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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2000-01-18 to 2000-02-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
p-phenylenebis(methylamine)
EC Number:
208-719-3
EC Name:
p-phenylenebis(methylamine)
Cas Number:
539-48-0
Molecular formula:
C8H12N2
IUPAC Name:
1,4-Bis(aminomethyl)benzene
Test material form:
solid
Specific details on test material used for the study:
Purity: 99.9%
Lot No.: Lot 4

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Japan, Inc.
- Age at study initiation: 5 weeks
- Weight at study initiation: 116±4.4 g (males), 98±3.7 g (females)
- Fasting period before study: fasted overnight
- Housing: Animals were reared in suspended metallic cages for rats, 6-10 per cage.
- Diet (e.g. ad libitum): pellet food for rat MF
- Water (e.g. ad libitum): tap water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2
- Humidity (%): 55±6
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.25, 0.5, 2, 5 and 20 (w/v)%
- Dose volume: 1.0 mL/100 g of body weight
Doses:
25, 50, 200, 500 and 2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed daily with respect to mortality and general signs and symptoms during the 14-day study period after administration. Animals were weighed shortly before administration on day 0 (day of administration) and day 2, 7 and 14 using an electronic balance.
- Necropsy of survivors performed: Dead animals were necropsied promptly after discovery. Surviving animals were necropsied upon completion of the study (on day 15) after exsanguinating them to death by cutting the abdominal aorta under anesthesia with diethyl ether.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No male died in the 25, 50, 200 or 500 mg/kg group, while all males died on day 0 in the 2000 mg/kg group.
No female died in the 25, 50, 200 or 500 mg/kg group, while all females died on day 0 in the 2000 mg/kg group.
Clinical signs:
Males showed no abnormality in the 25, 50 or 200 mg/kg group. In the 500 mg/kg group, brown loose stools were observed on stool pans on day 1 and 2, but no abnormality was noted thereafter. In the 2000 mg/kg group, some animals showed drooping body about 10 min after administration with all 6 animals showing drooping body and sedation 30 min after administration, followed later by writhing, abnormal breath sounds and red fluid attached to the nose in one animal each. Drooping body and blepharoptosis lasted thereafter, gradually followed by decreases in motor activity, collapse and pallor. All animals died by 5.5 hours after administration. Two of the dead animals showed soilage around the anus probably attributable to diarrhea.
Females showed no abnormality in the 25, 50 or 200 mg/kg group. In the 500 mg/kg group, 2 females had diarrhea 5 hours after administration, but recovery was seen the following day and no abnormality was seen thereafter. In the 2000 mg/kg group, all 6 females showed drooping body and sedation 30 min after administration. Drooping body and blepharoptosis persisted thereafter, followed by gradual decreases in motor activity. All 6 females died by 6 hours after administration showing collapse and pallor.
Body weight:
Males in 25, 50 and 200 mg/kg groups showed changes in body weight similar to those seen in the control group (given only distilled water). In the 500 mg/kg group, slight inhibition in body weight gain was observed on day 2, but normal weight gain tendency was observed thereafter with changes in body weight similar to those observed in the control group.
In females in 25, 50, 200 and 500 mg/kg groups, changes in body weight similar to those observed in the control group were observed.
Gross pathology:
All dead males in the 2000 mg/kg group showed severe hemorrhage from the glandular stomach mucosa and hemorrhage from the intestinal mucosa. No abnormality was observed in any animal that survived the study in 25, 50, 200 and 500 mg/kg groups.
In females, all dead animals in the 2000 mg/kg group showed severe hemorrhage from the glandular stomach and intestinal mucosa with two also showing hemorrhage/hyperemia in the anterior stomach mucosa. No abnormality was observed in any animal that survived the study in 25, 50, 200 and 500 mg/kg groups.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of this substance was estimated to range between 500 and 2000 mg/kg bw in both male and female rats.