4,4'-methylenedi-o-toluidine

Acute Toxicity: oral

Administrative data

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: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1961

Report date:

1961

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limited reporting, application volumes exceeds 10 ml/kg, observation period only 7 days

Principles of method if other than guideline:

22 rats received a single oral dose of 4,4'-methylenedi-o-toluidine by gavage. Animals were observed for clinical signs and mortality for seven days after dosing. Gross pathology was performed in animals that died prematurely

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-methylenedi-o-toluidine

EC Number:

212-658-8

EC Name:

4,4'-methylenedi-o-toluidine

Cas Number:

838-88-0

Molecular formula:

C15H18N2

IUPAC Name:

4-[(4-amino-3-methylphenyl)methyl]-2-methylaniline

Details on test material:

- Name of test material (as cited in study report): 4,4´-Diamino-3,3´-dimethyl-diphenylmethan = o-"Toluidinbase", destilled, grinded
- Physical state: crystalline powder, creme-like coloured
- Analytical purity: 99-100%

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Lutrol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10%
MAXIMUM DOSE VOLUME APPLIED: 16 ml/kg bw

Doses:

200, 400, 800, 1600, 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Weighing was only at the beginning of the study for dose calculation. Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 1 600 - < 2 000 mg/kg bw

Remarks on result:

other: LD50 derived from raw data differ from study report, however are considered more reliable.

Mortality:

2000 mg/kg bw: 3/3 (delayed mortality between d2 and d7)
1600 mg/kg bw: 1/3
200 - 800 mg/kg bw: 0/3

Gross pathology:

Fatty liver

Any other information on results incl. tables

Delayed mortality was observed in the two highest dose groups (between d2 and d7).

There is limited information on the gross pathology of the animals treated with 4,4'-methylenedi-o-toluidine in Lutrol. However, in a similar study with 4,4'-methylenedi-o-toluidine in traganth (observation period was 7d, LD50 >4000 mg/kg, delayed death) fatty degeneration in the liver was reported in the animals that died prematurely. No clinical signs were reported.