Registration Dossier

Administrative data

Description of key information

PCBTF is practically non-toxic to laboratory animals after acute exposure via oral, dermal or inhalatory administration. 

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:
key study
Study period:
September - October 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: NON GLP, no guideline reported.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Please refer to the Executive Summary for details on method.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 121-148 g
- Housing: plastic cages on sawdust
- Fasting: no food since 16 hs before treatment
- Diet : ALTROMIN 1324 ad libitum
- Water: ad libitum


IN-LIFE DATES: From: 28 September To: 12 October
Route of administration:
oral: gavage
Vehicle:
vegetable oil
Remarks:
sesam oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%

MAXIMUM DOSE VOLUME APPLIED: 10.000 mg/kg
Doses:
4000, 6300, 10000 mg/kg
No. of animals per sex per dose:
10 (males)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs.
Statistics:
Probit analysis
Preliminary study:
No
Sex:
male
Dose descriptor:
LD50
Effect level:
5 546 mg/kg bw
Based on:
test mat.
95% CL:
> 4 575 - < 6 724
Mortality:
4000 mg/kg: 1/10 rat
6300 mg/kg: 8/10 rat
10000 mg/kg: 9/10 rat
Clinical signs:
convulsions, loss of balance,
Gross pathology:
whitish mucosa in the small intestine
Other findings:
No finding in macroscopic evaluation.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other: Handbook of Toxicology (1957), W.S. Spector
Conclusions:
The test item LD50 is 5546 mg/kg for male rats. The test item results practically non-toxic.
Executive summary:

After a fasting period of 16 days, the test item Parachlorbenzotrifluorid was administered by oral gavage to 10 male Wistar rats for each dose level (4000, 6300 and 10000 mg/kg b/w). The observed mortality 'til day 4 was as follows:

dose level 4000 mg/kg : 1/10 rats died

dose level 6300 mg/kg : 8/10 rats died

dose level 10000 mg/kg: 9/10 rats died

The registered clinical signs were: loss of balance and convulsions.

The LD50 was calculated by Probit analysis and was found to be 5546 mg/kg b/w.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
5 546 mg/kg bw
Quality of whole database:
The key study is no GLP compliant, but is of high quality (Klimisch score = 2)

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, in accordance with guidelines
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WISK (SPF71), Hoechst AG, Kastengrund
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males: mean 191 g (range 186-195 g); females: mean 190 g (range 185-194 g).
- Fasting period before study:
- Housing: Macrolon cages Type 4, air-conditioned, with pellet wood floor, housed in groups of 5 animals.
- Diet (e.g. ad libitum): Altromin 1324 rodent food ad libitum
- Water (e.g. ad libitum): ad libitum, tap water in plastic bottles.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50± 20%
- Photoperiod (hrs dark / hrs light): 12 dark, 12 light h

IN-LIFE DATES: From: 1 April 1992 To: 15 April 1992
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
The dry compressed air arrives in the 2 component nozzle up to the exposure tubes, with a flow of 800 L/h. The test item is injected with a constant speed.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gaschromatography equipped with FID detector
Duration of exposure:
ca. 4 h
Concentrations:
32.03 mg /L air.
No. of animals per sex per dose:
5 per each sex.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: twice a day. Weighing: day 8 and day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 32.03 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was registered.
Clinical signs:
Increase of respiration rate, ataxia, irregular respiration, stupor, ruffled coat, stilted gait, ataxic gait, uncorrodinated gait, prone position, tremors, palpebral fissure narrow, increase of salivation.
Body weight:
Regular increase of bw in both male and female animals.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Based on this study results, the test item LC50 is > 32.03 mg/L air, after a 4 hours exposure. The test item results practically non toxic to rats.
Executive summary:

