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Administrative data

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:
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:
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:
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