2-Cyclopentene-1-carboxylic acid, 5-(dimethylphenylsilyl)-2-(hydroxymethyl)-, (1R,2R)-2-amino-1,3-dihydroxy-1-(4-nitrophenyl)propyl ester, (1R,5S)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 10, 2000 to May 29, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted in 2000 according to OECD Method # 423 and in accordance with GLP. The study material is well characterized.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Commission Directive 96/54/EC, B1 tris

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

445-910-2

EC Name:

-

Cas Number:

1388152-30-4

Molecular formula:

Hill formula: C24 H32 N2 O7 Si CAS formula: C15 H20 O3 Si . C9 H12 N2 O4

IUPAC Name:

(1R,2R)-1,3-Dihydroxy-1-(4-nitrophenyl)propyl-2-ammonium (1R, 5S)-5-(dimethylphenylsilyl)-2-(hydroxymethyl)cyclopent-2-ene-1-carboxylate

Details on test material:

Light beige powder; stored at room temperature in the dark; received at testing laboratory on 2000-17-04.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

At the start of the study the males weighed 215 to 225g, and the females 210 to 219g, and were eight to twelve weeks old. With exception of an overnight fast before dosing and 3-4 hours after dosing, free access to mains drinking water and food was allowed. The temperature and relative humidity were set to achieve limits of 19 to 25 C and 30 to 70% respectively. The rate of air exchange was at least 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours of darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

Using all available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
dose level: 2000 mg/kg
concentration: 100 mg/ml
dose volume 10 ml/g
3 females per dose, followed by a group of 3 males per dose

Doses:

Male: 2000 mg/kg bw
Female: 2000 mg/kg bw

No. of animals per sex per dose:

Male: 2000 mg/kg bw; Number of animals: 3;
Female: 2000 mg/kg bw; Number of animals: 3

Control animals:

no

Details on study design:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals. The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after the final dose and subsequently once daily for fourteen days. At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological observations. This consisted of external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearances of any macroscopic abnormalities were recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: There were no signs of systemic toxicity. All animals showed expected gains in bodyweight over the study period.

Gross pathology:

Effects on organs:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was estimated as being greater than 2000 mg/kg bodyweight.

Executive summary:

The acute toxicity test was considered valid and assigned a reliability rating of 1 (reliable without restriction). The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after the final dose and subsequently once daily for fourteen days. At the end of the observation period the animals were subjected to gross pathological observations. There were no deaths. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the tert material in the Sprague-Dawley CD strain rat was estimated as being gratert than 2000 mg/kg body weight.