Methyl 3-aminocrotonate

Endpoint summary

Description of key information

Two oral tox. studies were performed. Only one study can be used as key study. Based on the higher number of animals of both sexes used within the key study, this study seems to have a higher reliability. The other study is a dose range finder study with two females and only used as a supporting study.

In the key study the acute oral toxicity of the test item was determined in male and female rats after single administration of seven concentrations with an application volume of 20 mL/kg

via stomach tube with an observation period of 14 d. The acute oral LD50 was 1760 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Single administration of seven concentrations with an application volume of 20 ml/kg to fasted rats (5 males and 5 females) via stomach tube with an observation period of 14 days

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Fasted (no food 16 h before and 4 h after application)

Route of administration:

oral: gavage

Vehicle:

other: Lutrol (PEG 400)

Doses:

1300, 1500, 1800, 1900, 2000, 2500 and 3100 mg/kg with an application volume of 20 ml/kg

No. of animals per sex per dose:

10 ( 5 males and 5 females)

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 760 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 610 - <= 1 910

Mortality:

All deaths occurred on the first day after administration.

Clinical signs:

other: No symptoms at dose 1300 mg/kg. All animals at dose 1500 mg/kg and above symptomatic (e.g. reduced general condition, cyanosis, ventral or lateral position, narcosis, dyspnea). Clinical signs occurred after 5 to 10 min after administration, on day 3 all

Gross pathology:

Bleedings in the mucous membrane of the stomach.

Other findings:

No abnormal findings seen at final necropsy

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 was 1760 mg/kg.

Executive summary:

The acute oral toxicity of methyl 3 -aminocrotonate was determined in fasted male and female rats after single administration of seven concentrations with an application volume of 20 ml/kg via stomach tube with an observation period of 14 d. The acute oral LD₅₀ was 1760 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 760 mg/kg bw

Quality of whole database:

reliable

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Feb. 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 1992

Deviations:

no

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

Specific details on test material used for the study:

White crystalline solid stored in the dark at ambient temperature.

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.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable

Justification for classification or non-classification

Based on the GHS criteria, the substance has to be classified as Acute Tox. 4; H302.