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Diss Factsheets

Administrative data

Description of key information

No skin sensitisation potential of the test substance was observed in a guinea pig maximization test.

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:
10.7.2001 - 17.8.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid and relaible guine-pig study is available. No further information is necessary.
Species:
guinea pig
Strain:
other: Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Füllinsdorf / Switzerland
- Age at acclimatization initiation: 4 - 6 weeks
- Weight at acclimatization initiation: 290 - 425 g
- Housing: individually in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Provimi Kliba 3418, batch nos. 90/01 and 91/01, guinea pig breeding / maintenance diet, containing Vitamin C (Provimi Kliba AG, CH-4303 Kaiseraugst), ad libitum.
- Water: Community tap water from Fullinsdorf, ad libitum.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): approximately 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
polyethylene glycol
Remarks:
PEG 300 (control groups only)
Concentration / amount:
100 %
Day(s)/duration:
7 days
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300 (control groups only)
Concentration / amount:
100%
Day(s)/duration:
48h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Concentration / amount:
75 %
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 in test group
5 in control group
Details on study design:
RANGE FINDING TESTS:
- Intradermal injections:
Four intradermal injections (0.1 ml/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiologicai saline were made into the shaved neck of one guinea pig. One week later intradermal injections (0.1 ml/site) were made into the clipped flank of the same guinea pig at concentrations of A = 100 %, B = 75 % and C = 25 % of the test item. Dermal reactions were assessed 24 hours later. Based on the results, the test item concentration of 100 % was selected for intradermal induction in the main study.
- Epidermal Application:
Four intradermal injections (0.1 ml/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiologicai saline were made into the shaved neck of two guinea pigs. One week later 4 patches of filter paper (3x3 cm) were saturated with the test item at D = 100 %, E = 75 %, F = 50 % and G = 25 % and applied to the clipped and shaved flanks. The dressings were removed after an exposure period of 24 hours. Twenty-one hours later the application site was depilated with an approved depilatory cream in order to visualize any resulting erythema.The reaction sites were assessed 24 and 48 hours after removal of the bandage. Based on the results obtained the concentration selected for induction and challenge in the main study was 100 % and 75 %, respectively.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
First induction
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shoulder of the guinea pigs as follows:
- adjuvant and saline (1:1)
- test article at 100%
- test article at 100%
Second induction
-epicutaneous: undiluted test item, approximately 0.3 ml
- Control group:
First induction:
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shoulder of the guinea pigs as follows:
- adjuvant and saline (1:1)
- PEG 300
- PEG 300 in adjuvant and saline (1:1)
Second induction:
-epicutaneous: PEG 300 only, approximately 0.3 ml
- Site: scapular region
- Frequency of applications: day 1 intradermal injections and 1 week later epicutanous induction (day 8)
- Concentrations: intradermal 100%; epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after the epidermal induction (day 22)
- Exposure period: 48 h
- Test and control groups: 75% of the test substance in PEG 300 (left flank) and PEG 300 (right flank)
- Evaluation (hr after challenge): 24, 48
Challenge controls:
The controls were also challenged with the test substance without having been induced.
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole
Positive control results:
The sensitivity and reliability of the experimental technique employed was assessed by use of 2-MERCAPTOBENZOTHiAZOLE which is recommended by the OECD 406 Guidelines and is known to have moderate skin sensitization properties in the guinea pig strain. The results from the most recent test run (RCC study number 905635, performed from 14-MAY- 2001 to 21-JUN-2001) are included in this report. All 10 test animals showed discrete/patchy to intense erythema and swelling at the 24- and 48-hour reading after the challenge treatment with 2-MERCAPTOBENZOTHIAZOLE at0.5 % (w/w) in mineral oil. No skin effect was observed in the control group.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No toxic symptoms
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No toxic symptoms
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No toxic symptoms
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No toxic symptoms
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No toxic symptoms
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No toxic symptoms
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No toxic symptoms
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No toxic symptoms
Group:
positive control
Remarks on result:
not measured/tested

VIABILITY / MORTALITY / MACROSCOPIC FINDINGS

There were no deaths during the course of the study, hence no necropsies were performed.

CLINICAL SIGNS, SYSTEMIC

No signs of systemic toxicity were observed in the animals.

BODY WEIGHTS

The body weight of the animals was within the range commonly recorded for animals of this strain and age.

Interpretation of results:
GHS criteria not met
Conclusions:
After challenge with either PEG 300 only or with 75% of the test substance in PEG 300, skin reactions were neither observed in the test group nor in the control group animals. Therefore, the test substance is considered to be not sensitizing.
Executive summary:

In order to assess the cutaneous allergenic potential of the test substance, a GLP-compliant Maximization-Test was performed in 15 (10 test and 5 control) male albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6.

Ttie intradermal induction of sensitization in the test group was performed in the nuchal region with the undiluted test item and with an emulsion of Freund's Complete Adjuvant (FCA) / physioiogical saline. The epidermal induction of sensitization was conducted for

48 hours under occlusion with the undiluted test item one week after the intradermal induction. The animals of the control group were intradermally induced with PEG 300 and FCA/physioiogical saline and epidermally induced with PEG 300 under occlusion. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 75 % in PEG 300 and PEG 300 alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing. No toxic symptoms were evident in the guinea pigs of the control or test group. No deaths occurred. None of the control and test animals showed skin reactions after the challenge treatment with the test item at 75 % (w/w) in PEG 300. Based on this result, the test substance does not have to be classified and labelled as a skin sensitizer.

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

In a GLP compliant Maximization-Test according to OECD TG 406, the skin sensitizing potential of the test substance was assessed in a group of 10 male guinea pigs (RCC, 2001). Five additional animals served as control. In the induction period, the animals of the test group were treated intradermally and epicutaneously with the test substance (100% each), control animals were treated with PEG 300. The challenge in both groups was performed epicutaneously with test substance (75%) and PEG 300. None of the animals of the test groups and no animal of the control groups showed skin findings 24 and 48 hours after the challenge. The sensitivity of the used animal strain was tested before with a positive control substance (not performed during this study). Based on the results of this study it was concluded that the test article does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for dermal sensitization is not warranted under Regulation (EC) No.1272/2008.