1,1'-(methylenedi-p-phenylene)bismaleimide

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

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. QA statement)

Remarks:

d.d. 12-12-11

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

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-(4-{[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl]methyl}phenyl)-2,5-dihydro-1H-pyrrole-2,5-dione

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 or test system 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:

other: There were no clinical signs of reaction to treatment 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.