Benzoyl chloride, 3-methoxy-2-methyl-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 May 1996 - 29 May 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

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. However, the test substance was found to be corrosive; its corrosive properties prevented thorough investigation of the systemic dermal toxic effects.

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 5

Qualifier:

according to guideline

Guideline:

other: Japan 59 NohSan Notification No. 4200

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

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 - males 51 days; females 63 days.
- Weight at study initiation: Males 219 - 256 g; females 201 - 234 g.
- Housing: The animals were individually housed in suspended stainless steel cages (7 x 13.5 x 8 in., i.e. 18 x 34 x20 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): All rats had free access and were fed PMI Certified Rodent Diet 5002(C) (Purina Mills Inc., Richmond, IN).
- Water (e.g. ad libitum): ad libitum filtered tap water (via automatic watering).
- Acclimation period: approximately 1 week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23 °C
- Humidity (%): 39 - 47 % relative
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours darkness

IN-LIFE DATES: From: To: 15 May 1996 - 29 May 1996

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

DOSE PREPARATION AND ADMINISTRATION
The hair around the entire trunk between the flank and shoulders was shaved closely with electric clippers approximately 24 hr prior to the application of the test substance. The test substance was ground with a mortar and pestle and moistened (1:1 w/v) with distilled water, and administered topically to the shaved intact skin of male and female rats at dose levels of 400, 1000, or 2000 mg/kg body weight. Dose was calculated on nominal concentrations; no adjustment was made for percent active ingredient. The entire trunk of each animal was wrapped in a polyethylene sheet covered with Elastoplast (Beiersdarf, Inc., Norwalk, CT) and PEG (Becton-Dickinson Co., Franklin Lakes, NJ) elastic bandages secured in place with adhesive tape.

The test substance remained in contact with the skin of each animal for 24 hrs. Each cuff was removed after the 24-hr exposure period, and the application site was wiped with paper towels saturated with tap water. The application site was blotted dry with paper towels, and the approximate dimensions of the contact area of the test substance were determined. Each animal was 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:

400, 1000 and 2000 mg/kg body weight.

No. of animals per sex per dose:

6 animals per sex per dose.

Control animals:

no

Details on study design:

OBSERVATIONS AND DETERMINATIONS
All animals were observed for signs of ill health, or reaction to treatment at approximately 1, 2 and 4 hrs 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. Body weights were determined for found-dead animals when they survived beyond the day of treatment.

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:

> 1 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals in the 2000 mg/kg group were euthanised for humane reasons on Day 2 due to evidence of irreversible destruction of dermal tissue on the application site. One female in the 1000 mg/kg group was found dead on Day 1; however, this death appeared to be due to an overly-restrictive occlusive dressing and not dermal toxicity. Another female in the 1000 mg/kg group was euthanised for humane reasons on Day 6 due to evidence of irreversible destruction of dermal tissue on the application site. All other rats (4 females and 6 males) in the 1000 mg/kg dose group survived until the end of the study. There were no mortalities in the 400 mg/kg group.

Clinical signs:

other: Treatment-related clinical signs of systemic toxicity (scant faeces) were noted on Day 1 post-exposure at all dose levels. Skin effects observed at all dose levels included: reddened/darkened areas, oedema, erythema, scabs, sores, areas of ulceration an

Gross pathology:

Necropsy of both the survivors and the animals euthanised for humane reasons revealed no gross changes related to the test substance.

Other findings:

After dermal application, the test substance covered an area of approximately 6 x 6 cm.

Periodically during the study, the fur surrounding the eyes and muzzle of several animals was observed to be red-stained; these effects were judged to be caused by the occluded testing methodology and by the use of collars and not related to the test substance.

Euthanised animals and the animal found dead apparently due to an overly-restrictive occlusive dressing, did not complete the full 14 day observation period and were not used to estimate the dermal LD50.

Applicant's summary and conclusion

Interpretation of results:

other: It was not possible to classify the substance as its corrosive properties prevented thorough investigation of the systemic toxic effects.

Conclusions:

The acute dermal LD50 of the test substance was estimated to be greater than 1000 mg/kg in male and female rats.

Executive summary:

The acute dermal toxicity of the test substance was determined in accordance with standardised guidelines OECD 402, US EPA OPP 81 -2, US EPA OPPTS 798.1100, EU Method B.3 and Japan 59 NohSan Notification No. 4200. Six male and female rats received single dermal applications of test substance moistened in water at dose levels of 400, 1000 and 2000mg/kg body weight. After the 24 hour exposure period, the application sites were wiped clear of test substance and assessed for signs of systemic toxicity over the following 14 day period. During the study, all animals in the 2000 mg/kg group were euthanised for humane reasons on Day 2 due to evidence of irreversible destruction of dermal tissue on the application site. One female in the 1000 mg/kg group was found dead on Day 1; however, this death appeared to be due to an overly-restrictive occlusive dressing and not dermal toxicity. Another female in the 1000 mg/kg group was euthanised for humane reasons on Day 6 due to evidence of irreversible destruction of dermal tissue on the application site. All other rats (4 females and 6 males) in the 1000 mg/kg dose group survived until the end of the study. There were no mortalities in the 400 mg/kg group. Skin effects observed at all dose levels included: reddened/darkened areas, oedema, erythema, scabs, sores, areas of ulceration and loss of skin and cutaneous musculature. There were no apparent dose-related body weight effects among survivors compared to historical control data. Necropsy of both the survivors and the animals euthanised for humane reasons revealed no gross changes related to the test substance. Euthanised animals and the animal found dead apparently due to an overly-restrictive occlusive dressing, did not complete the full 14 day observation period and were not used to estimate the dermal LD50. The acute dermal LD50 of the test substance was estimated to be greater than 1000 mg/kg in male and female rats.