Prasterone

Endpoint summary

Description of key information

Oral (Rat): LD50 > 3300 mg/kg (formulated in fatty ointment) [Schering AG, Report No. 838, 1973-01-22]

Oral (Female Mouse): LD50 > 4130 mg/kg (formulated in fatty ointment) [Schering AG, Report No. 848, 1973-01-18]

Oral (Male Mouse): LD50 > 4130 mg/kg (formulated in fatty ointment) [Schering AG, Report No. 846, 1973-01-18]

Oral (Dog): LD50 > 4000 mg/kg (formulated in fatty ointment, administered in gelatine capsules) [Schering AG, Report No. 843, 1973-01-17]

Published data cited in RTECS confirm the low acute toxicity for the substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sep to Oct 1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Short report of study; basic scientific principles are met; study conducted before GLP principles were implemented

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

pre-guideline study

Principles of method if other than guideline:

Single oral administration of one substance concentration formulated in fatty ointment (10 g in 100 g) to rats (5 males and 5 females); Observation period was 22 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: fatty ointment

Doses:

33 g/kg formulation (equivalent to 3.3 g/kg active ingredient)

No. of animals per sex per dose:

5

Control animals:

other: yes, concurrent vehicle (fatty ointment)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 300 mg/kg bw

Based on:

act. ingr.

2 h up to 5 days after application apathy and occasionally lacrimation, ruffled fur and cachexia were observed.

Two animals (1 male and 1 female) died on day 3 and one female animal died on day 4. All other animals were sacrificed on day 22 without clinical symptoms.

Autopsy of the animals which died revealed substance remains in the stomach and hyperaemia of the cutaneous gastric mucosa. Furthermore petechiae and haemorrhagic erosions of the glandular gastric mucosa were found. No treatment-related pathological findings were observed for the sacrificed animals.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 of the substance in rats was concluded to be > 3300 mg/kg.

Executive summary:

The acute oral toxicity of the substance formulated in fatty ointment was investigated in male and female rats after one single administration of 3300 mg/kg (based on active ingredient) and within an observation period of 22 days.

2 h up to 5 days after application apathy and occasionally lacrimation, ruffled fur and cachexia were observed. Three animals (1 male and 2 females) died on day 3 or 4. Autopsy of these animals revealed substance remains in the stomach and hyperaemia of the cutaneous gastric mucosa. Furthermore petechiae and haemorrhagic erosions of the glandular gastric mucosa were found. All other animals were sacrificed on day 22 without clinical symptoms. No treatment-related gross pathological findings were observed in these animals.

Therefore, the acute oral LD₅₀ of the substance in rats was concluded to be > 3300 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 3 300 mg/kg bw

Quality of whole database:

Klimisch score 2

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity of the substance was studied in rats, mice and dogs.

 

An acute oral toxicity study on male and female rats was conducted with the substance formulated in fatty ointment and administered via gavage at a single dose of 3.3 g/kg. The study meets basic scientific principles, as it can be concluded from the short report. The observation period was 22 days. 2 hours up to 5 days after administration apathy and occasionally lacrimation, ruffled fur and cachexia were observed. Three animals (1 male and 2 females) died on day 3 or 4. Autopsy of these animals revealed substance remains in the stomach and hyperaemia of the cutaneous gastric mucosa. Furthermore petechiae and haemorrhagic erosions of the glandular gastric mucosa were found. All other animals were sacrificed on day 22 without clinical symptoms and pathology did not reveal treatment-related findings for them. Therefore, the acute oral LD50 of the substance is > 3300 mg/kg. A publication cited in RTECS (Jan 2012) confirms the low oral toxicity of the substance for rats [LD50 > 10 g/kg; British UK Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) #2208473 (BAXXDU)].

 

In two acute oral toxicity studies on male and female mice the substance, formulated in fatty ointment, was administered via gavage at a single dose of each 4.13 g/kg. The animals were observed for 22 days. 5 females showed apathy approx. 3 h after application, still observable on day 2 for 3 animals. No clinical signs were observed in male mice. Two females died on day 3 and 1 male on day 4. All other animals were sacrificed on day 22 without clinical symptoms. No treatment-related findings were observed at autopsy neither in males nor in females. Therefore, the acute oral LD50 of the substance in male and female mice is > 4130 mg/kg. The low oral toxicity in mice is confirmed by a publication cited in RTECS (Jan 2012) [LD50 > 10 g/kg; British UK Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) #2208473 (BAXXDU)].

 

An acute oral toxicity study on male and female dogs is available, in which the substance in fatty ointment was administered in gelatine capsules at a dose of 4000 mg/kg. The observation period after administration was 22 days. No clinical signs were observed and no animal died. Autopsy did not reveal treatment-related findings. Therefore, the acute oral LD50 of the substance in dogs is > 4000 mg/kg.

 

There are also data available related to acute toxicity in humans. A case report of a 55 -year-old man was published and is cited in RTECS (Jan 2012) as acute toxicity data. The patient noticed palpitations within two weeks after start taking the high dose of 50 mg of Androst-5-en-17-one, 3-hydroxy-, (3.beta.)- /day. 4 months after discontinuing, use of the substance was once again started (again 50 mg/day) and arrhythmias (premature atrial and premature ventricular contractions) recurred within 36 h. Therefore, taking high dosages of the substance seemed to be an etiologic factor in palpitations [Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- v. 129, p. 588, 1998 (AIMEAS)].

 

The acute subcutaneous toxicity of the substance was studied in rats and mice as cited in RTECS (Jan 2012).

 

The acute subcutaneous LD50 was reported to be 1000 mg/kg for rats and 900 mg/kg for mice [British UK Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) #2208473 (BAXXDU)].

 

RTECS (Jan 2012) cited a further study for acute toxicity. This study investigates amongst others the influence of high subcutaneous administered concentrations of the substance on angiogenesis using the Matrigel plug assay. 5 female 7 -week-old Swis nu/nu mice were injected subcutaneously 300 µl of liquid Matrigel with or without 1 µg bFGF, with vehicle alone or with the substance (100 µg). Ten days after injection, tissue containing the Matrigel plugs was assessed histopathologically. In Matrigel containing the substance, the bFGF-induced formation of new blood vessels was decreased by about 70% [European Journal Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967- v. 502, p. 21, 2004 (EJPHAZ)].

Justification for selection of acute toxicity – oral endpoint
Study in the preferred species (=rat) was selected.

Justification for classification or non-classification

Based on the data the substance has not to be classified for acute toxicity according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP).