Registration Dossier

Administrative data

Description of key information

The test item showed no positive responders in a study according to OECD Guideline 406 and is not considered to be sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Sep 02- Sep 26, 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
Test was performed before enforcement of the OECD guideline for LLNA.
Species:
other: guinea pig HsdPoc:DH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen
- Age at study initiation: about 5 weeks
- Weight at study initiation: 323 g (range from 296 to 367 g).
- Housing: Two guinea pigs were housed in type IV Makrolon cages with a shelter and placed on mobile racks.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days before dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 74 %
- Air changes (per hr): --
- Photoperiod (hrs dark / hrs light): 12 / 12 h

IN-LIFE DATES: From: day 1 To: day 25
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
50 g/L
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:
polyethylene glycol
Concentration / amount:
200 g/L
Day(s)/duration:
Day 8/ 48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
50 g/L
Day(s)/duration:
Day 22/ 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Pre test: 5 (f)
Number of animals in negative control group: 5 (f)
Number of animals in test material group: 10 (f)
Details on study design:
+ ++ +++
I . . . . . . . I . . . . . . . . . . . . . l . . I
1 8 22 25 day of experimental part

Induction: stage I + intradermal injection
stage II ++ topical application
Challenge: +++ topical challenge


Positive control data have been taken from another GLP study.
Positive control substance(s):
yes
Remarks:
2-Hexylcinnamaldehyde
Positive control results:
Positive Reactions:
Vehicle 48h: 0/10
Vehicle 72h: 0/10
Test material 48h: 5/10
Test material 72h: 3/10

Overall:
Vehicle: 0%
Test material: 50%
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
5 g/L
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs were observed
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
5 g/L
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs were observed
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 g/L
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs were observed
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0 g/L
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs were observed
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
10 g/L
No. with + reactions:
5
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
78
Group:
positive control
Dose level:
10 g/L
No. with + reactions:
3
Total no. in group:
10

Group 1: negative control group

After challenge with polyethylene glycol 400, no erythema or edema were observed at the readings. A single treatment was performed with the test material (50 g/L polyethylene glycol 400) to exclude primary irritation of the test material concentration. No positive reactions were observed in the treated areas at any reading.

Group 2: test material group

After challenge with the test material (50 g/L preparation in polyethylene glycol 400) no positive skin reactions were observed at the readings. This results in 0 % positive reactions after challenge.

After challenge, no positive reactions were observed in the areas treated with polyethyleneglycol 400 alone at any reading.

Interpretation of results:
GHS criteria not met
Conclusions:
After challenge no positive reactions in the test material treated skin sites at both readings were seen. Thus, the test item showed no positive responders and is not considered to be sensitizing to skin.
Executive summary:

Study design

The test material was evaluated for skin sensitizing properties in. the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969).

5 Female guinea pigs in the negative control group (group 1) treated with the vehicles (liquid paraffin and ethylene glycol 400) and 10 females in the test material group (group 2) were investigated.

Induction included intradermal injection of test material preparation in liquid paraffin (50 g/L with and without Freund's complete adjuvant) on day 1, and topical application of test material preparation in propylene glycol for 48 hours (200 g/L) starting on experimental day 8.

Challenge by topical application of test material preparation in propylene glycol for 24 hours (50 g/L) was performed two weeks after topical induction. Readings were taken at 48 and 72 hours.

Results

Reaction after challenge

Induction with
test material
challenged with 
test material

positive / total animals

positive / total animals

48 h 72 h overall
50 g/L i.d.; 200 g/L topical 50 g/L 0 / 10 0 / 10 0 / 10


After challenge no positive reactions were observed in the test material treated skin sites.

Conclusions

In conclusion, the test item showed no positive responders and is not considered to be sensitizing to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the data provided which are considered to be reliable and suitable for classification, the test item is not classified for skin sensitization according to Regulation (EC) No 1272/2008.