1,2,4-trichlorobenzene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1982

Reference 2

Reference Type:

secondary source

Title:

European Union Risk Assessment Report - 1,2,4-Trichlorobenzene

Author:

European Commission - European Chemicals Bureau

Year:

2003

Bibliographic source:

Office for Official Publications of the European Communities

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Analytical purity not reported. Acclimation period not reported. Body weights were not reported.

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2,4-trichlorobenzene

EC Number:

204-428-0

EC Name:

1,2,4-trichlorobenzene

Cas Number:

120-82-1

Molecular formula:

C6H3Cl3

IUPAC Name:

1,2,4-trichlorobenzene

Details on test material:

- Name of test material (as cited in study report): 1, 2, 4-trichlorobenzene
- Physical state: liquid
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 9 (males) - 14 (females) weeks
- Weight at study initiation: 159-173 g (males); 159-172 g (females)
- Fasting period before study: the animals were fasted from 16 to 4 hours before the dosing
- Housing: Rats were housed in number of 5 per cage in Makrolon cages type III
- Diet (e.g. ad libitum): Altromin R 1324, Altromin GmbH, Lage, Germany
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 60 ± 5%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light (7am/7pm)



IN-LIFE DATES: From: April To: July 1981

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: cremophore/tap water mixture (1 : 4)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

630-3100 mg/kg

No. of animals per sex per dose:

5

Control animals:

other: not applicable

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice per day and once on weekends and holidays. The animals were weighed at the moment of the exposure, after 1 week, and at the end of the 14-day oberservation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology analysis

Statistics:

The calculation of the LD50 with the confidence interval for p <0.05 was performed with the Probit analysis according to Fink und Hund (Arzneim.-Forsch. 15:1965, 624)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

930 mg/kg bw

95% CL:

>= 840 - <= 1 050

Remarks on result:

other: Slope=9.11

Mortality:

The deaths occurred during the first 3 days of the treatment

Clinical signs:

other: See remark

Body weight:

other body weight observations

Remarks:

body weight was not reported

Gross pathology:

In the section of deceased male and female animals were noted alterations of the stomach and intestine mucous membrane, and gastric bleeding .
The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1.0 and 1.25 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

Any other information on results incl. tables

Male
Dose mg/kg	Number of dead animals	Animals with symptoms	Total number of animals employed	Time of death
630	0	0	5
730	1	5	5	2^ndday
800	3	5	5	2^nd-3^rdday
1000	3	5	5	2^ndday
1250	5	5	5	24 hours-2^ndday
1600	5	5	5	24 hours
3100	5	5	5	24 hours
Female
Dose mg/kg	Number of dead animals	Animals with symptoms	Total number of animals employed	Time of death
630	0	0	5
730	0	5	5
800	2	5	5	3^rdday
1000	3	5	5	2^nd-3^rdday
1250	3	5	5	24 hours-2^ndday
1600	5	5	5	24 hours-2^ndday
3100	5	5	5	24 hours

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

Groups of 5 rats of each sex with starting weights between 159 g and 173 g were given 1,2,4-trichlorobenzene (630-3100 mg/kg) by gavage according to OECD guideline 401 with deviations (Analytical purity not reported. Air changes not reported. Acclimation period not reported.Body weights not reported).

The LD50 was 930 mg/kg with 95% confidential limit of 840-1050.

The deaths occurred during the first 3 days of the treatment.

The oral single doses from 730 to 3100 mg/kg provoked the following poisoning symptoms: worsening of the general conditions, sedation, necrosis, side-prone position.

In the section of deceased male and female animals were noted alterations of the stomach and intestine mucous membrane, and gastric bleeding.

The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1000 and 1250 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

On the basis of theses findings it is possible to classify 1,2,4 -trichlorobenzene in Category 4 (Acute Tox. 4, H302 according to GHS.