N,N-dimethyl-p-toluidine

Endpoint summary

Description of key information

The substance N,N-dimethyl-p-toluidine is toxic via oral. inhalation and dermal route

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:

weight of evidence

Reliability:

4 (not assignable)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The objectives are to evaluate rates and routes of excretion, tissue distribution, and metabolism of [14C]DMPT.

GLP compliance:

not specified

Test type:

standard acute method

Species:

mouse

Strain:

not specified

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

other: Alkamules

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2.5, 25, or 250 mg/kg
- Amount of vehicle (if gavage): in 10% aqueous Alkamuls
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

Doses:

2.5, 25, or 250 mg/kg

No. of animals per sex per dose:

Groups of three or four male mice

Control animals:

not specified

Details on study design:

Mice received oral doses of [14C]DMPT, then were housed individually in metabolism cages; urine, feces, volatile organics (VOCs), and CO2 were collected for up to 72 h.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

250 mg/kg bw

Based on:

test mat.

Mortality:

Death of one mouse at ~24 h, the remaining mice were euthanized. Mice excreted little urine and feces during the study

Clinical signs:

decreased activity and labored breathing was observed at 250 mg DMPT/kg 6 h after dosing

Other findings:

This result indicated near complete absorption and excretion of the high dose over the extended holding period. N,N-Dimethyl-p-toluidine derived radioactivity was excreted at similar rates over time in the 2.5 and 25 mg/kg male mouse dosing groups. Disposition data are not reported here for mice receiving 250 mg/kg by gavage due to acute toxicity, including mortality in the group

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The Acute oral LD50 value of N,N-dimethyl-p-toluidine in mice was observed at dose concentration on 250 mg/kg. These results suggest that the N,N-dimethyl-p-toluidine is toxic to mouse via oral route of exposure and falls under acute oral category 3.

Executive summary:

The objectives are to evaluate rates and routes of excretion, tissue distribution, and metabolism of [14C]DMPT. Mice received oral doses of [14C]DMPT, then were housed individually in metabolism cages; urine, feces, volatile organics (VOCs), and CO2 were collected for up to 72 h. At sacrifice the tissue distribution of carbon-14 was determined. Death of one mouse at ~24 h, the remaining mice were euthanized. Mice excreted little urine and feces during the study. decreased activity and labored breathing was observed at 250 mg DMPT/kg 6 h after dosing. This appears to be the case in mice since the 250 mg/kg oral dose, which is close to the IP LD50 in this species, was acutely toxic. Hence LD50 was considered to be 250 mg/kg.

These results suggest that the N,N-dimethyl-p-toluidine is toxic to mouse via oral route of exposureand falls under acute oral category 3.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

250 mg/kg bw

Quality of whole database:

K2 level data from publication

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)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from RTECS

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

0.3, 0.99, 1.73, or 5.27mg/l.

No. of animals per sex per dose:

5/sex/group

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.4 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Clinical signs:

other: Clinical signs of toxicity included hypoactivity,a comatose/prostrate condition,dyspnea, rapid respiration, salivation, eye and nasal discharge and red material around nose

Body weight:

Exposure did not affect body weight gain

Gross pathology:

Mottled lungs, Red ovaries and gas filled gastrointestinal organs were seen at 1.73 and 5.27 mg/l

Interpretation of results:

Toxicity Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute Inhalation toxicity (LC50) value of N,N-dimethyl-p-toluidine was examined in rats on the basis of motality effect at a dose concentration of 1.4 mg/l after 4 hrs of exposure. From this value it is concluded that the substance N,N-dimethyl-p-toluidine is toxic to rat by inhalation route in category 2

Executive summary:

N, N Dimethyl-p toluidene was aerosolized and administered for 4 hrs by wholebody inhalation exposure to Sparague-dawley derived rats (5/sex/group) at concentration of 0.3, 0.99, 1.73, OR 5.27 mg/l. Exposure did not affect body weight gain.Clinical signs of toxicity included hypoactivity,a, a comatose/prostrate condition, dyspnea, rapid respiration, salivation, eye and nasal discharge and red material around nose.Mottled lungs, Red ovaries and gas filled gastrointestinal organs were seen at 1.73 and 5.27 mg/l. Hence LC50 was considered to be 1.4 mg/l air

From this value it is concluded that the substance N,N-dimethyl-p-toluidine is toxic to rat by inhalation route in category 2

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1.4

Quality of whole database:

K4 level data from publication

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Data is from Study report

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

not specified

Vehicle:

other: neat

No. of animals per sex per dose:

10

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Details of toxic effects not reported other than lethal dose value

Mortality:

50 percent kill

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute dermal toxicity (LD50) value of N.N-dimethyl-p-toluidine in rabbit was found to be >2000 mg/kg . From this value it is concluded that N.N-dimethyl-p-toluidine is not toxic to rabbit by dermal route

Executive summary:

Dermal toxicity (LD50) of N,N-dimethyl-p-toluidine was examined in rabbit at dose concentration of >2000 mg/kg of skin exposure. Details of toxic effects not reported other than lethal dose value. These results suggest that the N,N-dimethyl-p-toluidine is non toxic to rabbit via dermal contact. However, since this substance has a harmonized classification of exhibiting Acute Toxicity Category 3 via the dermal route; for the purpose of the chemical safety assessment the harmonized classification shall be adhered to.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

K4 level data from study report

Additional information

Acute toxicity Oral:

Based on studies of target substance CAS NO 99-97-8 reviewed for acute oral toxicity from reliable sources having Klimisch rating 2 and 4 considering the weight of evidence approach.