Ten animals, 5 males and 5 females, were exposed to a nose-only inhalation treatment at a concentration of 32.03 mg/L air of p-Chlorbenzotrifluoride, for 4 hours. Clinical signs, body weights and mortality was observed and registered up to a post-exposure observation period of 14 days. No mortality was observed. The reported clinical signs comprised: increase of respiration rate, ataxia, irregular respiration, stupor, ruffled coat, stilted gait, ataxic gait, uncorrodinated gait, prone position, tremors, palpebral fissure narrow, increase of salivation. These clinical signs were fully reversible within 5 days. The body weight gain was regular. Based on this study ' results, the test item LC50 is > 32.03 mg/L air, after a 4 hours exposure. The test item results practically non toxic to rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
32 032 mg/m³
Quality of whole database:
The key study is GLP compliant and it is of high quality (Klimisch score = 1)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March-April 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, no guidelines; liver function was the focal parameter
Qualifier:
no guideline followed
Principles of method if other than guideline:
6 rabbits were applied with a single dose of the test item on the shaved neck skin for 5 hours and observed for 7 days. Before the application and at day 1, 3 and 7, the activity of aspartate- and alanine aminotransfrase (AST and ALT) were measured in the peripheral blood. The survived animals were sacrificed at the end of the study and their liver was analyzed for hystologic abnormalities.
GLP compliance:
no
Test type:
other: liver functioning assessment after single dermal application
Limit test:
yes
Species:
rabbit
Strain:
Himalayan
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5 - 2 kg
- Housing: in single cages and with a plastic collar allowing to avoid the oral contact with the treated skin area

IN-LIFE DATES: From: 29 march 1976 To: 6 april 1976
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
REMOVAL OF TEST SUBSTANCE
- Washing: with a sponge and cold water
- Time after start of exposure: 5 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 g
Duration of exposure:
5 h
Doses:
5000 mg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: blood was collected and analysed for AST and ALT activity on days: 0, 1, 3 and 7
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, beahviour, micro and macroscopic examination of the liver
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 3 300 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No clinical sign reported
Body weight:
No data
Gross pathology:
No abnormality reported
Other findings:
After 24 hours the activities of of AST and ALT were slightly increased, but this effect was fully reversible whithin 7 days after the application.

Liver functioning parameters before and after the test item dermal application

 

AST

ALT

 

Initial value

t = 24 h

t = 3 d

t = 7 d

Initial value

t = 24 h

t = 3 d

t = 7 d

n

6

6

6

6

6

6

6

6

mean

4.7

14

5.3

2.3

31.3

57.5

41.7

31.7

S.D.

2.1

4.7

1.2

0.5

4.0

10.3

5.1

4.1

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Parachlorbenzotrifluorid exerted no adverse effect to rabbits after dermal application of 5000 mg for 5 hours. After 24 hours the activities of AST and ALT were slightly increased, but this effect was fully reversible whithin 7 days. No mortality, neither abnormal behaviour were observed during the 7 -days post-application period. No micro-, nor macroscopic findings were observed after hystological liver analysis.
Executive summary:

6 rabbits were applied with a single dose of the test item on the shaved neck skin for 5 hours and observed for 7 days afterwards. Before the application and at day 1, 3 and 7, the activities of aspartate- and alanine aminotransfrase (AST and ALT) were measured in the peripheral blood. After 24 hours the activities of AST and ALT were slightly increased, but this effect was fully reversible whithin 7 days after the application. No mortality, neither abnormal behaviour were observed during the 7 -days period. The survived animals were sacrificed at the end of the study and their liver was analyzed for hystologic abnormalities. No micro-, nor macroscopic findigs were reported.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
3 300 mg/kg bw
Quality of whole database:
The two studies are non GLP and non-guideline compliant; however they together form a reliable weight of evidence.

Additional information

Even if the presented studies are quite old, the whole data base is deemed to be sufficient to satisfy the data requirements for the tonnage band 100 -1000 t/a, as information on all the route of exposure are available, showing an overall low acute toxicity of PCBTF to the test animals. The test species are in agreement with those indicated in the most recent test guidelines and therefore are relevant and adequate for the classification and the CSA.


Justification for selection of acute toxicity – oral endpoint
Lowest available LD50

Justification for selection of acute toxicity – inhalation endpoint
only key study available

Justification for selection of acute toxicity – dermal endpoint
The most ducumented study between the two available. However both studies coherently indicate that no adverse effect is observed after the dermal application of PCBTF to laboratory animals at doses of 2000 mg/kg bw and 3300 mg/kg bw (5000 mg applied to wors case rabbit of 1.5 kg bw).

Justification for classification or non-classification

The substance is not classified for acute toxicity because no effects because the acute oral LD50>2000 mg/kg and the acute inhalatory LC50> 32 mg/L and the dermal LD50>3300 mg/kg bw