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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1983-12-14 to 1984-01-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1.a: GLP OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): p-chlorbenzotrichlorid
- Substance type: halogenated
- Physical state: yellowish liquid
- Analytical purity: at least 97 %
- Storage condition of test material: in dark at 22 °C
- Other:
Substance code: GLHE 155
No further information

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, kastengrund, SPF-Zucht
- Weight at study initiation: mean of 184g for male (min: 170g, max: 189g) and of 180f for female (min: 167g, max: 194g)
- Fasting period before study: 16 hour prior the test and two after the exposure
- Housing: five rats by cage (type 4) in a ventilated room. woodchips on the ground of the cages
- Diet (e.g. ad libitum): granules Altromin 1324 ad libitum
- Water (e.g. ad libitum): tap water in drinking flasks ad libitum
- Acclimation period: five days prior the test


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10 %
- Photoperiod (hrs dark / hrs light): 12 hours dark/light alternance
No further information

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 75 %
- Amount of vehicle (if gavage): from 1.25
- Justification for choice of vehicle: hydrolyzed in water and available vehicle


MAXIMUM DOSE VOLUME APPLIED: 3.2 mL/kg bw (corresponding to 800 mg/kg bw of test substance)
No further information

Doses:
For both sexes: 315 (only female), 500, 630 and 800 mg/kg bw
No. of animals per sex per dose:
5 rats (male and female) per dose except for the dose at 315 mg/kg bw (for female only)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations but once a week for the weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and gross pathology
No further information
Statistics:
LD50 were established by a probit analysis (method from Lindner and Weber) and confidence intervals were established with the method of Fieller or Sidak by a software.
LD50 for males and females were compared to check whether a statistical difference could be found between both sexes.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
652 mg/kg bw
95% CL:
>= 518 - <= 844
Sex:
female
Dose descriptor:
LD50
Effect level:
581 mg/kg bw
95% CL:
>= 442 - <= 724
Sex:
male/female
Dose descriptor:
LD50
Effect level:
614 mg/kg bw
95% CL:
>= 528 - <= 706
Mortality:
At the end of the observation period (14 days):
- three males were dead when exposed to 630 mg/kg bw
- four males were dead when exposed to 800 mg/kg bw
- two females were dead when exposed to 500 mg/kg bw
- two females were dead when exposed to 630 mg/kg bw
- all females (5) were dead when exposed to 800 mg/kg bw
Clinical signs:
After one and two days, both sexes rats exhibited adverse effects on their breathing, locomotion and behavioral posture. Myosis was also observed. At the highest tested dose in males, there was an increase of reflexes and lacrimation (blood colored tears).
Body weight:
Surviving male rats exhibited a decrease of their body weight after seven days
Gross pathology:
In both sexes, liver was noticed to be bright and spotted, the stomachal content was clear and no food was found in the big intestine. At the highest tested dose, the spleen was also bright. In females, liver lobes were scattered and in males, surrenales were dark brown and the small intestine was filled with a yellowish-orange mucus.
All surviving rats (in both sexes) were killed after 14 days of observation and exhibited no effects after a gross pathology exmination.
Other findings:
No further information

Any other information on results incl. tables

In the following tables, the details on body weight variations of rats exposed to various concentrations of 4 -Cl-benzotrichloride are given:

Body weight of female rats exposed orally to 315 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 176 196 +11 215 +22
2 171 192 +12 214 +25
3 180 199 +11 198 +10
4 176 200 +14 201 +14
5 175 193 +10 201 +15

Body weight of male rats exposed orally to 500 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 189 204 +8 249 +32
2 183 168 -8 224 +22
3 170 156 -8 217 +28
4 181 181 0 232 +28
5 184 209 +14 252 +37

Body weight of female rats exposed orally to 500 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 178 dead 2d p.a    
2 181 201 +11 206 +14
3 183 205 +12 197 +8
4 189 dead 2-3d p.a    
5 181 204 +13 204 +13

