Androsta-2,16-dien-17-ol, 17-acetate, (5.alpha.)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

25 July 1996 to 27 August 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to internationally accepted guideline and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

dienone

IUPAC Name:

dienone

Details on test material:

- Name of test material (as cited in study report):Dienone
- Substance type: off-white powder
- Physical state: solid
- Analytical purity: 99.5% (by DSC)
- Lot/batch No.: Y08696/002 C166/1
- Storage condition of test material: Ambient temperatures in the dark

Test animals

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rodent Breeding Unit, Zeneca Pharmaceuticals, Alderly Park
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:
TEST ANIMALS
- Source:
- Age at study initiation:8-9 weeks
- Weight at study initiation: males: 255-339g and females 186-245g
- Fasting period before study: yes, overnight, immediately prior to dosing.
- Housing:maxium 5 rats per group were housed per cage, sexes separately, in multiple rat racks suitable for animals of this strain and the weight range expected during the course of the study. The males at the top dose-level were singly housed from day 2 onwards, due to aggressive behaviour.
- Diet (e.g. ad libitum): PCD, supplied by Special Diet Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: 6 days at laboratory, prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):21+/- 2 deg C
- Humidity (%): 40-70%
- Air changes (per hr):25-30 changes/hour
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:10 ml/kg

MAXIMUM DOSE VOLUME APPLIED:10 ml/kg

Doses:

2000 mg/kg; 500 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:observations daily (also, once within 2 hrs, and between 4-7 hours after dosing); bodyweight: Days -1, 1, 2, 3, 8, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

500 mg/kg bw

Based on:

test mat.

Applicant's summary and conclusion

Conclusions:

Although one female was found dead following a dose of 500 mg/kg, no significant signs of toxicity were seen in the remaining animals at this dose-level. In addition, as there were no signs of toxicity seen in this animal prior to death, its death is thought to be unrelated to treatment. The discriminating dose for dienone is therefore considered to be 500mg/kg to male and female rats. By read-across, didenac is also considered to generate a discriminating dose of 500 mg/kg.

Executive summary:

There are no available acute toxicity studies on didenac. Results of a study conducted with a structurally similar compound (dienone) are reported and used for read-across.