Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

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:
2015
Report Date:
2015

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:
- Name: Dimethyl Sulphide
- Synonyms: DMS, dimethyl sulfure, sulfure de dimethyle, dimethyl sulfide
- Batch number: C8753
- Description: Colorless liquid
- Storage condition: At room temperature
- Purity: 99.7%
- Purity test date: 09/01/2015
- Expiration date of the lot/batch: 08 April 2017

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Argenvilliers, France.
- Age at study initiation: 3 to 4 months old
- Weight at study initiation: 3130 g to 3510 g
- Housing: individually housed in noryl cages
- Diet: pelleted breeding diet "type 110C", ad libitum
- Water:. ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): 5 to 15
- Photoperiod (hrs dark / hrs light): 12h/12h

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
3-minute, 1- and 4-hour
Observation period:
1 hour, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: right and left anterior and/or posterior flanks
- coverage: 6 cm²
- Type of wrap if used: semi-occlusive dressing and restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
Dermal irritation was graded in each animal according to the following scoring scale:

Erythema and eschar formation:
. no erythema: 0
. very slight erythema (barely perceptible): 1
. well-defined erythema: 2
. moderate to severe erythema: 3
. severe erythema (beet redness) to slight eschar formation (injuries in depth): 4


Edema formation
. no edema: 0
. very slight edema (barely perceptible): 1
. slight edema (edges of area well-defined by definite raising) : 2
. moderate edema (raised by approximately 1 millimeter): 3
. severe edema (raised by more than 1 millimeter and extending beyond area
of exposure): 4

STUDY DESIGN
Rationale for design selection
The sequential study design was as follows:
The test item was applied for 3 minutes on the skin of a single animal (D31251):
¿ as no full thickness destruction of skin tissue was observed in the first hour after removal of the pad, the test item was applied on another treatment site for 1 hour.

After the 1-hour application on animal D31251:
¿ as no full thickness destruction of skin tissue was observed in the first hour after removal of the pad, the test item was applied on another treatment site for 4 hours.

After the 4-hour application on animal D31251:
¿ as mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema and for edema, the test item was applied on the skin of two other animals for 4 hours (D31252 and D31253).

For each animal, the day of dose application was recorded as Day 1 of its observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: #1, 2 and 3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1, 2 and 3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No cutaneous reactions were observed during the study.

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:
¿ erythema: 0.0, 0.0, 0.0; showing no significant inflammation,
¿ edema: 0.0, 0.0; 0.0; showing no significant inflammation.
Other effects:
MORTALITY
No unscheduled deaths occurred during the study.

BODY WEIGHT
The body weight of the animals was unaffected by the test item treatment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Dimethyl Sulphide was non-irritant when applied topically to rabbits.
Executive summary:

The potential corrosive and irritant properties of Dimethyl Sulphide, following dermal application on rabbits was evaluated in a study conducted in compliance with the OECD Guideline No. 404. Dimethyl Sulphidewas first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema and for edema, the test item was applied on the skin of two other animals for 4 hours. A dosage-volume of 0.5 mL/flank was used. The test item was placed on a gauze pad, which was then applied to a skin area of approximately 6 cm2. The gauze pad was held in place by a non-irritation semi-occlusive dressing and a restraining bandage.After required period of contact with the skin, the dressing was removed. Each animal was observed once a day for mortality and clinical signs. For each exposure period, cutaneous reactions were evaluated approximately 1, 24, 48 and 72 hours after removal of the dressing. The mean values of the scores for erythema and edema were calculated for each animal. Body weight was recorded on the day of treatment and at the end of the evaluation of cutaneous reactions.

No unscheduled deaths occurred during the study and no clinical signs were noted in any animals. The body weight of the animals was unaffected by the test item treatment. No cutaneous reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.         erythema: 0.0, 0.0, 0.0; showing no significant inflammation,

.         edema: 0.0, 0.0; 0.0; showing no significant inflammation.

Dimethyl Sulphide was non-irritant when applied topically to rabbits.