1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported study performed under GLP and using a standard test method.

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:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

EC Number:

278-928-2

EC Name:

1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Cas Number:

78491-02-8

Molecular formula:

C8H14N4O7

IUPAC Name:

1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Pre-test bodyweights 267-356g (males), 246-352g (females).

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Intradermal induction: 1% in water (mixed 1:1 with FCA at one of the 3 injection sites) - determined to be non-necrotic in preliminary testing.
Topical induction: 75% in water - determined to be systemically tolerated and produce no more than mild/moderate irritation in preliminary testing.
Challenge: 25% in water - selected as the highest, non-irritant concentration from preliminary testing.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

Intradermal induction: 1% in water (mixed 1:1 with FCA at one of the 3 injection sites) - determined to be non-necrotic in preliminary testing.
Topical induction: 75% in water - determined to be systemically tolerated and produce no more than mild/moderate irritation in preliminary testing.
Challenge: 25% in water - selected as the highest, non-irritant concentration from preliminary testing.

No. of animals per dose:

Test group:10 males, 10 females.
Vehicle control group: 5 males, 5 females.

Details on study design:

Preliminary test:
- 3 animals dosed intradermally at 1, 10, 25 and 50%
- 6 animals dosed topically at 10, 25, 50, 75% (0.1 ml, 24h under occlusive patch).
Main test:
- 6 intradermal injections/animal. 2x 0.1 ml FCA, 2x 0.1 ml test solution or water(controls), 2x 50% FCA/test solution or 50% FCA/water(controls)
- 7 days later, 0.2 ml test solution or water(controls) applied topically between injection sites (48h under occlusive patch)
- 14 days later, topical application of 0.2 ml test solution (site 1) and water (site 2) to test and control animals (24h under occlusive patch).

Challenge controls:

Test solution and water applied to all animals.

Positive control substance(s):

yes

Remarks:

2-mercaptobenzothiazole: study performed 3 months earlier in the same laboratory and using the same test methods.

Results and discussion

Positive control results:

2-mercaptobenzothiazole, animals induced by intradermal injection (5%) and topical application (50%), then challenged (25%): 5/10 males and 3/5 females showed positive challenge reactions. Vehicle (acetone) control group: 2/10 showed positive challenge reactions.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Water only

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Water only. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Water only

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Water only. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Local reactions to induction treatments in the test group (scores of 1 or 2 after intradermal injection, 0, 1 or 2 after topical application) indicated that the selected concentrations were appropriate.

Local reactions to topical application in the preliminary test (2/6 animals showing score 1 at 25%, 1/6 showing score 2 at 50%) indicated that the selected challenge concentration was appropriate.

No test group animal showed skin reactions to water application at challenge.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the complete absence of reactions to challenge in this study, the test substance has no demonstrated potential to cause delayed contact sensitisation of the skin.