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

Endpoint summary

Description of key information

study conducted according to OECD test guideline 401, result: not classified (CLP); Category 5 (GHS)

study conducted accoding to OECD test guideline 402, result: not classified

acute toxicity study (i.p. application), result: LD50 2000 - 5000 mg/kg bw (in mice)

 

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

Study period:

June 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Feb. 1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Moallegaard Breeding Centre Ltd, Ejby, DK-4623 Ll. Skensved.
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 143-152 g
- Fasting period before study: 18 h
- Housing: The rats were individually ear-tagged and kept in Macrolone cages Type Ill (42 x26 x 15 cm) 2 or 3 to a cage, males and females separated. The bedding was
softwood sawdust "Spanvall Special White" from Spanvall Ltd, Jorlose, DK-M90 Jerslev.
- Diet (e.g. ad libitum): ad libitum; complete rodent diet “Altromin 1314" from Chr. Petersen Ltd, DK-4100 Ringsted
- Water (e.g. ad libitum): ad libitum; drinking watern acidified with hydrochloric acid to pH 2.5
- Acclimation period: None

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/- 2
- Humidity (%): 55+/-15
- Air changes (per hr): 6
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.0 mL/100 g bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed 1, 3 and 6 hours after administration and thereafter daily for a period of 14 consecutive days. Body weights (b.wt.) were recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other:

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Since no rats died of the treatment the oral LD50 must exceed 2000 mg "Amino-butane-triol-acetonide"/kg b.wt.

Executive summary:

In an acute oral toxicity study according to OECD test guideline 401 (1987), groups of fasted, young adult Wistar rats (5/sex) were given a single oral dose of Aminodioxepan (100% a.i.) at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined = > 2000 mg/kg bw

No mortality occurred during this limit test.

Aminodioxepan is of LOW Toxicity based on the LD50 in both males and females. 

There were no treatment related clinical signs, necropsy findings or changes in body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

guideline study, the quality is expected to be high

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan. 1993 to May 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

3 animals/ group instead of 5

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1989

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering
- Weight at study initiation: 90-109 g males; 89-105 g females
- Fasting period before study: 19 h
- Housing: individually under conventional conditions
- Diet (e.g. ad libitum): ad libitum; pell. Altromin® R
- Water (e.g. ad libitum): ad libitum, demineralized acidified water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 52-63


IN-LIFE DATES: From: 1993-01-05 To: 1993-01-18

Type of coverage:

not specified

Vehicle:

physiological saline

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing on days 1, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of Aminodioxepan in male and female rats after a single dermal application is > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study according to Roll, R. et al., Bundesgesundheitsblalt 8/89, 336-340, groups of young adult Wistar rats (3/sex) were dermally exposed to Aminodioxepan (100% a.i) in 0.9% NaCl for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Combined => 2000 mg/kg bw

No mortality occurred in this limit test.

Aminodioxepan is of LOW Toxicity based on the LD50 in male and female Wistar rats.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

guideline study, the quality is expected to be high

Additional information

In an acute oral toxicity study according to OECD test guideline 401 (1987), groups of fasted, young adult Wistar rats (5/sex) were given a single oral dose of Aminodioxepan (100% a.i.) at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined = > 2000 mg/kg bw

No mortality occurred during this limit test.

Aminodioxepan is of LOW Toxicity based on the LD50 in both males and females. 

There were no treatment related clinical signs, necropsy findings or changes in body weight.

 

In an acute dermal toxicity study according to Roll, R. et al., Bundesgesundheitsblalt 8/89, 336-340, groups of young adult Wistar rats (3/sex) were dermally exposed to Aminodioxepan (100% a.i) in 0.9% NaCl for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Combined => 2000 mg/kg bw

No mortality occurred in this limit test.

Aminodioxepan is of LOW Toxicity based on the LD50 in male and female Wistar rats.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

 

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.

Justification for classification or non-classification

Based on the available data, Aminodioxepan is not classified as acutely toxic by oral and dermal route according to Regulation (EC) No.1272/2008 (CLP).