Methyl 3-aminocrotonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 October 1999 - 23 March 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Feb. 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid

Details on test material:

Expiry date: 21 May 2000
Batch: 624

Specific details on test material used for the study:

White crystalline solid stored in the dark at ambient temperature.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and 5 female (nulliparous and non-pregnant) young adult rats of the Sprague-Dawley strain were used. They were approximately 8 weeks old and
weighed 164-230 g on arrival. They were supplied by Harlan UK and arrived at lnveresk Research on 20 October 1999. The animals were allowed to acclimatise for 8 days prior to commencement of the study. The animals were housed individually in suspended polypropylene cages (dimensions 42 x 27 x 20 em), with stainless steel grid tops and bottoms, suspended over absorbent paper lined trays.
Each cage was supplied with a stainless steel food hopper and polypropylene water bottle with cap and stainless steel nozzle.
Mean environmental maximum and minimum temperatures were 22°C and 19°C, and the mean relative humidity was 48%. A 12 h light/dark cycle was in
operation (light hours 0700-1900 h) with a minimum of 15 air changes per hour.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

10 (5 male and 5 females)

Control animals:

no

Details on study design:

The test material was administered topically in a single 24 h application, under occlusion as follows:
One day prior to test material application the dorsal area of the trunk of each rat was clipped free of hair (approximately 7 cm x 8 cm),
taking care to avoid abrading the skin. On the following day, the appropriate quantity of finely ground test material,
which was calculated to be approximately 41 mg.cm-2 was applied onto the water moistened dorsal skin and spread uniformly over the trunk
(approximately 4% of the total body surface). The test material was then covered b,t a water moistened gauze patch (5 cm x 6 cm), secured with
Micropore (3M Medical-Surgical Division, USA) semi-occlusive tape, and a strip of non-irritating occlusive tape (Sleek, Smith and Nephew Medical
Limited, USA) wound round the trunk. The dose was calculated based on the weight of the animal on the day of dosing.
After a contact period of 24 h the patches were removed and the test sites delineated. The skin was then wiped with sterile distilled water.

Statistics:

No formal statistical analysis was conducted.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no premature decedents during the study.

Clinical signs:

other: On the day of dosing, clinical signs were limited to red discharge from the eyes and nose. Other clinical signs noted were dry flaky skin and/or scabbing from Day 6 up to Day 15. A wet perigenital area was noted in 2 of the female animals on Day 2 only.

Gross pathology:

Dry, red, scabbing on the dorsal surface was noted in 2 female animals.

Other findings:

No other abnormalities were noted in the remaining animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the Median Dermal Lethal Dose (LD50) of LZ937 in Sprague-Dawley rats is estimated to be greater than 2000 mg/kg bw.

Executive summary:

A acute dermal toxicity study was performed in year 1999/2000 according to OECD Guideline 402 and GLP. One group of 5 male and 5 female rats was exposed to a 24 h dermal

application of 2000 mg/kg b.w.. The test material was applied topically to the water moistened dorsal trunk of each animal under water moistened occlusive patches.

The animals were observed daily for viability and signs of reaction to treatment for up to 14 days after dosing. There were no premature decedents or major clinical signs noted during the

study. Body weight performance was generally considered to have been satisfactory, and there were no major findings noted at necropsy.

Under the conditions of the study, the Median Dermal Lethal Dose (LD50) of LZ937 in Sprague-Dawley rats is estimated to be greater than 2000 mg/kg bw.