3,5-dimethylbenzoyl chloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 February 1992 - 1 July 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Method described by Draize: Draize J.H., Woodard G.C., & Calvery H.O.: J. Pharmacol. Exp. Therapeut. 8

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3,5-dimethylbenzoyl chloride

EC Number:

413-010-9

EC Name:

3,5-dimethylbenzoyl chloride

Cas Number:

6613-44-1

Molecular formula:

C9H9ClO

IUPAC Name:

3,5-dimethylbenzoyl chloride

Details on test material:

3,5-Dimethylbenzoyl chloride
Appearance: pale yellowish transparent liquid

Test animals

Species:

rabbit

Strain:

other: Japanese white rabbits (male)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kitayama Labs (Inc.)
- Weight at study initiation: 2.3 - 2.6 kg
- Diet (e.g. ad libitum): Solid feed for the rabbit (Oriental Yeast Co.) given ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2 °C
- Humidity (%): 55 ± 6 %

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.25 mL

Duration of treatment / exposure:

24 hours

Observation period:

19 days

Number of animals:

6

Details on study design:

The day before the test, back hair of rabbits was removed by means of an electric shaver, and the skin intended to be used as the abraded site had the corneum removed by scratching with an 18 gauge injection needle by crossing pattern after sterilization.

Method of application:
0.25 mL of the test substance was applied on the areas (3 cm²) of intact and abraded skin, and the surface was covered with two-layer gauze and fixed as a closed patch with Tegaderm (3 M) and Tubicot #5 (Tokyo Eizai Labs.). Test sample was exposed to the skin for 24 h, and after then the skin region was wiped using gauze wet with water.

Judgement:
After 24-h exposure of the sample to the skin, any change in the skin was judged by the appropriate criteria. The degree of erythema and oedema was evaluated by the Draize criteria, as illustrated below. In addition, necrosis, crust and scar formation at the test site were observed and evaluated by the criteria shown below.
According to the Draize method, crust and scar formation and oedema observed after 24 and 72 h of sample application were scored. The obtained individual score was divided by the score at the judgement (or "4"), and then the average score of 6 rabbits was obtained to give the primary irritation index (P.I.I.).
Observation was continued until all skin symptoms of 6 rabbits were recovered (for 19 days).

Criteria for judgement for primary irritation (according to Draize)
1. Erythema and scar formation
No erythema 0
Very slight erythema 1
Distinct erythema 2
Medium erythema 3
Strong erythema - slight crust formation 4

2. Oedema
No oedema 0
Very slight oedema 1
Slight oedema (swollen and bordered) 2
Medium oedema (approx 1 mm swelling) 3
Severe oedema (more than 1 mm swelling) 4


Criteria for judgement for the skin symptoms
1. Necrosis (judged by area)
No necrosis 0
Less than ¼ 1
¼ - ½ 2
½ - ¾ 3
¾ - 4/4 4

2. Scar (judged by area)
No scar 0
Less than ¼ 1
¼ - ½ 2
½ - ¾ 3
¾ - 4/4 4

3. Eschar
No eschar 0
Fine layered eschar 1
Scale or desquamatous dried eschar 2
Eschar slightly hard to remove 3
Escher difficult to remove and deep damage 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 1.5

Max. score:

3

Results 2

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 1.25

Max. score:

2

Results 3

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 1.5

Max. score:

3

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1.5

Max. score:

2

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1.75

Max. score:

3

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0.75

Max. score:

1

Results 7

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Results 8

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Results 9

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 1.5

Max. score:

3

Results 10

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Results 11

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1.5

Max. score:

3

Results 12

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Results 13

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.5

Max. score:

10

Irritant / corrosive response data:

Results of observation from the end point of 24-h exposure of the test sample on the skin to the end of the test period are shown in Table 1.
After 24 h exposure, the first observation revealed necrotic change, grey-white to brown-yellowish colour, in all 6 rabbits on the intact and abraded skin, and then very slight oedema was observed.
From 48 h to 120 h period after the exposure to the sample, the erythema and oedema of the skin showed aggravation, and distinct medium erythema and slight to medium oedema were observed.
Ulcer formation was observed at the intact and abraded sites in 5 rabbits after 48 to 144 h of the exposure. After 144 h, the surface of the skin began to dry and harden leading to crust. Then during the recovery of the subcutaneous tissue, the surface skin was removed, and erosion was caused in 5 rabbits. Ulcer region was gradually changed to scar, and erosion was healed to form scar, and eventually skin of all 6 rabbits showed healing after 19 days.

According to the evaluation by P.I.I., the irritation score falls into the category of medium irritation, but greyish-white and brownish discolouration, probably due to necrosis was found. Also, ulcer and erosion were present so the test sample was judged to be corrosive.

Any other information on results incl. tables

Table 1 P.I.I. of DMBC

Items of Observation			Erythema		Oedema		Average Score for Individual Rabbits
Time of Observation			After 24 h	After 72 h	After 24 h	After 72 h
No. of Rabbit	1	Intact Abraded	0 0	2 2	1 0	1 1	1.75
	2	Intact Abraded	0 0	3 3	1 0	3 3	3.25
	3	Intact Abraded	0 0	2 2	1 1	2 2	2.50
	4	Intact Abraded	0 0	3 3	0 1	3 2	3.00
	5	Intact Abraded	0 0	2 2	1 0	2 2	2.25
	6	Intact Abraded	0 0	2 2	0 0	3 3	2.50
P.I.I							2.5

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize Scale

Conclusions:

DMBC was judged to be corrosive.

Executive summary:

Primary skin irritation tests of 3,5-dimethylbenzoyl chloride were performed by the Draize method using white rabbits (Draize, J.H., Woodard G.C., & Calvery H.O.; J. Pharmacol. Exp. Therapeut. 8).

 It was found that after 24 h exposure of the test sample on the skin, colour change to brownish yellow, probably due to necrosis, occurred and was accompanied by ulcerous change and erosion.

Thus, the test sample was judged to be a corrosive material.