Registration Dossier

Administrative data

Description of key information

Valid acute oral and acute inhalation toxicity studies are available. A dermal study is not required because a reliable oral and inhalation study is on hand.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
female animals not tested; analytical purity not reported; fasting period not perforemed, acclimation period not performed, LD50 expressed in mL/Kg instead mg/kg; air changes not reported.
Principles of method if other than guideline:
Ten male rats received doses of 100, 200, 500, 1000 or 1500 µl (129, 258, 645, 1290, 1935 mg/kg) of undiluted 1,3-dichlorobenzene per gavage. During the post-observation period of 14 days, mortality, weight and clinical signs were registered.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: 176 g
- Housing: Makrolon cages type III
- Diet (e.g. ad libitum): Altromin R 1324 (Altromin GmbH, Lage, Germany) ad libitum
- 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 (artificial lighting from 7 a.m. to 7 p.m)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:



MAXIMUM DOSE VOLUME APPLIED:


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

MAXIMUM DOSE VOLUME APPLIED:


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
0.1, 0.2, 0.5, 1.0, 1.5 mL/kg (129, 258, 645, 1290, 1935 mg/kg)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the observation period the animals were examined twice a day (once a day during the weekend and holidays). The animals were individually weighed at the time of the application and at the end of the 14-day observation period.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight.
Statistics:
The calculation of LD50 with the confidence interval was carried out with the program Probit-Analysis according to Fink and Hund (Arzneim.-Forsch. 15: 1965, 624).
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 580 mg/kg bw
Mortality:
The deaths occurred from the 2nd to 7th day of the experiment.
Clinical signs:
0.2-0.5 mL/kg: necrosis, hair loss, tears.
0.5-1.5 mL/kg: bloodily eyes and nose.

 The calculated LD50 was 0.45mL/kg (580 mg/kgbw). The slope of the Probit regression line (Probitslope factor) showed a value of b = 3.47.The dose of 0.1 mL/kg bw was without symptoms.

  

 

 

Toxicologic results

Dosis mL/kg

Sex

Dead animals

Symptoms

Amount of animals

0.1

male

0

0

10

0.2

male

2

10

10

0.3

male

4

10

10

1.0

male

9

10

10

1.5

male

10

10

10

 

 Signs of intoxication were: narcosis, hair loss, lacrimation, bloody eyes and nose

Executive summary:

An acute oral toxicology analysis was carried out with 1,3-dicholorobenzene in male rats.

Animals were administered by gavage with 0.1, 0.2, 0.5, 1.0, 1.5 mL/kg (129, 258, 645, 1290, 1935 mg/kg) of 1,3-dichlorobenzene with a method similar to OECD guideline 401 with deviations (female animals not tested; analytical purity not reported; fasting period not perforemed, acclimation period not performed, LD50 expressed in mL/Kg instead mg/kg; air changes not reported).

 

The calculated LD50 for male rats was 0.45 mL/kg (580 mg/kg) bw (b=3.47).

On the basis of these results 1,3-dichlorobenzene is classified as Xn R22, harmful if swallowed according to EU classification and Acute Tox. Cat 4, H302 according to GHS classification.

 

The following symptoms of poisoning were observed: narcosis, tears, hair loss, bloodily eyes and nose.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
580 mg/kg bw
Quality of whole database:
The materials/methods and results are described in detail und are sufficient for evaluation.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
other: Hoe: WISKf (SPF71)
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 m+ 5 f rats: 14.8 mg m-dichlorobenze/l air
5 m+ 5 f rats: 17.63 mg m-dichlorobenze/l air
No. of animals per sex per dose:
5 m+ 5 f rats: 14.8 mg m-dichlorobenze/l air
5 m+ 5 f rats: 17.63 mg m-dichlorobenze/l air
Control animals:
no
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 17.6 mg/L air
Based on:
test mat.
Exp. duration:
4 h

After an expostion to 17.6 mg m-dichlorobenzene no of the animals died. The test atmosphere consited maily as vapor.

Based on this result, the LC50(4h) was > 17.6 mg dichlorobenzene/l.

Of the animals exposed to 14.8 mg m-dichlorobenene 2 male and 3 female rats died. The test atmosphere had a higher content of aerosol compared with the test group which received 17.6 mg m-dichlorobenzene/l air.

The animals exposed to 17.6 mg m-dichlorobenzene/l air showed unregular breathing, uncoordinated gait, ataxia, prone position, rough fur, drowsiness, tremor, constricted palpebral fissures, reduced startled reflexes, increased salivation and foamy nose effluent.

Animals which received furthermore reduced breathing rate, staggared gait, reducted activity, narcosis, coma, no startled reflexes, bloody nose and eye lids, closed palpebral fissures, reduced body temperature, convulsions, cyanosis bad nutrition state and sneezing.

The section of animals which died intercurrent had darkred spots on the lungs, darkened liver and blood engorgement in the lungs. The animals which were killed after the post-observation period revealed no findings.

Interpretation of results:
other:
Remarks:
LC50(4h) > 17.6 mg m-dichlorobenzene (vapour)/l air.
Executive summary:

Five male and five female Wistar rats were exposed nose-only for 4 hours to concentrations of 14.8 or 17.63 mg dichlorobenzene/liter air. Animals were observed for mortality, body weight and clinical signs during a post-observation period of 14 days. A necropsy was performed on the animals at the end of the post-observation period.

The LC50(4h) was > 17.6 mg m-dichlorobenzene (vapour)/l air.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
17 600 mg/m³
Quality of whole database:
GLP guideline study

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key study for acute oral toxicity, male rats were administered by gavage 0.1, 0.2, 0.5, 1.0, 1.5 ml/kg (129, 258, 645, 1290, 1935 mg/kg) of 1,3-dichlorobenzene with a method similar to OECD guideline 401; in this study no vehicle was used and the undiluted compound was administered. A LD50 of ca. 580 mg/kg bw was determined (Bayer AG, 1980).

In a second experiment female rats were dose with 1,3-dichlorobenzene in sesam oil and a higher LD50 = 2306 mg/kg bw was found (Hoechst, 1979).

In the key study for acute inhalation toxicity, 5 male and 5 female Wistar rats were exposed nose-only for 4 hours to concentrations of 14.8 or 17.63 mg dichlorobenzene/liter air. None of the animals died at the highest applied dose (17.6 mg/kg bw). The LC50(4h) was > 17.6 mg 1,3-dichlorobenzene (vapour)/l air.

Several studies were published with intraperitoneal injection of m-dichlorobenzene. Aim of these studies was to evaluate the acute hepatic toxicity of the test compound in different rat strains and in mice.

A dose-dependent significant increase in alanine aminotransferase (ALT) activity in the plasma, increased liver weights, liver cell necrosis and liver degeneration was found.


Justification for selection of acute toxicity – oral endpoint
The most reliable study was used as key study and for classification.

Justification for selection of acute toxicity – inhalation endpoint
The most reliable study was used as key study and for classification.

Justification for classification or non-classification

LD50(oral) = ca. 580 mg/kg bw

LC50(inhalation) > 17600 mg/m³ (highest applied dose). None of the animals died.

LD50(dermal) = no data

The primary toxic effect of m-dichlorobenzene is an increase of alanine aminotransferase (ALT) activity in plasma and hepatotoxicity.

A classification as Acute Tox 4;H302 is justified.