Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In a guinea pig maximisation test, the test item caused 70 to 80 % skin reactions in the ten animals of the treatment group and no effects in the five control animals. Based on the results of this study the test item has to be regarded as strong sensitiser according to the grading of Magnusson and Kligman.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: EPA, Title 40 Code of Federal Regulations Parts 160 and 792
Version / remarks:
August 17, 1989
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17, 1992
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Directive 92/69/EEC, July 31, 1992
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
the study was conducted in 1994
Species:
guinea pig
Strain:
other: Pirbright-White, Tif: DHP
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Ciba-Geigy Limited, Animal Production, 4332 Stein, Switzerland
- Weight at study initiation: males: mean 383 g (range: 335 - 411 g); females: mean 372 g (reange: 360 - 397 g)
- Housing: individually in Makrolon type 3 cages in fully air-conditioned rooms
- Diet: standard guinea pig pellets, NAFA no. 845, Gossau SG, ad libitum; all batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer
- Water: fresh water, ad libitum; quality of the drinking water according to the parameters of the "Schweizerisches Lebensmittelbuch"
- Acclimation period: 5 days
- Randomisation: cages assigned to different groups by means of random numbes generated by the random number generator

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20%
- Air changes (per hr): fully air-conditioned
- Photoperiod (hrs dark / hrs light):12/12

The sensitivity of the strain is checked once or twice per year wiht a known mild to moderate sensitizer (e.g. mercaptobenzothiazole, hexyl cinnamic aldehyde, potassium dichromate)
No. of animals per dose:
10 animals in the treatment group
5 animals in the control group

4 animals in the group for the determination of the primary non-irritant concentration
Details on study design:
RANGE FINDING TESTS:

The concentration for the intradermal injections was selected on account of its local and systemic tolerability in a pretest:
intradermal injection: 5 % (w/v) in physiological saline could be injected and was well tolerated

The concentration for the epidermal applications were selected on account of the primary irritation potential of the test substance. The following concentrations have been examined in two animals (m/f) per concentration for the determination of the maximum subirritant concentration: 10, 20, 30 and 50 % in physiological saline. 50 % was the highest possible concentration of the test item in physiological saline. Reactions were observed with concentations >/= 20 %.

MAIN STUDY
A. INDUCTION EXPOSURE

DAY 0: intradermal injections

3 intradermal injections (0.1 mL per injection) were made simultaneously into the left and right side of the shaved neck of the test and control group animals

test group:
- adjuvant/saline mixture 1:1 (v/v)
- 5 % test substance in physiological saline (w/v)
- 5 % test substance in the adjuvant/saline mixture (w/v)

control group:
- adjuvant/saline mixture 1:1 (v/v)
- adjuvant/saline mixture 1:1 (v/v)
- physiological saline

DAY 8: epidermal application

50 % test substance in physiological saline was applied on a filterpaper patch to the neck of the animals (patch 2 x 4 cm, approx. 0.4 g per patch; occluded administration for 48 hours). The control group was treated with the vehicle physiological saline only.


B. CHALLENGE EXPOSURE

DAY 22: epidermal application

the test and control group animals were tested on one flank with 10 % test substance in physiological saline and on the other flank with the vehicle only (patch 2 x 2 cm, approx. 0.2 g per patch; occluded administration for 24 hours)

24 and 48 hours after removal of the dressings the challenge reactions were graded according to the Draize scoring scale.
The body weights were recorded at the start and the end of the study.

Positive control substance(s):
no
Positive control results:
Reference values with 2-mercaptobenzothiazole puriss., Test 930018 (January 2 to January 27, 1994):

intradermal induction: 5 % in Oleum arachidis
epidermal induction: 50 % in vaseline
epidermal challenge: 30 % in vaseline

result:
no positive reaction observed in the control group (10 animals)
100 % of the animals in the test group showed positive reactions

Test and results fullfill the requirements for the reliability check of the OECD 406
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
no clinical signs recorded
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
no clinical signs recorded
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Key result
Group:
positive control
Remarks on result:
other: The positive control group was not included in this idividual study. Positive controls were performed separately at regular intervals.

No effects on body weight gains or clinical signs were observed.

No clinical signs were recorded.

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Remarks:
Regulation (EC) no 1272/2008
Conclusions:
In a guinea pig maximisation test, the test item caused 70 to 80 % skin reactions in the ten animals of the treatment group and no effects in the five control animals. Based on the results of this study the test item has to be regarded as strong sensitiser according to the grading of Magnusson and Kligman.
Executive summary:

Testing for sensitizing properties of the test item was performed in female and male guinea pigs according to the method of MAGNUSSON & KLIGMAN. Intradermal induction was performed using 5 % test item in physiological saline and adjuvant/saline mixture 1:1. Dermal induction was carried out with 50 % test item in physiological saline. Challenge treatment were carried out with 10 % test item in physiological saline. At the 48 hours reading 70 % and at the 72 hours reading 80 % of the test animals showed positive skin reactions. The validity of the study was confirmed by negative controls (no skin reactions) and a separate test performed with the reference substance 2 -mercapto- benzothiazole.

Based on the results of this study the test item has to be classified as skin sensitizing category 1B according to the criteria of Regulation (EC) no 1272/2008 (guinea pig maximisation test, >/= 30 % animals responding at > 1 % intradermal induction dose)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a guinea pig maximisation test, the test item caused 70 to 80 % skin reactions in the ten animals of the treatment group and no effects in the five control animals. Based on the results of this study the test item has to be regarded as strong sensitiser according to the grading of Magnusson and Kligman.

Categories Display