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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
Study period:
23 March 2012 - 03 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
d.d. 12-12-11
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): BMI, N,N’-Diphenylmethane bismaleimide, 1,1’-(methylenedi-p-phenylene)bismaleimide
- Physical state: Light yellow or brown powder
- Analytical purity: 94.2%
- Purity test date: 29th February 2012 (Date of CoA)
- Lot/batch No.: 1K72J
- Expiration date of the lot/batch: 30 November 2014
- Storage condition of test material: Room temperature (c.a. 20°C)

Test animals

Species:
rat
Strain:
other: Crl:CD "SD"
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 - 12 weeks prior to dosing
- Weight at study initiation: 211 to 249 g
- Fasting period before study: Food supply was withdrawn overnight before dosing, and for 4 hours after dosing
- Housing: Solid bottomed polycarbonate cages with stainless steel lids.
- Diet (e.g. ad libitum): Free access to diet, except during fasting period described above
- Water (e.g. ad libitum): free access
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light per 24 hours

IN-LIFE DATES: From: 17 April 2012 (Date of first treatment) To: 10 May 2012 (date of last necropsy)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% (w/v) Aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL (Depending on dose level)
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no previous toxicological information was available, 300 mg/kg was chosen as the starting dose, in compliance with the test guidelines.
Doses:
300 mg/kg, 2000 mg/kg
No. of animals per sex per dose:
6 females per dose group (2x3 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at least twice daily after dosing. Bodyweights were recorded on days 1 (prior to dosing), 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination of organs

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths during the study
Clinical signs:
There were no clinical signs of reaction to treatment throughout the study
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on day 15

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
According to Regulation (EC) No 1272/2008
Conclusions:
The acute median lethal oral dose (LD50) to rats of BMI was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

An acute oral toxicity study in rats was performed by oral gavage according to internationally accepted guidelines and in accordance with GLP principles. Following a preliminary dose at 300 mg/kg/bw that showed no lethality, a limit test was conducted at 2000 mg/kg/bw. No mortality or adverse signs were observed. This results in an LD50 >2000 mg/kg/bw.