Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 231-164-3 | CAS number: 7440-56-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- No information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Acute and sub-acute inhalation toxicity of germanium metal powder in rats
- Author:
- Arts JHE, Reuzel PGJ, Falke HE and Beems RB
- Year:
- 1 990
- Bibliographic source:
- Food Chem Toxicol. Vol. 28, No. 8, pp. 571-579
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Germanium
- EC Number:
- 231-164-3
- EC Name:
- Germanium
- Cas Number:
- 7440-56-4
- Molecular formula:
- Ge
- IUPAC Name:
- germanium
- Test material form:
- solid: particulate/powder
- Details on test material:
- Name of test material (as cited in study report): germanium powder
- Physical state: grey powder
- Analytical purity: 99.8%
Constituent 1
Test animals
- 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, FR
- Age at study initiation: 5 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:
- other: no data
- Mass median aerodynamic diameter (MMAD):
- ca. 1.8 - ca. 2.4 µm
- Remarks on MMAD:
- MMAD / GSD: dose 9.9 mg/m3; MMAD: 1.8 , GSD: 1.7
dose 65.1 mg/m3; MMAD: 2.4, GSD: 1.8
dose 251.4 mg/m3; MMAD: 1.8, GSD: 1.8 - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: An aerosol was generated by delivering appropriate quantities of the test material by an AccuRate dry material feeder (series 300, AccuRate, Whitewater, WI, USA) to an atomizer (Institute's design). Next, the aerosol was passed through a cyclone (Institute's design) for separating the larger particles from the aerosol. The aerosol was subsequently diluted with clean air before entering the inhalation chamber.
- Particle size distribution: Mean particle size was between 2.0 and 2.4 µm determined with an 11-stage cascade impactor.
-Exposure chambers. The modified H 1000 multi-tiered inhalation chambers for the sub-acute study (Hazleton Systems Inc., Aberdeen, MD, USA) were constructed of stainless-steel with glass doors on two sides, which allowed observation of the animals during exposure. The normal capacity of the chambers was reduced to an effective exposure volume of about 1 m 3. The rats were housed in a cage unit consisting of 24 individual cages. The chambers were operated at a negative pressure of l~J, mm H20 to prevent leakage of the test material. Ports in the walls allowed sampling of the test atmosphere. During exposure the rats were housed at 18.0 + 0.1 C and at a relative humidity of 55 + 2% . The flow-rate through the chambers was between 25 and 35 m3/hr.
-- Method of holding animals in test chamber: rats were housed in an animal room under conventional conditions, five per cage, separated according to sex, in stainless-steel cages with wiremesh
floors and front
- Temperature, humidity, pressure in air chamber: 22 + 3"C and at a relative humidity of 30-70%, A 12-hr light/dark cycle was
maintained
- Air change rate: changed about ten times per hour.
TEST ATMOSPHERE
- Analytical method used: The actual mass concentration of germanium in the test atmosphere was determined by gravimetry.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- none
- Duration of treatment / exposure:
- 4 wk
- Frequency of treatment:
- 6h/day, 5day/wk for 4 wk
Doses / concentrationsopen allclose all
- Dose / conc.:
- 9.9 mg/m³ air
- Dose / conc.:
- 65.1 mg/m³ air
- Dose / conc.:
- 251.4 mg/m³ air
- No. of animals per sex per dose:
- The control group and top-concentration group consisted of 10 male and 10 female rats each, the other two groups of 5 males and 5 females each.
The control and the high-concentration group were divided into a main group and a satellite group of 5 males and 5 females each. - Control animals:
- yes, concurrent no treatment
- Details on study design:
- none
- Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
-pathology: adrenals, heart, kidneys, liver, spleen, testes, thyroid and lungs with trachea and larynx were weighed. Tissue samples of these organs and of the nose were preserved in a 4% aqueous, neutral phosphate buffered formaldehyde solution. After fixation, the noses were decalcified in nitric acid. Organs and tissues were embedded in paraffin wax. sectioned at 5 ltm and stained with haematoxylin and eosin. Kidneys were also stained with periodic acid Schiff reagent.
Full microscopic examination was carried out on the liver, kidneys, nose, trachea and larynx of all control rats and rats exposed to the high concentration and on the lungs of all animals of the main groups and of the recovery groups
BODY WEIGHT: Yes
HAEMATOLOGY: haematological and biochemical variables were measured in rats in the main groups after 28-30 days, and in rats in the recovery groups after a further 26-31 days of observation. The haematological variables determined at the end of the
exposure period were haemoglobin concentration, packed cell volume, erythrocyte count, and total and differential leucocyte counts. Total and differential leucocyte counts were also determined in rats of the recovery groups.
