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EC number: 231-146-5 | CAS number: 7440-36-0
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- 0.263 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.6
- Dose descriptor:
- other: HEC-adjusted NOEC - expressed as Sb
- Value:
- 0.155 mg/m³
- AF for differences in duration of exposure:
- 1
- Justification:
- The DNEL derivation is based upon chronic inhalation data and correction for exposure duration is not warranted.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- In as much as antimony is not metabolized, interspecies variability from this source would not be expected. Moreover, the HEC calculations performed account for expected toxicokinetic differences related to pulmonary deposition and clearance, further reducing uncertainty in extrapolation between species. Since the HEC calculations address and correct for a difference assessment factors are designed to address, the application of both would be redundant. Indeed, the HEC correction lowers the expected human NOAEC by a factor of 6.5, more than twice the recommended default assessment factor of 2.5. A minimal Assessment Factor of 1.0 is thus appropriate for HEC corrected local effects in the lung.
The NOAEC (based upon antimony content) remains at 0.155 mg/m3 after consideration of interspecies differences. - AF for intraspecies differences:
- 3
- Justification:
- An additional assessment factor is suggested to account for variability in response between workers. Assessment factors recommended range from 5 in the ECHA R8 to 3 as suggested by ECETOC (2003).
An assessment factor of 3 appears to be applicable to antimony (III) compounds since the pulmonary impacts of concern are local and do not entail metabolism of deposited aerosols (ECETOC, 2010). Hattis and Silver (1994) similarly concluded in an analysis of variability in toxicodynamic responses for local irritants (including pulmonary toxicants) that an assessment factor of 3 was more appropriate. Justification for lower assessment factors was also found in greater homogeneity of worker populations where occupational hygiene regimens and other risk management practices are in place to reduce sources of variability in responses to exposure. For example, routine monitoring of urinary antimony excretion and pulmonary function (by both spirometry and annual radiographic evaluations of the lungs) essentially precludes the development of pneumonitis in workers.
Application of an assessment factor of 3 yields a DNEL estimate of 0.052 mg/m3 based upon antimony content. Note that this DNEL is specific to respirable aerosols of water insoluble antimony compounds. - AF for the quality of the whole database:
- 1
- Justification:
- Three other chronic rat inhalation studies have been conducted and there is reasonable consistency in the inflammatory responses that have been produced (Newton et al., 1994; Groth et al., 1986; Watt, 1983).
- AF for remaining uncertainties:
- 0.2
- Justification:
- The DNEL calculation is based upon experimentally generated respirable aerosols of antimony trioxide with a MMAD of 1.2 µm. Studies of the particle size distribution of occupational environments engaged in the production or packaging of antimony trioxide have determined that the majority of material in these aerosols is far coarser than the respirable aerosols used rodent inhalation studies (Hughson, 2005). This is further problematic in that majority of occupational exposure data routinely collected in occupational environments is indexed to the inhalable fraction of aerosols. Comparison of the DNEL derived for respirable aerosols is thus difficult to relate to present and historical occupational exposure data unless some means of scaling a respirable DNEL to its inhalable equivalent is employed.
Vetter (2018) analysed the particle size distributions observed by Hughson (2005) and concluded that, on a mass comparison basis, the respirable fraction of occupational aerosols is on average 20% of the total aerosol. A DNEL for a respirable aerosol would most likely be congruent with an inhalable limit approximately five-fold larger. Thus, a respirable DNEL of 0.052 mg/m3 would be comparable to an inhalable measurement of 0.263 mg/m3.
The relatively coarse nature of occupational aerosols observed here is typical of that observed for other nonferrous metal sectors and is reflective of factors such as the relatively coarse nature of sulfidic feed materials for smelters and particle agglomeration in occupational aerosols (Spears et al. 1998; Battersby and Boreiko, 2004). Moreover, granulometry studies performed for different antimony compounds indicate that diantimony trioxide has a significantly smaller particle size distribution than materials such as antimony metal powder or diantimony trisulfide.
A scaling factor of 5 thus likely significantly overestimates the respirable fraction of the aerosols that would be associated with antimony metal powder.
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:
- 56.4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: The DNEL derivation for antimony metal is based on state-of-the-art approaches and using substance-specific information.
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 686 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 409 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Selection of the relevant dose-descriptor
In accordance with the diantimony trioxide CSR, the NOAEL of 1686 mg/kg bw/d from a subchronic oral toxicity study in rats is selected as being the most relevant for estimating systemic effects that might be associated with dermal uptake of antimony metal or antimony (III) compounds. In the absence of studies defining systemic toxicity from dermal exposure, route-to-route extrapolation is required.
