5-Thiazolecarboxylic acid, 2-(4-hydroxyphenyl)-4-methyl-, ethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01/06/2011-17/06/2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 2-(4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate

EC Number:

605-268-8

Cas Number:

161797-99-5

Molecular formula:

C13H14ClNO3S

IUPAC Name:

ethyl 2-(4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan SLC, Inc.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 125-132 g
- Fasting period before study: 16 hours
- Housing: in an animal room
- Diet (e.g. ad libitum): a commercial pellet diet, CRF-1 n(Oriental Yeast) ad libitum
- Water (e.g. ad libitum): free access
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Doses:

300 or 2000 mg/kg of the test substance (vehicle: 0.5% methyl cellulose solution)

No. of animals per sex per dose:

5 animals (1 in the sighting study and 4 in the main study)

Control animals:

yes

Details on study design:

day 0 (the day of dosing): the animals were observed once within the first 30', and thereafter, once an hour until 4 hours after the dosing. From day 1 to day 14, the animals were observed once daily.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All the animals survived throughout the observation period.

Clinical signs:

other: No abnormalities were observed in any of the animals.

Gross pathology:

No abnormal changes were observed in any organs of any of the animals.

Any other information on results incl. tables

Sighting study

First, 1 animal received 300 mg/kg of the test substance and exhibited no abnormalities in general condition, body weight, or necropsy findings. Next, 1 animal which received 2,000 mg/kg of the test substance also exhibited no abnormalities, similar to

the animal given the test substance at 300 mg/kg.

Main study

Based on the results of the sighting study, the dose level in the main study was designated as 2,000 mg/kg. The other 4 animals were given the test substance at 2,000 mg/kg, which resulted in no abnormalities detectable by any of the examinations.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

None of the 5 animals (1 in the sighting study and 4 in the main study) exhibited any noteworthy abnormalities at the dose level of 2,000 mg/kg.
Since the lethal dose 50% (LD50) of this test substance was judged to be more than 2,000 mg/kg in rats under the conditions of the present study, Manufacturing Intermediate of TMX-67 (Thiazole Derivative (Free Base Form)) was categorized as “Unclassified” according to the GHS classification system1).