CLINICAL CHEMISTRY: haematological and biochemical variables were measured in rats in the main groups after 28-30 days, and in rats in the recovery groups after a further 26-31 days of observation.
Biochemical variables were measured in rats of the main groups at the end of treatment (day 28) and in recovery rats after another 33 days of observation.
The following biochemical variables were measured using a Cobas-Bio centrifugal analyser in plasma obtained from heparinized blood samples at the end of the exposure period: albumin, alkaline phosphatase, total bilirubin, calcium, chloride, creatinine*,
;,-glutamyltransferase, glucose*, aspartate aminotransferase (ASAT)*, alanine aminotransferase (ALAT)*, inorganic phosphate, potassium, sodium, total protein and urea*. The parameters marked with an asterisk were also measured in rats in the recovery
groups.
URINALYSIS: Urinalysis was carried out in rats of the main groups at day 28. Volume and density were determined, and protein, glucose, occult blood and ketones were measured using test strips (Boehringer, Mannheim, FRG). The sediment in pooled samples of each group was examined microscopically. Volume and density were also determined at day 26 of the recovery period. - Sacrifice and pathology:
- pathology: At the end of the exposure period (day 30) or the recovery period (day 61) in the sub-acute study, the rats were killed by exsanguination from the abdominal aorta under ether anaesthesia. They were autopsied and examined for gross pathological changes. From rats in the subacute study the adrenals, heart, kidneys, liver, spleen, testes, thyroid and lungs with trachea and larynx were weighed. Tissue samples of these organs and also of the nose were preserved in a 4% aqueous, neutral phosphate buffered formaldehyde solution. After fixation, the noses were decalcified in nitric acid. Organs and tissues were embedded in paraffin wax, sectioned at 5 #m and stained with haematoxylin and eosin. Full microscopic examination was carried out on the liver, kidneys, nose, trachea and larynx of all control rats and rats exposed to the high concentration and on the lungs of all animals of the main groups and of the recovery groups.
- Statistics:
- Body weight (during exposure period): one-way analysis of covariance using pre-exposure (day 0) weights as the covariate; if group means were
significantly different (P < 0.05), individual pairwise comparisons were made using Dunnett's multiple comparison tests.
Body weights (during the recovery period): two-sample t-test.
Organ weights, and haematological, urinalytical and clinicochemical data (obtained during the exposure period): analysed for each sex by one-way analysis of
variance (ANOVA). If significant differences among the means were indicated (P < 0.05), Dunnett's test was performed to determine which exposed groups
differed from the control.
Two-sample t-tests were applied to data obtained during the recovery period instead. In case of group mean differences (P < 0.05), pairwise comparisons between control and exposed groups were determined by Mann-Whitney U-tests. Mann-Whitney U-tests were applied during the recovery period instead. Incidences of histopathological changes were analysed by Fisher's exact probability test. All pairwise comparisons were two tailed. Group mean differences with an associated probability of less than 0.05 were considered to be statistically significant.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- no exposure-related changes in condition, health, behaviour, body weight or mortality
- Mortality:
- no mortality observed
- Description (incidence):
- no exposure-related changes in condition, health, behaviour, body weight or mortality
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- no exposure-related changes in condition, health, behaviour, body weight or mortality
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- At the end of the exposure period, haematological variables were similar in all groups.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In females, blood urea was significantly increased in the high-concentration group and creatinine levels were significantly increased in the mid- and high-concentration groups in comparison with the controls. Males of the high-concentration group showed a significantly decreased fasting blood glucose level and relatively high ASAT and ALAT levels . At the end of the recovery period, there were no treatment-related differences between controls and rats of the high-concentration group, since the decreased ASAT level found in females of the high-concentration group was considered to be the consequence of a very high level in female controls and, therefore, was not considered to be of toxicological relevance.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In females, urine volume and density showed slight, but significant, changes at the end of the exposure period. Urine volume reached a significantly increased level in the high-concentration group, and urine density was significantly decreased in the midconcentration group. The finding of a significantly decreased urine density in males of the low-concentration group was considered to be fortuitous, since other parameters of kidney function were unaffected in these rats and this change was limited to this group only. At the end of the recovery period, urine volume was significantly increased in males of the high-concentration group.
