1,1'-(benzene-1,3-diyldimethanediyl)bis(1H-pyrrole-2,5-dione)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-04-03 to 2017-07-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December, 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-({3-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]phenyl}methyl)-2,5-dihydro-1H-pyrrole-2,5-dione

EC Number:

695-930-2

Cas Number:

13676-53-4

Molecular formula:

C16H12N2O4

IUPAC Name:

1-({3-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]phenyl}methyl)-2,5-dihydro-1H-pyrrole-2,5-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: step 1, animals no. 1 – 3: 152 - 169 g; step 2, animals no. 4 – 6: 165 - 174 g; step 3, animals no. 7 – 9: 173 - 186 g
- Fasting period before study: food was withheld from the test animals for 16 to 19 h prior to test start
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): ad libitum; Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): ad libitum; tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least five days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.3 g and 2.0 g
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: vehicle was chosen due to its non-toxic characteristics
- Lot/batch no. (if required): MKBZ9899V

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

300 mg/kg bw in the first step and 2000 mg/kg bw in the second and third step

No. of animals per sex per dose:

3 per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing on day 1 (prior to start), 8 and 15, clinical examination was performed after dosing with special attention during the first 4 h post-dose period and once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy incl. macroscopic findings

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Remarks:

experimental

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

During step 1 (dose: 300 mg/kg bw) of the test no mortality was observed, during step 2 (dose 2000 mg/kg bw) one animal died spontaneously. During step 3 no compound-related mortality was reported.

Clinical signs:

other: The animals in step 1 (dose 300 mg/kg bw) exhibited the following clinical signs either until day 2 post exposure (animal 1 & 2) or 240 min post exposure (animal 3): Slightly reduced spontaneous activity, sunken flunks, slight piloerection, hunched postur

Gross pathology:

The necropsy of the spontaneously died animal revealed a dark discoloured duodenum, jejunum and ileum with Peyer’s patches. No specific pathological changes were recorded for surviving animals.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

In the present study conducted according to OECD guideline 423 (adopted 17 December 2001), m-Xylylenebismaleimide was tested in three steps and two doses for acute oral toxicity. In step 1 300 mg/kg bw were adminstered and in steps 2 and 3 2000mg/kg bw were administered to three female rats each group and the animals were observed for 14 days. There were no premature deaths in step 1, thus step 2 was performed, one animal died in step 2 and all animals showed clinical signs during the first 5 to 7 days which were reversible. Body weight loss occurred in step 2 and 3 but all animals gained weight in a normal range at the end of the study.
Thus, according to Regulation (EC) No 1272/2008 (CLP) m-Xylylenebismaleimide is not classified with regard to acute oral toxicity; according to GHS (Globally Harmonized Classification System) m-Xylylenebismaleimide is classified into Category 5 and has obligatory labelling requirements for toxicity.