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Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-02-26 to 1990-03-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The purpose of this skin sensitization study was to assess the allergenic potential of the test item when administered to the skin of albino guinea pigs.
This study should provide a rational basis for risk assessment of the sensitizing potential of the test article in man.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[4-[[2-(cyanoimino)hexahydro-4,6-dioxo-5-pyrimidyl]azo]phenyl]-6-methylbenzothiazole-7-sulphonic acid, compound with 2,2',2''-nitrilotris[ethanol] (1:1)
EC Number:
259-470-2
EC Name:
2-[4-[[2-(cyanoimino)hexahydro-4,6-dioxo-5-pyrimidyl]azo]phenyl]-6-methylbenzothiazole-7-sulphonic acid, compound with 2,2',2''-nitrilotris[ethanol] (1:1)
Cas Number:
55067-15-7
Molecular formula:
C19 H13 N7 O5 S2 . C6 H15 N O3
IUPAC Name:
2-[4-[[2-(cyanoimino)hexahydro-4,6-dioxo-5-pyrimidyl]azo]phenyl]-6-methylbenzothiazole-7-sulphonic acid, compound with 2,2',2''-nitrilotris[ethanol] (1:1)
Specific details on test material used for the study:
- Lot/batch No.: Op. 604/89

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Ibm: GOHI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, Fullinsdorf, Switzerland
- Age at study initiation: 7-8 weeks (at acclimatization start)
- Weight at study initiation: males: 328-382 g, females: 330-359 g (at acclimatization start)
- Housing: individually
- Diet: ad libitum Pelleted standard Kliba 342, "Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst
- Water: tap water ad libitum, once weekly additional supply of ascorbic acid via the drinking water
- Acclimation period: one week under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal injections: 0.1 mL per site, test group:
1) Freund's complete adjuvant 50:50 with bi-distilled water
2) The test article, diluted to 5 % with bi-distilled water.
3) The test article at the concentration used in (2), emulsified in a 50:50 mixture of Freund's complete adjuvant and the vehicle used in (2)
Control group:
1) Freund's complete adjuvant 50:50 with bi-distilled water.
2) Vehicle used in (2) for test group.
3) Freund's complete adjuvant 50:50 with bi-distilled water.

Epidermal application: 25 % in bidistilled water
Challenge: 25 % in bidistilled water (non-irritant concentration), vehicle only
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal injections: 0.1 mL per site, test group:
1) Freund's complete adjuvant 50:50 with bi-distilled water
2) The test article, diluted to 5 % with bi-distilled water.
3) The test article at the concentration used in (2), emulsified in a 50:50 mixture of Freund's complete adjuvant and the vehicle used in (2)
Control group:
1) Freund's complete adjuvant 50:50 with bi-distilled water.
2) Vehicle used in (2) for test group.
3) Freund's complete adjuvant 50:50 with bi-distilled water.

Epidermal application: 25 % in bidistilled water
Challenge: 25 % in bidistilled water (non-irritant concentration), vehicle only
No. of animals per dose:
10 males, 10 females for the test group, 5 males, 5 females per control group
Details on study design:
RANGE FINDING TESTS:
Intradermal injections (0.1 mL/site) were made into the clipped flank of two guinea-pigs at concentrations of 5%, 3% and 1 % of the test article in bidistilled water. The resulting dermal reactions were assessed 24 hours later.
Epidermal applications:
Patches of filter paper ( 2 x 2 cm) were saturated with concentrations of 25%, 15%, 10% and 5% of the test article in bi-distilled water and applied to the clipped and shaved flanks of each of four guinea-pigs. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape. This procedure ensured the intensive contact of the test article. The dressings were removed after an exposure period of 24 hours and the reaction sites were assessed for erythema and edema. To confirm the results observed at first epidermal pretest without depilating the test sites prior to the first reading, a second pretest was performed 5 days before primary challenge on a further 4 guinea pig individuals according to the same method.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: Approximately 24 hours prior to the epidermal application the test area was pretreated with 10 % Sodium-Lauryl-Sulfat (SLS) in petrolatum-oil, because no primary irritation concentration could be determined in the corresponding pretest. The SLS was massaged into the skin with a glass rod without bandaging to provoke a mild inflammatory reaction.
Epidermal application: one week after injections, a patch containing test article was applied to the shaved skin over the injection sites and fixed for an exposure time of appr. 48 hours. Reaction sites were evaluated immediately, 24 h and 48 hours after removal.
- Control group: The guinea-pigs of the control group were treated as described above with the omission of test article.
- Site: scapular region (dorsal)


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: two weeks after the epidermal induction application
- Exposure period: 24 hours
- Test groups: Two patches ( 2 x 2 cm) of filter paper were saturated with a) non-irritant concentration (25 % in bi-distilled water) of the test article and b) with the vehicle only and applied to the (a) left flank and (b) right flank using the same method as for the epidermal application.
- Control group: control animals were treated in the same way.
- Site: left adn right flank
- Evaluation (hr after challenge): immediately, 24 and 48 hours

Challenge controls:
The control animals were treated in the same way.
Positive control substance(s):
yes
Remarks:
formaldehyde

Results and discussion

Positive control results:
According to the results observed it is considered that HCHO possess an extreme skin sensitizing (contact allergenic) potential in the guinea pig strain used.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 % test article dilution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs were observed.
Remarks on result:
other: Reading: 1st reading. Hours after challenge: 24.0. Group: test group. Dose level: 25 % test article dilution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No clinical signs were observed.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 % test article dilution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs were observed.
Remarks on result:
other: Reading: 2nd reading. Hours after challenge: 48.0. Group: test group. Dose level: 25 % test article dilution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No clinical signs were observed.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group
Dose level:
vehicle only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No clinical signs were observed.
Remarks on result:
other: Reading: 1st reading. Hours after challenge: 24.0. Group: other: control group. Dose level: vehicle only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No clinical signs were observed.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group
Dose level:
vehicle only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No clinical signs were observed.
Remarks on result:
other: Reading: 2nd reading. Hours after challenge: 48.0. Group: other: control group. Dose level: vehicle only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No clinical signs were observed.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction: 20 % HCHO, challenge: 15 % HCHO
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. Hours after challenge: 24.0. Group: positive control. Dose level: induction: 20 % HCHO, challenge: 15 % HCHO. No with. + reactions: 9.0. Total no. in groups: 10.0.

Any other information on results incl. tables

CONTROL GROUP:

No positive reactions were evident after the first challenge application, neither when treated with bi-distilled water alone nor when treated with a 25 % test article dilution.

TEST GROUP:

Immediately after removal of the challenge patches, one male animal of the test article treated test group exhibited slight erythema and slight edema (score 1). No positive reactions were evident after the first challenge application after 24 and 48 hours, neither when treated with bi-distilled water alone nor when treated with a 25 % test article dilution.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met