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Administrative data

Description of key information

1,4-dichlorobenzene is of low  acute toxicity. This finding was confirmed in several studies using different exposure routes:
LD50(rat, oral and dermal) > 2000 mg/kg bw
LC50 (rat, inhalation) > 5000 mg/m³ .

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: GLP declaration given but no certificate
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CFY ( Sprague-Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 103-145 g
- Housing: in groups
- Diet ad libitum
- Water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 54
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Single oral application by gavage as 20% (w/v) concentration in corn oil and administered at a volume of 10.0
Doses:
single dose of 2000 mg/kg bodyweight.
No. of animals per sex per dose:
5 F
5 M
Control animals:
no
Details on study design:
All animals were observed 14 days after dosing and then sacrificed and subjected to macroscopic examination.
Statistics:
no
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no animal died;
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no animal died during the observation period and recovered from unspecific findings (piloerection, hunched posture) by day 3
Mortality:
no animal died
Clinical signs:
Signs of reaction to treatment observed in rats doses orally with paradichlorbenzene:

Signs No.of rats in group of 5 showing signs
Male Female
Pilo-erection 5 5
Abnormal body carriage 5 5
(hunched posture)
Abnormal gait (waddling) 5 5
Lethargy 1 0
Decreased respiratory rate 1 0
Pallor of extremities 1 1
Increased salivation 5 5
Body Tremors 1 1
Prostrate 1 0
Body weight:
Individual bodyweight (g) of rats dosed orally with paradichlorbenzene (dose: 2000mg/kg)

Sex Day 1 Day 8 Day 15
Male 112 192 266
103 178 241
110 188 262
108 158 237
108 180 264
Female
130 184 220
128 184 220
145 191 230
130 172 205
128 190 226
Gross pathology:
Terminal ausopsy findings were normal.
There were no deaths following a single oral dose of paradichlorobenzene at 2000 mg/kg bodyweigt.
Executive summary:

In a study according OECD Guideline 401 (Acute Oral Toxicity) and GLP 10 male and female rats were tested of aute toxicity receiving 2000 mg/kg bw by gavage. Within 3 hours post application the rats displayed

salivation, piloerection, hunched posture and abnormal gait but recovered within 3 days. No animal died during the 14 day observation period. The acute lethal dose of paradichlorobenzene in rat was found to be greater than 2000 mg/kg bodyweight .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and of high quality (Klimisch score 2)

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No particle size of Paradichlorobenzene mentioned.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
The acute inhalation toxicity of p-dichlorobenzene was assessed by exposing 10 rats for a period of 4 hours to vapour produced by passing air through the test substance; control group was included. After termination of the observation period of 14 days the animals were sacrificed and subjected to macroscopic examination.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
10 male rats at the age of 6 weeks.
10 female rats at the age of 8 weeks.
These ages of rats were selected so that the males and females were at similar bodyweight (ca. 200g).
Housing : in groups of 5
acclimisation pereiod: 5 days
room temperature: 21-22 °C
relative humidity: 48-50 %
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
5 male and 5 female rats were exposed continously for 4 hours to a test atmosphere containing vapour from the test substance.
another 5 male and 5 female rats acting as a control received clean air only for 4 hours.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
control group and a test group exposed to 5,07 mg/l atmosphere concentration of Paradichlorobenzene vapour.
No. of animals per sex per dose:
5 male and 5 female rats.
Control animals:
yes
Details on study design:
The acute inhalation toxicity of p-dichlorobenzene was assessed by exposing 10 rats for a period of 4 hours to vapour produced by passing air through the test substance; control group was included. After termination of the observation period of 14 days the animals were sacrificed and subjected to macroscopic examination.
Statistics:
no
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.07 mg/L air
Exp. duration:
4 h
Remarks on result:
other: unspecific reactions to exposure, recovery within 1 day, no animal died
Mortality:
There were no deaths during the study.
Clinical signs:
other: Signs during exposure: closing of eyes, wetness around the mouth, fluid discharge from the mouth, exagerated respiratory movements. Signs during observation period: increased respiration rate, wet fur around snout and jaws, yellow staining around the urog
Body weight:
small losses in body weight were observed in all rats exposed to paradichlorbenzene for 1 day following exposure. Subsequently weight gain was
similar to that of the control rats.
Gross pathology:
The lung weight to body weight ratio for all rats was within the normal limit. ther were no abnormalities in th rats.

There were no deaths following an acute inhalation toxicity 4- hour exposure to vapour with paradichlorobenzene.

Executive summary:

The acute inhalation toxicity of p-dichlorobenzene was assessed by exposing 10 rats for a period of 4 hours to 5070 mg/m³ vapour produced by passing air through the test substance; control group was included. The test precedure was equivalent to OECD TG 403 and performed under GLP condions. After termination of the observation period of 14 days the animals were sacrificed and subjected to macroscopic examination. Immediately following exposure an increased respiration rate was seen. This and other minor signs disappeared by the day following exposure and subsequently all rats were normal. No animal died.