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- There were distinctly concentration-related increases in absolute and relative lung weights in rats of the mid- and high-concentration groups at the end of the exposure period. At the end of the recovery period, lung weights were still significantly increased in rats of the highconcentration group, although the difference was less pronounced than at the end of the exposure period
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Gross examination at autopsy at the end of the exposure period revealed a greyish fur and/or tail in rats of the high-concentration group, and to a lesser extent in rats of the mid-concentration group. The mediastinai lymph nodes were enlarged and/or greyish in several females of the highconcentration group and in a single female of the mid-concentration group. Greyish lungs were observed in all treatment groups. The greyish discoloration was still seen in females of the high--
concentration recovery group, albeit to a lesser degree. - Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examination revealed: accumulation of particulate material in the lungs of all treated groups, accumulation of alveolar macrophages in the mid- and high-concentration groups, and alveolitis mainly in the high-concentration group.
After the 4-wk recovery period, in exposed rats of both sexes, lung weights were still increased and histopathological changes were present, but to a lesser extent than at the end of the exposure period - Histopathological findings: neoplastic:
- not examined
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 9.9 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- histopathology: non-neoplastic
- Dose descriptor:
- LOAEL
- Effect level:
- 65.1 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- histopathology: non-neoplastic
- Dose descriptor:
- NOAEL
- Effect level:
- 254.1 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- histopathology: non-neoplastic
- urinalysis
Target system / organ toxicity
open allclose all
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 65.1 mg/m³ air
- System:
- respiratory system: lower respiratory tract
- Organ:
- lungs
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 65.1 mg/m³ air
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- no
- Dose response relationship:
- no
- Relevant for humans:
- no
Any other information on results incl. tables
none
Applicant's summary and conclusion
- Conclusions:
- 1) Kidney effects:
slight changes in the creatinine content of the blood plasma and a reduced specific gravity of the urine were observed at 65.1 mg / m³. The creatinine content is considered as a sensitive indicator of renal function and the kidney is a major target organ of the toxic effect of germanium, however these slight changes at 65.1 mg/m3 occurred only in one sex and not dose-dependently and were only marginal. Histopathological changes in the kidney did not occur in this study even at higher concentrations. For systemic effects, the concentration of 251.4 represents a NOAEC
2) Lung effects: concerning effects on the lung: the LOAEC for histopathological lung effects is 65.1 mg / m³ and the NOAEC is 9.9 mg / m³.
In the similar study with germanium dioxide (Arts et al., 1994) no histopathological changes were found in the lungs at 309 mg / m³, apart from the relative weight gain). The two studies on germanium powder and germanium dioxide show even greater differences in effect concentrations (germanium powder histopathological effects at 65.1 mg / m³, germanium dioxide no histopathological findings, only weight gain at 309 mg / m³). There is also no supportive information that the endpoint (lung) has human relevance in the low-concentration range (Swennen et al., 2000 -Epidemiological survey of workers exposed to inorganic germanium compounds). - Executive summary:
A study was conducted to determine the effects of sub-acute exposure of the test material on the respiratory system in Wistar rats.
Four groups of five male and five female rats were exposed to 0, 9.9, o5.1 or 251.4 mg/m 3 for 6 hr/day, 5 days/wk for 30 days. Two additional (recovery) groups of five male and five female rats exposed
to 0 or 251.4 mg/m 3 were kept untreated for 31 days after exposure. At the end of the treatment period, fasling blood glucose was decreased in males exposed to the high concentration. In females of this group,
blood creatinine and urea levels, and urine volumes were increased, but urine density was decreased. Increased blood creatinine levels and urine volume and decreased urine density were also observed in
females exposed to 65.1 mg/m 3. The absolute and relative lung weights were increased in rats in the mid and high-concentration groups. Histopathological examination revealed: accumulation of particulate
material in the lungs of all treated groups, accumulation of alveolar macrophages in the mid- and high-concentration groups, and alveolitis mainly in the high-concentration group. After the 4-wk recovery
period, urine volume was increased in males that had been exposed to germanium. In exposed rats of both sexes, lung weights were still increased and histopathological changes were present, but to a lesser extent than at the end of the exposure period. It was concluded by Arts et al 190, that the no-adverse-effect level in the 4-wk study was 9.9 mg/m 3 air.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.