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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 233-116-7 | CAS number: 10038-98-9
- 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
Endpoint summary
Administrative data
Description of key information
-28d repeated dose inhalation publication (Arts et al., 1994) (KL=1):
In a guideline study, conducted to GLP, administration of rats to Germanium dioxide by inhalation 6h/d and 5d/wk for 4wk at doses of 0,16, 72, or 309 mg/m3, had adverse effects at the highest dose especially on growth, kidneys and liver. A NOAEL of 72mg/m3 was established.
- Six repeated dose oral toxicity studies were retained for a potential read across approach.
The study reporting the most sensitive (most relevant) data point (Sanai et al., 1991) was used: LOAEL (40w) = 0.0375g/kg BW/d inducing systemic toxicity by weight loss, anemia, and hypo-proteinemia and renal dysfunction (indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance). This effect concentration was converted to a LOAEL for the standard exposure period of 13weeks (0.115g/kg BW/d).
Remark: the lowest LOAEL, which was reported by Yim et al., 1999 (0.01g/kg BW/d), was not retained for further assessment since this effect concentration was solely based on the subcellular effects mitochondrial myopathia.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- 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
- Principles of method if other than guideline:
- In a 40 weeks pair-feeding study the dose dependency of GeO2 induced nephrotoxicity was investigated experimentally in rat groups orally treated with high, moderate or low doses of GeO2 and in an untreated group.
It is not according to OECD guideline 408 for which the normal standard exposure period is of 13weeks - GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Kyushu University Animal Center, Japan
- Age at study initiation: 10 weeks
- Weight at study initiation: 140-170g
- Fasting period before study:no information
- Housing: no information
- Diet (e.g. ad libitum): the amount of food administered was adjusted to the level of the group with minimal ingestion
- Water (e.g. ad libitum): no information
- Acclimation period:no information
ENVIRONMENTAL CONDITIONS
- Temperature (°C):no information
- Humidity (%):no information
- Air changes (per hr):no information
- Photoperiod (hrs dark / hrs light):no information - Route of administration:
- oral: feed
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- daily
- Frequency of treatment:
- 40 weeks
- Remarks:
- Doses / Concentrations:
37.5, 75 or 150 mg/kg/day
Basis:
nominal in diet - No. of animals per sex per dose:
- 37.5 mg/kg/day: n=4
75 mg/kg/day : n=6
150 mg/kg/day : n=5
control group: n=8 - Control animals:
- yes, concurrent no treatment
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no information
BODY WEIGHT: Yes
- Time schedule for examinations: every 4 weeks in all the dose groups
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
In order to maintain an equal calorie and protein intake, the amount of food administered was adjusted to the level of the group with minimal ingestion
HAEMATOLOGY: Yes
hematocrit and blood urea nitrogen (BUN) were examined every 4 weeks in all the groups and also at week 10 in the high dose and control groups
URINALYSIS: Yes
24h urinary protein excretion, creatinin clearance (Ccr), serum total protein, albumin and urinalysis were examined at an early stage (weeks 5-16), an intermediate stage (weeks 17-28) and a late stage (weeks 29-40) of the experiment - Sacrifice and pathology:
HISTOPATHOLOGY: Yes- Statistics:
- Data are expressed as mean +/- SD. Statistical differences were calculated using the one-way analysis of variance among groups and the unpaired t test with Bonferroni's method
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- GeO2-H group: appeared inactive and listless after week 8, 1 rats died from azotemia at week 10
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- GeO2-H group: appeared inactive and listless after week 8, 1 rats died from azotemia at week 10
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- GeO2-H: BW (93±8g): significantly lower than control group ( 185±5g) at week 10 (p<0.001); GeO2-M: BW( 103±12g): sign lower than control group (177±5g) at week 24(p<0.001); GeO2-L: BW(171.4g) sign lower than control group at week 40 (205±6) (p<0.001)
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Hematocrit: GeO2-H: 38.8±2.6%): significantly lower than control group ( 46.3±2%) at week 10 (p<0.001); GeO2-M: slightly but sign reduced at wks 12 and 16and at week 36 in GeO2-L when compared to that in the control group (p<0.05 for both groups)
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal tissue content of Ge were significantly elevated in the GeO2-H
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher dose group of GeO2
- Histopathological findings: neoplastic:
- not examined
- Dose descriptor:
- LOAEL
- Effect level:
- 37.5 mg/kg bw/day (nominal)
- Sex:
- female
- Basis for effect level:
- other: systemic toxicity and dose dependant renal dysfunction
- Critical effects observed:
- not specified
- Conclusions:
- GeO2 induced nephrotoxicity develops dose dependently
- Executive summary:
In a 40-week pair-feeding study, a a dose-dependent effect of GeO2 is demonstrated in rats. This study
also demonstrated that the higher the dose the shorter the exposure duration required to develop the adverse effects. A lowest observed adverse effect dose of 37.5 mg/kg body wt/day of GeO2 or 26 mg/kg body wt/day of Ge was established for decreased growth, anemia, renal dysfunction, and renal tubular degeneration accompanied with elevated urinary and renal germanium.
