Germanium

Endpoint summary

Description of key information

For assessing the acute oral toxicity of Ge, reference has been made to toxicity data obtained by standard acute oral toxicity testing on GeO2. Bio-elution data in artificial gastric body fluids demonstrate that the solubility of Ge in Ge metal powder is lower than the solubility of Ge from GeO2.

Assessment of the acute oral toxicity of germanium dioxide in Arulnesan et al 2012:

An Acute Oral Toxicity Study of Germanium Dioxide, was carried out according to OECD 425. 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.

Assessment of the acute inhalation toxicity of germanium in Arts et al 1990:

The acute (4 -hour) inhalation toxicity of germanium powder was studied by exposing total-body group of rats, consisting of five male and five female rats, to a test atmosphere containing germanium powder at a concentration of 3.86 or 5.34 g/m3 in air respectively for one single time for a period of 4 hours. It was concluded that the 4 hours LC50 value of germanium powder was higher than 5.34 g/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF-reared, Wistar derived rats (strain code Bor:WISW) delivered by Winkelmann, Versuchstierzucht GmbH & Co KG, Borchen, FRG
- Age at study initiation: no information
- Weight at study initiation: mean body weight: M: 272g, F: 198g
- Housing: individually in wire-mesh stainless steel cages
- Diet : cereal based Institute's stock diet ad libitum
- Water : bottled tap water ad libitum
- Acclimation period: acclimatized for at least 16 days in a cleaned and desinfected animal room in the inhalation facilities

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 ± 0.90C
- Humidity (%): between 29 and 46 (average 37)
- Air changes (per hr): 30 to 44
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

not specified

Mass median aerodynamic diameter (MMAD):

ca. 2.3 - ca. 2.5 µm

Geometric standard deviation (GSD):

ca. 1.4 - ca. 1.5

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION:
Before the generation of the test atmosphere, the test material was dried in an oven (settings 2.5 hours, 15O0C). Thereafter the test material was ground using a blender. An aerosol was generated by delivering appropriate quantities of the test material to an atomizer. Next the aerosol was passed through a cyclone placed close to the bottom of the chamber for separating the larger particles from the aerosol. The aerosol was subsequently diluted with clean air before entering the inhalation chamber.
TEST ATMOSPHERE
The actual mass concentration of germanium powder in the test atmosphere was determined at least two times each hour by gravimetry. Measured test atmosphere samples were drawn through fiber glass filters (Sartorius). The weights of the deposits on the filters were obtained by weighing the filters before and after sampling using a micro balance. The nominal concentration was determined by dividing the total amount of test material used by the total volume of air passed through the inhalation chamber. The particle size distribution of the test material in the test atmosphere was determined once in a sample taken from the test atmosphere in the chamber using an 11-stage cascade impactor.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

3.86 g/m3: first group exposed
5.34 g/m3: second group exposed

No. of animals per sex per dose:

per exposed group : 5 rats per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 times (prior to exposure, at days 7 and days 14)
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,histopathology

Statistics:

no statistics reported

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 340 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

One male animal died shortly after exposure to 3.86 g/m3, one female animal died shortly after exposure to 5.34 g/m3.

Clinical signs:

other: During the first hour of exposure the animals were restless. One male animal exposed to 3.86 g/m3 showed mouth breathing. During the rest of the exposure period observations were impossible due to very high dust concentrations which did not allow any view

Body weight:

One male animal exposed to 5.34 g/m3 showed a slight weight loss seven days after exposure, whereas weight gain was observed at the end of the
14-day observation period. Body weights of the other animals were not affected by exposure.

Gross pathology:

Gross examination at autopsy revealed red spotted lungs in most animals exposed to 3.86 g/m3
In most animals autopsied after exposure to 5.34 g/m3, lungs showed grey-white, occasionally red, coloured spots or were palely discoloured with dark coloured spots.

Other findings:

none

none

Interpretation of results:

GHS criteria not met

Conclusions:

4 hours LC50 value of germanium powder was higher than 5.34 g/m3

Executive summary:

The acute (4 -hour) inhalation toxicity of germanium powder was studied by exposing total-body group of rats, consisting of five male and five female rats , to a test atmosphere containing germanium powder at a concentration of 3.86 or 5.34 g/m3 in air respectively for one single time for a period of 4 hours.

It was concluded that the 4 hours LC50 value of germanium powder was higher than 5.34 g/m3

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 340 mg/m³ air

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)

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on read across from the results of the available and reliable acute oral rat study with germanium dioxide, germanium does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).

Based on the results of the available acute inhalation rat study, germanium does not require classification for acute inhalation toxicity according to EU CLP criteria (EC 1272/2008).

There are no available data on which to evaluate acute dermal toxicity. However, acute dermal toxicity can be considered to be low in view of the poor absorption by this route and the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route. Therefore, germanium does not require classification for acute dermal toxicity according to EU CLP criteria (EC 1272/2008)

No clear evidence of specific target organ toxicity was noted. As such, classification for STOT-SE is not considered appropriate.