4-isocyanato-2-methyl-1-{4-[(trifluoromethyl)thio]phenoxy}benzene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted: 24 February, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

as amended by Directive 92/69/EEC (31 July, 1992)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-isocyanato-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenoxy}benzene

EC Number:

690-654-9

Cas Number:

106310-19-4

Molecular formula:

C15H10F3NSO2

IUPAC Name:

4-isocyanato-2-methyl-1-{4-[(trifluoromethyl)sulfanyl]phenoxy}benzene

Test material form:

liquid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Homegeneity and stability was confirmed by analytical examination and assured at room temperature for a period at least 2 hours..


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation: The applied formulation was well mixed by shaken and by pumping the syringe several times before removal of the dosage.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: 173-191 g (males), 176 -191 g (females)
- Fasting period before study: ca. 16 hours before and 2 hours after treatment
- Housing: 5 animals/cage (polycarbonat cages type III)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21° +- 1.5° C
- Humidity (%): 40-70%
- air exchange rate: at least10 times per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

once 5 ml/kg bw

Doses:

200 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes (gross pathology examination)
- behavior and appearance: several times on the day of treatment and at least once a day thereafter
- body weights: before administration and on day 4 and 8 after administration and afterwards the weekly and all animals that died or were sacrificed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 200 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 200 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: apathy, spastc duct, difficulties with respiration soft faeces dose mg/kg / number with symptom / duration time males 200/ 5/ 2 d – 4d 2000/ 5/ 4h – 2d females 200/ 0/ 2000/ 5/ 4h – 2d

Gross pathology:

No findings indicative for a specific test compound effect.

Applicant's summary and conclusion

Executive summary:

A single oral administration of the test substance by gavage to male and female rats at 200 mg/kg bw and 2000 mg/kg bw was tolerated without mortalities. Transient clinical signs were observed at doses of 200 mg/kg bw and above. There was no effect on body weight gain. The gross pathology investigations performed at the end of the follow-up period did not afford any findings indicative for a specific test compound effect. The LD50 was determined to be > 2000 mg/kg bw in both sexes.