Tetrakis(phenylmethyl)thioperoxydi(carbothioamide)

Endpoint summary

Description of key information

Based on guinea pigs study, Tetrabenzylthiuram disulfide is not considered as a skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

As described in the Annex of EEC Directive 84/449 of 25 April 1984

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

OECD Testing Guideline 406, adopted on 12 May 1981

Deviations:

no

GLP compliance:

yes

Type of study:

split adjuvant test

Justification for non-LLNA method:

The skin sensitisation study on guinea pigs was performed before REACH regulation.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Thirty-five young adult female guinea pigs of the Dunkin-Hartley strain, approximately 2 months old at the start of the experiment, SPF-quality, were obtained from Charles River Wiga, FRG. The animals were nulliparous and non-pregnant; they were identified by means of a tattoo behind the ears.
A few days before the start of the experiment, the bodyweights ranged from 292 to 437 g (see Tables 1 and 2). The animals were housed in metal cages with wire-mesh floors (ITL, Bergen, The Netherlands; 2 animals per cage). They were fed standard guinea pig diet, including ascorbic acid (1600 mg/kg) obtained from Hope Farms, Woerden, The Netherlands (LC 23-B, pellet diameter 4 mm) and had free access to tap-water (via automatic nozzles). Certificates of analyses for both diet and drinking water are retained in the RCC NOTOX archives. In addition, once a week hay was provided.
The animal room temperature was between 19 and 22°c and the relative humidity between 60 and 80 per cent. The artificial light sequence was 12 hours light, 12 hours dark.
A combined quarantine/acclimatisation period of 13 days was allowed (7 days for the animals of the primary irritation experiment).

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

25% (w/w) in milli-RO water

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

50%, 25%, 5% and 0% (w/w)

No. of animals per dose:

Number of animals in test group: 20
Number of animals in negative control group: 10

Details on study design:

Primary irritation experiment
A primary irritation test was carried out using five guinea pigs to determine the concentrations to be applied in the challenge phase (these should not produce any substantial irritation). Four guinea pigs were shaved and their flank was exposed for 24 hours in an amount of 0.05 ml to 50%, 25%, 10% and 5% (w/w) of the test substance in aqueous methyl cellulose 1% occlusively administered by means of
four Square chambers (v.d. Bend, Brielle, The Netherlands).
One additional animal was treated epicutaneously with 0.5 ml of the test substance, 50% in aqueous methyl cellulose 1%, on a patch of Metalline (Lohmann, W.-Germany) for evaluation of the toxicity of the compound. In this case, the test substance caused no skin irritation.
No systemic toxic effects resulted from these treatments in any of the animals

Induction
The experimental animals had an area of skin clipped and shaved on the back behind the right shoulder. The animal was wrapped in a "window dressing" which consisted of Cohan elastic bandage (Smith and Nephew, England). A 2 x 2 cm opening was cut in the dressing over the exposure site. Dry ice was applied to the test site for approximately 5 sec with firm pressure. Then 0.2 ml of test substance, 25% (w/w) in Milli-RO water was applied and this was covered with a Metalline patch (Lohmann). The patch was then covered with water-impervious tape (Sleek, Smith and Nephew, England).
On day 2, the dressing covering the window was removed, 0.2 ml of the test material in Milli-RO water was applied, and the window reclosed with the same dressing.
On day 4, the window was again opened and 0.1 ml of Freund's complete adjuvant (Difeo, Detroit, USA) injected intradermally on both sides of the exposure site. This was followed by a further application of 0.2 ml of the test substance in Milli-RO water, and the window closed.
On day 7, the test material was again applied.
On day 9, all wrappings were removed.
(On day 4, the negative control animals received intradermal injections of Freund's complete adjuvant to exclude interpretation difficulties in the challenge phase caused by a specific lowering of the skin irritation threshold by this substance).

Challenge
On day 21, the flank was carefully shaved and the protruding long hairs from the edges cut away with scissors. The test substance, suspended in Milli-RO water, was applied in a volume of 0.05 ml on Square chambers (v.d. Bend, Brielle, The Netherlands), mounted on Micropore-tape. Each animal received 4 different concentrations of test substance; all animals were treated similarly.
The concentrations tested were: 50%, 25%, 5% and 0% (w/w) of the test substance in Milli-RO water. The elastic bandage (Cohan) was kept in place for 24 hours.
Twenty-four and fourty-eight hours after removal of the dressings, readings were made.
If considered necessary for the proper evaluation of skin reaction, the treated side of all animals was shaved after the first reading on day 23.

Challenge controls:

Positive controls were carried out regularly to show the proficiency of the testing facility and the sensitivity of the strain of guinea pigs, in accordance with the OECD Testing Guideline 406 and EEC test method B.6, Methods for the Determination of Toxicity, "Acute toxicity - skin sensitization", as described in the Annex of EEC Directive 84/449 of 25 April 1984.

Positive control substance(s):

yes

Remarks:

A positive control experiment was carried out in February 1987 (RCC NOTOX Study Ref. No. 0000/663) using solutions of formaldehyde 37% at 5%, 2% and 0.5% (w/w) in milli-RO water.

Positive control results:

A sensitisation rate of 50% was obtained with the 0.5% concentration.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0%

No. with + reactions:

0

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0%

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Maximum concentration not causing irritating effects in preliminary test.

Signs of irritation during induction: None

Evidence of sensitation of each challenge concetration: None

Other observations:

Red spots (signs of irritation were observed in 3 test animals at concetrations 50% (24 and 48 hrs), 25% (48 hrs) and 0% (48 hrs) respectively and in one controlanimal (48 hrs). No signs of systemic toxicity were observed in any of the animals during the study period.

Interpretation of results:

GHS criteria not met

Remarks:

Not skin sensitizer

Conclusions:

The results indicate a sensitization rate of 0%. It is therefore improbable that the test substance has sensitizing properties.

Executive summary:

Tetrabenzylthiuram disulfide (TBzTD) was tested in the Split Adjuvant Test to determine its sensitizing potential.

Adult female guinea pigs (Dunkin-Hartley strain) were induced by epicutaneous applications of the test substance, 25% (w/w) in Milli-RO water. After being challenged with a series of test substance concentrations (50%, 25% and 5%) in Milli-RO water, no positive response (grade 2 or more) was observed to the concentrations tested in any of the animals.

These results indicate a sensitization rate of 0%. It is therefore improbable that the test substance has sensitizing properties.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Tetrabenzylthiuram disulfide (TBzTD) was tested in the Split Adjuvant Test to determine its sensitizing potential.

Adult female guinea pigs (Dunkin-Hartley strain) were induced by epicutaneous applications of the test substance, 25% (w/w) in Milli-RO water. After being challenged with a series of test substance concentrations (50%, 25% and 5%) in Milli-RO water, no positive response (grade 2 or more) was observed to the concentrations tested in any of the animals.

These results indicate a sensitization rate of 0%. It is therefore improbable that the test substance has sensitizing properties.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, Tetrabenzylthiuram disulfide should not be classified as skin sensitizer according to the Regulation EC n°1272/2008.