A mixture of: 7,9,9-trimethyl-3,14-dioxa-4,13-dioxo-5,12-diazahexadecane-1,16-diylprop-2-enoate; 7,7,9-trimethyl-3,14-dioxa-4,13-dioxo-5,12-diazahexadecan-1,16-diylprop-2-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 01, 1993 to December 15, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: 7,9,9-trimethyl-3,14-dioxa-4,13-dioxo-5,12-diazahexadecane-1,16-diylprop-2-enoate; 7,7,9-trimethyl-3,14-dioxa-4,13-dioxo-5,12-diazahexadecan-1,16-diylprop-2-enoate

EC Number:

412-260-6

EC Name:

A mixture of: 7,9,9-trimethyl-3,14-dioxa-4,13-dioxo-5,12-diazahexadecane-1,16-diylprop-2-enoate; 7,7,9-trimethyl-3,14-dioxa-4,13-dioxo-5,12-diazahexadecan-1,16-diylprop-2-enoate

Cas Number:

52658-19-2

Molecular formula:

C21H34N2O8 (molecular formula of the two isomers constituting the substance)

IUPAC Name:

2-({[(2R)-2,4,4-trimethyl-6-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)hexyl]carbamoyl}oxy)ethyl prop-2-enoate; 2-({[(2S)-2,4,4-trimethyl-6-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)hexyl]carbamoyl}oxy)ethyl prop-2-enoate; 2-({[(3R)-3,5,5-trimethyl-6-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)hexyl]carbamoyl}oxy)ethyl prop-2-enoate; 2-({[(3S)-3,5,5-trimethyl-6-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)hexyl]carbamoyl}oxy)ethyl prop-2-enoate; 2-({[2,2,4-trimethyl-6-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)hexyl]carbamoyl}oxy)ethyl prop-2-enoate; 2-({[2,4,4-trimethyl-6-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)hexyl]carbamoyl}oxy)ethyl prop-2-enoate

Test material form:

liquid: viscous

Details on test material:

- Lot/batch No.: 30351 received on 2 November 1993
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd. Bicester, Oxon, England
- Strain: Hsd/Ola: Sprague-Dawley (CD)
- Age at study initiation: 4 - 7 weeks
- Weight at study initiation: 100 - 117 g
- Fasting period before study: overnight prior to and 4 hours after dosing
- Housing: in groups of up to 5 rats of the same sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): standard laboratory diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 50
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSAGE PREPARATION (if unusual): not applicable

Doses:

2.0 g/ kg b.w.

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: Mortality was checked at least twice daily. Clinical signs were recorded daily. Body weight recorded on day 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examinations

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths following a single oral dose of the test substance at 2.0 g/kg b.w.

Clinical signs:

other: Piloerection and increased salivation were observed in all rats within five minutes of dosing. Piloerection persisted until day 2 and was accompanied at later intervals on day 1 by abnormal body carriage (hunched posture) and soft or liquid faeces. Recove

Gross pathology:

No macroscopic abnormalities were observed for animals killed on day 15.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

M

Conclusions:

Under the study conditions, the acute lethal oral dose to rats of the test substance was found to be greater than 2000 mg/kg bw/d.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance to rat according to EU Method B.1. A group of ten fasted rats (five males and five females) was administered a single dose of the test substance, as supplied, at a dose level of 2000 mg/kg bw by gavage. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There was no mortality. Clinical signs of reaction to treatment included piloerection, abnormal body carriage (hunched posture), soft or liquid faeces and increased salivation in all rats. Recovery as judged by external appearance and behaviour, was complete by Day 3. No abnormalities were recorded at the macroscopic examination on Day 15. Under the study conditions, the acute oral LD50 of the test substance was found to be greater than 2000 mg/kg bw in rats (Parcell, 1993).