Benzene, 1-chloro-4-isocyanato-2-(trifluoromethyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Study period:

April 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-4-isocyanato-2-(trifluoromethyl)benzene

EC Number:

608-783-6

Cas Number:

327-78-6

Molecular formula:

C8 H3 Cl F3 N O

IUPAC Name:

1-chloro-4-isocyanato-2-(trifluoromethyl)benzene

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Strain: Hsd Cpb:WU
- Age at study initiation: 9-10 weeks
- Mean weight at study initiation: 144-173 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

- Application volume: 5 mL/kg bw

- Rationale for the selection of the starting dose:
As described in the flow charts of Annex 2, OECD guideline 423, the starting dose level should be that which is most likely to produce mortality in
some of the dosed animals. Therefore, the limit dose 2000 mg/kg bw was chosen as starting dose. The substance is tested using a stepwise procedure, each step using three animals of a single sex (normally females). Because of the late time of dath the dose 2000 mg/kg bw was given to two groups of 3 rats.

Doses:

2000 mg/kg, 300 mg/kg bw

No. of animals per sex per dose:

6 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weight gain)
- Necropsy of survivors performed: yes

Statistics:

none

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

other: LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

The dose of 2000 mg/kg bw was lethal. All 6 treated females died at days 3 to 5 after administration. In the 300 mg/kg bw group (6 females) one animal died on day 5.

Clinical signs:

other: The only clinical sign observed in all animals was diarrhea.

Gross pathology:

In the animals of the 2000 mg/kg bw group that died during the observation period the only observation at gross pathology was autolysis. The one animal of the 300 mg/kg bw group that died during the observation period showed a slightly collapsed lung. The necropsies performed at the end of the observation period showed no treatment-related findings.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information

Executive summary:

The acute oral toxicity of the test material was moderate with an LD50 cut-off value of 500 mg/kg bw in rats according to OECD TG 423 (2001). All females died after oral ingestion of 2000 mg/kg bw. As clinical signs only diarrhea occurred. Besides autolysis no treatment-related findings were observed at gross-pathology in the high-dosed animals. Only one of the six females dosed with 300 mg/kg bw did not survive. As clinical signs diarrhea became obvious for all animals. Body weight development was not affected at 300 mg/kg bw in the surviving animals.