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Administrative data

Description of key information

LD50 (experimental) >2000 mg/kg bw (LD50 cut-off = 5000 mg/kg bw), study conducted according to OECD 423, GLP

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17 December, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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

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
Key result
Sex:
female
Dose descriptor:
LD50
Remarks:
experimental
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
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:
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 posture, slight piloerection. In step 2 (dose: 2000 mg/kg bw) the 2 remaining animals showed the following clinical signs up to post exposure day 7: Slightly reduced spontaneous activity, Moderately reduced spontaneous activity, sunken flunks, slight piloerection, prone position, further reduced spontaneous activity, half eyelid closure, hunched posture, moderate diarrhoea, weight loss. Between observation day 7 and 15 no specific findings were recorded. Animal 6 died spontaneously 240-270 min after exposure and exhibited the following clinical signs: Moderately reduced spontaneous activity, sunken flunks, moderate piloerection, half eyelid closure, moderate ataxia. In step 3 of the test (dose: 2000 mg/kg bw) two of the three animals showed the following clinical signs until post exposure day 5: Slightly reduced spontaneous activity, sunken flunks, slight piloerection, half eyelid closure, hunched posture, moderate diarrhoea, weight loss (animal 9) and alopecia at day 6 to day 9 (animal 8). Animal 7 exhibited the same clinical signs but in a more pronounced form, e.g. weight loss was higher as compared to animal 9.
Body weight:
None of the animals in step 1 showed weight loss during the observation period. Animals of step 2 and step 3 showed weight loss in between which returned to normal after a few days.
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.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The value was determined in a study conducted according to OECD guideline 423 and was GLP-compliant. Therefore, the results are of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

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. Most prominent clinical signs were reduced spontaneous activity, sunken flunks, piloerection , half eyelid closure, prone position and between observation day 3 and 4 diarrhoea and weight loss. Body weight loss occurred in step 2 and 3 but all animals gained weight in a normal range at the end of the study. between observation day 7 and 15 there were no specific findings in step 2 and 3. The animal that died showed discoloured, dark duiodenum, jejunum, ileum - with Peyer´s patches- during necropsy. Necropsy was also performed with the remaining animals at day 15 but showed no specific findings.

Oral LD50 (rat, females) >2000 mg/kg bw (LD50 cut-off = 5000 mg/kg bw)

Justification for classification or non-classification

Based on the available, reliable and relevant data m-Xylylenebismaleimide is not classified with regard to acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP); according to GHS (Globally Harmonized Classification System) m-Xylylenebismaleimide is classified into Category 5 and has obliatory labelling requirements for toxicity.