Registration Dossier
Registration Dossier
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: 233-043-0 | CAS number: 10025-82-8
- 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

Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 6.3 µg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 10
- Dose descriptor:
- other: corrected NOAEC
- Value:
- 63 µg/m³
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation route
- AF for other interspecies differences:
- 1
- Justification:
- Rats considered more sensitive than humans for inhaled inorganic particles
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.12 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 70 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - workers
Derivation
of respirable DNEL (local effects, long term, inhalation route)
1) Define the most relevant dose descriptor:
The most relevant dose descriptor has been derived from a 3-Month whole body Inhalation Toxicity Study of indium oxide in Fischer 344 rats (Nagano et al 2011). The NOAEL was 0.1 mg/m³ In2O3.
2) Derive a corrected NOAEL, using the Multiple path particle deposition (MPPD) model
The European Chemical Agency guidance (described in ‘Chapter R.8: characterization of dose [concentration]-response for human health) on the DNEL/DMEL derivation for respiratory effects starting from animal inhalation studies does not address the issue of particle size differences between animals and workers or differences in dosimetry (ECHA, 2008). As a result, these DNEL/DMELs based on animal aerosols will not be directly comparable to the workplace exposures and may overestimate the risks associated with the coarser and more heterogeneous workplace indium exposures. Therefore, we can apply an approach to calculate the equivalent human concentrations (EHC) to the animal aerosols for local respiratory effects after inhalation (Oller and Oberdörster, 2010). The daily deposited dose can be calculated by using this MPPD model (Asgharian et al. 2009) and applying either rat or human parameters. The equivalent deposited dose per unit of surface area in the lungs of humans and rats are calculated. In practice this can be done by
· Using the PSD of the rat aerosol to calculate daily deposited doses in rats and in humans. The MPPD model calculates the deposition fraction for both rat and human respiratory tract allowing for variations of PSD, breathing parameters, exposure parameters. With the particle deposition fraction, the daily deposited doses in rats and humans can be calculated by applying the formula:
a = deposition fraction x concentration (mg/m3) x tidal volume (m3) x length of exposure (min) x respiratory frequency (min-1)
· Calculating the ratio of deposited doses (rat/human)
· Multiplying this ratio by the rat NOAEC to get the respirable EHC corresponding to the rat NOAEC
The MPPD model was applied under the assumptions shown in Table below
Table-Assumptions used in applying the multiple path particle deposition model
Parameter |
Rat |
Human- Adult Worker |
Human-Adult General Population |
Particle Density (g/cm3) |
|
|
|
Indium oxide |
7.16 |
7.16 |
7.16 |
|
|
|
|
MPPD Models (version 2.1.1) |
asymmetric multiple path |
5-Lobar Yeh-Schum |
5-Lobar Yeh-Schum |
|
|
|
|
Breathing Parameters |
|
|
|
Type |
nasal |
oro-nasal normal augmenter |
nasal |
Functional Respiratory Capacity (cm3) |
4.0 |
3,300 |
3,300 |
Upper Respiratory Tract Volume (cm3) |
0.42 |
50 |
50 |
Respiratory Frequency (min-1) |
102 |
20 |
12 |
Tidal Volume (cm3) |
2.1 |
1,024 |
625 |
Inspiration fraction |
0.5, no pause |
0.5, no pause |
0.5, no pause |
Inhalability adjustment |
yes |
yes |
yes |
|
|
|
|
Surface Area at FRC(a) |
|
|
|
Tracheo-bronchiolar (cm2) |
24.2 |
4,149 |
4,149 |
Alveolar (cm2) |
2,422 |
634,620 |
634,620 |
|
|
|
|
Exposure Parameters |
|
|
|
Daily (hr/day) |
6 |
8 |
24 |
|
|
|
|
(a) Functional respiratory capacity (cm3)
