Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In an acute oral toxicity study 10 male or female Wistar rats were treated via gavage with 20 ml/kg bw of test substance.
The LD 50 was 379 mg/kg bw  or 385 mg/kg bw , respectively(Löser E, Bayer AG, 1982).
In an acute dermal toxicity study in male and female Wistar rats the LD50 was 921 mg/kg bw in female animals. Male rats did not react more sensitive.  (Hofmann/ Jung, Hoechst AG, 1988)

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: No OECD guideline or GLP defined.
Principles of method if other than guideline:
Method: other: acute toxicity oral: male rats
GLP compliance:
not specified
Test type:
other: acute oral toxicity study
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
oral: gavage
Vehicle:
other: Lutrol
Doses:
20 ml/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Dose descriptor:
LD50
Effect level:
379 mg/kg bw

SO-Freetext: Hoechst AG  Frankfurt 80
Hoechst AG  Frankfurt/Main

RM-Freetext:
maennlich

RM-Freetext:
Verabreichung per Magensonde, Symptome: Narkose, struppiges
Fell, Bauch- und Seitenlage, Herabsetzung des Allgemeinbe-
findens, erhoehte Diurese, keine substanzbedingten makros-
kopischen Veraenderungen.

Executive summary:

In an acute oral toxicity study 10 male Wistar rats were treated via gavage with 20 ml/kg bw of test substance.

Signs of intoxication were: narcosis, face-down position and lateral position, scrubby fur, diminuated general condition.

The LD 50 was 379 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
379 mg/kg bw
Quality of whole database:
The studies are performed similar to the respective guidelines

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
other: acute dermal toxicity study
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
other: 0.9 % saline
Duration of exposure:
24 h
Doses:
male rats: 2000 mg/kg bw.; female rats: 500, 800, 1000, 1250, 2000 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
not specified
Dose descriptor:
LD50
Effect level:
921 mg/kg bw

Mortality:

 male rats     female rats   
  Dose (mg/kg bw)  absolute  relative (%)  absolute  relative (%)
500  -  -  0/5 0 
 800  -  - 2/5  40
 1000  -  -  2/5  40
 1250  -  -  5/5  100
 2000  4/5  80  5/5  100

LD50 (mg/kg bw.) 921

Executive summary:

In an acute dermal toxicity study in male and female Wistar rats the LD50 was 921 mg/kg bw in female animals. Male rats did not react more sensitive. Doses up to 2000 mg/kg bw. were applied occlusively to the back skin of the rats. Mortality occurred mostly in the night. Symptoms observed were, unspecific symptoms and disturbed course of movement.. In one animal narrowed palpebral fissures were observed. One female animal of the 1250 mg/kg group showed pallidness of skin, drowsiness, diminuated startle reflexes and diminuated breathing frequency.

5 days after treatment all surviving animals were free of symptoms.

No bodyweight abnormalities were observed.

Died animals showed staining at liver, lung and spleen. In the killed animals no abnormalities were observed.

Regarding the LD50 of 921 mg/kg bw the test substance was found to be slightly toxic according to directive 83/467/EWG and therefore classified as R21.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
921 mg/kg bw
Quality of whole database:
This is the only available study which was performed according to the respective guideline and GLP and evaluated with Klimisch Score 1

Additional information

ORAL APPLICATION

In an acute oral toxicity study 10 male Wistar rats were treated via gavage with 20 ml/kg bw of test substance. Signs of intoxication were: narcosis, face-down position and lateral position, scrubby fur, diminuated general condition. The LD 50 was 379 mg/kg bw (Löser E, Bayer AG, 1982). In an acute oral toxicity study 10 female Wistar rats were treated via gavage with 20 ml/kg bw of test substance. Signs of intoxication were: narcosis, face-down position and lateral position, scrubby fur, hightened diuresis, diminuated general condition.The LD 50 was 385 mg/kg bw (Löser E. Bayer AG, 1982).

Furthermore, in an acute oral gavage toxicity study in cats the animals received 10 and 50 mg/kg bw of test substance in a single dose.

The met-hemoglobin concentration and the number of HEINZ-bodies were not increased after 3, 7, and 24 hours.

Up to 8 hours after application a loss of appetite was observed. No other symptoms were noticed.

Based on these results and taking into account that cats are highly susceptible for blood toxicity (e.g. methemoglobin formation) it can be concluded that 1,3 -dichloronitrobenzene does not induce methemoglobin formatation

DERMAL APPLICATION

In an acute dermal toxicity study in male and female Wistar rats the LD50 was 921 mg/kg bw in female animals. Male rats did not react more sensitive. Doses up to 2000 mg/kg bw. were applied occlusively to the back skin of the rats. Mortality occurred mostly in the night. Symptoms observed were, unspecific symptoms and disturbed course of movement.. In one animal narrowed palpebral fissures were observed. One female animal of the 1250 mg/kg group showed pallidness of skin, drowsiness, diminuated startle reflexes and diminuated breathing frequency. 5 days after treatment all surviving animals were free of symptoms. No bodyweight abnormalities were observed. Died animals showed staining at liver, lung and spleen. In the killed animals no abnormalities were observed. Regarding the LD50 of 921 mg/kg bw the test substance was found to be slightly toxic according to directive 83/467/EWG and therefore classified as R21 (Hofmann/ Jung, Hoechst AG, 1988).


Justification for selection of acute toxicity – oral endpoint
There are 2 studies available which were performed in equal quality : one with male rats leading to LD50 of 379 mg/kg bw and one with female rats leading to LD50 of 385 mg/kg bw

Justification for selection of acute toxicity – dermal endpoint
This is the only available study which was performed according to the respective guideline and GLP and evaluated weoth Klimisch Score 1

Justification for classification or non-classification

1,3-dichloro-4-nitrobenzene should be classified R21/22 according to 67/548/EWG, as "acute tox oral cat 4" and "acute tox dermal cat 3" according to 1272/2008 (GHS).