Reference
none
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 37.5 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- 6 repeated dose oral toxicity studies on GeO2 are available and retained for potential read across approach but the study of Sanai et al (1991) was used since reporting the most sensitive and most relevant data point.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- 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
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- 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
- 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
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: no data
- Remarks on MMAD:
- MMAD / GSD: dose 16 mg/m3 : MMAD: 1.2 µm, GSD: 1.9µm
dose 72mg/m3: MMAD: 1.6 µm, GSD: 1.8µm
dose 309mg/m3: MMAD: 2.0 µm, GSD: 1.7µm - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: equipment according to the ASHRAE standard
- System of generating particulates/aerosols: aerosol was generated by dispersing the test material into the air using equipment according to the ASHRAE standard. Two ASHRAE trays were used, one for generation of the high concentration, the other one for the mid concentration test atmosphere. Both trays were placed in a hood. The aerosols were subsequently diluted with clean air before entering the inhalation chamber. The low concentration test atmosphere was trapped from the inlet tube of the high concentration chamber, using an air mover and dilution before entering the low concentration chamber.
- Particle size distribution: determined with an I l-stage cascade impactor (Institute's design)
- Temperature, humidity, pressure in air chamber: 21-22 C, mean relative humidity of 42-56%, flow rate through chambers was between 17 and 34m3/hr
TEST ATMOSPHERE
- Analytical method used: The actual mass concentration of germanium dioxide 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
- Remarks:
- Doses / Concentrations:
16, 72, 309 mg GeO2/m3
Basis:
nominal conc. - No. of animals per sex per dose:
- 5 rats of each sex per dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- none
- Positive control:
- None
- 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 adrenals, heart, spleen, thyroid, liver, kidneys, nose, lungs and trachea and larynx of all control and high concentration rats, on the kidneys of all animals of the intermediate groups, and on the kidneys and lungs of all animals of the recovery groups.
BODY WEIGHT: Yes
HAEMATOLOGY: haematological variables were measured in all fasted rats towards the end of treatment (day 23) and after a further 28 days of observation in fasted rats of the recovery groups. The variables included haemoglobin concentration, packed cell volume (haematocrit), erythrocyte and thrombocyte count, prothrombin time, and total and differential leucocyte counts.
CLINICAL CHEMISTRY: 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 in plasma obtained from heparinized blood samples at the end of the exposure period (Cobas-Bio centrifugal analyser): albumin, alkaline phosphatase, total bilirubin, calcium, chloride, creatininc, 7-glutamyltransferase, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), inorganic phosphate, potassium, sodium, total protein and urea. Fasting blood glucose was determined towards the end of treatment (day 23) and after a further 28 days of observation in rats fasted for 16 hr and deprived of water for 24 hr. Albumin, total bilirubin, creatinine, ASAT, ALAT, total protein and urea were also measured in rats of the recovery groups.
