2-Pyridinesulfonamide, N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-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:

6 May 1997 to 20 May 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed to GLP and in line with standardised guidelines OECD 401, EU Method B.1 and EPA OPP 81-1 with no deviations thought to impact on the reliability of the presented results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

A limit dose of 5000 mg/kg was used, this is not considered to impact on the validity of the results.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

A limit dose of 5000 mg/kg was used, this is not considered to impact on the validity of the results.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: J-MAFF 59 NohSan No. 4200

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

sodium 4,6-dimethoxy-N-({[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonyl}carbamoyl)pyrimidin-2-aminide

EC Number:

688-332-8

Cas Number:

199119-58-9

Molecular formula:

C14H13F3N5O6SNa

IUPAC Name:

sodium 4,6-dimethoxy-N-({[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonyl}carbamoyl)pyrimidin-2-aminide

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: solid (powder)
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

other: TIF:RAIf

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 168-200 g
- Housing: 5 same sex animals per cage
- Fasting period before study: Rats were fasted overnight prior to dosing
- Diet: commercial diet available ad libitum
- Water: municipal water available ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes: approximately 13-14 air changes per hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From 6 May 1997 to 20 May 1997

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Doses were prepared by weighing 15 g of test material and adding to 30.0 mL of distilled water
- Amount of vehicle (if gavage): Each dose volume was calculated for animals individually based on its weight at the time of dosing.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight was administered as a standard dose volume

Doses:

5000 mg/kg bw, 0 mg/kg bw (vehicle control)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were observed for mortality twice daily, morning and afternoon. Clinical observations were recorded individually at 1, 3 and 5 hours after dosing, then daily thereafter. All animals were weighed immediately before dosing then on days 7 and 14.
- Necropsy of survivors performed: Animals were sacrificed by CO2 asphyxiation. All animals were subject to a necropsy examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed in either sex

Mortality:

Following a single oral dose of 5000 mg/kg, none of the animals died. Signs of slight systemic toxicity were seen in all test material dosed animals from 1 hour through 1 day after dosing; all animals appeared normal by day 2.

Clinical signs:

other: Hunched posture and slight piloerection were observed in all animals at the 5000 mg/kg dose level beginning 1 hour after treatments and persisting through day 1 after treatment. All animals appeared normal by day 2. There were no remarkable clinical obser

Gross pathology:

Necropsy examinations revealed haemorrhage of the lung in all 5000 mg/kg females and two males in the 5000 mg/kg dose group. A mottled lung was seen in one 5000 mg/kg male. There were no observable abnormailities among the 0 mg/kg animals.

Any other information on results incl. tables

Table 1: Bodyweights (g)

Dose group	Animal	Females			Animal	Males
		Day 0	Day 7	Day 14		Day 0	Day 7	Day 14
5000 mg/kg	101	183.1	205.6	223.9	1	200.3	284.8	318.2
	102	185.6	218.0	235.6	2	187.7	264.0	291.1
	103	178.1	214.8	223.8	3	194.4	282.7	322.5
	104	171.6	219.4	234.2	4	188.8	264.6	301.6
	105	193.5	235.2	247.9	5	187.4	268.4	318.9
	Mean	182.4	218.6	233.1	Mean	191.7	272.9	310.5
	SD	8.2	10.7	10.0	SD	5.6	10.1	13.5
0 mg/kg	106	168.1	197.9	221.6	6	188.4	268.3	323.9
	107	179.4	209.8	211.2	7	188.2	262.8	291.8
	108	184.5	224.9	236.8	8	183.3	267.5	308.5
	109	172.1	200.6	221.2	9	195.0	286.2	336.5
	110	175.0	221.5	236.0	10	194.5	269.7	308.9
	Mean	175.8	210.9	225.4	Mean	189.9	270.7	313.7
	SD	6.4	12.1	10.9	SD	4.9	8.5	16.6

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the test, the LD50 of the test material was determined to be > 5000 mg/kg to male and female rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 401, EU Method B.1 and EPA OPP 81 -1. Five male and female rats received a single oral dose of 5000 mg/kg of the test material, by gavage, and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died. Piloerection and hunched posture were seen in all high dose animals from 1 hour through day 1 post dose; all animals appeared normal by day 2. Body weights were not affected by treatment. Necropsy examinations revealed haemorrhage of the lung in all 5000 mg/kg females and two 5000 mg/kg males. A mottled lung was seen in one 5000 mg/kg male. The acute oral median lethal dose of the test material was estimated to be in excess of 5000 mg/kg to both male and female rats.