Disilver oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-06-23 to 1989-07-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study. At the time of conduct, GLP was not compulsory. However, the study was conducted in accordance with the principles of GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disilver oxide

EC Number:

243-957-1

EC Name:

Disilver oxide

Cas Number:

20667-12-3

Molecular formula:

Ag2O

IUPAC Name:

silver(1+) oxide

Constituent 2

Reference substance name:

disilver(I)oxide

IUPAC Name:

disilver(I)oxide

Details on test material:

- Name of test material (as cited in study report): silver(I) oxide
- Physical state: brown-grey powder
- Stability under test conditions: According to information from the sponsor, the test substance was stable throughout the experimental period.
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

other: Wistar Bor: WISW (SPFTNO)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co.KG, Borchen
- Age at study initiation: 7 - 8 weeks (males) and 9 - 10 weeks (females)
- Weight at study initiation: 132 - 189 g (males) and 138 - 167 g (females)
- Fasting period before study: 16 hours before treatment
- Housing: in Macrolon cages type II, individually housing
- Diet: ad libitum (standard diet, ssniff R, "Special Diet for Rats")
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 21
- Humidity (%): 50 - 65
- Photoperiod: 12 hours dark/light cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: approx. 110, 162 and 237 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 21.5 ml/kg

Doses:

2370 mg/kg body weight
3480 mg/kg body weight
5110 mg/kg body weight

No. of animals per sex per dose:

15 males and 15 females divided in 3 dosing groups, 5 animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
The animals were continuously observed for the first 4 to 8 hours after administration and then once daily. The nature of the toxicity as well as the onset, the intensity and the duration of the signs were recorded.
Mortality was checkt twice daily. Time of death and number of dead animals per dose were documented.
The body weights were recorded at the beginning and also 7 and 14 days after administration or after death of the animals on days 2 to 14.
- Necropsy of survivors performed: yes; at the end of the observation period the animals were sacrificed with CO2.
Gross necropsy: was performed on all animals deceased intercurrently or sacrificed at the end of the observation period. Macroscopic examination included external appearance, body orifices, body cavities and their contents.
Histopathology: Samples of spleen and stomach were fixed in a 4% neutral buffered formaldehyde solution (10% formalin). The preserved tissues were trimmed, embedded in paraffin wax, sectioned at approximately 4 µm, stained with Hematoxylin and Eosin and examined microscopically.

Statistics:

probit analysis

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

3 702 mg/kg bw

95% CL:

9.11

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

3 970 mg/kg bw

95% CL:

9.94

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 804 mg/kg bw

95% CL:

12.4

Mortality:

Deaths occurred 4 hours to 7 days after administration.
Mortality rates, males:
2370 mg/kg = 0%
3480 mg/kg = 20% (1 rat died on day 7 after exposure)
5110 mg/kg = 100% (2 animals died after 4 days and 6 days, respectively, and 1 rat died at day 5 after exposure)

Mortality rates, females:
2370 mg/kg = 0%
3480 mg/kg = 40% (1 rat died after 24 hours and another rats died on day 5 after exposure)
5110 mg/kg = 100% (2 animals died after 4 hours and 3 rats died after 2, 5 and 7 days after exposure, respectively)

Clinical signs:

other: After administration of silver(I) oxide rats performed slight to severe hypokinesia, stilted gait, slight to moderate clonic convulsions, diarrhea, piloerection, sunken sides, cyanosis and strenuous respiration. In addition red nasal discharge and vocalis

Gross pathology:

At necropsy in deceased animals the forestomach was tightly filled, the glandular part was empty. The mucosa of glandular stomach and intestine was moderately to severly reddened. The small and large intestine contained yellow to black cloured mucous liquid. Additionally the spleen appeared small in two males. Sacrificed rats showed only thickening of the mucosa of the forestomach.
Microscopical examination revealed slight focal hyperkeratosis of the forestomach. In the glandular stomach focal submucosal edema, slight submucosal and mucosal mixed inflammatory cell infiltration and/or focal acute hemorrhages were found. The spleen exhibited slight to marked extramedullary hematopoiesis. In one intercurrently deceased male the spleen was markedly atrophic.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material, silver(I) oxide, in the rat was found to be greater than 3804 mg/kg body weight. No symbol and risk phrase are required.