Germanium dioxide

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Acute and subacute inhalation toxicity of germanium dioxide in rats.

Author:

Arts JH, Til HP, Kuper CF, de Neve R and Swennen B

Year:

1994

Bibliographic source:

Food Chem Toxicol. 32(11):1037-1046

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1990

Materials and methods

Test guideline

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

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:

Name of test material (as cited in study report): germanium dioxide (GeO2)
- Physical state: hexagonal and amorphous quality, white powder
- Analytical purity: 99% or more
- Impurities (identity and concentrations): hexagonal: total metal impurity concentration less than 10ppm; Cl<500ppm; amorphous: NH3, Cl<0.2%, Fe<5ppm, Cu, Ni, Cr, Mn, Co<1ppm

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan CPB (Austerlitz, the Netherlands)
- Age at study initiation: 10 weeks
- Weight at study initiation: mean body weight: M: 197g, F: 138g
- Housing: individually in wire-mesh stainless steel cages
- Diet : cereal based Institute's stock diet ad libitum
- Water : ad libitum
- Acclimation period: acclimatized to the laboratory conditions in the inhalation facilities until the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

not specified

Mass median aerodynamic diameter (MMAD):

ca. 1.7 - ca. 2 µm

Geometric standard deviation (GSD):

ca. 1.5 - ca. 1.6

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION:
The hexagonal/ amorphous germanium dioxide test atmosphere was generated by continuously delivering controlled quantities of the test material by an AccuRate dry material feeder to an air driven jet mill. A vibration apparatus was placed at the outlet of the AccuRate feeder in order to
prevent compaction of the test material. The resulting aerosol was mixed with the supply air and transported to the inlet of the exposure chamber.
TEST ATMOSPHERE
The actual concentration of hexagonal/amorphous germanium dioxide 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 13430-44-S). The weights of the deposits on the filters were obtained by weighing the filters before and after sampling using a microbalance (Mettler AE163). The nominal concentration was determined by
dividing the amount used per hour by the AccuRate feeder by the total volume of air passed through the inhalation chamber.
The particle size distribution of the test material 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:

3.10g/m3 (amorphous GeO2); 1.42g/m3 (hexagonal)

No. of animals per sex per dose:

one group of 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

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3 100 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: amorphous

Remarks:

3100 mg/m3 is the maximum attainable concentration

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 420 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: hexagonal

Remarks:

1420 mg/m3 is the maximum attainable concentration

Mortality:

none of the rats died

Clinical signs:

other: Rats were restless at the start of exposure (hexagonal grade) or during the entire exposure period (amorphous grade). Swallowing was observed soon after the start of exposure (amorphous). Piloerection started about 30-40min after the start of exposure an

Body weight:

body weights were reduced 7 days after exposure to amorphous GeO2; body weights were generally unaffected by exposure to the hexagonal grade

Gross pathology:

greyish and spotted lungs after exposure to hexagonal GeO2
microscopic examination: (multi)focal accumulation of alveolar macrophages was observed in almost all rats, whereas (multi)focal increased septal cellularity was observed in 30-50% of the rats. One male rat exposed to amorphous GeO2 showed multifocal alveolar bronchiolization; focal pneumonitis was observed in 2 male rats exposed to hexagonal GeO2

Other findings:

none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:

other: study combined with Dustiness test indicates GHS criteria are not met for classification

Remarks:

The non-classification for acute toxicity by inhalation route, is supported by a dustiness test on dust fractions of 1g GeO2. It can be concluded from this dustiness test that the tested sample is showing little dustiness with very small dustiness values for the alveolar fraction. Therefore it can be concluded that the LC 50 > 3.10 g/m3 ir > 1.42 g/m3 (maximum attainable concentration) implicates LC 50 > 5 g/m3 indicating GHS criteria not met for classificaiton (reference: Final - Report on the determination of the dust generation tendency (“dustiness”) of germanium dioxide - Report no. APS 2 00 007, 2017, DMT GmbH & Co. KG

Conclusions:

4 hours LC50 value of amorphous germanium dioxide was higher than 3.10g/m3
4 hours LC50 value of hexagonal germanium dioxide was higher than 1.42g/m3

Executive summary:

The acute (4 -hour) inhalation toxicity of amorphous and hexagonal germanium dioxide was studied by exposing total-body one group of rats, consisting of five male and five female rats , to a test atmosphere containing amorphous germanium dioxide and hegonal germanium dioxide at a concentration of 3.10 and 1.42 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 amorphous germanium dioxide was higher than 3.10g/m3 and that the 4 hours LC50 value of hexagonal germanium dioxide was higher than 1.42g/m3