16α,17,21-trihydroxypregna-1,4,9(11)-triene-3,20-dione 21-acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

16α,17,21-trihydroxypregna-1,4,9(11)-triene-3,20-dione 21-acetate

EC Number:

278-593-2

EC Name:

16α,17,21-trihydroxypregna-1,4,9(11)-triene-3,20-dione 21-acetate

Cas Number:

77017-20-0

Molecular formula:

C23H28O6

IUPAC Name:

2-[(1S,2R,3aS,3bS,9aS,11aS)-1,2-dihydroxy-9a,11a-dimethyl-7-oxo-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,11H,11aH-cyclopenta[a]phenanthren-1-yl]-2-oxoethyl acetate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): DIOLO
- Substance type: Organic
- Physical state: Yellow powder
- Analytical purity: >90%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DEPRE breeding centre (Z.I. malitorne - B.P. 70 - 3, -rue Joliot-Curie - 18230 SAINT DOULCHARD - FRANCE)
- Age at study initiation: Over 6 weeks at the time of administration
- Weight at study initiation: 154.6 ± 5.7 for female; and 170 ± 6.7 of male
- Fasting period before study: overnight
- Housing: Rats were housed in groups of five animals, males and females separated, were kept in standard size cages, on dust-free radiation sterilised white whood shavings as bedding.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days before treatment, in the area where the study had taken place

ENVIRONMENTAL CONDITIONS
- Temperature (°C): air-conditioned between 19 an 23°C
- Humidity (%): constant relative humidity between 45 and 65%
- Air changes (per hr): ten time per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The dose administered was expressed in mg/kg and adjusted to the weight of the animal as determined immediately before administration.
- Amount of vehicle (if gavage): max 10 mL/kg

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were examined twice on the day of treatment, then daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and macroscopically examined.

Results and discussion

Preliminary study:

Test substance was expected to be non-toxic by opral route, thus no preliminary study had been carried out.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study

Clinical signs:

other: No clinical signs were observed during the course of the study

Gross pathology:

Macroscopic examination at the end of the observation period did not reveal any teatment-related gross alteration

Other findings:

No organ or tissiue gross findings were seen at necroscopsy

Any other information on results incl. tables

Dose applied, mean body weights and mortality or rats male and female:

	Dose (mg(kg)	Mean body weight (g) on day			Mortality (per 5 animals)
Sex		0	7	14
Males	2000	170.7	236.8	287.0	0/5
Female	2000	154.6	194.1	222.2	0/5

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity of diol acetate is less than the limit for classification as harmful.

Executive summary:

Under the experimental conditions adopted, oral administration of the test substance DIOLO at dose of 2000 mg/kg caused no mortality and did not require euthanasia during 14 -day period, in the male or female Sprague-Dawley Rat.