Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03-08-2010 to 31-03-2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Purity: 99.3%
Lot No.: 006001

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Co., Ltd
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 184-202 g
- Fasting period before study: 16 hours before administration
- Housing: Aluminum front and floor stainless steel mesh breeding cage (W 19.7 × D 26.3 × H 18.0 cm) containing the animals individually.
- Diet: Radiation sterilized solid feed (CRF-1, Lot No. 100203, 100302) ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.8 to 23.2 °C
- Humidity (%): 53.8 to 64.8%
- Air changes (per hr): 12 times
- Photoperiod (hrs dark / hrs light): 12 hrs

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% (w/v) aqueous solution of methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 20 mg/mL
- Amount of vehicle (if gavage): 1 ml/100g bw
- Lot no.: 7085417

Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Mortality:
At 2000 mg/kg bw, all animals were dead by Day 4. At 300 mg/kg bw, there were no mortalities.
Clinical signs:
At 2000 mg/kg bw, mydriasis, mucous stool, soiled fur of anogenital region, ptosis and lacrimation were observed.
At 300 mg/g bw, mucous stool and loose stool as the treatment-related slight effects on the digestive system were observed until 4 hours after administration in one or two animals.
Body weight:
At 2000 mg/kg bw, all animals were dead by Day 4 so no final body weights were recorded.
At 300 mg/kg bw, there were no effects on body weights noted on Day 14.
Gross pathology:
At necropsy of the 2000 mg/kg bw group, dilated lumen and liquid contents of stomach were observed in all animals, and red patch of glandular stomach and reddish contents of small intestine were observed. Some findings suggesting digestive injury were considered to be treatment-related effects.

There were no changes noted at necropsy in the 300 mg/kg bw group.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral study in the rat, the LD50 (female) for N,N′-m-phenylenedimaleimide was >300-2000 mg/kgbw.
Executive summary:

In an acute oral toxicity study (C541 (314 ‐022)), groups of Crl:CD(SD) female rats (3/sex) were given single oral doses of N,N′-m-phenylenedimaleimide  (99.3%) in 0.5 w/v% methylcellulose solution at doses of 300 and 2000 mg/kg bw and observed for 14 days.

LD50 (male/female): was >300-2000 mg/kg bw.

At 2000 mg/kg bw, all animals were dead by Day 4. At 300 mg/kg bw, there were no mortalities. At 2000 mg/kg bw, mydriasis, mucous stool, soiled fur of anogenital region, ptosis and lacrimation were observed. At 300 mg/g bw, mucous stool and loose stool as the treatment-related slight effects on the digestive system were observed until 4 hours after administration in one or two animals. At 2000 mg/kg bw, all animals were dead by Day 4 so no final body weights were recorded. At 300 mg/kg bw, there were no effects on body weights noted on Day 14. At necropsy of the 2000 mg/kg bw group, dilated lumen and liquid contents of stomach were observed in all animals, and red patches of glandular stomach and reddish contents of small intestine were observed. Some findings suggesting digestive injury were considered to be treatment-related effects. There were no changes noted at necropsy in the 300  mg/kg bw group.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 401) in the rat.