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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class 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:
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: 209-230 g
- Fasting period before study: overnight
- Housing: by three 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

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
Doses:
2000 mg/kg bw
Control animals:
no
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:
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:
Piloerection was noted in 3/6 females on Day 1, associated with hunched posture in two of them.
Body weight:
When compared to CiToxLAB France historical control data, a lower body weight gain was noted in 4/6 females over the whole study period (+41 to +48 g vs. +60 ± 6.0 g in control data base) including 1/6 females (+27 g vs. 41 ± 7.2 g) between Day 1 and Day 8 and 1/6 females (+6 g vs. +20 ± 6.7 g) between Day 8 and Day 15.
The body weight gain of the other animals was unaffected by the test item treatment.
Gross pathology:
The test item administration did not induce any macroscopic findings.
The macroscopic finding noted at necropsy (i.e. dilated uterus with translucent content in three females) is commonly recorded in the rat as a consequence of the estrous cycle (proestrus or estrus), and was therefore considered to be incidental.

Any other information on results incl. tables

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

 

Sex

                                                             Female

Group

Historical control data

1

2

Dose-level (mg/kg)

0

2000

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

198 (± 6.6)

216 (± 6.1)

226 (± 3.5)

. Day 8

239 (± 8.6)

249 (± 11.0)

272 (± 12.7)

. Day 15

258 (± 8.6)

261 (± 6.1)

293 (± 21.4)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+41 (± 7.2)

+34 (± 7.0)

+46 (± 12.1)

. Days 8-15

+20 (± 6.7)

+11 (± 4.6)

+20 (± 9.0)

. Days 1-15

+60 (± 6.0)

+45 (± 3.8)

+66 (± 21.2)

SD: standard deviations.

Applicant's summary and conclusion

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

The potential acute toxicity of Dimethyl Sulphide, following a single oral administration (gavage) to rats was evaluated in astudy conducted in compliance with OECD Guideline No. 423. Dimethyl Sulphide in corn oil was administered once by oral route (gavage) at the dose level of 2000 mg/kg bw to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. After the first assay, as no toxicity was observed, the results were confirmed in other females. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.

No unscheduled deaths occurred during the study. Piloerection was noted in 3/6 females on Day 1, associated with hunched posture in two of them. When compared to historical control data, a lower body weight gain was noted in 4/6 females over the whole study period (+41 to +48 g vs.+60 ± 6.0 g in control data base) including 1/6 females (+27 g vs.41 ± 7.2 g) between Day 1 and Day 8 and 1/6 females (+6 g vs. +20 ± 6.7 g) between Day 8 and Day 15. The body weight gain of the other animals was unaffected by the treatment. No macroscopic findings were observed. The oral LD0 of Dimethyl Sulfide was higher than 2000 mg/kg in rats.