2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Study period:

November 04 to 12, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well documented and reported study, conducted equivalent or similar to internationally accepted technical guideline in recognized industrial research organization. A quality assurance inspection report with reference to GLP, but not a GLP compliance statement, was included in the study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

of 1984

Deviations:

yes

Remarks:

exposure period was 24 hours instead of 4 hours

GLP compliance:

no

Remarks:

but Quality Assurance statement with reference to IKS GLP guidance document was included in the report

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide

EC Number:

239-350-6

EC Name:

2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide

Cas Number:

15308-01-7

Molecular formula:

C14H10Cl3NO

IUPAC Name:

2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide

Details on test material:

- Name of test material (as cited in study report): PBS 3248.3 (Voltachlorid)
- Description: beige crystalline powder
- Expiration date of the lot/batch: December 1986
- Storage conditions: room temperature
Analyzed by Pharmaceuticals Production: Test Article Data Sheet of September 30, 1985

Test animals

Species:

rabbit

Strain:

other: albino, Chbb:HM (SPF)

Details on test animals or test system and environmental conditions:

- Animal supplier: Thomae, FRG
- Age: Approximately 5 - 8 months.
- Number and Sex: 3 males and 3 females
- Weight on day of treatment (before application): Minimum 1.85 kg, maximum 2.22 kg.
- Housing: Individual housing in metal cages.
- Diet (ad libitum): Commercially available pelleted standard diet (NAFAG No. 814, batch 73/85, analysed by the
manufacturer, NAFAG, Gossau, Switzerland).
- Water (ad libitum): Tap water. (Periodically analysed)
- Acclimation period: Approximately 2 weeks under laboratory conditions.


ENVIRONMENTAL CONDITIONS

Air conditioned room:
- Temperature (°C): 18 ± 2°C
- Relative Humidity (%): 60 ± 10%
- Photoperiod: 14 hrs light/day

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 g test material per approx. 6 cm2 skin per animal. The unchanged test material was loaded on gauze patches moistened with distilled water.

Duration of treatment / exposure:

24 hours

Observation period:

From prior to treatment (i.e. pretest) until 7 days post patch removal

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE PREPARATION:

3 days before treatment, both flanks of the rabbits were shaved with an electric clipper and an electric shaver.

- Area of treated skin: Approx. 6 cm2 (= 2.5 x 2.5 cm gauze patch).
- Type of wrap used: Gauze patches were covered with impermeable foil and fastened to the rabbit body with elastic bandage and adhesive tape.

TEST MATERIAL AND DOSE PREPARATION

- Administration Volume/animal (i.e. one gauze patch of 2.5 x 2.5 cm per animal):
0.5 g unchanged test material was loaded on a gauze patch moistened with distilled water.

TREATMENT PERIOD AND REMOVAL OF TEST SUBSTANCE

Epicutaneous, occlusive treatment lasted 24 hours. Then the dressings were removed and residual test material was gently washed off the skin with warm water

SCORING SYSTEM:

The treated skin patches were evaluated at pretest and 30 minutes 24, 48 and 72 hours and 7 days post patch removal. Skin reactions were evaluated for erythema/eschar formation and edema according to Draize (see Table 1). In addition, scaling was recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Remarks:

according to Draize as defined above

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0.06

Max. score:

8

Reversibility:

fully reversible within: 24 to 48 h.

Remarks on result:

other: By 24 h all but one, by 48 h all animals were free from erythema/edema. The one grade 1 erythema seen at 24 h was also seen at pretest in this animal.

Results 2

Irritation parameter:

erythema score

Remarks:

according to Draize as defined above

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0.06

Max. score:

4

Reversibility:

fully reversible within: 24 to 48 h

Remarks on result:

other: By 24 h all but one, by 48 h all animals were free from erythema. The one grade 1 erythema seen at 24 h was also seen at pretest in this animal.

Results 3

Irritation parameter:

edema score

Remarks:

according to Draize as defined above

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: All animals were free from edema throughout the study

Irritant / corrosive response data:

Erythema and edema result tables for each individual animal are presented under "Remarks on results including tables and figures"

Other effects:

Skin scaling, mainly slight in degree in one incidence slight to marked in degree, was seen in a number of animals (males No. 10 and 12 and female No. 41) on the treated or both flanks at 24, 48 and/or 72 h after patch removal having fully reversed by 7 days.

