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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
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 402, EU Method B.3 and EPA OPP 81-2 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 402 (Acute Dermal 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.3 (Acute Toxicity (Dermal))
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 81-2 (Acute Dermal 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-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: 202 - 246 g g
- Housing: animals were housed individually
- 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

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: the back of each animal (4 cm x 5 cm area, 10% of body surface) was clipped free of hair with electric clippers to allow administration of the test material.
- Type of wrap if used: The test material was evenly applied to the shorn back of each animal and was kept in contact with the skin for approximately 24 hours using a semiocclusive dressing wrapped around the trunk. Each dressing consisted of a gauze patch to cover the treated area and was held in place by a adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin at the site of application was cleansed of any residual test material with lukewarm water
- Time after start of exposure: At the end of the 24 hour contact period.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.0 g test material in 10.0 mL of distilled water. 0.4 mL was applied per 100 g bodyweight. The amount of test material applied was calculated for each animal according to its weight at the time of dosing.
Duration of exposure:
24 hours
Doses:
0 (vehicle control), 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were checked twice daily for mortality, morning and afternoon. Clinical observations were recorded individually within the first hour after dosing, then daily for the duration of the observation period. The application site was examined daily for signs of dermal irritation. Bodyweights were recorded immediately before dose administration and then on day 7 and day 14.
- Necropsy of survivors performed: All animals were killed by CO2 asphyxiation and subjected to a necropsy examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was noted in either sex
Mortality:
No animals died during the study.
Clinical signs:
other: There were no remarkable clinical observations for any animals in either dose group.
Gross pathology:
Necropsy examinations revealed no observable abnormalities.
Other findings:
There were no remarkable findings at the application site for any animal.

Any other information on results incl. tables

Table 2: Bodyweights (g)

Dose group

Animal 

Day 0

Day 7

Day 14

Animal 

Day 0

Day 7

Day 14

Females

Males

2000 mg/kg

101

203.7

219.3

226.2

1

230.9

272.0

317.7

102

202.8

203.8

220.3

2

241.0

286.6

325.4

103

218.6

229.8

244.0

3

232.8

270.7

307.0

104

202.6

209.8

230.9

4

215.4

251.0

309.2

105

203.0

211.1

233.9

5

227.7

270.5

310.2

Mean 

206.1

214.8

231.1

Mean 

229.6

270.2

313.9

SD

7.0

10.1

8.9

SD

9.3

12.7

7.6

0 mg/kg

106

206.3

209.6

220.3

6

226.1

256.5

290.2

107

206.6

215.5

228.4

7

222.3

256.7

290.0

108

209.3

210.2

225.0

8

246.4

276.2

310.8

109

201.8

204.4

222.6

9

224.9

257.5

303.7

110

229.1

234.9

249.9

10

226.1

256.6

295.4

Mean 

210.4

214.9

229.2

Mean 

229.2

260.7

298.0

SD

10.8

11.8

11.9

SD

9.7

8.7

9.0

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, the acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg in 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 dermal toxicity of the test material was determined in accordance with standardised guidelines OECD 402, EU Method B.3 and EPA OPP 81 -2. During the study, five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.

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