Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

EC Number:

428-290-8

EC Name:

Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

Cas Number:

120606-08-8

Molecular formula:

C16H20ClNO2

IUPAC Name:

benzyl[2-(2-methoxyphenoxy)ethyl]amine hydrochloride

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Meosixtetroxy (Tetrome I. intermediate)
- Physical state: white crystalline powder
- Purity test date: 07. 10. 1998
- Lot/batch No.: 9801
- Expiration date of the lot/batch: : 10. 1999
- Storage condition of test material: at 2-5 °C temperature (cooled)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CHARLES RIVER HUNGARY Ltd. Budapest
- Age at study initiation: 7 weeks
- Fasting period before study: overnight (after the test item administration food was withheld for 3 hours)
- Housing: 5 animals / box, in OMKER II type plastic boxes. (40x28x10cm)
- Diet (e.g. ad libitum): ad libitum, CRLT / N standard diet for rodent (produced by Farmer Prompt Ltd. Hungary)
- Water (e.g. ad libitum): potable water, ad libitum, offered daily in 500-ml MAKROLON type drinking bottles
(sterilized before use (121 °C, 20 minutes)
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9-24.3 °C
- Humidity (%): 31.9-38.7 %
- Air changes (per hr): 10-15 / h
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h artificial light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Oleum Helianthi PH.HG. VII.

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg / kg bodyweight = 20 ml / kg test item in vehicle suspension

Doses:

2000 mg / kg
740 mg / kg
270 mg / kg
100 mg / kg
control

No. of animals per sex per dose:

5 (total 50)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: for 6 hours after treatment and then at least twice a day
- Necropsy of survivors performed: yes ( macroscopic)
- Other examinations performed: clinical signs of toxicity, status of skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

936 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

838 mg/kg bw

Mortality:

Three males and one female died after 740 mg/kg doses, four males and all of the females died after single oral administration of the test article in the 2000 mg/kg dose group. No lethalities occured in other dose group.

Clinical signs:

Test article absorbed rapidly and animals showed clinical symptoms in all treated groups. Serious CNS disturbances and respiratory failure (decreased body tone, dyspnea, moderate somnolence) were observed in the 100 and 270 mg/kg dose groups. The animals besame symptom-free on the 2nd day.
In addition, clonic convulsion and hypersalivation in the 740 mg/kg dose group also clonic convulsion in the 2000 mg/kg dose group observed. The survivors became symptom-free not earlier than the 3rd day after treatment.
The death of he animals in the 740 and 2000 mg/kg happened rapidly after treatment. The death of animals was preceded by the mentioned several toxic symptoms, mainly dyspnea and clonic convulsion.

Body weight:

The mean body weight of females in 740 mg/kg dose group was significantly below the control (-11%, p<0.05), but not dose-dependently above the control, in all dose groups during the study (from 1-14 days). This alteration is due to the lower body weight gain of three control animals, whitout test article.related toxicological meaning.

Gross pathology:

In the animals died on study, mottled and congested lungs with haemorrhages, congested brain wih haemorrhages, foamy or bloody-foamy oral discharge, point-like haemorrhages in the thymus, bleedings or point-like haemorrhages on the mucous membrane of the stomaxh and mucosal haemorrhages of small intestines was found. The latters suggested the local irritative effect of the test article.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions the LD50 values of the test materila administered by oral route to Wistar rats was 936 mg/kg at males and 838 mg/kg at females, so according to the requirements of the 4/1997. (II.21.) NM regulation the article was classified to the Xn Harmful cathegory. According to the IATA specifications the test article is not classified.