Sodium 4-(4-substitutedanilino)-4-substituedbut-2-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 July - 18 July 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 Dec 2001

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test item was stored in a cold dark place (prefabricated refrigerator, 8.6 to 11.4°C), protected from light, in a well-closed container.
- Stability of test article: stable for one year, at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: The test substance was dissolved in water at 200 mg/mL just before dosing.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Slc:Wistar [SPF]

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan SLC Inc., Japan
- Age at study initiation: 8 weeks
- Weight at study initiation: 133 - 137 g
- Fasting period before study: animals were fasted overnight prior to administration
- Housing: individual in wire-mesh cages with an automatic water flushing breeding rack (Toyoriko). The cages were exchanged every two weeks and the feeders once a week.
- Diet: pellet diet CRF-1 (Oriental Yeast, lot No. 131108), ad libitum
- Water: tap water, ad libitum (analysis was performed)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.7 - 23.2
- Humidity (%): 49.4 to 57.7
- Air changes (per hr): ≥ 12
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: 4 July To: 18 July 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 1.0 mL/ 100 g bw
- Lot/batch no.: K3K81(Otsuka Pharmaceutical Factory, Inc.; Japan)

MAXIMUM DOSE VOLUME APPLIED: 1.0 mL per 100 g bw

- Rationale for the selection of the starting dose:
The acute oral toxicity of the test substance was predicted to be very low and the LD50 was estimated to be > 2000 mg/kg bw (information from sponsor). Therefore, 2000 mg/kg bw, the upper limit level described in the test guideline, was set for the dose level of the sighting study.
As a result of the sighting study, no animal died. Therefore, the dose of 2000 mg/kg bw was selected as a dose of the main study.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females (including one female in the sighting study)

Control animals:

no

Remarks:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On Day 0, all animals were observed once within 30 minutes and once each at 1, 2, 3 and 4 hours after dosing. From the next day of dosing (from Day 1 to Day 14), the animals were observed once daily. All animals were weighed on Days 0 (before dosing), 7 and 14.
- Necropsy of survivors performed: yes
- The following organs and tissues were examined macroscopically: external surfaces, orifices, the organs and tissues in the abdominal, thoracic, pelvic and cranial cavities

Statistics:

Statistical analysis was not used.

Results and discussion

Preliminary study:

No mortality or clinical signs indicative for systemic toxicity were observed during the sighting study.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

On Day 1, diarrhea was observed in 4 of 5 animals. From Day 2 to Day 14, no clinical signs were observed in any of the animals.

Body weight:

All animals showed normal body weight gains during the observation period.

Gross pathology:

All animals showed no abnormal gross findings in the examined organs and tissues.

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

CLP: not classified