N,N''-methylenebis[N'-[3-(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]urea]

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Report of skin sensitisation studies using two different methods (equivalent to OECD guidelines) and with sufficient detail to support study conclusions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Principles of method if other than guideline:

Separate experiments in Guinea pigs and mice

GLP compliance:

no

Type of study:

other: Guinea pig maximisation (Magnusson Kligman) test and mouse local lymph node assay

Species:

other: Guinea pigs and mice

Strain:

other: Albino Dunkin Hartley Guinea pigs, CBA/Ca mice

Sex:

male/female

Details on test animals and environmental conditions:

Guinea pigs ca. 350g at study start: sex unspecified.
Mice 8-12 wks old: single sex used (male or female not specified)

Route:

intradermal

Vehicle:

other: 0.9% saline

Concentration / amount:

Induction:
- intradermal injections, 2.5%
- occluded patch, 75%.
Challenge:
- occluded patch, 75%

Route:

epicutaneous, occlusive

Vehicle:

other: 0.9% saline

Concentration / amount:

Induction:
- intradermal injections, 2.5%
- occluded patch, 75%.
Challenge:
- occluded patch, 75%

No. of animals per dose:

Minimum 10 (deduced from citation of the method of Magnusson and Kligman, 1970)

Details on study design:

Induction 6x intradermal injections followed 8 days later by 48h occluded patch applicied over injection site.
Challange 12-14 days later: 24h occluded patch (maximum non-irritant concentration).
Reactions scored for erythem and oedema 24 and 48h after challenge patch removal

Challenge controls:

Assumed to have been included, based on citation of the method of Magnusson and Kligman, 1970

Positive control substance(s):

not specified

Positive control results:

Not applicable

Reading:

other: Combined result from 1st and 2nd readings

Hours after challenge:

48

Group:

test chemical

Dose level:

75% challenge concentration

No. with + reactions:

80

Clinical observations:

80% of test group reacted to challange

Remarks on result:

other: Reading: other: Combined result from 1st and 2nd readings. . Hours after challenge: 48.0. Group: test group. Dose level: 75% challenge concentration. No with. + reactions: 80.0. Clinical observations: 80% of test group reacted to challange.

Parameter:

SI

Value:

1.7

Test group / Remarks:

10%

Parameter:

SI

Value:

3.1

Test group / Remarks:

25%

Parameter:

SI

Value:

5.5

Test group / Remarks:

50%

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Both in vivo assay systems employed showed clear evidence of contact sensitisation following exposure to the test substance at concentrations > 10%.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The available studies lead to a conclusion that contact sensitisation occurs in vivo.

Migrated from Short description of key information:

In a Guinea pig maximisation test induction by intradermal injection (2.5%) and topical, occluded patch (75%) followed by topical patch challenge (75%) caused sensitisation reactions in 80% of test animals.

In a mouse local lymph node assay, an SI value >3 was reported for mice treated topically at 25 and 50% (and in a supporting local lymph node/ATP assay, treatment at 25% gave SI >3).

Justification for selection of skin sensitisation endpoint:

This key study shows clear evidence of contact sensitisation at concentrations > 10% in two different in vivo bioassays: Guinea pig maximisation test and mouse local lymph node assay.

Justification for classification or non-classification

The observed level of potency in the key study and supporting local lymph node assay report lead to classification as Skin Sensitiser Category 1B, H317 under the terms of the CLP Regulation as amended.