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Administrative data

Description of key information

Several acute oral studies are available. In the most reliable study (Kimmerle, 1972), a LD50 (rat) of 1053 mg/kg bw was found.

In the acute inhalation study, a LC50(rat) > 7.69 mg/L was detected (maximal examined concentration).

The acute dermal LD50 (rat) (4 hours exposure) was 650 µl 3-chloro-p-toluidine/kg bw (= ca. 765 mg/kg bw).

3-chloro-p-toluidine causes methemoglobinemia.

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:
Acute oral toxicity study in male rats.
GLP compliance:
not specified
Test type:
other: Acute oral toxicity in rats
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
oral: gavage
Vehicle:
other: Lutrol
Doses:
100, 250, 500, 950, 1000, 1100, 1150, 1300 mg/kg bw.
No. of animals per sex per dose:
15
Control animals:
not specified
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 053 mg/kg bw

Results:

 Dose (mg/kg bw)  Toxicological result after 14 days        Signs of intoxications     Timepoint of death after days
   Nr. of death animals  Nr. of animals with symptoms  Nr. of animals used  Start Endpoint   
  100  0  0  15  -  -  -
  250  0  15  15  30 min  4 days  -
  500  0  15  15  15 min  7 days  -
  950  3  15  15  10 min  7 days  1 day
 1000  3  15  15  8 min  7 days  1 -2 days
 1100  9  15  15  6 min  7 days  1 -2 days
 1150  13  15  15  5 min  7 days  1 -2 days
 1300 days  15  15  15  4 min  -  1 day

The animals showed cyanosis, labored breathing, sedative effects and a clearly diminuated general condition after 30 min after the oral application. The signs of intoxication could be observed 4 -7 days. The timepoint of death occurred within 48 hours.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD 50 was 1053 mg/kg bw.
Executive summary:

In an acute oral toxicity test in male Wister rats the animals were administered by gavage with the test substance dissolved in Lutrol.

The doses tested were: 100, 250, 500, 950, 1000, 1100, 1150, 1300 mg/kg bw.

The animals showed cyanosis, labored breathing, sedative effects and a clearly diminuated general condition after 30 min after the oral application. The signs of intoxication could be observed 4 -7 days. The timepoint of death occurred within 48 hours.

The LD 50 was 1053 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 053 mg/kg bw
Quality of whole database:
Scientifically acceptable and sufficient documented.

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:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Six groups of 5 male and 5 female Wistar rats were nose/head-only exposed to analytical concentrations of 0, 375.6, 906.5, 1968.9, 3292.8 or 7619.5 mg 3-chloro-p-toluidine/m³ air for 4 hours. The animals were observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: polyethylenglycol - ethanol 1:1
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0, 375.6, 906.5, 1968.9, 3292.8 or 7619.5 mg 3-chloro-p-toluidine/m³ air.
No. of animals per sex per dose:
5 male and 5 female rats/dose
Control animals:
yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 7.62 mg/L air
Based on:
test mat.
Exp. duration:
4 h

At 7620 mg 3-chloro-p-toluidine/m³ air (maximal examined concentration) one of five female rats died. Clinical signs were a low irritation potential of mucuous membranes, methamoglobinemia and unspecific central nervous symptoms.

Interpretation of results:
GHS criteria not met
Executive summary:

Six groups of 5 male and 5 female Wistar rats were nose/head-only exposed to analytical concentrations of 0, 375.6, 906.5, 1968.9, 3292.8 or 7619.5 mg 3-chloro-p-toluidine/m³ air for 4 hours. The animals were observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.

At 7620 mg 3-chloro-p-toluidine/m³ air (maximal examined concentration) one of five female rats died. Clinical signs were a low irritation potential of mucuous membranes, methamoglobinemia and unspecific central nervous symptoms.

LC50 > 7.69 mg/L.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
7 690 mg/m³
Quality of whole database:
GLP guideline study.

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: scientifically acceptable and sufficinet documented
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Undiluted 3-chloro-p-toluidine was applied on the shaved belly skin of rats for 4 hours in doses of 100 to 1000 µl/kg (117 to 1170 mg/kg). After 4 hours the substance was removed with water and soap. The animals were observed for 7 days.
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
4 hours
Doses:
100 µl (= 117 mg)/kg bw, 250 µl (= 292.5 mg/kg bw), 500 µl (= 585 mg/kg bw), 600 µl (= 702 mg/kg bw), 800 µl (= 936 mg/kg bw), 1000 µl (= 1170 mg/kg bw).
No. of animals per sex per dose:
5 rats (100 µl), 5 rats (250 µl), 10 rats (500 µl), 10 rats (600 µl), 10 rats (800 µl), 5 rats (1000 µl).
Control animals:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 765 mg/kg bw
Based on:
test mat.

From 2 to 6 hours after application of the test substance,typical signs of intoxication (cyanosis, laboured breathing, sedation) were observed. The highest dose without findings was 100 µl (117 mg/kg bw) and the lowest lethal dose was 600 µl (702 mg/kg bw).

Executive summary:

Undiluted 3-chloro-p-toluidine was applied on the shaved belly skin of rats for 4 hours in doses of 100 to 1000 µl/kg (117 to 1170 mg/kg bw). After 4 hours the substance was removed with water and soap. The animals were observed for 7 days.

LD50 (4 hours exposure) = 650 µl 3-chloro-p-toluidine/kg bw (= ca. 765 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
765 mg/kg bw
Quality of whole database:
Scientifically acceptable and sufficinet documented.

Additional information

Justification for classification or non-classification

In the acute oral toxicity study (key study) a LD50 (rat) of 1053 mg/kg bw was found.

In the acute inhalation study, a LC50(rat) > 7.69 mg/L was detected (maximal examined concentration).

The acute dermal LD50 (rat) (4 hours exposure) was 650 µl 3-chloro-p-toluidine/kg bw (= ca. 765 mg/kg bw).

3-chloro-p-toluidine causes methemoglobinemia. Therefore the classification is raised by one grade.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Acute Tox. 3 ( H301: Toxic if swallowed), Acute Tox. 4 ( H332: Harmful if inhaled) and Acute Tox. 2 ( H310: Fatal in contact with skin) is proposed.