The LC50 of paradichlorobenzene in rat was found to be greater than 5,07 mg/l air (5070 mg/m³ air).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 000 mg/m³
Quality of whole database:
The study is GLP compliant and of high quality (Klimisch score 2)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP declaration given but no certificate
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CFY (Sprague-Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 202-251 g
- Fasting period before study:
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 54
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
other: gauze which was held in place with an impermeable dressing encircled firmly around the trunk.
Vehicle:
water
Details on dermal exposure:
To the clipped back of rats the testsubstance was applied as paste and covered by gauze which was held in place by an impermeable dressing encircled firmly around the trunk for 24 hours.
Duration of exposure:
24 hours exposure period.
Doses:
single dermal dose of 2000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
no
Details on study design:
To the clipped back of rats the testsubstance was applied as paste and covered by gauze which was held in place by an impermeable dressing encircled firmly around the trunk for 24 hours. Afterwards the dressing was removed and the treated area of the skin was washed with warm water and blotted dry. the observation period was 14 day. then all animal were sacrificed and macroscopically examined.
Statistics:
no
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no animal died
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no clinical signs of systemic reaction to treatment, no dermal changes or irritation responses, no animal died
Mortality:
no deaths following a single dermal dose of Paradichlorbenzene at 2,0 g/kg bodyweight.
Clinical signs:
no clinical signs of systemic reaction to treatment.
no dermal changes or irritation responses.
Body weight:
see table: in any other information on results
Gross pathology:
Terminal autopsy findings were normal

   Bodyweight (g) at Day    

 Sex

 1 15 

 Male

 232

282 329 
  250  316  396 
   249 316  386 
   251 316  380 
  250 320  385 

 Female

206  240  284 
   250 275  290 
   202 232  255 
   206 236  260 
   250 286  325 
Executive summary:

In a study according OECD Guideline 402 (Acute Dermal Toxicity) and GLP acute dermal toxicity was tested by applying 2000 mg/kg bw as paste to the back of male and female rats for 24 hours. No clinical signs of systemic reaction to treatment and no dermal changes or irritation responses were observed. No animal died during the 14 day observation period.

The acute lethal dermal dose of paradichlorobenzene to rats was found to be greater than 2000 mg/kg bodyweight .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and of high quality (Klimisch score 2)

Additional information

1,4-dichlorobenzene is of low acute toxicity. This finding was confirmed in several studies using different exposure routes:

Oral

In a study according OECD Guideline 401 (Acute Oral Toxicity) and GLP 10 male and female rats were tested for acute toxicity receiving 2000 mg/kg bw by gavage. Within 3 hours post application the rats displayed salivation, piloerection, hunched posture and abnormal gait but recovered within 3 days. No animal died during the 14 day observation period. The acute lethal dose of paradichlorobenzene in rat was found to be greater than 2000 mg/kg bw(Gardner 1987)

This finding was in accordance with another acute study in rats were the LD50 for male rats was found to be 3863 mg/kg bw and the LD50 for female rats 3790 mg/kg bw (Gaines 1986).

Inhalation:

The acute inhalation toxicity of p-dichlorobenzene was assessed by exposing 10 rats for a period of 4 hours to 5070 mg/m³ vapour produced by passing air through the test substance; control group was included. The test precedure was equivalent to OECD TG 403 and performed under GLP conditions. After termination of the observation period of 14 days the animals were sacrificed and subjected to macroscopic examination. Immediately following exposure an increased respiration rate was seen. This and other minor signs disappeared by the day following exposure and subsequently all rats were normal. No animal died.

The LC50 of paradichlorobenzene in rat was found to be greater than 5,07 mg/l air (5070 mg/m³ air; Hardy 1987).

Dermal:

In a study according OECD Guideline 402 (Acute Dermal Toxicity) and GLP acute dermal toxicity was tested by applying 2000 mg/kg bw as paste to the back of male and female rats for 24 hours. No clinical signs of systemic reaction to treatment and no dermal changes or irritation responses were observed. No animal died during the 14 day observation period.

Thus, in rats the LD50 after dermal exposure was >2000 mg/kg bw (Gardner 1987).

Conclusion:

Given the available animals data, the acute toxicity of 1,4-dichlorobenzene is judged to be low, regardless of the exposure route (oral, dermal, inhalation)


Justification for selection of acute toxicity – oral endpoint
This study is a guideline study which is GLP compliant and evaluated with Klimisch score 2

Justification for selection of acute toxicity – inhalation endpoint
This study is equivalent to a guideline study and GLP compliant and evaluated with Klimisch score 2

Justification for selection of acute toxicity – dermal endpoint
This study is a guideline study which is GLP compliant and evaluated with Klimisch score 2

Justification for classification or non-classification

Based on the available data no classification according to EU directive 67/548/EEC or Regulation (EC) No. 1272/2008 is required.