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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplier: ARKEMA / Groupement de Recherche de Lacq
Name: TPS 44
Batch number: 05-11-04
Sulfur content 44.46%

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, Franc
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 2.4 ± 0.1 kg
- Housing: individually in polystyrene cages
- Diet (e.g. ad libitum): 110C pelleted diet (SAFE, Villemoisson, Epinay sur-Orge, France)
- Water (e.g. ad libitum): Filtered tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours.
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
Since there were persistent irritation reactions at 72 hours, the observation period was extended. In the absence of complete reversibility of skin reactions on day 15, the study was ended.
Number of animals:
3
Details on study design:
TPS 44 was first evaluated on a single animal (No. 382). The durations of exposure were 3 minutes, 1 hour and 4 hours.
Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals (Nos. 751 and 752).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Remarks on result:
other: 4-hour exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 4-h exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: 4-hour exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 4-h exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 4-h exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: 4-h exposure
Irritant / corrosive response data:
After a 3-minute exposure (one animal)
A very slight or well-defined erythema (grade 1 or 2) was noted from day 1 up to the end of the observation period (day 15).
A very slight or slight edema (grade 1 or 2) was observed from day 3 up to day 9.
Dryness of the skin was also recorded from day 5 up to the end of the observation period (day 15).

After a 1-hour exposure (one animal)
A very slight or well-defined erythema (grade 1 or 2) was noted from day 1 up to the end of the observation period (day 15).
A very slight or slight edema (grade 1 or 2) was observed from day 4 up to day 9.
Dryness of the skin was also recorded from day 6 up to the end of the observation period (day 15).

After a 4-hour exposure (three animals)
A very slight or well-defined erythema (grade 1 or 2) was noted in all animals from day 1 up to day 12, 13 or 15 (end of the observation period).
A very slight or slight edema (grade 1 or 2) was observed in 2/3 animals from day 1 up to day 3 or 7.
Dryness of the skin was also recorded in all animals between days 5 and 15 (end of the observation period).

Mean scores over 24, 48 and 72 hours for each animal were 2.0, 2.0 and 2.0 for erythema and 0.0, 1.0 and 2.0 for edema.

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
TPS 44 was a mild irritant when applied topically to rabbits.
Executive summary:

The potential of di-tert-butyl polisulfides (TPS 44) to induce skin irritation was evaluated in rabbits according to OECD No. 404 and EC (2004/73/EC, B.4) guidelines and in compliance with the principles of GLP. TPS 44 was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals. A single dose of 0.5 mL of undiluted TPS 44 was applied to the closely-clipped skin of one flank. TPS 44 was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until the end of the observation period. The mean values of the scores for erythema and edema were calculated for each animal.

After a 3-minute exposure (one animal), a very slight or well-defined erythema was noted from day 1 up to the end of the observation period (day 15). A very slight or slight edema was observed from day 3 up to day 9 and dryness of the skin was also recorded from day 5 up to the end of the observation period (day 15). After a 1-hour exposure (one animal), a very slight or well-defined erythema was noted from day 1 up to the end of the observation period (day 15). A very slight or slight edema was observed from day 4 up to day 9 and dryness of the skin was also recorded from day 6 up to the end of the observation period (day 15). After a 4-hour exposure (three animals), a very slight or well-defined erythema was noted in all animals from day 1 up to day 12, 13 or 15 (end of the observation period). A very slight or slight edema was observed in 2/3 animals from day 1 up to day 3 or 7 and dryness of the skin was also recorded in all animals between days 5 and 15 (end of the observation period). Mean scores over 24, 48 and 72 hours for each animal were 2.0, 2.0 and 2.0 for erythema and 0.0, 1.0 and 2.0 for edema.