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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
Study period:
6 Nov 1985 to 12 Dec 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: Toxic Substances Control Act, Health Effects Test Guidelines; Office of Toxic Substances; Office of Pesticides and Toxic Substances; United States Environmental Protection Agency, August 1982; Dermal Sensitisation.
Principles of method if other than guideline:
The procedure was a modification of that described in "Delayed Contact Hypersensitivity in the Guinea-pig" Buehler E.V. (1965), Arch. Dermatol. 91, 171.
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Buehler test has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel bis(dibutyldithiocarbamate)
EC Number:
237-696-2
EC Name:
Nickel bis(dibutyldithiocarbamate)
Cas Number:
13927-77-0
Molecular formula:
C18-H36-N2-Ni-S4
IUPAC Name:
Nickel(II) Dibutyldithiocarbamate
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Name of the test item (as cited in study report): Nickel dibutyldithiocarbamate
- Batch No.: C 0131100 NF
- Appearance: Green, powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 300-350 g
- Housing: The guinea-pigs were housed individually in suspended cages with wire mesh floors
- Diet: ad libitum, Vitamin C-enriched Guinea·Pig Diet F.D.1 (Special Diets Services Limited). Hay was given once weekly.
- Water: ad libitum, tap water
- Acclimation period: 13 days

ENVIRONMENT
- Temperature (°C): 21
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
0.5 mL of the test substance, 40% w/w in liquid paraffin.
Day(s)/duration:
9 days in 3 weeks / 6 hours exposure
Adequacy of induction:
not specified
Challenge
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
0.5 mL of the test substance, 40% w/w in liquid paraffin.
Day(s)/duration:
6 hours
Adequacy of challenge:
not specified
No. of animals per dose:
Ten animals
Details on study design:
PRELIMINARY INVESTIGATIONS
The topical irritancy of a range of dilutions of the test substance in liquid paraffin was investigated to identify (a) a slightly irritant concentration, where possible, suitable for the induction phase of the main study and (b) a
non-irritant concentration for the challenge phase.

INDUCTION
Prior to each induction application, the skin on the left shoulder region of the guinea-pig was clipped free of hair using electric clippers. A 2 x 2 cm patch of surgical gauze (three layers thick) was saturated with approximately 0.5 mL of the test substance, 40% w/w in liquid paraffin. The patch was placed on the skin and covered by a length of impermeable plastic adhesive tape (5 cm width "Blenderm"). This in turn was firmly secured by elastic adhesive bandage ("Elastoplast" 5 cm width) wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. Contact with the skin was maintained for approximately 6 hours for each induction exposure. The dressings were then removed and the resulting dermal reactions assessed approximately 24 hours later for erythema and oedema. Nine induction applications were made in this manner three times a week during a three week period.

CHALLENGE
The test and untreated control animals were challenged topically two weeks after the ninth induction application using the test substance, 40% w/w in liquid paraffin. Hair was removed by clipping from a 5 x 5 cm area on the right flank of each guinea-pig. A 2 x 2 cm gauze patch (3 layers thick) was saturated with approximately 0.5 mL of the test sample in a similar fashion to that used for the induction applications. The patch was sealed to the flank for approximately 6 hours under a 5 cm strip of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek". The untreated controls were treated similarly to the test animals, but received the test sample applied specifically to an anterior site on the left flank.
The challenge site was evaluated 24, 48 and 72 hours after removal of the patch.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Reading:
other: no reading
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Clinical signs

There were no signs of ill health or toxicity observed in any of the test or untreated control animals throughout the duration of the study.

Bodyweight changes

Bodyweight changes recorded in test animals were similar to those noted in untreated control animals

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met