Benzoyl chloride, 3-methoxy-2-methyl-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 April 1996 - 14 May 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 5

Qualifier:

according to guideline

Guideline:

other: Japan 59 NohSan No. 4200

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

427-440-1

EC Name:

-

Cas Number:

24487-91-0

Molecular formula:

C9H9ClO2

IUPAC Name:

2-Methyl-3-methoxy benzoyl chloride

Test material form:

other: solid

Details on test material:

MMBC
Appearance: Tan Solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Animals, Denver, PA.
- Age at study initiation: approximately 29 weeks.
- Weight at study initiation: 3662 g.
- Housing: The animal was individually housed in a stainless steel cage (18 x 24 x 14.5 in., i.e. 46 x 61 x 37 cm) suspended above an absorbent-paper pan liner which was changed 3 times per week.
- Diet (e.g. ad libitum): approximately 125 g/day of PMI Certified High Fiber Rabbit Diet 5325 (Purina Mills Inc., Richmond, IN).
- Water (e.g. ad libitum): ad libitum filtered tap water (via automatic watering).
- Acclimation period: approximately 2 weeks.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21 °C
- Humidity (%):44 - 55 %
- (hrs dark / hrs light): 12 hours light, 12 hours darkness.

IN-LIFE DATES: From: To: 30 April 1996 - 14 May 1996

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

0.5 g, moistened with 0.5 mL distilled water (1:1 w/v).

Duration of treatment / exposure:

4 hours.

Observation period:

14 days.

Number of animals:

1

Details on study design:

DOSE PREPARATION AND ADMINISTRATION
Approximately 24 hr prior to application of the test substance, the hair around the entire trunk between the flank and shoulders was shaved closely with electric clippers. The test substance (0.5 g) was moistened with 0.5 mL of distilled water (1:1 w/v), was applied onto a (1.0-in.) square gauze-lined adhesive bandage which was then applied to the shaved intact skin of the rabbit. A semi-occluded dressing (i.e., fabric cuff secured with adhesive tape) was used to wrap the entire trunk of the animal. The rabbit was returned to its cage for a 4 hour exposure period. The cuff and patch were removed after the 4-hr exposure and the application site wiped with a paper towel saturated with tap water. The application site was blotted dry with paper towels.

OBSERVATIONS AND DETERMINATIONS
Skin irritation was evaluated at approximately 1, 24, 48, and 72 hrs and at 7 and 14 days after patch removal. The degree of irritation was evaluated according to the criteria of Draize (see below). In addition, all other skin reactions or signs of systemic toxicity were recorded. The animal was observed daily for mortality and signs of morbidity.


Skin Irritation Scoring (Draize Criteria)

Erythema Scores (maximum = 4)
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) oto slight eschar formation (injuries in depth) 4

Oedema Scores (maximum = 4)
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4


Skin irritation was categorized on the basis of the 1, 24, 48 and 72-hr primary irritation index (PII). The PII is the sum of the erythema and edema scores divided by the number of observations (4), then divided by the number of animals (1).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: Mean scores at 1, 24, 48 and 72 hours

Score:

8

Reversibility:

not reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Severe erythema and oedema as well as blanching with a blackened perimeter were observed at 1 hr and persisted through day 7. The Primary Irritation Index (PII) was 8.0. Deep ulceration was observed on day 14. Skin irritation effects and observations recorded by a veterinary pathologist included (but were not limited to): deep ulceration which extended into the subcutis, and perimeter red with a wide zone of mild to moderate subcutaneous oedema. Additional skin irritation effects are shown in Table 1. These effects were indicative of irreversible destruction of dermal tissue.

Other effects:

No mortality or clinical signs of systemic toxicity (other than skin effects) were observed during the study.

Any other information on results incl. tables

Table 1 Skin Irritation Scores

	Time after patch removal
	1 hour	24 hours	48 hours	72 hours	7 days	14 days
Erythema Score	4*†	4*†	4*†	4*†	4*†	4‡
Oedema Score	4	4	4	4	3	4

* Blanching

† Perimeter of application site: blackened

‡ Ulceration and irreversible destruction of dermal tissue confirmed by veterinary pathologist

 

PII

Erythema total scores = 16

Oedema total scores = 16

 

Overall sum = 32, therefore PII = 8.0

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

When applied to the shaved intact skin of one male rabbit for 4 hrs, the test substance produced effects indicative of corrosivity (i.e., Irreversible destruction of dermal tissue).

Executive summary:

The skin irritation potential of the test substance was determined in accordance with standardised guidelines OECD 404, EPA OPP 81 -5, EPA OPPT 798.4470, EU Method B.4 and Japan 59 NohSan No 4200. During the study the test material was seen to produce effects indicative of corrosivity (i.e., irreversible destruction of dermal tissue) when applied to the shaved intact skin of one male rabbit for 4 hrs. Under the conditions of the study, the test material is considered to be corrosive to the skin.