Androsta-1,4-diene-3,17-dione

Endpoint summary

Description of key information

The acute toxicity (LD50) of androstadiendion in rats is > 2000 mg/kg bw after oral (Stark & Wick, 1998; Kurth, 1994) or dermal (Kurth, 1995) administration.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug to Sep 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No animal died in the course of the study. The main clinical findings after administration of 2000 mg/kg ZK 4947 were apathy, disturbances in gait, prone or lateral position while conscious, vocalization, biting of objects, convulsions, eyelid closure, sialorrhea and disturbances in respiration mainly on the application day. All animals were without compound-related findings from day 3 onwards. The body weight gain on days 8 and 14 was within the normal range for rats of this age and strain, which are routinely used in the laboratory. Autopsy revealed no compound-related findings.

Executive summary:

A single oral administration (gavage) of the test substance to female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, effects on body weight gain and gross pathological findings. The main clinical findings were apathy, disturbances in gait, prone or lateral position while conscious, vocalization, biting of objects, convulsions, eyelid closure, sialorrhea and disturbances in respiration mainly on the application day. All animals were without compound-related findings from day 3 onwards. According to OECD TG 423 the oral LD50 of ZK 4947 (androstadiendion) in female rats is therefore > 2000 mg/kg body weight.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sep to Nov 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water

Doses:

200, 2000 mg/kg

No. of animals per sex per dose:

200 mg/kg: 3 males and 3 females
2000 mg/kg: 3 males

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 mg/kg bw

Based on:

test mat.

After administration of 2000 mg/kg one out of three animals was found dead on day 2 of the test while no animal died after application of 200 mg/kg.

The main clinical findings after application of 2000 mg/kg were apathy, prone position, disturbances in gait, upright tail, spasmodic twitches, increased muscle tone and sialorrhea. All surviving animals of this dose group were without findings from day 2 onwards. The animals dosed with 200 mg/kg were without clinical findings over the whole study period.

The body weight gain on days 8 and 14 was within the normal range for rats of this age and strain, which are routinely used in the laboratory. No compound-related clinical findings could be detected at the end of the study on day 14.

Autopsy revealed paleness of spleen in the animal which died after application of 2000 mg/kg and no compound-related findings in the animals which were sacrificed at the end of the study.

Executive summary:

A single oral administration (gavage) of the test substance to male and female rats at 200 mg/kg was tolerated without mortalities, clinical signs, effects on body weight gain and gross pathological findings (equivalent to OECD TG 423). After oral administration of 2000 mg/kg to three males one animal was found dead on day 2. The main clinical findings in this dose group were apathy, prone position, disturbances in gait, upright tail, spasmodic twitches, increased muscle tone and sialorrhea. All surviving animals at 2000 mg/kg were without findings from day 2 onwards. Autopsy revealed paleness of spleen in the animal which died after application of 2000 mg/kg. Therefore, the oral LD50 of ZK 4947 (androstadiendion) in male and female rats is > 200 mg/kg body weight, presumably close to 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The studies are of high quality (Klimisch score=1)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb to Mar 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

3 instead of 5 animals/sex used

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

physiological saline

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

No animal died in the course of the study. A single dermal application of 2000 mg/kg was tolerated without compound-related findings. The body weight gain on days 8 and 14 was within the normal range for rats of this age and strain, which are routinely used in the laboratory. No compound- related clinical findings could be detected at the end of the study on day 14. Autopsy revealed no compound-related findings.

Executive summary:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 402 the dermal LD50 of ZK 4947 (androstadiendion) is therefore > 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

The acute oral toxicity of androstadiendion was low with a LD50 value exceeding 2000 mg/kg bw in rats according to OECD TG 423 (Stark and Wick, 1998; Kurth, 1994). At the limit-dose 2000 mg/kg no female animal died and no effects on body weight gain or gross pathological findings were observed in females during the 14-day post observation period. The main clinical findings were apathy, disturbances in gait, prone or lateral position while conscious, vocalization, biting of objects, convulsions, eyelid closure, sialorrhea and disturbances in respiration mainly on the application day. All female animals were without compound-related findings from day 3 onwards (Stark and Wick, 1998). After oral administration of 2000 mg/kg to males one out of three animals was found dead on day 2. The main clinical findings in this dose group were apathy, prone position, disturbances in gait, upright tail, spasmodic twitches, increased muscle tone and sialorrhea. All surviving males at 2000 mg/kg were without findings from day 2 onwards. Autopsy revealed paleness of spleen in the male animal which died after application of 2000 mg/kg (Kurth, 1994). In summary, in both acute oral toxicity studies five out of six treated animals survived a single dose of 2000 mg/kg resulting in a common LD50 of > 2000 mg/kg for both sexes.

The acute dermal toxicity of androstadiendion was low with a LD50 value exceeding 2000 mg/kg bw in rats according to OECD TG 402 (Kurth, 1995). At the limit-dose 2000 mg/kg no animal died and no clinical signs, effects on body weight gain or gross pathological findings were observed during the 14-day post observation period.

Justification for selection of acute toxicity – oral endpoint
No study was selected since in both acute toxicity studies rats survived a dose of 2000 mg/kg (2/3 males (Kurth, 1994) and 3/3 females (Stark and Wick, 1998)).

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.