2-imino-1-methylimidazolidin-4-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14.02.2002 - 30.04.2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

A guideline for the LLNA was not available when the study was performed.

Test material

Test material information

Constituent 1

Reference substance name:

2-imino-1-methylimidazolidin-4-one

EC Number:

200-466-7

EC Name:

2-imino-1-methylimidazolidin-4-one

Cas Number:

60-27-5

Molecular formula:

C4H7N3O

IUPAC Name:

2-imino-1-methylimidazolidin-4-one

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Creatinin
- Physical state: solid
- Expiration date of the lot/batch: 28.01.2004
- Stability under test conditions: stable

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pribright White, BOR DHPW

Sex:

female

Details on test animals and environmental conditions:

In contrast to the title of the study guinea pigs were used instead of rabbits. This is an error in the study report.

TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: 294.1 - 354.1 g
- Housing: housed with 2 or 3 animals in Makrolon-cages No.4. A non-barrier system with air conditioning was used
- Diet (e.g. ad libitum): The animals received food "3022" from Altromin International, Lage, Germany as pelleted diet, offered ad libitum
- Water (e.g. ad libitum): normal tap water fro, municipal sources ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C (17 - 23 °C)
- Humidity (%): 30 -70 %;
- Air changes (per hr): 8 times/hour
- Photoperiod (hrs dark / hrs light): Lighting was in a 12-hour-light/dark-cycle

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: saline solution

Induction 2

Concentration / amount:

Pilot experiment
Intradermal: 0.1 mL of 5 %, 3.5 %, 2 % and 0.5 % (w/w) solution in saline
Dermal: 0.5 g 50 % (w/w) saline suspension and 0.5 g of the test substance moistened with 0.5 mL saline solution
Challenge: Duhring chamber with 20 %, 40 %, 50 % (w/w) saline suspension and the moistened test substance

Main experiment
Intradermal: 0.1 mL of 5 % (w/w) solution in saline
Dermal: 0.5 g of the test substance moistened with 0.5 mL saline solution
Challenge: Duhring chamber with 20 % (w/w) saline suspension

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: saline solution

Challenge 2

Concentration / amount:

Pilot experiment
Intradermal: 0.1 mL of 5 %, 3.5 %, 2 % and 0.5 % (w/w) solution in saline
Dermal: 0.5 g 50 % (w/w) saline suspension and 0.5 g of the test substance moistened with 0.5 mL saline solution
Challenge: Duhring chamber with 20 %, 40 %, 50 % (w/w) saline suspension and the moistened test substance

Main experiment
Intradermal: 0.1 mL of 5 % (w/w) solution in saline
Dermal: 0.5 g of the test substance moistened with 0.5 mL saline solution
Challenge: Duhring chamber with 20 % (w/w) saline suspension

No. of animals per dose:

10 females in main experiment

Details on study design:

see "any other information on material and method"

Challenge controls:

see "any other information on material and method"

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Results and discussion

Positive control results:

Sensitation rate of 60 %

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

20 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

20 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

20 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 5

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

2-mercaptobenzothiazole 5 %

No. with + reactions:

3

Total no. in group:

5

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Symptoms:

Toxic symptoms caused by the test substance were not observed during the whole study.

Body Weight:

Body weight development was positive and within normal range.

Pilot Experiment:

The intradermal application of the 0.5 % (w/w), 2 % (w/w) and 3.5 % (w/w) test substance in saline solution led to no reaction. The intradermal application on the 5 % (w/w) test substance in saline solution resulted only in a very slight reaction.The dermal application without Duhring chambers caused no erythema and edema formations with the moistened test substance and the 50 % (w/w) suspension in saline solution. The dermal application with Duhring chambers caused a slight reaction with the moistened test substance and very slight reaction with the 50 % (w/w) and 40 % (w/w) suspensions in saline solution. The application of a 20 % (w/w) suspension in saline solution elicited no skin reaction.

Induction:

The intradermal injection led to no to slight erythema and edema formation were detected with 5 % (w/w) solution of the test substance in saline solution after 24 hours. To induce skin reactions 10 % sodium lauryl sulphate in vaseline was applicated one day before dermal application. In the dermal induction phase no to slight erythema and edema formations were observed.

Challenge:

No erythema or edema formation were obsered in the test group and in the control group 24 h and 48 h post application.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The sensitisation rate of 0 % indicates that the test substance Creatinine is a non-sensitising copound in this test system.

Executive summary:

Creatinine was tested regarding its sensitisation potential according to OECD 406 ("Skin Sensitisation"). Ten female guinea pigs of the strain "Pirbright White" were treated intradermally with 0.1 mL of a 5 % (w/w) soultion of the test substance in saline. (In contrast to the title of the study guinea pigs were used instead of rabbits. This is an error in the study report which does not have any influence on the study result.). For the dermal application 0.5 g of the test substance moistened with 0.5 mL saline solution was used. Intradermal application of the 5 % (w/w) solution of the test substance in saline caused no to slight erythema and edema formations. 24 hours before topical application of the moistened test substance animals were treated with 10 % sodium lauryl sulphate which resulted in no to slight erythema and edema formations. In the challenge application Duhring chambers with a 20 % (w/w) suspension of the test substance in saline was used, a concentration which was definitely a subirritative concentration.

Systemic toxic symptoms after application were not observed at any time during the study. Body weight development was positive and within normal ranges. In the challenge no erythema and edema were observed at any time point. Therefore the test substance Creatinine has to be regarded as non-sensitizing under the applied test conditions when exposed to the skin of experimental animals.