URINALYSIS: Urinalysis was carried out in all rats on day 23 and in rats of the recovery groups after another 28 days of observation. Rats were deprived
of water for 24 hr and of food during the last 16 hr of this period. Urine was collected during the last 16 hr of the deprivation period. Analyses included protein, glucose, occult blood, ketones, urobilinogen, bilirubin and pH (using test strips: Boehringer), and urinary volume and density. The sediment was also examined microscopically in pooled samples of recovery rats - Sacrifice and pathology:
- 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 adrenals, heart, spleen, thyroid, liver, kidneys, nose, lungs and trachea and larynx of all control and high concentration rats, on the kidneys of all animals of the intermediate groups, and on the kidneys and lungs of all animals 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. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- no exposure-related changes in condition, health, behaviour or mortality
- Mortality:
- no mortality observed
- Description (incidence):
- no exposure-related changes in condition, health, behaviour or mortality
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights were significantly lower in rats of the high concentration group during almost the entire study, recovery period included
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- decreases in haematocrit (females) and thrombocyte count (both sexes), and increases in neutrophil count (both sexes) and white blood cell count (females)
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- urinary volume was elevated, and urine density and pH were lowered in both sexes.
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Relative weights of kidneys, spleen, heart and lungs were higher than in controls.
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- At the end of the treatment period , changes were observed only in rats of the high concentration group
CLINICAL SIGNS AND MORTALITY: no exposure-related changes in condition, health, behaviour or mortality
BODY WEIGHT AND WEIGHT GAIN: decreased body weight
HAEMATOLOGY: decreases in haematocrit (females) and thrombocyte count (both sexes), and increases in neutrophil count (both sexes) and white blood cell count (females)
CLINICAL CHEMISTRY: decreased fasting blood glucose (females), decreased total protein concentration (both sexes),
increased plasma alanine aminotransferase and aspartate aminotransferase activities (females). increased plasma urea nitrogen (males) and increased plasma bilirubin level (females) were observed
URINALYSIS: urinary volume was elevated, and urine density and pH were lowered in both sexes.
ORGAN WEIGHTS: Relative weights of kidneys, spleen, heart and lungs were higher than in controls.
HISTOPATHOLOGY: NON-NEOPLASTIC: Microscopical examination revealed treatment-related changes in the kidneys, consisting of an increased occurrence of proximal as well as distal basophilic tubules in high concentration rats of both sexes, in addition, tubules with hypertrophic
epithelial cells were observed. Increased occurrence of proximal basophilic and tubules with hypertrophic cells concomitant with distal tubular and collecting tubular vacuolation of epithelial cells was still present in the tubular cells of exposed rats at the end of the recovery period. PAS-positive granules were present both at the end of treatment at 309 mg/m3 and after recovery; the granules were larger at the end of the recovery period than just after treatment. No treatment-related histopathological changes were observed in the adrenals, heart, nasal cavity, larynx, trachea, lungs, liver, spleen and thyroid. - Dose descriptor:
- NOAEL
- Effect level:
- 72 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: effects on growth rate, kidney
- Dose descriptor:
- LOAEL
- Effect level:
- 309 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Critical effects observed:
- not specified
- Conclusions:
- Considering the observed effects on growth, kidneys and liver in rats exposed to 309 mg/m3, it is concluded that the no-toxic-effect level in the present study is 72 mg/m3
- 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.
The test material was administered by inhalation 6 h /d and 5 d/wk for 4wk at 0, 16, 72, or 309 mg/m3 to groups of 5 rats/sex/dose. Two additional groups of 5 rats per sex, exposed either to 0 or to 309 mg/m3. were kept for a 33,.day post-exposure period. At the end of the treatment period, changes were observed only in rats of the high concentration group: these changes were decreased body weight gain (both sexes), decreases in haematocrit (females) and thrombocyte count (both sexes), and increases in neutrophil count (both sexes) and white blood cell count (females). On clinical chemistry evaluation, decreased fasting blood glucose (females), decreased total protein concentration (both sexes), increased plasma alanine aminotransferase and aspartate aminotransferase activities (females). increased plasma urea nitrogen (males) and increased plasma bilirubin level (females) were observed. In addition, urinary volume was elevated, and urine density and pH were lowered in both sexes. Relative weights of kidneys, spleen, heart and lungs were higher than in controls. Microscopic examination revealed effects on renal tubular epithelium. Effects on growth, kidneys, and liver were still present at the end of the 33-day recovery period.
