Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
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 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

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:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 338 g (range: 326 g to 354 g) for males and 244 g (range: 230 g to 258 g) for females
- Housing: by 5 from the same group in polycarbonate cages
- Diet: SSNIFF R/M-H pelleted maintenance diet, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back, approximately 7 cm x 5 cm for males and 6 cm x 5 cm for females
- % coverage: ca. 10
- Type of wrap if used: aerated hypoallergenic dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
CLINICAL EXAMINATIONS
Morbidity and mortality
Each animal was checked for mortality and morbidity, once a day during the acclimation period, frequently during the hours following administration, then once a day until the end of the observation period, including weekends.

linical signs
Each animal was observed after treatment as follows:
at least once during the first 30 minutes,
periodically during the first 4 hours,
then once a day, at approximately the same time, for the recording of clinical signs.
Any clinical signs observed were recorded individually for each animal, along with the times of onset and recovery.

Body weight
The body weight of each animal was recorded on the day of group allocation then on the day of treatment and on Days 8 and 15.
The body weight gain of the test item-treated animals was compared to that of CiToxLAB France historical control data generated from animals of the same strain and age treated with drinking water treated by reverse osmosis under similar experimental conditions.

PATHOLOGY
Euthanasia
On completion of the observation period, all animals were deeply anesthetized by an intraperitoneal injection of pentobarbital sodium and euthanized by exsanguination.

Macroscopic post-mortem examination
A macroscopic post-mortem examination was performed on all animals. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. All gross observations were recorded individually for each animal.

Preservation of tissues
For all animals, the macroscopic lesions were preserved in 10% buffered formalin.
Any histological specimens (tissues in fixative) were destroyed at the finalization of the study report.

Microscopic examination
No microscopic examination was performed.
Statistics:
None

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
A very slight or well-defined erythema was noted at the application site in all females from Day 2 or 3 until Days 5, 8 or 12 and 1/5 males from Day 4 to Day 10, associated with scabs in 2/5 females and the affected male.
Body weight:
Body weight of animals was unaffected by the test item treatment when compared to CiToxLAB France historical control data.
Gross pathology:
No macroscopic findings that could be related to treatment were observed in males and females.
2/5 females (animals D28132 and D28133) presented a bilateral dilation of the uterine horns with a translucent content, which was consistent with a physiologic pro-estrus or early estrus state in these female rats.
The gross findings observed were of those commonly reported in the rat of this strain and age and therefore a relationship to treatment was excluded.

Any other information on results incl. tables

The mean body weights and the mean body weight changes (g) recorded in test item-treated animals during the observation period and in CiToxLABhistorical control data are summarized in the table below:

 

Sex

Female

Male

Group

CiToxLAB France historical control data

1

CiToxLAB France historical control data

2

Dose-level (mg/kg)

0

2000

0

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

228 (± 8.5)

244 (± 10.5)

379 (± 15.1)

338 (± 12.8)

. Day 8

253 (± 13.5)

273 (± 15.1)

410 (± 16.7)

373 (± 16.6)

. Day 15

270 (± 13.5)

303 (± 10.2)

422 (± 22.6)

418 (± 21.4)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+25 (± 9.5)

28 (± 7.3)

+30 (± 9.3)

35 (± 6.6)

. Days 8-15

+17 (± 7.1)

30 (± 6.4)

+33 (± 11.5)

45 (± 5.8)

. Days 1-15

+41 (± 9.6)

59 (± 7.5)

+63 (± 12.2)

80 (± 11.5)

SD: Standard Deviations.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD0 of Dimethyl Sulphide was higher than 2000 mg/kg in rats.
Executive summary:

The potential toxicity of Dimethyl Sulphide following a single dermal application to rats was evaluated in a study conducted in compliance with OECD Guideline No. 402. Dimethyl Sulphide was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From Day 2, any local reactions at the treatment site were also noted. Body weight was recorded before allocation into group, then on Days 1, 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No microscopic examination was performed. 

No unscheduled deaths occurred during the study. No clinical signs indicative of systemic toxicity were observed in any animals. A very slight or well-defined erythema was noted at the application site in all females from Day 2 or 3 until Days 5, 8 or 12 and 1/5 males from Day 4 to Day 10, associated with scabs in 2/5 females and the male. Body weight of animals was unaffected by the test item treatment.

No treatment-related macroscopic findings were observed. The dermal LD0 o Dimethyl Sulphide was higher than 2000 mg/kg in rats.