Registration Dossier

Diss Factsheets

Administrative data

Description of key information

To assess the skin sensitisation potential of the test substance, a study was conducted under OECD TG 406. This was a guinea pig maximisation test (GPMT), the test was conducted by trimming the right-side of the guinea pigs fur and an occlusive patched placed on the area. The patches contained samples of the test substance. The left side of each test subject was also trimmed and used as a negative control, using a known non-sensitising agent. Each patch consisted of a 25% solution of the test substance and a vehicle. In this case the vehicle was 1% Tylose in double distilled water. Each of the animals were then checked for any signs of distress or sensitisation after both 24 and 48 hours. This was the same procedure conducted on 10 different test animals. Across all these tests no signs of sensitisation occurred.

 

In addition the left side of each animal contained a semiocclusive patch coated in just the test vehicle. This serves as a control group however, as with the test, no signs of sensitisation was noted. To ensure the test was valid a positive control was also conducted. The positive control was a known sensitiser which was applied to 10 different test animals, kept and treated in the same conditions. During the 24 and 48 hour observations the positive control showed signs of sensitisation in 9/10 test animals. It can therefore be concluded that the test method and conditions were valid.

Due to the lack of reaction it was concluded the test substance was non-sensitising agent and as such is not classified under Regulation No. 1272/2008.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
GPMT
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Specific details on test material used for the study:
Batch number: Fixapret 140 Nr. 766.
Date of manufacturing: 24 March 2001.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Test animals
Source: Harlan Winkelmann GmbH, Borchen, FRG.
Age at study Initiation: About 5 weeks.
Weight at study Initiation: 279 -366g.
Housing: Group Housed (5 to a cage).
Diet: Kuba Labordiät (Kaninchen Meerschweinchen-Hautungsdiät) Provimi Kuba SA, Kaiseraugst, Switzerland, ad libitum.
Water: Tap water, ad libitum.
Acclimatisation Period: 7 days befire the first test substance application.
Identification: Ear tattoo.

Environmental conditions
Temperature (°C): 20-24
Humidity (%): 30-70
Air Changes: None recorded but the room was fully air-conditioned.
Photoperiod (hrs dark/hrs light): 12/12.
Positive control results:
In a concurrent 'positive control study' performed according to guidelines based on the Magnusson and Kligmann (1969), the sensitivity of Harlan Guinea pigs was assessed using the known sensitiser, α-hexylcinnamaldehyde (85%). As positive results were seen in the majority of the Guinea pig after 24 and 48 hours with little sign of decreasing it was deemed that α-hexylcinnamaldehyde (85%) has a positive sensitising effect on Guinea pig in the conditions chosen.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

The GPMT was run on 2 groups (each containing 5 Guinea pigs), the tests used a 25% concentration of the test substance and were appled to each test animal. When the patch was removed observations were recorded at both 24 and 48 hours of all 10 test animals however, no indication of sensitisation could be seen. The table recording this is seen below:

Right flank posterior: Right flank posterior:
Form of application: Form of application:
Test substance 25% in 1% Tylose in doubly distilled water 1% Tylose in doubly distilled water
Animal No. Findings 24 hours after removal of patch Findings 48 hours after removal of patch Findings 24 hours after removal of patch Findings 48 hours after removal of patch
731 0 0 0 0
732 0 0 0 0
733 0 0 0 0
734 0 0 0 0
735 0 0 0 0
736 0 0 0 0
737 0 0 0 0
738 0 0 0 0
739 0 0 0 0
740 0 0 0 0

In addition to ensure the test conditions were valid, tests were conducted using both positive and negative controls. The posititive control group was tested with a known sensitising agent ( α-hexylcinnamaldehyde) also across 10 animals split into 2 groups. Across both viewings an average of 9 test animals showed signs of irritation. The test conditions can therefore, be assumed to be valid.

Similar to this on the other side of the test animal, a patch was used testing just the vehicle at the same concentration as with the test material. After 24 and 48 hours, this showed no signs of sensitisation. Therefore, the vehicle can be concluded to be a non-sensitiser under CLP Regulation (EC) 1272/2008.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the test substance is not considered to be a sensitising agent.
Executive summary:

The study was conducted under the guidelines of OECD 406 under GLP regulations to assess the sensitisation potential of perhydroimidazo[4,5 -6]imidazole-2,5 -dione in guinea pigs. The GPMT test was conducted by placing occlusive patches on the right hand side of each of the test animals. Each patch consisted of a 25% solultion of the test substance and a vehicle. In this case the vehicle was 1% Tylose in double distilled water. Each of the animals were then checked for any signs of distress or sensitisation after both 24 and 48 hours. This was the same procedure conducted on 10 different test animals. Across all these tests no signs of sensitisation occurred.

In addition the left side of each animal contained a semiocclusive patch treated with the test vehicle alone. This serves as a control group however, as with the test, no signs of sensitisation was noted. To ensure the test was valid a possitive control was also conducted. The positive control was a known sensitiser which was applied to 10 different test animals, kept and treated in the same conditions. During the 24 and 48 hour observations the positive control showed signs of sensitisation in 9/10 test animals. It can therefore be concluded the test method and conditions were valid. Therefore under the conditions of the study it is concluded that perhydroimidazo[4,5 -6]imidazole-2,5 -dione is a non-sensitising agent based on the criteria classification criteria under the CLP Regulation (EC) 1272/2008.

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

Justification for classification or non-classification

The study was conducted under the guidelines of OECD 406 under GLP regulations to assess the sensitisation potential of perhydroimidazo[4,5 -6]imidazole-2,5 -dione in guinea pigs. The GPMT test was conducted by placing occlusive patches on the right hand side of each of the test animals. Each patch consisted of a 25% solultion of the test substance and a vehicle. In this case the vehicle was 1% Tylose in double distilled water. Each of the animals were then checked for any signs of distress or sensitisation after both 24 and 48 hours. This was the same procedure conducted on 10 different test animals. Across all these tests no signs of sensitisation occurred.

In addition the left side of each animal contained a semiocclusive patch treated with the test vehicle alone. This serves as a control group however, as with the test, no signs of sensitisation was noted. To ensure the test was valid a possitive control was also conducted. The positive control was a known sensitiser which was applied to 10 different test animals, kept and treated in the same conditions. During the 24 and 48 hour observations the positive control showed signs of sensitisation in 9/10 test animals. It can therefore be concluded the test method and conditions were valid. Therefore under the conditions of the study it is concluded that perhydroimidazo[4,5 -6]imidazole-2,5 -dione is a non-sensitising agent based on the criteria classification criteria under the CLP Regulation (EC) 1272/2008.

Categories Display