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Toxicological information

Acute Toxicity: oral

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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
Body weight:
not measured
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.

Applicant's summary and conclusion