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Description of key information

A valid oral toxicity guideline study is available. From a secondary source data from an acute inhalation toxicity study is on hand.
Acute dermal LD50 values were determined in a valid dermal toxicity study.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline stdy
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: 84/449/EWG
Principles of method if other than guideline:
Five male and 5 female Wistar rats received per gavage 100, 250, 312, 400, 500 or 1000 mg m-chloroaniline/kg bw. Animals were observed for mortality, clinical signs and body weight gain during a post-observation period of 14 days. A pathological examination was performed on all animals which died during the observation period or were sacrificed at the end of the study period.
GLP compliance:
yes
Test type:
standard acute method
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Doses:
100, 250, 312, 400, 500 or 1000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female animals/dose
Control animals:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 353 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 400 mg/kg bw
Based on:
test mat.

At a dose of 100 mg/kg bw a bad general condition, ruffle fur, discharge of the nose, sedation, bloody shout and salivation was observed. Beginning with 250 mg/kg bw most of the animals revealed cyanosis and some animals showed gasping. At a dose of 1000 mg/kg bw 2 females had a lateral position 2 hours after application of the test substance and one female showed convulsions.

Pathological signs of the deceased animals at doses of 400 to 1000 mg/kg bw were changes of the gastrointestinal tract, brownish discoloured and edematuos lungs and at 500 mg/kg bw black discoulered livers. All animals sacrificed at the end of the study revealed no pathological signs.

The LD50 for male rats was ca. 400 mg/kg bw and the approximative LD50 for females was 353 mg/kg bw.

Executive summary:

Five male and 5 female Wistar rats received per gavage 100, 250, 312, 400, 500 or 1000 mg m-chloroaniline/kg bw. Animals were observed for mortality, clinical signs and body weight gain during a post-observation period of 14 days. A pathological examination was performed on all animals which died during the observation period or were sacrificed at the end of the study period.

The LD50 was approx. 353 mg/kg bw for female and 400 mg/kg bw for male rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
353 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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature
Reference:
Composition 0
Principles of method if other than guideline:
Determination of LC50 in mice after inhalation
GLP compliance:
no
Test type:
other: no data
Test material information:
Composition 1
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
550 mg/m³ air
Based on:
not specified
Exp. duration:
4 h

no data

Executive summary:

The inhalation LC50(mouse) of m-chloroaniline is 550 mg/m³

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
550 mg/m³
Quality of whole database:
secondary source (an inhalation study is not required because a reliable oral and dermal study is available)

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 000 mg/kg bw
Quality of whole database:
The materials/methods and results are described in detail und are sufficient for evaluation.

Additional information

Five male and 5 female Wistar rats received per gavage 100, 250, 312, 400, 500 or 1000 mg m-chloroaniline/kg bw. Animals were observed for mortality, clinical signs and body weight gain during a post-observation period of 14 days. A pathological examination was performed on all animals which died during the observation period or were sacrificed at the end of the study period.

At a dose of 100 mg/kg bw a bad general condition, ruffle fur, discharge of the nose, sedation, bloody shout and salivation was observed. Beginning with 250 mg/kg bw most of the animals revealed cyanosis and some animals showed gasping. At a dose of 1000 mg/kg bw 2 females had a lateral position 2 hours after application of the test substance and one female showed convulsions.

Pathological signs of the deceased animals at doses of 400 to 1000 mg/kg bw were changes of the gastrointestinal tract, brownish discoloured and edematuos lungs and at 500 mg/kg bw black discoulered livers. All animals sacrificed at the end of the study revealed no pathological signs.

The LD50 was approx. 353 mg/kg bw for female and 400 mg/kg bw for male rats.

A weight of evidence with 3 inhalation studies was conducted and the lowest LC50 is taken for risk assessment.

The LC50 was determined to be 550 mg/m³.

Five male and 5 female Wistar rats were occlusively applied 1000 or 2000 mg m-chloroaniline/kg bw. The test substance was applied on gauze covering about 10% of the body surface and caped with aluminium foil. After 24 hours the test substance was remouved with lukewarm water. The animals were observed for mortality, clinical signs and body weight gain during a post-observation period of 14 days. A pathological examination was performed on all animals which died during the observation period or were sacrificed at the end of the study period.

Signs of intoxicition at a dose of 2000 mg/kg bw were cyanosis and sedation on male and female rats. A single female rats showed at a dose of 1000 mg/kg bw cyanosis, gaunt flanks and a bad general condition. All other animals revealed no symptoms at a dose of 1000 mg/kg bw.

The LD50 is > 1000 and < 2000 mg/kg bw for female rats and ca. 2000 mg/kg bw for male rats.


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
A weight of evidence with 3 studies was conducted and the lowest LC50 is taken for risk assessment

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

Justification for classification or non-classification

LD50(oral) = 353 mg/kg bw

LC50(inhalation) = 550 mg/m³

LD50(dermal) > 1000 mg/kg bw

The primary toxic effect of m-chloroaniline is methemoglobin formation.

Therefore the classifcation based on the key values for chemicals safety assessment is one level stronger compared with the classification according to Directive 67/548 (EEC) and Regulation (EC) 1272/2008.

A classification as R25, R23 and R24 (GHS: Acute Tox 3;H301, Acute Tox. 2; H330 and Acute Tox.3; H311) is justified.