Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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 study, OECD 423 compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Nossan S.r.l., Correzzana (Ml), Italy.
- Age at study initiation: 5 to 6 weeks old
- Weight at study initiation: 126 to 150 grams
- Fasting period before study: one overnight
- Housing: in groups of up to 5 animals of the same sex, in polycarbonate cages measuring 59x20x39 cm and equipped with a stainless steel mesh lid and floor.
- Diet (e.g. ad libitum): a commercially available laboratory rodent diet (Altromin MT, A. Rieper S.p.A., Bolzano, Italy) ad libitum throughout the study
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark each day.

IN-LIFE DATES: From 04/08/1999 to 11/11/1999

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: in a previous study, doses of 500 and 200 mg/kg were tested with 100% mortality. That's why the starting dose of 25 mg/kg was chosen.

MAIN STUDY:
The study progressed in a stepwise manner as follows:
A group of 3 male animals was dosed at a fixed level of 25 mg/kg body weight. No animal died or exhibited significant toxicity. As a result, a second group of 3 female animals was dosed at the same level. None of these animals died or exhibited significant toxicity.
Three male animals were dosed at a higher level of 200 mg/kg. All animals showed significant toxicity and died following dosing.
Following this, an additional group of 3 males was dosed at an intermediate level of 50 mg/kg. None of the animals died or exhibited significant toxicity. This finding was confirmed by dosing a group of 3 females at the same level.
Doses:
25, 50 and 200 mg/kg
No. of animals per sex per dose:
3 males and 3 females at 25 and 50 mg/kg
3 males at 200 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study all animais were checked twice daily. All animals were weighed on allocation to the study (Day -1) and immediately prior to dosing (Day 1). Surviving animals were weighed on Days 8 and 15. Animals found dead were weighed when found.
- Necropsy of survivors performed: yes
All surviving animals were killed on Day 15 by carbon dioxide narcosis. Animais killed in this way and those dying during the study were subjected to a gross necropsy exarnination for both extemal and internal abnormalities. The cranial, thoracic and abdominal cavities were opened to allow examination of their contents. Larger organs were sectioned. Both the stomach and representative sections of the gastro-intestinal tract were opened for examination of the mucosal surfaces.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 - < 200 mg/kg bw
Based on:
test mat.
Mortality:
0/6 at 25 and 50 mg/kg.
3/3 at 200 mg/kg.
Clinical signs:
25 mg/kg: staining of the skin/fur was noted in 2 animals following dosing. This was no longer apparent after 3 days.

200 mg/kg: All animals exhibited salivation, pallor, lethargy and tremors within approximately 1 hour of dosing. Two animals were unconscious and the remaining animal exhibited convulsions after approximately 2 hours. Two animals had died within 4 hours and the remaining animal was found dead the next day, approximately 24 hours after dosing.

50 mg/kg: No clinical signs or effects of treatment were observed following dosing (males). Animals exhibited a hunched posture, reduced activity and piloerection within hours of dosing. Recovery had occurred within 2 days (females).
Body weight:
25 and 50 mg/kg: Changes in body weight were within the expected range.
Gross pathology:
25 mg/kg: examination revealed no abnormal findings.

200 mg/kg: examination revealed staining of the skin/fur of the muzzle and, in 1 animal, around the urogenital region. A pale area was noted on the gladular region of the stomach of 1 animal and the lungs of this animal were abnormally dark and not collapsed as expected. A red or white mucoid material was found in the jejunum of all 3 animals.

50 mg/kg: No abnormalities were found on necropsy.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
TFSIH is toxic by ingestion and classified Acute oral toxicity Category 3 (H301) according to the CLP 1272/2008 criteria.
Executive summary:

The acute toxicity of bis-trifluoromethane sulfonimide (TFSIH) was investigated following administration of a single oral dose to the rat. The study proceeded in a stepwise manner as follows:

A group of 3 male animals was dosed at a fixed level of 25 mg/kg body weight. No animal died or exhibited significant clinical signs. This was confirmed by dosing a second group of 3 female animals at the same level. None of these animals died or exhibited significant toxicity.

Three male animals were dosed at a higher level of 200 mg/kg. All animals exhibited significant toxicity and died within 24 hours. Three additional males were dosed at an intermediate level of 50 mg/kg. No animal died or exhibited significant clinical signs following dosing. This finding was confirmed by dosing a second group of 3 female animals at the same level. None of these animals died or exhibited significant toxicity.

These results indicate that the test substance has a significant toxic effect in the rat following oral administration of a single dose. The observed toxicity indicates the median lethal dose (LD50) to be greater than 50 mg/kg but less than 200 mg/kg.

In these conditions, TFSIH is toxic by ingestion and classified Acute oral toxicity Category 3 (H301) according to the CLP 1272/2008 criteria.