DS-2920A-E

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): DS-2920A-E
- Physical state: orange solid
- Analytical purity: no data
- Lot/batch No.: 004
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

other: Sprague-Dawley (Crl : CD ® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd ., Margate, Kent, U.K.
- Age at study initiation: eight to twelve weeks.
- Weight at study initiation: males: 201 - 217g, females: 200 - 214g,
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: up to five by sex in solid floor polypropylene cages furnished with woodflakes
- Diet: Rat and Mouse Expanded Diet No . 1, Special Diet Services Limited, Witham, Essex, U.K.), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 54 - 67
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg / ml
- Amount of vehicle (if gavage): The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
- Justification for choice of vehicle: No data

DOSE VOLUME APPLIED: 10 ml / kg

DOSAGE PREPARATION (if unusual):
- For the purpose of the study the test material was freshly prepared, as required, as a solution at the appropriate concentration in distilled water.
- The concentration, homogeneity and stability of the test material preparations were not determined by analysis.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

• Range-finding Study:
2000 mg / kg bodyweight were administered at a concentration of about 200 mg / mL at a dose volume of 10 mL / kg to one male and one female rat, respectively.
- Duration of observation period following administration: five days.
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1 2, and 4 hours after dosing and subsequently once daily for five days. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes.
- Necropsy of survivors performed: no
There were no deaths or clinical signs of toxicity.

• Main Study:
Based on the information of the range-finding study, a dose level of 2000 mg / kg bodyweight was selected for the main study.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality. No signs of systemic toxicity.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study. The faeces of all animals was stained orange one and two days after treatment. The urine of all females was also stained orange during this period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No other findings.

Any other information on results incl. tables

Table 1: Mean body weight
		Mean	SD
Day 0	Males	208.6	5.86
	Females	206.0	5.83
Day 7	Males	269.2	9.68
	Females	238.0	8.80
Day 14	Males	315.4	17.52
	Females	257.2	11.82

Table 2: Body weight gain (g) during week
		Mean	SD
Week 1	Males	60.6	8.11
	Females	32.0	3.94
Week 2	Males	46.2	8.93
	Females	19.2	3.90