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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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 (Date of re-analysis)
- 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 8-12 weeks)
- Weight at study initiation: 202 to 249 g
- Housing: Macrolon Type 3 cages with soft wood bedding (Société Parisienne des Sciures, Patin, France); individual housing
- 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: August 22, 2000 To: September 5, 2000

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 0.5% (w/v)carboxymethyl cellulose in 0.1% (w/v) aqueous polysorbate 80

Details on dermal exposure:

TEST SITE
- Area of exposure: An area of about 6 cm x 6 cm on the back
- % coverage: Approximately 10% of body surface
- Type of wrap if used:
Gauze patches, 6 cm x 4 cm (Rhena Gaze Kompresse, IVF, Neuhausen, Switzerland)
lsocomfort™ self-adhesive wrap (lsoplast AG, Brugg, Switzerland)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): 10.0006 g test item moistened with 10 g vehicle
- Constant volume or concentration used: yes/no 400 mg per 100 g body weight

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

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 within the first two hours after dosing, then daily for the duration of the observation period.
Local tolerance: The application site was examined daily for signs of dermal irritation. Any deviations from normal were recorded using the Draize scale.
Mortality: Checked twice daily, morning and afternoon.
Body weight: Measured and recorded immediately before dose administration 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:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality in the study.

Clinical signs:

other: There were no remarkable clinical observations for any animal in either dose group.

Gross pathology:

Necropsy examinations revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 in male rats: Greater than 2000 mg/kg body weight
LD50 in female rats: Greater than 2000 mg/kg body weight
LD50 in rats of both sexes: Greater than 2000 mg/kg body weight

Executive summary:

Groups of 5 male and 5 female fasted Hanlbm:WIST (SPF) rats were administered a single dose of CA 3105 A (intermediate of CGA 362622), batch no. EZ001002, by dermal application at a dose level of 2000 mg/kg for 24 hours under semiocclusive conditions, followed by a 14-day post-treatment observation period. There was no mortality. There were no remarkable clinical observations for any animal.

Very slight erythema at the skin application site was recorded in one male on days 3 and 4, in one male on day 4 only, and in two females on days 2 and 3. Well defined erythema was seen in one female on day 2 only. Crust at the application area was seen in one male on day 5 through day 12, and in one female on day 3 through day 9.

A slight loss of body weight was recorded in one female during the first week after treatment.

Necropsy examinations revealed no observable abnormalities.

The following acute dermal LD50 values were determined for CA 3105 A (intermediate of CGA 362622):

LD50 in male rats: Greater than 2000 mg/kg body weight.

LD50 in female rats: Greater than 2000 mg/kg body weight.

LD50 in rats of both sexes: Greater than 2000 mg/kg body weight.