Germanium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

see section 13 in IUCLID for read-across justification report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Germanium dioxide

EC Number:

215-180-8

EC Name:

Germanium dioxide

Cas Number:

1310-53-8

Molecular formula:

GeO2

IUPAC Name:

Germanium dioxide

Test material form:

solid: particulate/powder

Details on test material:

Product Name: Germanium Dioxide
CAS No.: 1310-53-8
Lot No./Batch No.: 1449
Colour / Form: White powder
Molecular formula: GeO2
Molecular weight: 104.59
Purity: 99.999%
Water Solubility: 4.5 g/L @ 25ºC
Storage: Room temperature (15-30°C), cool and dry place
Handling Precautions: As per MSDS (Appendix VIII)
Supplier: Teck Metals Ltd.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Canada, Montreal, Quebec
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Approximately 10 to 11 weeks
- Weight at study initiation: 225.7 - 238.1 g after fasting. The weight variation in animals at the start of the study did not exceed ± 20 percent of the mean weight
- Fasting period before study: yes
- Housing: Female rats were individually housed in separate quarters in solid bottom cages. Individual animals were identified by colour coding, the animal number and group number also appeared on the outside of each cage to preclude mix-up.
The cage cleaning schedule, air filtration and recirculation, health checks and facility maintenance were carried out in accordance with the applicable Nucro-Technics’ Standard Operating Procedures, and such activities were recorded in the animal room
records.
Animals were housed and maintained according to the AAALAC International Guide for the Care and Use of Laboratory Animals, CCAC Guidelines for Care and Use of Experimental Animals and Nucro-Technics’ Standard Operating Procedures.
Animal Selection:
The test population of animals was selected from newly arrived, previously unused rats.
- Diet/ Water: Teklad Certified Rodent Diet and water were offered ad libitum throughout the acclimatization and study periods. All animals used for the Limit Test were fasted over-night. Food but not water was withheld from 4:00 to 4:30 p.m. on the day preceding dosing. Food was returned to the cages approximately 1 hour after dosing.
- Acclimation period:10 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: suspended in 1% methyl cellulose to obtain a concentration of 200.0 mg/mL of test item


MAXIMUM DOSE VOLUME APPLIED: The animals were dosed at 2000 mg/kg (10.0 mL/kg by volume of test item preparation). The individual doses of the test item preparation were individually calculated for each animal based on the body weight of the
animal.


PROCEDURE:
The chemical composition indicated that the test item was likely to be non-toxic, therefore, a decision was made to proceed with the Limit Test. The first animal was dosed at 2000 mg/kg. Since this animal survived, four additional animals were sequentially dosed at 2-day intervals. A total of five animals were tested.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were individually observed once during the first 30 minutes after dosing and periodically during the first 24 hours following dosing (with special attention given during the first 4 hours). Observations once daily were carried out for the remainder of the study. The animals were observed for 14 days after the dosing. Cageside observations were directed towards any changes in the skin and fur; eyes and mucous membranes; respiratory, circulatory, autonomic and central nervous system; and also somatomotor activity and behaviour pattern. Particular attention was directed to any observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and/or coma. All observations were recorded daily for the entire study period using the In-Life Module V.6.1, and the entries were monitored by the Study Director. The body weights of the animals were determined prior to test item administration (i.e., Day 0), on Day 7 and on Day 14. Body weight gains were calculated.
- Necropsy of survivors performed: yes: Gross necropsy was performed on each rat at the end of the 14-day observation period and necropsy included an examination of: external surfaces of the body; all orifices; cranial cavity; external surfaces of the brain and spinal cord; nasal cavity and paranasal sinuses; thoracic, abdominal, and pelvic cavities and viscera.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

For calculation of LD50, results were entered into the Acute Oral Toxicity statistical program, V.1.0.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed post dosing and during the 14-day observation period in any of the animals.

Clinical signs:

other: no specific abnormal clinical signs

Gross pathology:

No gross pathological findings were observed in any of the rats at necropsy.

Any other information on results incl. tables

Mean group body weights are presented in Table 1.

Table 1: Body Weight Summary

Mean Group Body Weight (g) ± S.D. (g); n = 5
initial	day 7	day 14	Mean Group Body Weight Gain (g) ± S.D. (g); n = 5
232.1 ± 4.8	249.4 ± 10.7	264.8 ± 11.9	32.7 ± 10.1

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

the acute oral LD50 in rats of the test item, Germanium Dioxide, was found to be in excess of 2000 mg/kg. Therefore, the test item is considered not to present a significant acute toxic risk if swallowed.

Executive summary:

An Acute Oral Toxicity Study of the test item, Germanium Dioxide, was carried out at Nucro-Technics according to Study Plan No. CNR/253801. The test item was suspended in 1% methyl cellulose at a concentration of 200 mg/mL. The first animal was dosed at 2000 mg/kg at a dose volume of 10.0 mL/kg. Since this first animal survived, four additional animals were dosed at 2-day intervals. A total of 5 female CD (Sprague-Dawley) rats were dosed. All animals received the test item by oral gavage using a feeding cannula inserted into the stomach of the animals. The animals were observed for a 14-day period after dosing. Body weights were recorded prior to test item administration (i.e., Day 0), on Day 7 and prior to necropsy on Day 14. No mortalities were observed post dosing and during the 14-day observation period in any of the animals. All rats gained body weight by Day 7 and at the end of the study. At the end of the 14-day observation period, each animal was sacrificed and submitted for gross necropsy. No gross pathological findings were observed in any of the rats at necropsy. Based on the foregoing results, the acute oral LD50 in rats of the test item, Germanium Dioxide, was found to be in excess of 2000 mg/kg. Therefore, the test item is considered not to present a significant acute toxic risk if swallowed.