Any other information on results incl. tables

 

Table 2: Gradings of Skin Reactions Attained for each Male Animal at Different Observation Time Points
Pretest / Time after Patch Removal	Pretest	0.5 h	24 h	48 h	72 h	7 days
Animal (Identification) No.	10 11 12	10 11 12	10 11 12	10 11 12	10 11 12	10 11 12
Erythema / Eschar	0   0   1	1   1   1	0   0   1	0   0   0	0   0   0	0   0   0
Edema	0   0   0	0   0   0	0   0   0	0   0   0	0   0   0	0   0   0

 

 

 

Table 3: Gradings of Skin Reactions Attained for each Female Animal at Different Observation Time Points
Pretest / Time after Patch Removal	Pretest	0.5 h	24 h	48 h	72 h	7 days
Animal (Identification) No.	40 41 42	40 41 42	40 41 42	40 41 42	40 41 42	40 41 42
Erythema / Eschar	0   0   0	0   1   0	0   0   0	0   0   0	0   0   0	0   0   0
Edema	0   0   0	0   0   0	0   0   0	0   0   0	0   0   0	0   0   0

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Epicutaneous occlusive administration of PBS 3248.3 (Voltachlorid) to intact skin of six albino rabbits led to very slight erythema (Grade 1, barely perceptible) and skin scaling in a number of animals. All findings were fully reversible within 7 days. According to EU classification rules (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008) the minor findings attained in this study do not necessitate any labelling regarding skin irritation.

Executive summary:

PBS 3248.3 (Voltachlorid) was tested for skin irritation similar to EU Method B.4 (Acute Toxicity: Skin Irritation) of 1984 (Dir. 84/449/EEC) in albino rabbits [Chbb:HM (SPF)]. The study was more comprehensive than foreseen in this test guideline in that six animals were exposed to the test material for 24 hours (instead of 4 hours).

 

Reliability grade 1 was assigned to the study. It was not conducted in compliance with GLP, but a Quality Assurance statement with reference to an IKS GLP guidance document* was included in the study report.

 

Intact shaved skin of each animal (3 males and 3 females) was treated on one flank by epicutaneous occlusive administration of 0.5 g of unchanged test material loaded on gauze patches (2.5 x 2.5 cm), the latter moistened with distilled water. The patches were covered with impermeable foil and fastened to the rabbit body with elastic bandage and adhesive tape. Shaved skin on the other flank served as a control. Skin reactions were recorded at pretest and 30 minutes 24, 48 and 72 hours and 7 days post patch removal and were evaluated for erythema/eschar formation and edema according to Draize. In addition, scaling was recorded.

 

There was no mortality. General symptoms or relevant changes in body weight were not evident.

Very slight erythema (Grade 1, barely perceptible) were seen in 4 of 6 animals at 30 minutes after patch removal and in one of these at 24 h. In the latter animal, this finding was also recorded at pretest. By 48 h after patch removal this finding had fully reversed to normal skin. In addition, skin scaling, was seen in a number of animals (two males and one female) on the treated or on both flanks at 24, 48 and/or 72 h after patch removal having fully reversed by 7 days. Edema were not evident throughout the study. The very slight erythema and skin scaling reactions were attributed to treatment with the test material.

 

The primary skin irritation index (i.e. sum of mean irritation scores read 30 minutes and 48 hours after patch removal for erythema and edema divided by 2) attained during this study was 0.4 (maximum possible value: 8) reflecting “minimal irritation” according to the skin irritation/corrosion classification scheme adopted in the study report. However, the mean Draize scores (24, 48, 72 h over 6 animals) were 0.06 for erythema and 0.00 for edema, and the maximum severity grade attained in any animal was grade 1. Therefore, according to EU classification rules (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008) the test material would be considered to be "not irritant" not necessitating any labelling regarding skin irritation. ----------------------------------------------------------------------------------------- * "Wegleitung der IKS betreffend gute Laboratoriumspraxis für nichtklinische Laborversuche, Unterabschnitt B.4.a.v."