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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 Feb 1988 to 05 Feb 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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

May 1981

GLP compliance:

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:

rabbit

Strain:

New Zealand White

Remarks:

KFM-NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 12 – 14 weeks old.
- Weight at study initiation: 2250 - 2510 g.
- Housing: Rabbits were individually housed in metal wire rabbit cages.
- Diet: standard rabbit pellet, ad libitum
- Water: fresh water, ad libitum. The quality of the drinking water was according to the specifications of the "Schweizerisches Lebensmittelbuch".
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g of the test substance

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

STUDY DESIGN
- The test was performed on 3 female rabbits, checked for normal skin conditions.
- The animals were checked daily for systemic symptoms and mortality.
- The body weight was recorded at start and on day 3 of the test.

TEST SITE
- Area of exposure: An area of at least 36 cm2 was shaved on both flanks of the animals approximately 24 hours before treatment.
- Type of wrap: A gauze patch (20 cm2) was applied to the flank. A control gauze patch was applied to the contralateral flank. Both gauze patches were moistened before application with distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80. The patches were loosely covered with an aluminium foil (36 cm2) and held in place by an adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Approximately 1, 24, 48 and 72 hours after the end of exposure

SCORING SYSTEM:
- Method of calculation: following the OECD TG 404 system. For criteria, see 'Any other information on materials and methods incl. tables'.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Two animals exhibited slight erythema reactions (score 1) one hour after treatment with test substance. Scores of erythema and oedema for the recordings 24 to 72 hours in all 3 animals were zero (considered to be non-irritating).

Other effects:

BODY WEIGHT
The body weights of all rabbits were considered to be within the normal range of variability.

DURATION OF THE IN-LIFE PHASE
Because no reactions were observed at 24 hours to 72 hours after removing the bandages, the test was ended after the 72 hours evaluation.

Any other information on results incl. tables

Table 2 Individual skin reaction score

	E R Y T H E M A				E D E M A
animal	#1	#2	#3		#1	#2	#3
	CF/TF	CF/TF	CF/TF		CF/TF	CF/TF	CF/TF
after 1 hr	0/0	0/1	0/1		0/0	0/0	0/0
after 24 hrs	0/0	0/0	0/0		0/0	0/0	0/0
after 48 hrs	0/0	0/0	0/0		0/0	0/0	0/0
after 72 hrs	0/0	0/0	0/0		0/0	0/0	0/0
mean 24-72 hrs.	0/0	0/0	0/0		0/0	0/0	0/0

CF = control flank TF = test flank

M = male F = female

Table 3 Body Weights

Animal	#1	#2	#3
At start of test	2250	2510	2480
After 3 days (end)	2310	2570	2490

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Because the mean values of the recordings 24 to 72 hours after application were scored zero, the test substance can be classified as non-irritant.

Executive summary:

The primary skin irritation potential of the test substance was investigated according to the GLP compliant OECD TG 404. An amount of 0.5 g unchanged test material was applied under occlusive conditions for 4 hours to the clipped backs of 3 females albino New Zealand White rabbits (KFM-NZW), using a gauze patch of 20 cm2. A control gauze patch was applied to the contralateral flank. Both gauze patches were moistened before application with distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80. The patches were loosely covered with an aluminium foil (36 cm2) and held in place for 4 hours by an adhesive tape. Scoring was performed at 1, 4, 24, 48 and 72 hours and after 3 days of application following OECD TG 404.

Two animals exhibited slight erythema reactions (score 1) one hour after treatment with test substance. Since no reactions were observed at 24 hours to 72 hours after removing the bandages, the test was terminated after the 72 hours evaluation. Scores of erythema and oedema for the recordings 24 to 72 hours in all 3 animals were zero. Under the conditions of this study, the test substance was considered not to be irritating to the skin of rabbits.