Disilver oxide

Endpoint summary

Description of key information

Acute oral toxicity:

A reliable in-vivo acute toxicity study performed via oral route (OECD 401 – GLP) is available, solid powder of Ag₂O (purity 93% of Ag) (Mayr, W et al. 1989). The study concluded that disilver oxide is not acute toxic via oral route. The LD50 was defined by the author at > 3804 mg/kg bw.

Acute inhalation toxicity:

The conduct of an acute inhalation study with disilver oxide is technically not feasible as shown in a feasibility test (Leuschner, 2010). Moreover, the study does not need to be conducted because exposure of humans via inhalation route is not likely to occur. The vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size limits the inhalation exposure.

Acute dermal toxicity:

The physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin (poorly water soluble). Moreover, the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route (LD50 >3804 mg/kg bw) and no systemic effects have been observed in in-vivo studies with dermal exposure (nor skin irritant neither skin sensitizer).

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:

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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

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

Sex:

female

Dose descriptor:

LD50

Effect level:

3 702 mg/kg bw

95% CL:

9.11

Sex:

male

Dose descriptor:

LD50

Effect level:

3 970 mg/kg bw

95% CL:

9.94

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 804 mg/kg bw

Quality of whole database:

good quality of the whole database

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Justification for type of information:

The physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin (poorly water soluble). Moreover, the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route (LD50 >3804 mg/kg bw) and no systemic effects have been observed in in-vivo studies with dermal exposure (nor skin irritant neither skin sensitizer).

Justification for classification or non-classification

A reliable study is available for acute oral toxicity of disilver oxide (rat, LD50 = 3804 mg/kg bw).

For disilver oxide, testing for acute inhalation is technically not feasible based on product characteristics (particles size, density) and coupled with the overall low systemic toxicity of silver substances, acute inhalation toxicity testing is not justified.

Acute dermal toxicity testing is not justified based on low overall systemic toxicity of silver compounds and low to negligible percutaneous absorption potential.

No hazard classification for acute toxicity is required for Ag2O.

Disilver oxide is not toxic after acute exposure via oral route. The inhalation acute toxicity study is technically not feasible and scientifically not necessary. The acute dermal