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Acute Toxicity: oral

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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 guidelineopen allclose all
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.
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.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
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

Constituent 1
Chemical structure
Reference substance name:
sodium (4,6-dimethoxypyrimidin-2-yl)({[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonyl}carbamoyl)azanide
Cas Number:
199119-58-9
Molecular formula:
C14H13F3N5O6SNa
IUPAC Name:
sodium (4,6-dimethoxypyrimidin-2-yl)({[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonyl}carbamoyl)azanide
Test material form:
solid: particulate/powder
Remarks:
migrated information: 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:
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 observations among the 0 mg/kg bw animals.
Body weight:
Bodyweights, and bodyweight gain, were not affected by treatment (see Table 1)
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.