It was concluded that the no-adverse-effect-level in the 4-wk study using hexagonal germanium dioxide was 72 mg/m3.
Reference
none
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 72 mg/m³
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The study is GLP compliant and of high quality (klimisch score=1). The other available studies are Klimisch score=4
Additional information
GeCl4is a data-poor substance. However, a relatively large amount of toxicity data is available for GeO2. Since GeCl4readily hydrolyses (even with the humidity in the air) to form GeO2and HCl, the applicability of using GeO2toxicity data to read across to GeCl4was evaluated.
In order to make a straightforward comparison possible between available data on GeCl4 and GeO2,the effect concentrations reported for GeCl4were converted to their GeO2equivalents (i. e. effects concentrations are corrected for molecular weight).
Repeated dose toxicity: inhalation:
A chemical is classified as a STOT RE (inhalation) cat 2 if the effect concentration < 600mg/m³ (for a 28-day toxicity study). Based on the repeated dose inhalation study (Arts et al., 1994), GeO2can be categorized as a STOT RE cat 2. However, this discussion on STOT RE classification is not relevant for GeCl4since the LOAEL given for GeO2, is too close to the acute lethal effect concentrations of GeCl4 (Terrill et al., 1990) expressed as normalized equivalents of GeO2 (see table below). This implies that the animals will have died before any STOT effect would be able to occur.
Repeated dose toxicity: oral:
A compound is considered to be a STOT RE (oral) cat 2 if 10 < effect conc < 100mg/kg BW/d. However these references values refer to effects seen in a standard 90-day toxicity study. Similar to Haber’s rule for inhalation (effective dose is directly proportional to exposure concentration and the duration of exposure), the LOAEL (Sanai et al., 1991) based on 40w experiment was converted to the 13w standard (LOAEL = 115mg/kg BW/d), resulting in no STOT RE classification. Remark: the lowest LOAEL, which was reported by Yim et al., 1999 (0.01g/kg BW/d), was not retained for further assessment since this effect concentration was solely based on the subcellular effects mitochondrial myopathia.
This discussion on classification, however, is not relevant for GeCl4, since the LOAEL of GeO2is higher than the extrapolated acute lethal concentration (expressed as normalized equivalent GeO2-see table below).
Table: Overview of available acute toxicity data on GeCl4 and GeO2 and overview of the conversion of GeCl4 effect data to GeO2 equivalents(based on molecular weight).
* route to route extrapolation: 3,316mg/L x 0,8L/min/kg x 60min ==> LD100 = 159mg/kg (allometric scaling principle - Echa guidance R8); **Classification/effects not relevant for GeCl4: LOAEL too close to acute lethal conc; *** Classification/effects not relevant for GeCl4: LOAEL >acute lethal conc
|
|
|
|
|
|
|
||||
|
Reference |
Klimisch |
Exposure range |
Duration |
Effectconc |
Qualifier |
Normalization to equivalent GeO2 Exposure range Effect |
|||
GeCl4 |
acute inhal (Terrill et al., 1990, Hazleton laboratories) |
2 |
3.316 |
/ |
g/m3 |
1h |
3.316g/m3 |
EC100 |
1.632 / |
1.632g/m3
|
data extrapolated to 4h standard |
|
|
|
|
4h |
0.829g/m3 |
EC100 |
|
0.408g/m3 |
|
route-to-route extrapolation* |
|
|
|
|
|
0.159g/kg |
ED100 |
|
0.078g/kg |
|
|
|
|
|
|
|
|
|
|
|
|
GeO2 |
acute inhal (Arts et al., 1994) |
2 |
3.1 |
/ |
g/m3 |
4h |
>3.1g/m3 |
LC50 |
