3-chloro-p-toluidine

Endpoint summary

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 air

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.

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.