index: number of animals with dermal scores greater than those of the negative control group at 24h or 48h, divided by the number of animals tested. Grades of 1 or greater are considered indicative of sensitization in the positive control group

*** Severity index: the sum of test grades divided by the number of animals tested (given for 24h and 48h observations separately)

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
A well conducted, well reported guinea-pig maximization test, on a closely related substance, identified a sensitization index of 5%. EU criteria for sensitization by skin contact would require a positive response in at least 30% of the test group.