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Administrative data

Description of key information

4-chloro-3-(trifluormethyl)-phenylisocyanat is harmful after single oral exposure (LD50 cut-off, rat: 500 mg/kg bw).

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:
other information
Study period:
April 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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
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
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:
The only clinical sign observed in all animals was diarrhea.
Body weight:
Body weight and body weight development of the surviving females in the 300 mg/kg bw group was not affected.
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
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The study is GLP compliant and is of high quality (Klimisch score=1)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

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.

No data are available for the substance with regard to inhalation toxicity. However, taking into account the structure of the substance as aromatic monoisocyanate and the well known local toxic properties of the highly reactive isocyanate group in the respiratory tract, the substance should be regarded as highly toxic after inhalation.


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for classification or non-classification

Based on the study results (oral LD50 cut-off: 500 mg/kg bw) a classification with R22 (harmful if swallowed) according to Directive 67/548/EEC or with Acute Toxicity Cat. 4 (H302:harmful if swallowed) according to Regulation (EC) No. 1272/2008 (CLP) is required.

No data are available for the substance with regard to inhalation toxicity. To protect the worker against potential risks via inhalation the following measures were taken:

Based on read-across with other aromatic monoisocyanates of this type the substance should be classified with Acute Toxicity Cat 1 (H330: fatal if inhaled) according to Regulation (EC) No. 1272/2008 (CLP). The substance should not be classified for acute inhalation toxicity according to Directive 67/548/EEC since protection of workers against inhalation is already covered in this Directive by the necessity to classify all skin sensitizing substances (R43) additionally as respiratory sensitizers (R42), even though neither experimental data nor human experiences point to such a property. High acute inhalation toxicity and respiratory sensitzation both require minimization of exposure.