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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 Feb 1988 to 01 Mar 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Feb 1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

410-690-9

EC Name:

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

Cas Number:

103055-07-8

Molecular formula:

C17 H8 Cl2 F8 N2 O3

IUPAC Name:

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

Test animals

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult of 7 to 8 weeks
- Weight at study initiation: 224 to 250 g
- Housing: Group of 5 (by sex); Macrolon cages, Type 3 with standardised soft wood bedding
- Diet: Rat diet, ad libitum.
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 16 Feb 1988 To: 01 Mar 1988

Administration / exposure

Type of coverage:

occlusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: an area on the back of the rat
- Pre-treatment: Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- % coverage: 10 % of the total body surface
- Type of wrap if used: The treated area was covered with a gauze-lined semi occlusive dressing fastened around the trunk with an adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours, the dressings were removed and treated area was the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly.

TEST MATERIAL
- Amount applied: 4 mL/kg
- Concentration: 2000 mg/kg bw test substance suspended in Oleum arachidis
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Remarks:

A control gauze patch was applied to the contralateral flank.

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of weighing: Individual body weights of the animals were recorded on Days 1, 7 and 14.
- Frequency of observations: Animals were observed daily; a.m. and p.m. on working days, a.m. on weekend days
- Necropsy of survivors performed: yes, on Day 15 and were subjected to gross necropsy at the end of the observation period.
- Clinical signs: Clinical signs were recorded daily. Ruffled fur, dyspnoea, abnormal body positions, and spontaneous activity were monitored.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Not treatment-related observations: ruffled fur, dyspnea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days.

Gross pathology:

No deviations from normal morphology were found at autopsy.

Any other information on results incl. tables

Table 1 Rate of deaths

Dose mg/kg	Totals			Hours aft. Treatment				Day of post exposure period
	in grp	Deaths		1	2	3	5	1	2	3	4	5	6	7	8	9	10	11	12	13	>13
		no	%
2000 mg/kg, males	5	0	0
2000 mg/kg, females	5	0	0

 

Table 2 Mean body weight and standard deviation

	Males			Females
dose mg/kg	day 1	day 7	day 14	day 1	day 7	day 14
2000	244/ 6.3	281/23.6	328/21.4	233/ 6.6	243/ 6.5	259/10.9

Table 3 Signs and symptons

Observations

Exposure day: hours

Day of post-exposure period

1

2

3

5

1

2

3

4

5

6

7

8

9

10

11

12

13

>13

2000 mg/kg, males

ruffled fur

x

x

x

x

x

x

x

x

dyspnoea

x

x

x

x

x

x

x

hunched post.

x

x

ventr.recumb

x

x

x

x

x

red.spont.act

x

x

x

x

2000 mg/kg, females

ruffled fur

x

x

x

x

x

x

x

x

dyspnoea

x

x

x

x

x

x

x

hunched post.

x

x

ventr.recumb

x

x

x

x

x

red.spont.act

x

x

x

x

x = slight xx = moderate XXX = marked

hunched post. = hunched posture ventr.recumb. = ventral recumbency

red.spont.act = reduced spontaneous activity

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal percutaneous dose (LD50) to rats of test substance was found to be greater than 2000 mg/kg bw.

Executive summary:

An acute dermal study was performed in accordance with OECD TG 402 following GLP principles. The test was conducted with Tif: RAI f (SPF) rats to determine the potential for the test substance to produce toxicity from a single topical application. Approximately 24 hours before treatment, an area of at least 10 % of the body surface of the back of one group of 10 rats (5/sex) was shaved with an electric clipper. Test article was evenly dispersed on the skin at a dosage of 2000 mg/kg bw in Oleum arachidis in a dose volume of 4 mL/kg bw and covered with a semi-occlusive dressing. After an exposure period of 24 hours, the dressing was removed and the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly. Mortality, signs and symptoms were recorded daily, body weight at start and on days 7 and 14 of the study, and the animals were subjected to gross necropsy at the end of the 14-day observation period.

No mortality occurred; ruffled fur, dyspnoea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days. Body weight growth was observed and no deviations from normal morphology were found at autopsy. Upon an acute dermal application and a 14-day post-treatment observation period, the LD50 for the test substance in rats was greater than 2000 mg/kg bw in both sexes.