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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
Sodium dimethyldithiocarbamate
EC Number:
204-876-7
EC Name:
Sodium dimethyldithiocarbamate
Cas Number:
128-04-1
IUPAC Name:
sodium dimethyldithiocarbamate
Constituent 2
Reference substance name:
SDMC
IUPAC Name:
SDMC

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 300 to 450g
- Housing: singly or in pairs in solid-floor polypropylene cages furnished with woodflakes
- Diet: Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, UK, ad libitum
- Water: mains tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradennal Induction: 5% v/v in distilled water
Topical Induction: 50% v/v in distilled water
Topical Challenge: 75% and 50% v/v in distilled water
Conclusion.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradennal Induction: 5% v/v in distilled water
Topical Induction: 50% v/v in distilled water
Topical Challenge: 75% and 50% v/v in distilled water
Conclusion.
No. of animals per dose:
Test group: 10, but 1 animal was found dead on day 17. The absence of this animal was considered no to affect the purpose of the study.
Control group: 5
Details on study design:
RANGE FINDING TESTS:
Selection of concentration for Intradermal Induction:
Intradermal injections (0.1 ml/injection site) were made on the clipped shoulder of two guinea pigs, using concentrations of 1% and 5% v/v in distilled water. The degree of erythema at the injection sites was assessed approximately 24, 48, 72 hours and 7 days after injection. The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.

Selection of concentration for topical induction:
Two guinea pigs (intradermally injected with Freund's Complete Adjuvant fourteen days earlier) were treated with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 hours. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 hours after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.

Selection of concentration for topical challenge
The undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water) were applied to the clipped flanks of two guinea pigs under occlusive dressings for an exposure period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to Day 14. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 hours after dressing removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2, intradermal and epicutaneous
- Exposure period: 48 hr for epicutaneous exposure
- Test groups: 10 animals
- Control group: 5 animals. The intradermal induction was performed using an identical procedure to that used for the test animals except that the test material was omitted from the intradermal injections. Injection b) was therefore the vehicle alone, injection c) was a 50% formulation of the vehicle in a 1: 1 preparation of Freund's Complete Adjuvant plus distilled water. Similarly, the topical induction procedure was identical to that used for the test animals except that the test material was omitted.
- Site: shoulder region
- Frequency of applications: 1 intradermal and 1 epicutaneous application
- Concentrations: Intradennal Induction: 5% v/v in distilled water, Topical Induction: 50% v/v in distilled water

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: 5 animals
- Site: both flanks
- Concentrations: 50% and 75%
- Evaluation (hr after challenge): 24 and 48 hr

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% in water
No. with + reactions:
5
Total no. in group:
9
Clinical observations:
Discrete or patchy erythema was noted at the challenge sites of 5 test group animals. These reactions were not apparent at the 48-hour observation and were therefore not attributed to contact sensitization
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% in water. No with. + reactions: 5.0. Total no. in groups: 9.0. Clinical observations: Discrete or patchy erythema was noted at the challenge sites of 5 test group animals. These reactions were not apparent at the 48-hour observation and were therefore not attributed to contact sensitization.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
2
Total no. in group:
9
Clinical observations:
desquamation was noted at the topical challenge sites of 2 test group animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 2.0. Total no. in groups: 9.0. Clinical observations: desquamation was noted at the topical challenge sites of 2 test group animals.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75%
No. with + reactions:
6
Total no. in group:
9
Clinical observations:
Discrete or patchy to moderate and confluent erythema, grades 1 or 2, with or without very slight oedema were noted in 2 animals. Discrete or pathy erythema was noted at the challenge site of 4 test animals, which was not apparent at 48 hr.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 6.0. Total no. in groups: 9.0. Clinical observations: Discrete or patchy to moderate and confluent erythema, grades 1 or 2, with or without very slight oedema were noted in 2 animals. Discrete or pathy erythema was noted at the challenge site of 4 test animals, which was not apparent at 48 hr..
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75%
No. with + reactions:
2
Total no. in group:
9
Clinical observations:
discrete or patchy to moderate and confluent erythema, grades 1 or 2, with or without very slight oedema, were noted in 2 animals at 48 hr. Small superficial scattered scabs or desquamation were noted in 2 animals.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 2.0. Total no. in groups: 9.0. Clinical observations: discrete or patchy to moderate and confluent erythema, grades 1 or 2, with or without very slight oedema, were noted in 2 animals at 48 hr. Small superficial scattered scabs or desquamation were noted in 2 animals..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reactions were noted at the challenge sites of the control group animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no skin reactions were noted at the challenge sites of the control group animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reactions were noted at the challenge sites of the control group animals
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no skin reactions were noted at the challenge sites of the control group animals.

Applicant's summary and conclusion