3,5-dimethylbenzoyl chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 November 1992 - 18 November 1992

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:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan 59 Nohsan Notification No. 4200

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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:

DMBC
Appearance: clear liquid

Test animals

Species:

rat

Strain:

other: Crl:CDBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, NY.
- Age at study initiation: Adult. At the time they were dosed, the males were approximately 55 days old and the females were approximately 65 days old.
- Weight at study initiation: The body weights ranged from 237 - 254 g for males, and from 211 - 239 g for females.
- Housing: The animals were housed 1 per cage throughout the quarantine/acclimation period, and the test period. Animals were housed in suspended cages (7 x 13.5 x 8 in., i.e., 18 x 34 x 20 cm) with wire mesh fronts and bottoms. Cages were suspended above absorbent-paper pan liners which were changed 3 times a week
- Diet (e.g. ad libitum): ad libitum Purina Certified Rodent Chow 5002(C) (Purina Mills Inc., Richmond, IN).
- Water (e.g. ad libitum): All rats had free access to filtered tap water (via automatic watering).
- Acclimation period: Approximately 1 week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23 °C.
- Humidity (%): 52 - 54 % relative.
- Photoperiod (hrs dark / hrs light): The light cycle was automatically controlled, 12 h on and 12 h off.

IN-LIFE DATES: From: To 4 November 1992 - 18 November 1992

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day prior to dosing (at least 24 hr before the application of the test substance), the hair around the entire trunk between the flank and shoulders was shaved closely with electric clippers.
The undiluted test substance was applied topically to the shaved intact skin. The entire trunk of each animal was wrapped in a polyethylene sheet covered with Elastoplast (Beiersdorf, Inc., Norwalk, CT) and PEG (Becton-Dickinson Co., Franklin Lakes, NJ) elastic bandages and secured in place with adhesive tape.

The test substance remained in contact with each animal for 24 h. After the 24 h exposure period, each cuff was removed, and the application site was washed with a 1.0 % soap solution and blotted dry with paper towels. The approximate dimensions of the contact area of the test substance were then determined. After dermal application, the test substance covered an area approximately 6 x 6 cm.

Each animal was then fitted with a cardboard collar to prevent preening of the application site. The collar was worn throughout the observation period.

Duration of exposure:

24 hours

Doses:

2000 mg/kg/bw

No. of animals per sex per dose:

5 animals per sex per dose.

Control animals:

no

Details on study design:

All animals were observed for signs of ill health, or reaction to treatment at approximately 1, 2, 4 and 5 hr after dosing and once daily thereafter for 14 days. Body weights were recorded on day 0 (prior to dosing) and on days 7 and 14.

Surviving rats were killed on day 14 and necropsied, Necropsy consisted of a gross examination of organs in situ.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: There were no clinical signs.

Gross pathology:

No gross changes.

Other findings:

Periodically during the study, the fur surrounding eyes and muzzle was observed to be red stained; however, these effects were judged to be caused by the occluded testing methodology and by the use of collars.

Erythema was observed in all animals on days 1 and 2, and was also sporadically observed in both sexes between days 5 and 11. Other skin irritation effects observed during the study included: sores on the perimeter of application site, desiccation on the application site, and/or scabs on the abdomen. Alopecia on the abdomen was observed between days 8 and 13. This effect was judged to be related to the skin irritation.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 >2000 mg/kg/bw

Executive summary:

The dermal toxicity of DMBC was evaluated in accordance with the methods described in OECD Guideline 402, US EPA 40 CFR Part 158; Guideline 81-2, US EPA 40 CFR Section 798.1100 and Japan 59 NohSan Notification No. 4200.

 

After topical application of the test substance to the shaved intact skin of rats at 2000 mg/kg body weight, the application sites were occluded for 24 h. After the 24 h exposure, the application sites were washed with a 1 % soap solution and rinsed with tap water.

There were no mortalities, clinical signs, or apparent body weight effects related to the test substance, though skin irritation was observed. Necropsy revealed no gross changes.

 

The acute dermal LD50 for DMBC was greater than 2000 mg/kg in male and female rats.