Body weight of male rats exposed orally to 630 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 184 dead 0-1d p.a    
2 188 dead 1-2d p.a    
3 185 187 +1 236 +28
4 185 185 0 235 +27
5 181 dead 0-1d p.a    

Body weight of female rats exposed orally to 630 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 174 dead 3-4d p.a    
2 187 dead 0-1d p.a    
3 194 200 +3 231 +19
4 192 209 +9 209 +9
5 189 199 +5 204 +8

Body weight of male rats exposed orally to 800 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 188 dead 0-1d p.a    
2 187 dead 0-1d p.a    
3 186 dead 0-1d p.a 231 +19
4 182 dead 0-1d p.a 209 +9
5 182 198 +9 251 +38

Body weight of female rats exposed orally to 800 mg/kg bw of 4-Cl-benzotrichloride
Animal number initial weight (g) weight after 7 days weight after 14 days
g % g %
1 174 dead 1d p.a    
2 179 dead 0-1d p.a    
3 164 dead 0-1d p.a    
4 178 dead 0-1d p.a    
5 167 dead 2-3d p.a    

In the following tables, the details on mortality of rats exposed to various concentrations of 4 -Cl-benzotrichloride are given:

Lethality table for female rats exposed orally to 315 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 2 days 3 days 5 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour 4 days 14 days
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5

Clinical symptoms table for male rats exposed orally to 500 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 2 days 3 days 4 days 5 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour 14 days
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5

Clinical symptoms table for female rats exposed orally to 500 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 2 days 3 days 5 days 6 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour 4 days 14 days
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 0/5 1/5 2/5 2/5 2/5

Lethality table for male rats exposed orally to 630 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 2 days 3 days 5 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour 4 days 14 days
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 2/5 3/5 3/5 3/5

Clinical symptoms table for female rats exposed orally to 630 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 3 days 4 days 5 days 6 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour 2 days 14 days
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 1/5 2/5 2/5 2/5 2/5

Clinical symptoms table for male rats exposed orally to 800 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 2 days 3 days 4 days 5 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour 14 days
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 4/5 4/5 4/5 4/5 4/5

Clinical symptoms table for female rats exposed orally to 800 mg/kg bw of 4-Cl-benzotrichloride
Time after the application from 0 10 min 30 min 1 hour 2 hour 4 hour 1 day 2 days 3 days
to 10 min 30 min 60 min 2 hour 4 hour 6 hour
Lethality of rats   0/5 0/5 0/5 0/5 0/5 0/5 4/5 4/5 5/5

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the OECD guideline 401, the authors estimated in a GLP study, the acute oral LD50 of 4-chloro-benzotrichloride on wistar rats at 614 mg/kg bw .
According to CLP regulation n°1272/2008, 4 -chloro-benzotrichloride should therefore be considered as a toxic class 4 or harmful according to the former 67/548/EC regulation.
Executive summary:

The authors tested the acute oral toxicity of 4-chloro-benzotrichloride (CAS n° 5216-25-1) according to the former OECD guideline 401. They administered one oral dose ranging from 315 mg/kg bw to 800 mg/kg bw with a gastric probe to wistar rats (both sexes) . They followed the mortality, performed clinical examinations and gross pathology on dead rats (surviving rats killed) over an observation period of fourteen days.

At the end of the experiment, the authors estimated by probit analysis a LD50 of 652 mg/kg bw for male rats and a LD50 of 581 mg/kg bw for female rats. The mortality was correlated with well documented clinical and gross pathology observations (e.g: breathing disruption, signs of anxiety...). After statistical analysis, the authors concluded that the LD50 for wistar rats in the test conditions was estimated at 614 mg/kg bw.

According to CLP regulation n°1272/2008, 4 -chloro-benzotrichloride should therefore be considered as a toxic class 4 or harmful according to the former 67/548/EC regulation.

The authors followed the OECD guideline 401 with a GLP procedure. The study report is very well documented and provides very clear information. Therefore this study should be considered as reliable without restrictions.