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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04. to 17. July 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
, doses were 1000 and 500 mg/kg
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4-Androstene- 3,17 -dione
- Lot/batch No.: 57120598
- Lot/batch No. of formulation: 1044-1
- Stability under test conditions: The formulation was freshly prepared on application day.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Wistar-Han-Schering
- Source: Schering
- Age at study initiation: not reported
- Weight at study initiation: 105-123 g
- Fasting period before study: about 19 h
- Housing: singly in conventional housing conditions
- Diet and water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 48-60
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: physiological saline containing 0.085 % Myrj 53
Doses:
500 and 1000 mg/kg bw
No. of animals per sex per dose:
3 males/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs thrice on day 1 (30 min., 1 h, and 2 h after substance sdministration), twice on day 2 (in the morning and in the afternoon), and at least once daily throughout the rest of the study. Body weights were determined at study start (day 1), on day 7 and at termination of the study (day 14).
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 500 - < 1 000 mg/kg bw
Based on:
test mat.
Mortality:
All three animals of dose group 1000 mg/kg died on day 3 of the study. No mortalities were observed after administration of 500 mg/kg.
Clinical signs:
Compound-related clinical signs were apathy, disturbance of gait and squatting position. In addition prone position, unconsciousness, disturbance in respiration and increased diuresis were observed at lethal dose (1000 mg/kg). The surviving animals were without clinical signs from day 2 onwards.
Body weight:
In the surviving animals (500 mg/kg) the body weight gain observed on days 7 and 14 was within the normal range for male rats of this age and strain compared to historical data.
Gross pathology:
Macroscopic findings in animals which died before the end of the observation period were paleness of liver and kidneys and black-brown foci in glandular mucosa of stomach. Animals at the dose of 500 mg/kg were without macroscopic pathological findings.

Applicant's summary and conclusion

Conclusions:
For acute oral toxicity classification is required as harmful (Xn, R22) according to Directive 67/548/EEC and as Category 4 (H302) according to Regulation (EC) 1272/2008.
Executive summary:

The single oral administration of the substance to male rats caused mortality at 1000 mg/kg in 3/3 animals on Day 3 of the study, whereas all three animals survived at 500 mg/kg. Compound-related clinical signs were apathy, disturbance of gait and squatting position and, additionally at lethal dose, prone position, unconsciousness, disturbance in respiration and increased diuresis. All surviving animals were without clinical signs from Day 2 up to the end of the 14 -day observation period. Macroscopic findings in animals which died prematurely were paleness of liver and kidneys and black-brown foci in glandular mucosa of stomach. Animals at the dose of 500 mg/kg were without macroscopic pathological findings. Thus, the LD50 after oral administration to male rats was concluded to be between 500 and 1000 mg/kg bw.