Calculation of the ratio of deposited doses in the pulmonary (alveolar) region of the respiratory tract (rat/human):
Used parameters in MPPD model:
Density 7.16 g/cm3
MMAD = 2.1 µm
GSD = 1.7µm
Aerosol concentration: 0.1 mg/m3
Daily deposited dose (Alveolar)
= deposition fraction x concentration (mg/m3) x tidal volume (m3) x length of exposure (min) x respiratory frequency (min-1)
• Deposition fraction rat: alveolar: 0.042
• Deposition fraction human (workers): alveolar: 0.109
• Daily deposited dose rat (6 h) =
0.042 x 0.1 x 2.1 10-6 x 360 x 102 = 323.8704 10-6mg
• Daily deposited dose human (workers) (8 h) =
0.109 x 0.1 x 1024 10-6x 480 x 20 = 107151.36 10-6mg
• Daily deposited dose in rats per surface area: 0.13 ng/cm2 (SArat= 2422)
• Daily deposited dose in humans per surface area: 0.17 ng/cm2 (SAhuman= 634620)
• Ratio of deposited doses rat/human: 0.76
Multiplying this ratio by the rat NOAEC to get the respirable EHC corresponding to the rat NOAEC:
0.1 mg In2O3/m3* 0,76 = 0,076 mg In2O3/m3* 0,83 = 63 µg In/m3
3) Assessment factors: animal to human assessment factors for local respiratory effects after inhalation
The corrected NOAEL has to be corrected by assessment factors to account for the uncertainties of the database that led to the establishment of the DNEL.
The DNEL is calculated by dividing the corrected NOAEL of 63 µg/m3 (=calculated EHC corresponding to the rat NOAEC), see above) by an assessment factor.
|
Comment |
ECHA default AF |
Applied |
Justification |
Starting point 63 µg/m3 |
Corrected NOAEL from 90days repeated dose inhalation toxicity study in rats |
|
|
|
AF |
Interspecies difference, allometric scaling rats - human |
1 (local) |
1 |
allometric scaling is usually not applied in the derivation of the inhalation DNEL. In that case, differences in the allometry are assumed to be compensated by differences in the respiration rate. |
|
Interspecies difference - remaining differences |
2.5 |
1 |
Rats considered more sensitive than humans for inhaled inorganic particles |
|
Intraspecies variation, worker |
5 |
5 |
|
|
Exposure duration (90d to 2y) |
2 |
2 |
subchronic to chronic |
|
Dose-response |
1 |
1 |
|
|
Quality of whole database |
1 |
1 |
|
DNEL expressed as In |
|
|
6.3 µg/m3 |
|
Interspecies difference- allometric scaling is usually not applied in the derivation of the inhalation DNEL. In that case, differences in the allometry are assumed to be compensated by differences in the respiration rate. (ECHA practical Guide 14, 2012). Allometric scaling in order to adjust for physiologically-based species differences is widely accepted for systemic toxicity after oral or dermal administration. However, it does not apply to local or systemic effects after inhalation because the inhalation rate in humans is 4-fold lower compared to rats according to the slower metabolic rate and thereby the allometric species difference is already implicitly taken into account (ECETOC 2010 TR No.110).
Interspecies difference - remaining differences:
- Interspecies Toxicokinetic differences. Toxicokinetic differences between rats and humans are mostly addressed by using the MPPD (Multiple Path Particle Deposition) model to calculate EHCs resulting in equivalent deposited (or retained doses) per unit of surface area of the lung. No additional factor for toxicokinetic differences needs to be applied.
- Interspecies Toxicodynamic differences. For respiratory (local) toxicity effects after inhalation of particles of most metal-containing substances in the respirable range, 1-5 μm diameter, rats seem to be more susceptible to toxicity effects than primates or humans (Oberdörster, 1995; Mauderly, 1997; ILSI, 2000; Nikula et al., 2001; Greim and Ziegler-Skylakakis, 2007). Further, given that any toxicity to the lungs is anticipated to be a local effect and (as an underlying paradigm) that rats and humans are even equally susceptible then, therefore the toxicodynamic component of the interspecies AF for indium oxide can be set to 1.