The summary of the results are presented below

Sr. No	End point	Value	Species	Remark
1	LD50	250 mg/kgbw	mouse	Data from publication for target chemical
2	LD50	1300 mg/kg(male) 1950 mg/kg(female) 1650 mg/kg(male/female)	Rat	Data from study report for target chemical
3	LD50	139 mg/kgbw	Mouse	Data from publication for target chemical
4	LD50	980 mg/kgbw	Rat	Data from publication for target chemical

 

Based on above table, endpoint value was found to vary between 139 mg/kg bw to 1950 mg/kg bw based on these values it can be concluded that the substance N,N-dimethyl-p-toluidine exhibits acute toxicity by the oral route in category 3. However, since this substance has a harmonized classification of exhibiting Acute Toxicity Category 3 via the oral route; for the purpose of the chemical safety assessment the harmonized classification shall be adhered to.

Acute toxicity Inhalation:

Based on studies of target substance CAS NO 99-97-8 and read across reviewed for acute Inhalation toxicity from reliable sources having Klimisch rating 4 considering weight of evidence approach

The summary of the results are presented below

Sr. No	End point	Value	Species	Remark
1	LC50	1.4 mg/l	Rat	Data from study report for target chemical
2	TCLo	800 mg/m3	mouse	Data from publication  for target chemical
3	LC50	1.92 mg/l	Rat	Data from study report for CAS no 91-66-7
4	LC50	1.9 mg/lair 4.3 mg/l air	Rat	Data from study report for CAS no 91-66-7

 

Based on the values summarized in above table, it was found that the endpoint values vary between 1.4 mg/L to 4.3 mg/l. and theTCLo value was found to be 800 mg/m3. From this value it can be concluded thatN,N-dimethyl-p-toluidine exhibits acute toxicity by the inhalation route Acute Toxicity Category 2. However, since this substance has a harmonized classification of exhibiting Acute Toxicity Category 3 via the oral route; for the purpose of the chemical safety assessment the harmonized classification shall be adhered to.

Acute Toxicity Dermal:

Based on studies of target substance CAS NO 99-97-8 and read across reviewed for acute dermal toxicity from reliable sources having Klimisch rating 4 considering weight of evidence approach

 The summary of the results are presented below

Sr. No	End point	Value	Species	Remark
1	LD50	>2000 mg/kg bw	Rabbit	Data from study report of target chemical
2	LD50	<935 mg/kg bw	Rabbit	Data from study report for CAS no 91-66-7

Based on the values summarized in above table, it was found that the endpoint values was found to be in the range of <935 mg/kg bw to >2000 mg/kg bw. From this value it can be concluded that N,N-dimethyl-p-toluidine exhibits acute toxicity by the dermal route in category 4. Since this substance has a harmonized classification of exhibiting Acute Toxicity Category 3 via the dermal route; for the purpose of the chemical safety assessment the harmonized classification shall be adhered to.

Justification for selection of acute toxicity – oral endpoint
The objectives are to evaluate rates and routes of excretion, tissue distribution, and metabolism of [14C]DMPT. Mice received oral doses of [14C]DMPT, then were housed individually in metabolism cages; urine, feces, volatile organics (VOCs), and CO2 were collected for up to 72 h. At sacrifice the tissue distribution of carbon-14 was determined. Death of one mouse at ~24 h, the remaining mice were euthanized. Mice excreted little urine and feces during the study. decreased activity and labored breathing was observed at 250 mg DMPT/kg 6 h after dosing. This appears to be the case in mice since the 250 mg/kg oral dose, which is close to the IP LD50 in this species, was acutely toxic. Hence LD50 was considered to be 250 mg/kg.
These results suggest that the N,N-dimethyl-p-toluidine is toxic to mouse via oral route of exposureand falls under acute oral category 3.

Justification for selection of acute toxicity – inhalation endpoint
N, N Dimethyl-p toluidene was aerosolized and administered for 4 hrs by wholebody inhalation exposure to Sparague-dawley derived rats (5/sex/group) at concentration of 0.3, 0.99, 1.73, OR 5.27 mg/l. Exposure did not affect body weight gain.Clinical signs of toxicity included hypoactivity,a, a comatose/prostrate condition, dyspnea, rapid respiration, salivation, eye and nasal discharge and red material around nose.Mottled lungs, Red ovaries and gas filled gastrointestinal organs were seen at 1.73 and 5.27 mg/l. Hence LC50 was considered to be 1.4 mg/l air
From this value it is concluded that the substance N,N-dimethyl-p-toluidine is toxic to rat by inhalation route in category 2

Justification for selection of acute toxicity – dermal endpoint
Dermal toxicity (LD50) of N,N-dimethyl-p-toluidine was examined in rabbit at dose concentration of >2000 mg/kg of skin exposure. Details of toxic effects not reported other than lethal dose value. These results suggest that the N,N-dimethyl-p-toluidine is non toxic to rabbit via dermal contact. However, since this substance has a harmonized classification of exhibiting Acute Toxicity Category 3 via the dermal route; for the purpose of the chemical safety assessment the harmonized classification shall be adhered to.

Justification for classification or non-classification

The substance N,N-dimethyl-p-toluidine is toxic via oral. inhalation and dermal route and hence classified as acute toxicity category 3( for Oral and dermal) and Acute toxicity category 2 (for Inhalation) as per CLP criteria