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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:
weight of evidence
Study period:
1989-10-24 to 1990-01-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
March, 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1'-(methylenedi-p-phenylene)bismaleimide
EC Number:
237-163-4
EC Name:
1,1'-(methylenedi-p-phenylene)bismaleimide
Cas Number:
13676-54-5
Molecular formula:
C21H14N2O4
IUPAC Name:
1,1'-[methylenedi(4,1-phenylene)]di(1H-pyrrole-2,5-dione)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 9 weeks, females 11 weeks
- Weight at study initiation: males 187-205 g, females 173-187 g
- Fasting period before study: 12-18 hours
- Housing: 5 animals per cage; Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet: ad libitum, pelleted Kliba 343, Batch 55/89 rat maintenance diet ("Kliba", Klingenmuehle AG, CH-4303 Kaiseraugst)
- Water: ad libitum, community tap water from Itingen
- Acclimation period: one week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test article was placed into a glass beaker on a tared Mettler PE 360 balance, and the vehicle (bi-distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultr-Turrax, Janke and Kunkel, Staufen). Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke and Kunkel, Staufen). The preparation was made immediately prior to each dosing.

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations: at 1, 2, 3 and 5 h after dosing and once daily thereafter
- Frequency of weighing: Test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
No statistics applied.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No adverse effects observed during the study
Mortality:
The following death rate was observed: 0% at 2000 mg/kg
Clinical signs:
Each animal was examined for changes in appearance and behavior four times during day 1, and daily during days 2-15. All abnormalities were recorded. No systemic signs were observed in any animal throughout the entire study.
Body weight:
The body weight gain of the animals was not affected by the test article treatment throughout the entire study period.
Gross pathology:
Necropsies were performed by experienced prosectors. All animals were necropsied. All animals were killed by intraperitoneal injection of sodium pentobarbitone. The following macroscopical organ changes were observed: 2000 mg/kg: sacrificed - lungs: discoloration, dark red

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
The acute oral toxicity of the test material in Wistar rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg, thus, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) with respect to acute oral toxicity.