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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-benzylethylenediamine
EC Number:
223-984-5
EC Name:
N-benzylethylenediamine
Cas Number:
4152-09-4
Molecular formula:
C9H14N2
IUPAC Name:
N-benzylethane-1,2-diamine
Test material form:
liquid
Details on test material:
charge: R1640 Fr.16/199/17-18
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: R1640 Fr.16/199/17-18
- Expiration date of the lot/batch: March 01, 2020
- Purity test date: 98.8 area %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: undiluted (for dose of 2000 mg/kg bw)
Solution in deionized water for doses of 300 mg/kg bw

FORM AS APPLIED IN THE TEST: The test item preparation for each test group was produced shortly before administration by stirring with a magnetic stirrer.

OTHER SPECIFICS:
Density [g/mL]: 0.990
Homogeneity: The test item was homogeneous by visual inspection.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: single housing (Makrolon cage, type III)
- Diet (e.g. ad libitum): R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Soest, Germany), ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C *+/- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Solution in deionized water

MAXIMUM DOSE VOLUME APPLIED:
2 mL/kg for doses of 300 mg/kg bw; 2.02 mL/kg for doses of 2000 mg/kg bw
Doses:
300 and 2000 and mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.
- Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
Statistics:
Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw: Mortality in all animals
300 mg/kg bw: No mortality occurred.
Clinical signs:
2000 mg/kg bw: in all animals: dyspnea, abdominal position, poor general state and salivation.
300 mg/kg bw (first test group): No clilnical signs were observed
300 mg/kg bw (second test group): two animals showed poor general state at hour 0 after administration. Impaired general state and piloerection was seen in all animals from hour 0 until hour 3 or from hour 1 until hour 3 or 4 after administration. Abdominal position was seen in two animals at hour 0, while cowering position was observed in all animals from hour 1 until hour 2 or 3 after administration. In one animal of this test group salivation was noticed at hour 0, only.
Body weight:
All surviving animals gained weight in a normal range throughout the study period.
Gross pathology:
The following macroscopic pathologic findings were observed in the animals that died (2000 mg/kg bw): in all animals dark spotted discoloration of the liver; red discoloration of the forestomach and glandular stomach in all animals; dark red discoloration of the contents of the stomach and of the small intestine in all animals;
Dark spotted discoloration of the spleen in one animal
There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (300 mg/kg bw)

Any other information on results incl. tables

Mortality

Mortality

Dose (mg/kg bw):

2000

Sex:

female

Administration:

1

No. of animals:

3

Mortality (animals):

3

Mortality

Dose (mg/kg bw):

300

300

Sex:

female

female

Administration:

1

2

No. of animals:

3

3

Mortality (animals):

No mortality

No mortality

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study the median lethal dose of N-benzylethylenediamine after oral administration was found to be > 300 mg/kg bw - 2000 mg/kg bw in rats.

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