trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Remarks:

after a single i.p. application

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

January 1993 to August 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test item is a new substance as defined by the Chemicals Law (Chemikaliengesetz). A micronucleus test is to be performed as part of the notification. "Acute toxicity information is required before doses can be established. For this purpose, data for one sex were regarded as being sufficient. The highest dose in the mutagenicity test should not exceed 2000 mg/kg. 2000 mg/kg are tolerated in rats without any mortalities or severe symptoms of intoxication after intragastric administration. To determined the LD50 range after i.p. application doses between 100 and 5000 mg/kg bw were used.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

EC Number:

419-050-3

EC Name:

trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

Cas Number:

79944-37-9

Molecular formula:

C7H15NO3

IUPAC Name:

6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: 17.5 - 22 g
- Fasting period before study: 16.5 - 19 h
- Housing: in groups of three animlas under conventional conditions
- Diet (e.g. ad libitum): ad libitum, pell. Altromin® R
- Water (e.g. ad libitum): ad libitum, tap water, demineralized, acidified
- Acclimation period: > 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 52-60

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

physiological saline

Doses:

100, 250, 500, 1000, 2000, 5000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observations: on day 1: after 5, 10, 15, 30 min and 1, 1.5, 3, and 5 h. On days 2-15 once daily; body weight: on days 1, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Two of the high dose animals (5000 mg/kg bw) died on day 1

Clinical signs:

100, 250 and 500 mg test item/kg body weight were tolerated without any clinical findings. The main findings after 1000 and 2000 mg/kg were apathy and eyelid closure.
Additionally, after 5000 mg/kg prone position, vocalisation, disturbances in gait and respiration, and spasmodic twitches were observed.

Body weight:

The body weight gain observed on day 7 or 8 and at the end of the test on day 14 or 15 respectively, was within or slightly above the normal range for mice (M) of the age and strain which are routinely used in the laboratory.

Gross pathology:

Autopsy revealed no compound-related findings.

Applicant's summary and conclusion

Conclusions:

The LD50 of Aminodioxepan in male mice after a single i.p. administration is between 2 and 5 g/kg body weight.

Executive summary:

In an acute toxicity study in male NMRI mice Aminodioxepan was administred once intraperitoneally at the doses of 100. 250, 500, 1000, 2000, and 5000 mg/kg bw. The animals were observed for 14 days. At the first three doses none of the animals showed any toxicologically relevant signs. Animals of the 1000 and 2000 mg/kg group showed signs like apathy (slight to moderate) and eyelid closure (incomplete or complete) within the first two days. At day 2-14 these animals were without findings. In the high dose group animals showed severe apathy, prone position, vocalisation, gait gasping breathing and complete eyelid closure. All animals of these group died within one day. Based one these results the LD50 for i.p. application in mice was determined between 2000 and 5000 mg/kg bw.