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Description of key information

Skin sensitization (OECD 406, RL1): guinea pig (m/f), not skin sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan 24- Feb 17, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was carried out before enforcement of the OECD guideline 429.
Species:
guinea pig
Strain:
other: Hsd.Poc: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: 324 g (range from 300 to 346 g).
- Housing: Two guinea pigs were housed in type GM/5 (EBECO) 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): 21 to 23°C
- Humidity (%): 49 to 61 %
- 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:
0.1 ml
Day(s)/duration:
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:
1 mL
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:
0.5 mL
Day(s)/duration:
Day 22/24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Number of animals in test group: 10
Number of animals in negative control group: 5
Number of animals in pre test group: 5
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

Induction was performed in two stages. First, the test material was intradermally injected with or without Freund's complete adjuvant on day 1. Then, after one week (day 8), the test material was topically applied under occlusive patch conditions for 48 hours.

The challenge was performed two weeks later by topical application in a non irritating concentration under the same conditions. The patches were then applied for 24 hours on the shaven side of the animals.

Positive control data have been taken from another GLP study T15929.
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: 6/10

Overall:
Vehicle: 0%
Test material: 70%
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
25 g/L
No. with + reactions:
5
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
25 g/L
No. with + reactions:
6
Total no. in group:
10

Findings in the induction phase

After intradermal injection, the common signs of irritation after injection of Freund's complete adjuvant were observed. The injection sites were swollen and red, later, scabs developed.

 

Findings after challenge

Group

Induction with

Challenge with

Positive animals

48h/72h

Positive/animals overall

1

Vehicles*

PEG400

0/5      0/5

0/5

 

 

Test item#

0/5      0/5

0/5

2

Test item

Test item

0/10      0/10

0/10

 

 

Test item

0/10      0/10

0/10

Vehicles          *=Liquid paraffin and PEG 400

# = Testing for primary irritation

The challenge was performed on the right side ofthe animals

 

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 item (10 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 (details, see Table 4)

After challenge with the test item (10 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.

 

Clinical findings and mortality

The clinical behavior of the guinea-pigs was normal during the study period. All animals survived the study period.

 

Body weight

The body weight development did not differ from that of the animals of the vehicle group. All animals survived the study period.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material is not considered to be a sensitizer according to CLP-Regulation (EC) No 1272/2008.
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 (25 g/L) starting on experimental day 8.

Challenge by topical application of test material preparation in propylene glycol for 24 hours (10 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.; 25 g/L topical 10 g/L 0 / 10 0 / 10 0 / 10


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

Conclusions

The test material has not to be classified as a sensitizer according to CLP-Regulation (EC) No 1272/2008.

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

Objective

The purpose of this Guinea-pig maximization test was to assess the skin sensitizing potential of the test material when applied to the skin of the animal.

This study should provide a rational basis for risk assessment to the sensitizing potential of the test item in man.

 

Study Design

For this purpose Induction was performed in two stages. At first the test material was intradermally injected with and without Freund's complete adjuvant. Then, after one week, the test material was topically applied under occlusive patch conditions for 48 hours. The challenge was performed two weeks later by topical application. The patches were then applied for 24 hours.

Results

induction phase:

After intradermal injection, the common signs of irritation after injection of Freund's complete adjuvant were observed. Tue injection sites were swollen and red, later, scabs developed.

 

after challenge:

After challenge with the test item (10 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. 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification