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Diss Factsheets

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:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
N-[6-(3-{6-[3-(6-formamidohexyl)-2,4-dioxo-1,3-diazetidin-1-yl]hexyl}-2,4-dioxo-1,3-diazetidin-1-yl)hexyl]formamide; N-{6-[3-(6-formamidohexyl)-2,4-dioxo-1,3-diazetidin-1-yl]hexyl}formamide
EC Number:
931-288-4
Molecular formula:
(C8H12N2O2)n
IUPAC Name:
N-[6-(3-{6-[3-(6-formamidohexyl)-2,4-dioxo-1,3-diazetidin-1-yl]hexyl}-2,4-dioxo-1,3-diazetidin-1-yl)hexyl]formamide; N-{6-[3-(6-formamidohexyl)-2,4-dioxo-1,3-diazetidin-1-yl]hexyl}formamide
Constituent 2
Reference substance name:
28182-81-2
Cas Number:
28182-81-2
IUPAC Name:
28182-81-2
Details on test material:
- Stability under test conditions: The test substance is stable in acetone for at least 96 hours. The test substance is not stable in corn oil. The test substance was prepared in acetone or corn oil prior to treatment. The test substance is soluble in corn oil at concentrations lower than 5% (w/w) and corn oil was the most suitable vehicle for intradermal injection of a dilution of the test substance.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Himalayan strain, albino guinea pig (SPF)
- Source: BRL Ltd. Basel Switzerland
- Age at study initiation: approx. 6 weeeks
- Weight at study initiation: 268-400 g
- Housing: group housing of 2 animals per labelled metal cage with wire-floors
- Diet and water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 21°C
- Humidity (%): approx. 50%
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: corn oil for intradermal injections, acetone for epidermal applications
Concentration / amount:
intradermal induction: 5% test substance
epidermal induction: undiluted test substance
challenge: 50, 25, and 10% (w/w) test substance
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: corn oil for intradermal injections, acetone for epidermal applications
Concentration / amount:
intradermal induction: 5% test substance
epidermal induction: undiluted test substance
challenge: 50, 25, and 10% (w/w) test substance
No. of animals per dose:
10 test animals/5 controls
Details on study design:
RANGE FINDING TESTS: Range finding tests were performed using 5 females.
- for intradermal induction: A %1 and 5% (w/w) test substance concentration in corn oil were injected into two sites (0.1 ml each).
- for epidermal induction: The undiluted test substance (0.5 ml) was applied epidermally on a shaved flank for 24 hours, using a non-woven patch (2.5 x 2.2. cm) and occlusive dressings.
- for challenge: Four concentrations of the test substance in acetone (100, 50, 25 and 10 % w/w, 0.05 ml each) were applied occlusively on a shaved flank of each of the four animals for 24 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
- for intradermal induction: On Day 1 animals received three pairs of injections (0.1 ml/site), which are a) FCA/water 1/1, b) test substance 5% in vehicle, c) test substance 5% in FCA/vehicle 1/1
- for epidermal induction: On Day 7 the clipped area was rubbed with 10% sodium-dodecyl-sulfate in petrolateum using a spatula. On Day 8 the clipped area between the injection sites was treated with0.5 ml of the undiluted test substance using a Scotchpak-non-woven patch (2x4 cm) mouted on Micropore tape and secured with Coban elastic bandage. After 48 hours, the dressing was removed and residual test substance removed using a tissue moistened with tap water.

B. CHALLENGE EXPOSURE
- On Day 22 animals were treated epidermally with 0.05 ml of each of the following test substance concentrations 50, 25 and 10 % (w/w) in acetone on the clipped and shaved flank. For negative control solely vehicle was applied. After 24 hours, the dressing was removed and residual test substance removed using a tissue moisted with tap water.

OTHER:
In addition to the skin reactions the following data were recorded: Mortality/ Viability/ Toxicity twice daily; Body weights prior to start and at termination of the study.
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamicaldehyde

Results and discussion

Positive control results:
The most recent control experiment with alpha-hexylcinnamicaldehyde, performed in July 1994, revealed a sensitization rate of 100% (test substance concentrations 10, 5, 2, 0%).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 4.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
50%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 50%. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
25%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25%. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
other: 1st and 2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: other: 1st and 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

Induction - experimental group: All animals showed slight or well-defined erythema after the 48 hours occluded epidermal induction exposure. The control animals showed no skin reaction after the induction application.

Challenge -control group: No skin reactions were evident after the challenge exposure.

Challenge - experimental group: Nine, eight and five animals showed a skin reaction in response to the 50, 25 and 10 % test substance concentrations, respectively. These lead to a sensitisation rate of 90%. The reactions were characterised by discrete/ patchy erythemy, moderate and confluent redness and scaliness.

No mortality occures and no symptoms of systemic toxicity were observed in the animals in the main study during the study period. The average body weight gain of experimental and control animals was similar.

Applicant's summary and conclusion

Executive summary:

A skin sensitization test (GPMT) was conducted according to OECD TG 406 on female guinea pigs (10 test animals and 5 controls). In this test the following concentrations were used based on a prior conducted range finding test: 5 % for intradermal induction (vehicle corn oil), 100 % for topical induction (vehicle acetone) and 50, 25, and 10 % for challenge (vehicle acetone). Before topical induction the skin was rubbed with 10 % sodium dodecyl sulfate in petrolateum. 48 and 72 hours after challenge exposure the treated sites were assessed.

In total, nine, eight and five animals showed a skin reaction in response to the 50, 25 and 10 % challenge concentrations, respectively (sensitisation rate up to 90%). No challenge skin reactions were observed in the control animals in response to all test substance concentrations. Thus, under the conditions of this study a skin sensitisation property was concluded for the substance.