N-benzylethylenediamine

Endpoint summary

Description of key information

Based on a GLP compliant acute toxic class study (OECD 423) in female rats the LD50 of the test substance after oral administration was found to >300 - 2000 mg/kg bw

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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.

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- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum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

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.

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)

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

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 an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 300 mg/kg bw of the test item N-benzylethylenediamine (undiluted or preparations in deionized water) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females and 300 mg/kg bw in 6 females).

The following test substance-related clinical observations were recorded, clinical signs occurred within the first 4 hours after administration:

2000 mg/kg (single test group):

Mortality in all animals

Poor general state in all animals

Dyspnoea in all animals

Abdominal position in all animals

Salivation in all animals

Macroscopic pathological findings in the animals that died:

Dark spotted discoloration of the liver in all animals

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

300 mg/kg (first test group):

No mortality occurred

No clinical signs were observed

300 mg/kg (second test group):

No mortality occurred

Poor general state in two animals

Impaired general state in all animals

Cowering position in all animals

Piloerection in all animals

Abdominal position in two animals

Salivation in one animal

All surviving animals gained weight in a normal range throughout the study period. There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (300 mg/kg bw, 6 females).

Justification for classification or non-classification

Classification, Labelling, and Pachaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance needs to be classified as harmful after acute oral administration GHS, cat. 4, H302 under Regulation (EC) No 1272/2008.