lethal conc GeO2 > GeCl4 lethal conc GeO2 > GeCl4
STOT RE 2 **
no STOT RE class ***
|
|
|
1.42 |
/ |
g/m3 |
4h |
>1.42g/m3 |
LC50 |
||||
acute oral (Faroon et al., 2007) |
3 |
/ |
/ |
g/kg |
NI |
3.7g/kg |
LD50 |
|||
acute oral (Faroon et al. , 2007) |
3 |
/ |
/ |
g/kg |
NI |
6.3g/kg |
LD50 |
|||
|
|
|
|
|
|
|
|
|||
repeated dose - inhal (Arts et al., 1994) |
1 |
0.016 |
0.309 |
g/m3/d |
6h/d ; 4w |
0.072g/m3/d 0.309g/m3/d |
NOAEL LOAEL |
|||
repeated dose - oral (Sanai et al., 1991) |
2 |
0.0375 |
0.15 |
g/kg/d |
40w |
0.0375g/kg/d
|
LOAEL |
|||
data extrapolated to 13w (90d) standard |
|
|
|
|
13w |
0.1154g/kg/d |
LOAEL |
|||
repeated dose - oral (Higuchi et al., 1989) |
2 |
0.1 |
0.15 |
g/kg/d |
4m |
0.1g/kg/d |
LOAEL |
|||
repeated dose - oral (Higuchi et al., 1991) |
2 |
/ |
0.1 |
g/kg/d |
up to 8m |
0.1g/kg/d |
LOAEL |
|||
repeated dose - oral (Nakano., 1987) |
3 |
0.1 |
0.5 |
g/kg/d |
9m
|
0.1 g/kg/d |
LOAEL |
|||
repeated dose - oral (Yim et al., 1999) |
2 |
0.005 |
0.15 |
g/kg/d |
4,8,16,24w |
0.01 g/kg/d |
LOAEL |
|||
repeated dose - oral (Matsumuro et al., 1993) |
2 |
/ |
0.1 |
g/kg/d |
up to 8m |
0.1g/kg/d |
LOAEL |
|||
|
|
|
|
|
|
|
|
Valid to read across based on GeO2data?
Based on this exercise it was envisaged to evaluate whether a read across from GeO2-induced systemic effects would be valid for GeCl4.The answer to this question is clearly negative. Corrosive effects of GeCl4 (attributable to hydrolysis with formation of HCl ) will occur at much lower concentration and before other potential GeO2-induced effects can be induced.
Because of the high corrosive potential of GeCl4at relatively low concentrations, it was concluded that read across based of GeO2toxicity data is not relevant: Severe corrosive effects of GeCl4will occur before systemic effects triggered by GeO2can be initiated.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
study reporting the most sensitive and most relevant data point and klimisch score 2
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
only one study availabe which is klimisch score=1
Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys
Repeated dose toxicity: inhalation - systemic effects (target organ) urogenital: kidneys
Justification for classification or non-classification
Repeated dose toxicity: inhalation:
A chemical is classified as a STOT RE (inhalation) cat 2 if the effect concentration < 600mg/m³ (for a 28-day toxicity study). Based on the repeated dose inhalation study (Arts et al., 1994), GeO2 can be categorized as a STOT RE cat 2. This discussion, however, on STOT RE classification is not relevant for GeCl4 since the LOAEL given for GeO2, is too close to the acute lethal effect concentrations (i.e. animals will have died before any STOT effect would be able to occur).
Repeated dose toxicity: oral:
A compound is considered to be a STOT RE (oral) cat 2 if 10 < effect conc < 100mg/kg BW/d. However these references values refer to effects seen in a standard 90-day toxicity study. Similar to Haber’s rule for inhalation (effective dose is directly proportional to exposure concentration and the duration of exposure), the LOAEL (Sanai et al., 1991) based on 40w experiment was converted to the 13w standard (LOAEL = 115mg/kg BW/d), resulting in no STOT RE classification. However, this discussion on classification is not relevant for GeCl4, since the LOAEL of GeO2is higher than the acute lethal concentration (normalized equivalent GeO2).
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.