N-[[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]carbamoyl]-2,6-difluorobenzamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 1999 to 24 August 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Acute Oral Toxicity Study, 1985.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-(2,6-difluorobenzoyl)urea

EC Number:

601-779-5

Cas Number:

121451-02-3

Molecular formula:

C17H7Cl2F9N2O3

IUPAC Name:

1-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-(2,6-difluorobenzoyl)urea

Test material form:

solid

Details on test material:

- Substance type: White solid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 106-165 g
- Fasting period before study: rats were fasted the night prior to treatment.
- Diet: pelleted rodent diet, ad libitum.
- Water: municipal water, ad libitum.
- Acclimation period: at least two weeks prior to study start.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 40-70 %
- Air changes (per hr): 12-15 times/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark photocycle, lights on at 6:00 a.m. and off at 6:00 p.m.

IN-LIFE DATES: From: 14 June 1999 To: 24 August 1999

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 %

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

Five per sex per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Detailed clinical observations were performed each day during the study.
Hand-held and open-field observations included a careful physical examination were performed during the study.
Each animal was weighed prestudy, the day of treatment, and on days 2, 8, and 15.
- Necropsy of survivors performed: yes
All rats submitted alive for necropsy were anesthetised by inhalation of methoxyflurane vapours and euthanised by decapitation after exposure and clamping of the trachea. A complete necropsy was conducted on all animals by a veterinary pathologist assisted by a team of trained individuals. The eyes were examined in situ using a moistened glass microscope slide applied to the corneal surface. Following inspection of the externum and body orifices, the nasal, cranial, oral, thoracic, and abdominal cavities were opened and the visceral organs were examined both in situ and following dissection.

Statistics:

Means and standard deviations were calculated for body weights. The data were evaluated for statistical outliers by a sequential test (Grubbs, 1969), however, outliers were not routinely excluded from statistical analysis.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: One male and one female had perineal faecal soiling on test days 1 or 2, and one male had perineal faecal soiling on test day 15. All other animals were clinically normal throughout the study.

Gross pathology:

There were no treatment related gross pathologic observations for any animal.

Any other information on results incl. tables

Table 1: Individual Body Weights

Dose (mg/kg)	Animal Sex	Animal No.	Day of Test
			-1	1	2	8	15
5000	Male	3901	172.6	160.5	179.1	202.2	225.6
		3902	175.9	164.5	181.8	207.4	231.9
		3903	170.5	157.5	175.3	198.0	219.9
		3904	176.4	164.2	182.7	205.0	232.4
		3905	167.4	154.1	172.4	196.3	216.8
		Mean	172.6	160.2	178.3	201.8	225.3
		SD	3.8	4.4	4.4	4.6	7.0
	Female	3906	120.7#	111.2#	123.1	140.9	151.9
		3907	115.1	106.3	120.5	132.1	145.0
		3908	116.3	106.0	121.2	135.0	146.3
		3909	115.9	105.9	120.7	134.2	144.3
		3910	115.4	105.8	120.6	133.2	142.6
		Mean	116.7	107.0	121.2	135.1	146.0
		SD	2.3	2.3	1.1	3.4	3.5

# statistical outlier included

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the acute oral LD50 of the test material in male and female Fischer 344 rats was greater than 5000 mg/kg.

Executive summary:

The acute toxicity of the test material was determined in an acute oral toxicity test performed under GLP conditions and in accordance with the standardised guidelines OECD 401, EPA OPPTS 870.1100, EU Method B.1 and Japan MAFF Acute Oral Toxicity Study.

Five male and five female Fischer 344 rats received 5000 mg/kg of the test material as a 50 % mixture in 0.5 % methylcellulose by single dose oral gavage. Parameters evaluated during the two-week observation period included body weights and detailed clinical observations. All animals were examined for gross pathologic changes.

All animals survived for the duration of the study. One male and one female had perineal faecal soiling on test days 1 or 2, and one male had perineal faecal soiling on test day 15. All other animals were clinically normal throughout the study. Rats had a transient body weight loss on day 1, which was associated with the overnight fast prior to treatment, and then gained body weight for the remainder of the study. There were no treatment-related gross pathologic observations for any animal.

Under the conditions of the test, the acute oral LD50 of the test material in male and female Fischer 344 rats was greater than 5000 mg/kg.