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

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 guideline

Test guideline 1

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.

Test guideline 2

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.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal 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: 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.