Exposure
duration (subchronic to chronic)
REACH
Technical Guidance document (TGD) Chapter
R.8 - ECHA -indicates
an assessment factor of 2 needs to be applied for extrapolation from
subchronic to chronic duration. Substance-specific
information does not indicate the default value could be modified
upwards or downwards
In conclusion, a DNEL (local) of 6.3µg In/m3) has been derived for the respirable fraction against which to judge the adequacy of workplace risk management measures (RMM) to control airborne exposure to indium compounds
Although there are several available studies on the exposure of workers to ITO, the data are not of EU origin and there is sufficient uncertainty in the data to suggest that they are not a suitable basis for deriving a DNEL or OEL for ITO. However, they could be used as supplementary information for setting e.g. recommended engineering controls or RPE at plant sites. Very limited data are available on IO in humans.
It is therefore considered that the high quality animal data should be used to set a DNEL for IO. It is recognised that the resulting inhalation DNEL will be conservative.
It is recommended that in cases of exposure to ITO or in mixed ITO/In compounds exposure, a specific ITO DNEL should be considered by the industry due to the significant difference in the level of toxicity observed with ITO in comparison to IO in animal studies and the confirmation from ITO production sites that a serious and potentially fatal inhalation disease has been observed in the workers.
Regarding the difference observed in toxicity of ITO and other in compounds, it appears that the sintering process by which SnO2 molecules are introduced into the crystal structure of In2O3, is critical for the unique toxicological properties of ITO (Lison et al 2009)
Derivation of dermal DNEL (systemic effects, long term, dermal route)
Oral systemic endpoint is used for the derivation of Dermal DNEL (systemic effects) by route to route extrapolation:
The study of Ungvary et al (2000) is used for the derivation of dermal DNEL, systemic effects, long term for the workers.
Daily indium chloride doses of control (0), 50, 100, 200, or 400 mg/kg were administered orally to Sprague-Dawley rats by gavage, on d 6-15 of gestation, and daily metal doses of control (0), 50, 100, or 200 mg/kg were administered to New Zealand rabbits on d 6-20 of gestation. Further groups of pregnant rats were treated with control (0) or 400 mg/kg indium chloride orally on one of d 8, 9, 10, 11, 12, 13, 14, or 15 of gestation. The dams and fetuses were examined on d 21 (rats) and 30 (rabbits) of gestation, using standard teratological methods (OECD 414 - Prenatal Developmental Toxicity).
The maternal and fetal toxicity NOAEL for rats and rabbits was 50 mg/kg bw. The LOAEL (maternal and fetal toxicity) in rats was 100 mg/kg and in rabbits (maternal and fetal) was 200 mg/kg
NOAEL= 50mg/kg/bw day
For the dermal systemic DNEL: (route to route extrapolation: oral to dermal):
Dermal NOAEL= oral NOAEL * (exp cond rat/exp cond human workers)* (ABS oral rat/ABS dermal rat) * ABS dermal rat/ABS dermal human
= 50mg/kg/bw day * (7days/5days) * 1/1
= 70mg/kg/bw day
DNEL derivation and applying AF
|
Value |
Comment |
Starting point |
70mg/kgbw/ day
|
NOAEL from an oral 21days developmental tox study in rats (Ungvary et al 2000) converted to corrected dermal NOAEL |
Assessment factor |
4 |
Interspecies difference, allometric scaling rat - human |
|
2.5 |
Interspecies difference - remaining differences |
|
5 |
Intraspecies variation, workers |
|
6 |
Exposure duration (subacute to chronic) |
|
1 |
Dose-response |
|
1 |
Quality of whole database |
DNEL |
0.23 mg InCl3/kgbw/ day = 0.12 mg In/kgbw/day |
|
The derived dermal DNEL (systemic effects, long term) would only be applicable if the indium metal/compound was presented in an acidic or alkaline solution to the skin. Otherwise, in neutral conditions, no hazard would be identified as indium metal/compound is known to precipitate at neutral pH (ECTX 2014)
In cases where the metal/compound is solubilised, a dermal penetration value of 5% is chosen as a worst case as it is considered that the potential for a compound/metal to penetrate skin is rarely (if ever) higher than oral absorption.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
- Explanation for the modification of the dose descriptor starting point:
All uses ends up incorporated in articles with unintended release
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
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.
