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

Endpoint summary

Description of key information

Skin irritation: the key study found no evidence of irritant action when the test substance was applied to rabbit skin.  This finding was supported by a separate study using an aqueous 50% solution of test material: again no significant evidence of irritation was seen.
Eye irritation: the key study found clear evidence of irritation when the test substance was instilled into the rabbit eye.  This finding is supported by a separate study using an aqueous 50% solution test material: although recorded responses were less, 3/6 test animals showed changes clearly indicative of irritant activity (24-48-72h mean conjunctival effect scores >2).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Bodyweight 2.2-2.6 kg and checked for absence of corneal, iridial or conjunctival abnormalities pre-test.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

67 mg (0.1 ml equivalent)

Duration of treatment / exposure:

3 rabbits: no removal of test substance up to 14 days post-treatment.
1 rabbit: treated eye washed with distilled water 30 seconds after treatment.

Observation period (in vivo):

Up to day 14 post-treatment.

Number of animals or in vitro replicates:

3 + 1

Details on study design:

One eye treated/animal: untreated eyes served as controls.

Irritation parameter:

cornea opacity score

Remarks:

: corneal opacity

Basis:

animal #1

Remarks:

mean score

Time point:

other: Across 24, 48, and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Score 2 also at 1h

Irritation parameter:

cornea opacity score

Remarks:

: corneal opacity

Basis:

animal #2

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Score 2 also at 1h

Irritation parameter:

cornea opacity score

Remarks:

: corneal opacity

Basis:

animal #3

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

0

Max. score:

0

Remarks on result:

other: Score 0 also at 1h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Score 2 also at 1h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Score 2 also at 1h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Also score 2 at 1h

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Score 3 at 1h

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Also score 2 at 1h

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean score

Time point:

other: Across 24, 48 and 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Also score 2 at 1h

Irritant / corrosive response data:

Iridial changes were less marked that those tabulated above:
- animal 1, score 1 at 24h only
- animal 2, score 1 at 48 and 72h only
- animal 3, score 0 only.

In the one additional animal eyewashed 30 seconds after treatment, no corneal or iridial changes were observed but conjunctival redness and discharge scores were 2 up to 72h (fully recovered by Day 14).

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this study, eye irritation was evident. All lesions were reversible, but the responses were sufficient to trigger classification under the CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Justification for selection of skin irritation / corrosion endpoint:
The test substance did not irritate rabbit skin.

Justification for selection of eye irritation endpoint:
The test substance caused corneal and conjunctival changes which were reversible but clearly indicated irritation.

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation: when both the test substance itself and an aqueous 50% solution were tested, no significant local reactions were seen. Hence no classification in respect of skin irritation is warranted.

Eye irritation: in the key study, mean scores sufficient to warrant classification as irritating to eyes were seen:

- corneal opacity score 2 in 2/3 test animals

- conjunctival redness score 2 in 3/3 test animals

- chemosis =/>2 in 3/3 test animals.

Accordingly, classification as irritating to eyes, Eye Irritant 2; H319 under the CLP Regulation (1272/2008, as amended) is appropriate.