Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 1989-January 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: in accordance with guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,2-dichloro-4-(trichloromethyl)benzene
EC Number:
235-869-7
EC Name:
1,2-dichloro-4-(trichloromethyl)benzene
Cas Number:
13014-24-9
Molecular formula:
C7H3Cl5
IUPAC Name:
1,2-dichloro-4-(trichloromethyl)benzene
Details on test material:
- Name of test material (as cited in study report): 3,4-Dichlorbenzotrichlorid
- Substance type: intermediate for synthesis
- Physical state: liquid, clear, colourless
- Analytical purity: 99.3%
- Purity test date: 23 March 1989
- Lot/batch No.: 16001/89
- Expiration date of the lot/batch: 23 September 1989
- Storage condition of test material: dark, room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: males: 7-8 weeks, females: 10-12 weeks
- Weight at study initiation: males: 168-188 g, females: 172-192 g
- Housing: Makrolon cages, type III, 5 animals per cage
- Diet (e.g. ad libitum): Altromin 1324 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 50%
- Air changes (per hr): 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light 12 hours dark

IN-LIFE DATES: From: 10 May 1989 To: 13 June 1989

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Chromophor EL solution (2% v/v) in deionised water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw


Doses:
1000, 1600 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
- Frequency of observations and weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, behavioural observation

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 424 mg/kg bw
Based on:
test mat.
95% CL:
> 1 065 - < 1 905
Sex:
female
Dose descriptor:
LD50
Effect level:
1 600 mg/kg bw
Based on:
test mat.
Mortality:
1000 mg/kg bw: males: 20%, females: 0%
16000 mg/kg bw: males: 60%, females: 40%
2000 mg/kg bw: males: 80%, females: 100%
Clinical signs:
Apathy, reduced motility, spastic walking, respiratory difficulty, body weight loss, reflex reduction, contraction, reclined position, salivation, bloody eyes, urination increase, bloody urine, paleness, cramp and in one case hypothermy.
Body weight:
Registered before application, on day 4 and day 8, then weekly and on death. On the 4th and 8th day, significant body weight loss in some of the animals, then recovered after the first or the second week of application.
Gross pathology:
Lung dilatation, pale or coloured liver, pale spleen, pale or grey kidney with deformed structure, reddish pelvis, reddish stomach walls, thickened or thinned and with ulceration, bladder containing urine from clear to reddish, hard fecesl in the colon, small intestine with dark mucus.

Any other information on results incl. tables

Toxicological results on male rats

Dose (mg/kg)

Toxicological results*

Duration of signs

Time of death

Mortality (%)

1000

1/5/5

15’-7 d

7 d

20

1600

3/5/5

40’- 12 d

2-5 d

60

2000

4/5/5

35 '-7 d

1-6 d

80

Toxicological results on female rats

Dose (mg/kg)

Toxicological results*

Duration of signs

Time of death

Mortality (%)

1000

0/5/5

45’-7 d

-

0

1600

2/5/5

20’- 11 d

3-10 d

40

2000

5/5/5

30'- 11 d

6-11 d

100

Notes:

* 1st figure= number of dead animals

2nd figure= number of animals with symptoms

3rd figure= number of treated animals

Applicant's summary and conclusion

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
The LD50 in male rat is 1424 mg/kg bw.
The LD50 in female rat is 1600 mg/kg bw.
Executive summary:

A toxicity study in which Wistar rats (5 males and 5 females/dose) received a single oral administration of the test article 3,4 -Dichlorbenzotrichloride at the doses of 1000, 1600 and 2000 mg/kg bw was conducted.

The test method was in accordance with OECD Guideline n. 401. The test article was administered in a Chromophor solution (2% v/v) in deionised water at the volume of 10 mL/kg bw .

The animals were weighed before treatment and on days 4, 8 and 14. They were clinically observed for 14 days after treatment.Animals which died and animals killed at the end of the study were submitted to a thorough autopsy. One male treated at 1000 mg/kg bw died on day 7. No female treated at 1000 mg/kg bw died on day 7. Three males treated at 1600 mg /kg bw died within days 2 and 5. At the same dose, 2 females died within days 3 and 10. Four males treated at 2000 mg/ kg bw died within day 1 and 6. At the same dose, 5 females died within day 6 and 11 of treatment.

Treated animals showed the following symptoms: lung dilatation, pale or coloured liver, pale spleen, pale or grey kidney with deformed structure, reddish pelvis, reddish stomach walls, thickened or thinned and with ulceration, bladder containing urine from clear to reddish, hard fecesl in the colon, small intestine with dark mucus. Recovery of all surviving rats was achieved from 15 minutes to 12 days. On days 4 and 8, significant body weight loss in some of the animals was registered, then recovered after the first or the second week of application.