Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-10-12 to 2009-11-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg, GERMANY
- Age at study initiation: 4-6 wk
- Weight at study initiation: 359-445 g
- Housing: 1/Makrolon Type 4 cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 2 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 2009-10-12 To: 2009-11-06

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
induction: intradermal 15%; epidermal 50%
challenge epidermal: 10%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
induction: intradermal 15%; epidermal 50%
challenge epidermal: 10%
No. of animals per dose:
test: 10
vehicle control: 5
postitive control: 10

pretest intradermal: 1
pretest epidermal: 2
Details on study design:
RANGE FINDING TESTS:
intradermal 5, 10, 15% tested in corn oil (15% was the maximum technically feasible), 1 wk following
following 1:1 FCA:saline [15% was selected as highest concentration technically possible, well tolerated systemically and causing mild skin irritation.]
epidermal 10, 15, 25, 50% in corn oil (50% was the maximum technically feasible). [50% (highest techincally possible and causing mild to moderate skin irritation) was chosen for induction and 10% (the highest non-irritant concentration) was chosen for challenge.]

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; 15% TS in corn oil; 15% TS in 1:1 FCA:saline
Intradermal - control group: 1:1 FCA saline; corn oil; 1:1 FCA:saline
Topical - test group: 50% TS in corn oil
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: 10% TS in corn oil; corn oil
- Evaluation (hr after challenge): 24 and 48 h following patch removal

Challenge controls:
There were no responses from any vehicle controls at challenge (see table).
Positive control substance(s):
yes
Remarks:
3% alpha-hexylcinnamaldehyde (see table)

Results and discussion

Positive control results:
One of ten animals showed skin reactions following challenge with 1% alpha-hexylcinnamaldehyde in PEG 300, with no responses in the control group. Eight of ten responded to a 3% challenge at 24 h, and 9 of ten responded at 48 h, again there were no responses in the controls (see table).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
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: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
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: 10.0. Clinical observations: none.
Reading:
other: 1st and 2nd (24 and 48 h)
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading:

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing

GROUP

MATERIAL

INTERVAL

DERMAL SCORES*

SENSITIZATION INCIDENCE INDEX**

SEVERITY INDEX***

0

1

2

3

 

 

Test

TS 10%

24h

10/10

0/10

0/10

0/10

0/10

0

48h

10/10

0/10

0/10

0/10

0/10

0

Corn oil

24h

10/10

0/10

0/10

0/10

0/10

0

48h

10/10

0/10

0/10

0/10

0/10

0

Positive control

hexylcinnamaldehyde1%

24h

9/10

1/10

0/10

0/10

1/10

0.1

48h

10/10

0/10

0/10

0/10

0/10

0

hexylcinnamaldehyde3%

24h

2/10

8/10

0/10

0/10

8/10

0.8

48h

1/10

9/10

0/10

0/10

9/10

0.9

Vehicle control

TS 10%

24h

10/10

0/10

0/10

0/10

0/10

0

48h

10/10

0/10

0/10

0/10

0/10

0

Corn oil

24h

10/10

0/10

0/10

0/10

0/10

0

48h

10/10

0/10

0/10

0/10

0/10

0

Skin reactions were graded

0 no visible change

1 discrete or patchy erythema

2 moderate and confluent erythema

3 intense erythema and swelling

There were no signs of systemic toxicity during the study. All animals gained weight during the study and there were no significant test-article related differences in vehicle and test group mean body weight.

* Number of animals showing skin reactions at each of grades 0 -3

** Incidence Index = number of animals showing post-challenge skin reactions at either 24 or 48 hours, divided by the number of animals in the group

*** Severity Index = Sum of post-challenge test grades divided by the total number of animals tested.

 

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
A well conducted, well reported guinea-pig maximization test reported no indication of sensitization potential from a challenge application of 10% of the test material in corn oil.