Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

GPMT (1983)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7th June to 5th July 1983

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

not specified

Remarks:

Huntingdon Research centre was fully audited by quality assurance unit at that time, a signed Quality statement is within report but no mention of GLP status in report

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Performed in 1983 and reliable/ valid study according to OECD 406 & based on method described by Magnusson and Kligman " Allergic contact Dermatitis in the Guinea Pig"

Test material

Test material information

Constituent 1

Reference substance name:

Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

EC Number:

283-381-8

EC Name:

Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

Cas Number:

84604-96-6

Molecular formula:

C38H76N2S4Zn

IUPAC Name:

bis({[bis(3,5,5-trimethylhexyl)carbamothioyl]sulfanyl})zinc

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Off white powder, stored at ambient temperature
High Purity

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Remarks:

albino

Sex:

male

Details on test animals and environmental conditions:

30 male animals, acclimitised to lab environment. Weight at start of study ( mean) 483g; End of study mean weight was 617g
The guinea pigs were housed in suspended cages with wire mesh floors. They had free access to tap water and a vitamin C enriched guinea pig diet and hay was given weekly. Animal room temperature was aproximately 21 degrees C and relative humidity 30-70%

Air exchange was maintained at approximately 15 air changes per hour & lighting was controlled by a time switch

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: alembicol D

Concentration / amount:

Induction - intradermal - 2.5% w/w test substance in alembicol D
topical : 60% w/w in Alembicol D

Challenge: 20% & 10% w/w in Alembicol D

Day(s)/duration:

Upon intradermal injections, one week elapsed before challenged.

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: alembicol D

Concentration / amount:

20 % and 10% w/w

Day(s)/duration:

Dressing was in place for 24

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 animals induction and all 20 in addition to 10 controls for challenge.

Details on study design:

RANGE FINDING TESTS: Preliminary investigation undertaken to determine substance concentration suitable for both induction and challenge.

Induction phase, selected concentration of test substnace that produced irritancy for both intradermal (2.5 %w/w ) and topical application (60% w/w )
Concentration for challenge phase was determined as 20% and 10% in vehicle

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal injection
All twenty test animals
- 4x6 cm area of dorsal skin on the scapular region of the guinea pig. Three pairs of injections perpared and injected simultaneously as follows

1. Fruends complete adjuvant (1;1 with water)
2. 2.5w/w of test substance in Alembicol D
3. 2.5% w/w of test substance in 50;50 mix of Freunds and Alembicol D

Topical Application
One week after injections, same interscapular area was shaved free of hair and 60%w/w of test substance was placed on the skin and covered with dressing for 48 hours.

B. CHALLENGE EXPOSURE
- All 30 animals were challenged topically two weeks after induction period with concentration of test substance at 20% and 10% w/w in vehicle

OTHER:

Challenge controls:

Freunds treated controls

Positive control substance(s):

no

Results and discussion

Positive control results:

n/a

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20%

No. with + reactions:

3

Total no. in group:

20

Clinical observations:

Localised dermal reaction

Remarks on result:

other: Too small a number to be statistically significant

Any other information on results incl. tables

Dermal reactions in the test animals elicited by the challenge applications were compared with the findings simulatneously obtained in the control animals.
A test animal was considered to show positive evidence of delayed contact hypersensitivity if the observed dermal reaction at challenge was definitely more marked and or presistant than the maximum reaction seen in animals of the control group

The numerical scores to dermal reactions elicited by the challenge is shown in table 1 attached. The dermal reactions ( defined erythema or slight erythema was observed in three out of twenty of the test animals at 72 hours which was more marked than controls. However, no evidence of delayed contact hypersensitivity was seen in the remaining seventeen guinea pigs at 72 hours. Based on these results the test substnace does not have to be classified and no classifcation criteria for skin sensitisation is required. (GHS 2015) nor CLP 1272/2008

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The threshold for delayed sensitivity in the study conducted to Magnusson and Kligman (1970) was not reached.
No evidence of delayed contact hypersensitivity was concluded for test substance .