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Toxicological information

Skin sensitisation

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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: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

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
Justification for non-LLNA method:
A GPMT was already performed 2003

Test material

Constituent 1
Reference substance name:
Hydroxyethyl Imidazolidone Methacrylate
IUPAC Name:
Hydroxyethyl Imidazolidone Methacrylate
Details on test material:
- Name of test material (as cited in study report): Hydroxyethyl Imidazolidone Methacrylate (MEIO)
- Physical state: whitish powder
- Analytical purity: 90%
- Lot/batch No.: OP2981

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, L`Arbresle, France
- Age at study initiation: 1-2 months
- Weight at study initiation: mean 380+/- 17 g male; mean 342 +/- 12g female
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
5 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
5 %
No. of animals per dose:
treated group 20
control group 10
Details on study design:
On day 1, three pairs of intradermal injections were performed in the interscapular region of all animals:
• Freund's complete adjuvant (FCA) diluted to 50% (v/v) with 0.9% NaCl (both groups),
• test item at the concentration of 5% in 0.9% NaCl (treated group) or vehicle alone (control group),
• test item at the concentration of 5% in a mixture FCA/0.9% NaCl (50/50, w/w) (treated group) or vehicle at the concentration of 50% (v/w) in a mixture FCA/0.9% NaCl (50/50, v/v) (control group).
On day 8, the animals of the treated group received a topical application of the test item at the concentration of 50% (w/w) in 0.9% NaCl to the same test site, which was then covered by an occlusive dressing for 48 hours. The animals of the control group received an application of the vehicle under the same experimental conditions.
On day 22, all animals of both groups were challenged by a cutaneous application of the test item at the concentration of 50% (w/w) in 0.9% NaCl to the right flank. The test item was maintained under an occlusive dressing for 24 hours. The vehicle was applied to the left flank under the same experimental conditions.
Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing.
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
discrete erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: discrete erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
discrete erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: discrete erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
No. with + reactions:
18
Total no. in group:
19
Clinical observations:
discrete, moderate or intense erythema/ oedma and/or crusts
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 %. No with. + reactions: 18.0. Total no. in groups: 19.0. Clinical observations: discrete, moderate or intense erythema/ oedma and/or crusts.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
18
Total no. in group:
19
Clinical observations:
moderate or intense erythema / oedema, dryness of the skin, crusts and/or brownish area
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 %. No with. + reactions: 18.0. Total no. in groups: 19.0. Clinical observations: moderate or intense erythema / oedema, dryness of the skin, crusts and/or brownish area.

Any other information on results incl. tables

No systemic clinical signs and no deaths related to treatment were noted during the study.

After the challenge application, a discrete erythema (grade 1) was observed in 1/10 animals of the control group at the 24-hour reading and in another animal at the 48-hour reading.

In the treated group, at the 24-hour reading, a discrete, moderate or intense erythema (grade 1, 2 or 3), together with an oedema and/or crusts in 6/19 animals, was noted in 1/19, 5/19 and 12/19 animals, respectively. At the 48-hour reading, a moderate or intense erythema (grade 2 or 3), together with an oedema, dryness of the skin, crusts and/or a brownish area in 16/19 animals, was recorded in 5/19 and 13/19 animals, respectively.

The cutaneous reactions observed in the animals of the treated group, which were of higher incidence and severity than those recorded in the animals of the control group, were attributed to delayed contact hypersensitivity.

Under our experimental conditions and according to the maximization method of Magnusson and Kligman, the test item HYDROXYETHYL IMIDAZOLIDONE METHACRYLATE (MEIO) (batch No. OP2981) induces delayed contact hypersensitivity in 18/19 (95%) guinea pigs and therefore should be considered as an extreme sensitizer.

Applicant's summary and conclusion

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