Androstane-3,17-diol, 2-(4-morpholinyl)-16-(1-pyrrolidinyl)-, 17-acetate, (2.beta.,3.alpha.,5.alpha.,16.beta.,17.beta.)-

Endpoint summary

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:

20 July 1999 - 5 August 1999

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

not specified

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Rive Deutschland, Sulzfeld, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: Male mean: 292 grams; Female mean 203 grams
- Fasting period before study: overnight before dosing and 3-4 hours after dosing.
- Housing: Group housing of 3 animals per sex in polycarbonate cages.
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 July 1999 To: 5 August 1999

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Vehicle was selected based on a pretest performed at NOTOX.


MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg (10 mL/kg) body weight

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability - Twice daily; Body weights - Days 1 (pre-administration), day 8, and day 15; Clinical signs - periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Internal macroscopic abnormalities

Statistics:

Not applicable

Preliminary study:

As the 2000 mg/kg limit test resulted in no adverse effects, or mortalities in this study group, no additional dose levels were required.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was reported within this study.

Clinical signs:

other: Diarrhea, red staining of the eye, hunched posture and/or piloerection were noted among the animals between day 2 and 4. Alopecia, was noted during the observation period, and is commonly seen in group housed rats and therefore was not counted as toxicolo

Gross pathology:

Macroscopic examination of animals reported irregular surface of the fore-stomach in three males and one female. In one female the serosa and the liver were reported to be grown together. In one male the serosa was reported to be grown together with the diaphram and liver.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 for the test substance, when administered as supplied to rats, is >2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

LC50

Value:

2 000

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:

11 - 25 August 1999

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks old
- Weight at study initiation: <3.5 kg
- Fasting period before study: none
- Housing: Individually housed in polycarbonate cages
- Diet (e.g. ad libitum): free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 degrees C
- Humidity (%): 50%
- Air changes (per hr): 15 air changes per hr
- Photoperiod (hrs dark / hrs light): Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: To: 17 August 1999 to 20 August 1999

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10% total body surface
- Type of wrap if used: Wrap consisted of surgical gauze patch, successively covered with aluminium foil and Coban flexible bandage. Micropore tape was used in females for fixation of bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): No data
- Constant volume or concentration used: Yes
- For solids, paste formed: No data

Duration of exposure:

24 hrs

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability - Twice daily; Body Weight - Days 1 (pre-administration), 8 and 15; Clinical Signs - At periodic intervals on the day of dosing and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Internal macroscopic abnormalities.

Statistics:

Not applicable

Preliminary study:

The test substance, when administered as supplied to rats, indicated an acute dermal LD50 greater than 2000 mg/kg.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Mortality:

No mortality occurred

Clinical signs:

other: No signs of systemic toxicity were reported. Alopecia, focal erythema, necrosis and/or scabs were seen in the treated skin-area of the animals during the observation period.

Gross pathology:

Macroscopic findings were only noted in two males; for one male liver nodules and a hernia of the diaphragm were reported and for the other male a thickened enlarged liver was reported.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance, when administered as supplied to rats, was greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Additional information

Justification for selection of acute toxicity – oral endpoint
The acute oral LD50 for Pymorolac, when administered as supplied to rats, was >=2000 mg/kg bw.

Justification for selection of acute toxicity – dermal endpoint
The acute dermal LD50 of Pymorolac, when administered as supplied to rats, was >= 2000 mg/kg bw.