2-Pyridinesulfonamide, 3-(2,2,2-trifluoroethoxy)-, sodium salt (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted test guidance and good laboratory practices guidance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

-Because of the loss of all 3 females at the 2000 mg/kg dose level, testing was continued at 200 mg/kg on August 11, 2000, with both sexes.
-Distilled water has been used as vehicle in this study instead of 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80 (CMCPS 80).

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

sodium 2-(azanidylsulfonyl)-3-(2,2,2-trifluoroethoxy)pyridine

EC Number:

700-926-1

Cas Number:

227605-94-9

Molecular formula:

C7H6F3N2NaO3S

IUPAC Name:

sodium 2-(azanidylsulfonyl)-3-(2,2,2-trifluoroethoxy)pyridine

Constituent 2

Reference substance name:

Sodium {[3-(2,2,2-trifluoroethoxy)-2-pyridinyl]sulfonyl}azanide

IUPAC Name:

Sodium {[3-(2,2,2-trifluoroethoxy)-2-pyridinyl]sulfonyl}azanide

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): CA 3105 A (intermediate of CGA 362622)
- Substance type: Organic mono constituent substance
- Physical state: White solid
- Analytical purity: 93.9%
- Lot/batch No.: EZ001002
- Expiration date of the lot/batch: July 2002 (Re-analysis date)
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

other: Hanlbm:WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Biotechnology & Animal Breeding Division, 4414 Füllinsdorf, Switzerland
- Age at study initiation: Young adult (approximately 7-11 weeks)
- Weight at study initiation: 170-213g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: Macrolon Type 4 cages with soft wood bedding (Société Parisienne des Sciures, Patin, France); three same-sex animals per cage
- Diet (e.g. ad libitum): NAFAG No. 890 (NAFAG, Gossau/SG, Switzerland), available ad libitum. All batches of diet are assayed by the manufacturer to ensure proper nutritional content and absence of contaminants. A report of the assay for the diet batch used in a specific test is available.
- Water (e.g. ad libitum): Available ad libitum from bottles; source is municipal water supply. The water is examined four times a year by the government water authority (Baudepartement des Kantons Aargau, Abteilung Gewässerschutz). A report of an assay conducted about the time of the test is available on request.
- Acclimation period: At least five days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50% ± 20%
- Air changes (per hr): Approximately 13-14/hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

IN-LIFE DATES:
From: 2000 mg/kg- August 10, 2000 (females only); 200 mg/kg - August 11 , 2000 (both sexes) (Start of treatment)
To: 2000 mg/kg- August 10, 2000 (females only);200 mg/kg- August 25, 2000 (both sexes)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
2000 mg/kg: 2.0002 g test article with vehicle ad 10 mL
200 mg/kg: 0.4013 g test article with vehicle ad 20 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The high dose level of 2000 mg/kg was selected based on the OECD/EEC guidelines and pre-test results.

Doses:

200 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

2000 mg/kg: three females
200 mg/kg: three males and three females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: Checked and recorded individually at 1, 3, 5, and 7 hours after dosing, then daily for the duration of the observation period.
Mortality: Checked twice daily, morning and afternoon.
Body weight: Measured and recorded immediately before dose administration, then on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy observations

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 200 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg: two females (nos. 101 and 103) were found dead, and one female (no. 102) was sacrificed elected on the treatment day for animal welfare reason.
There was no mortality in the 200 mg/kg male and female groups.

Clinical signs:

other: At 2000 mg/kg (females): slight Straub tail was seen in all females, slightly reduced activity and recumbency in two females (nos. 101 and 103), slight tonic convulsions in two females (nos. 101 and 102), and slight bilateral ptosis, slightly up to modera

Gross pathology:

At 2000 mg/kg: Necropsy examinations revealed a reddish small intestine in all females.
At 200 mg/kg: Necropsy examinations in the male and female groups revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The following acute oral LD50 values were determined:
LD50 in male rats: Greater than 200 mg/kg body weight.
LD50 in female rats: Greater than 200 mg/kg, lower than 2000 mg/kg body weight.

Executive summary:

Groups of 3 male and 3 female fasted Hanlbm:WIST (SPF) rats were administered a single dose of test substance by gavage at dose levels of 200 mg/kg (both sexes) and 2000 mg/kg (females only), followed by a 14-day post-treatment observation period.
At 2000 mg/kg, two females were found dead, and one female was sacrificed elected on the treatment day for animal welfare reason.
There was no mortality in the 200 mg/kg male and female groups.

At 2000 mg/kg (females): Slight Straub tail was seen in all females, slightly reduced activity, recumbency, and slight tonic convulsions in two females, and slight bilateral ptosis, slightly up to moderately or markedly reduced activity, slightly hunched posture, slight abnormal gait, and paddling movements in one female on the treatment day.
At 200 mg/kg (males): Slightly reduced activity was observed in all males on the treatment day, which lasted in one male through day 2, slightly hunched posture in two males on the treatment day through day 2, and in one male on the treatment day through day 3, slight piloerection in all males on the treatment day, which lasted in one male through day 1. All males appeared normal on day 4 after treatment.
At 200 mg/kg (females): Slightly reduced activity, slightly hunched posture, and slight piloerection were seen in all females on the treatment day. All females appeared normal on day 1 after treatment.

Body weights were not affected by treatment in any animals.

At 2000 mg/kg: Necropsy examinations revealed a reddish small intestine in all females.
At 200 mg/kg: Necropsy examinations revealed no observable abnormalities.

The following acute oral LD50 values were determined for CA 3105 A (intermediate of CGA 362622):
LD50 in male rats: Greater than 200 mg/kg body weight.
LD50 in female rats: Greater than 200 mg/kg, lower than 2000 mg/kg body weight.