Cytidine, 5'-deoxy-5-fluoro-, 2',3'-diacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct. 1995 - Jan. 1996

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: FHSA, 16 CFR 1500.3(c)(2)(i)

Principles of method if other than guideline:

10 healthy male Wistar Albino rats were dosed orally with this substance at 2000 mg/kg of body weight. Body weight wete recorded pretest. Mortality and systemic observations were recorded 3-4 hours post dose and daily thereafter for 14 days.

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2R,3R,4R,5R)-4-(acetyloxy)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydropyrimidin-1-yl)-2-methyloxolan-3-yl acetate

EC Number:

605-260-4

Cas Number:

161599-46-8

Molecular formula:

C13 H16 F N3 O6

IUPAC Name:

(2R,3R,4R,5R)-4-(acetyloxy)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydropyrimidin-1-yl)-2-methyloxolan-3-yl acetate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

White Powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Animals were received from Ace Animals, Boyertown, PA on 5/02/95.
Following a quarantine period of at least one week, ten healthy male Wistar Albino rats were selected for this test from a larger group.

The animals were born the week of 3/24/95.
The pretest body weight range was 236-272g. Animals were identified by cage notation and an indelible body mark corresponding to the numbers 1 through 10.
The animals were housed 5/cage in suspended wire mesh cages. Bedding was placed beneath the cages and changed at least three times/week. Fresh Purina Rat Chow (Diet #5012), supplied by Davis Feed of Bucks County, Perkasie, PA was freely available except for 16-20 hours
prior to dosing. Water was freely available at all times.
The animal room, reserved exclusively for rats on acute tests, was temperature controlled, bad a 12 hour light/dark cycle and was kept clean and vermin free.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test article was mixed with corn oil to make dosing by gavage possible. The dose was based on the dry weight of the test article.
The test article was administered orally, one time, by syringe and dosing needle at 2000 mg/kg of body weight.

Doses:

10 g of test article was mixed with corn oil to a total volume of 50 ml

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

Type and frequency of observations :

In Vivo - Animals were observed 3·4 hours post dose and once daily thereafter for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded pretest.

P·ost Mortem: Animals were not examined for gross pathology.

Results and discussion

Preliminary study:

No preliminary study

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

0

Clinical signs:

other: All animals appeared normal during the 14 day observation period.

Gross pathology:

Animals were not examined for gross pathology.

Other findings:

Not applicable

Applicant's summary and conclusion

Interpretation of results:

other: not hazardous

Remarks:

Criteria used for interpretation of results: not specified

Executive summary:

The LD50 is greater than 2000 mg/kg of body weight.

All animals survived the 2000 mg/kg oral dose in good health.