Modification of the dose descriptor to the correct starting point
Because the route of exposure in animal toxicity studies (oral) is not the same for which extrapolations to humans are to be made (dermal), an evaluation must be undertaken to determine if there is a need to adjust the animal NOAEL starting point. In principle this entails evaluation of whether different rates of uptake are to be expected via the two different exposure routes.
In the specific case of the antimony compounds under consideration, uptake rates after oral or dermal exposure are quite limited and can, for the purpose of DNEL derivation, be presumed to be the same: the absorption of antimony compounds such from the gastrointestinal tract after oral exposure is, based upon studies in rodents, very low and on the order of 0.05 to 0.3%. In vivo dermal uptake studies are lacking, but in vitro percutaneous absorption studies suggest that dermal uptake does not exceed 0.1%. Dermal uptake rates are thus comparable to, or less than, oral uptake rates. Indeed, dermal uptake will likely be lower than oral uptake, building additional conservatism into calculated DNELs that impart an extra margin of safety.
Since the effects of diantimony trioxide are presumed to be mediated by release and subsequent dermal uptake of the Sb (III) oxyanion, read across to other antimony (III) compounds is possible. The NOAEL can thus be adjusted for the antimony content of diantimony trioxide yielding a NOAEL indexed to antimony content of 1409 mg/kg bw/d.
- AF for dose response relationship:
- 1
- Justification:
- Adequate data available
- AF for differences in duration of exposure:
- 2
- Justification:
- Subchronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Correction for differences in metabolic rate (AS)
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining differences (e.g. toxicokinetics/dynamics)
- AF for intraspecies differences:
- 5
- Justification:
- Workers
- AF for the quality of the whole database:
- 1
- Justification:
- No need for a further assessment factor
- AF for remaining uncertainties:
- 1
- Justification:
- Route extrapolation: oral to dermal
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:
- no hazard identified
Additional information - workers
General Population - 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:
- 0.08 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 2
- Dose descriptor:
- other: HEC-adjusted NOEC - expressed as Sb
- Value:
- 0.155 mg/m³
- AF for differences in duration of exposure:
- 1
- Justification:
- The DNEL derivation is based upon chronic inhalation data and correction for exposure duration is not warranted.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- In as much as antimony is not metabolized, interspecies variability from this source would not be expected. Moreover, the HEC calculations performed account for expected toxicokinetic differences related to pulmonary deposition and clearance, further reducing uncertainty in extrapolation between species. Since the HEC calculations address and correct for a difference assessment factors are designed to address, the application of both would be redundant. Indeed, the HEC correction lowers the expected human NOAEC by a factor of 6.5, more than twice the recommended default assessment factor of 2.5. A minimal Assessment Factor of 1.0 is thus appropriate for HEC corrected local effects in the lung.
The NOAEC (based upon antimony content) remains at 0.155 mg/m3 after consideration of interspecies differences. - AF for intraspecies differences:
- 10
- Justification:
- Calculation of the inhalable DNELs for chronic, local effects in consumers or for the general population exposed via the environment requires an Assessment factor of 10 for intra-species variability. Given lack of any indication that children or other vulnerable populations will be more susceptible to local effects from inhalation exposure to antimony metal or antimony (III) compounds and indications that humans are less susceptible to pulmonary impacts than the rodents upon which the DNELs are based, no additional assessment factors are proposed for children.
- AF for the quality of the whole database:
- 1
- Justification:
- Three other chronic rat inhalation studies have been conducted and there is reasonable consistency in the inflammatory responses that have been produced (Newton et al., 1994; Groth et al., 1986; Watt, 1983).
- AF for remaining uncertainties:
- 0.2
- Justification:
- The DNEL calculation is based upon experimentally generated respirable aerosols of antimony trioxide with a MMAD of 1.2 µm. Studies of the particle size distribution of occupational environments engaged in the production or packaging of antimony trioxide have determined that the majority of material in these aerosols is far coarser than the respirable aerosols used rodent inhalation studies (Hughson, 2005). This is further problematic in that majority of occupational exposure data routinely collected in occupational environments is indexed to the inhalable fraction of aerosols. Comparison of the DNEL derived for respirable aerosols is thus difficult to relate to present and historical occupational exposure data unless some means of scaling a respirable DNEL to its inhalable equivalent is employed.
Vetter (2018) analysed the particle size distributions observed by Hughson (2005) and concluded that, on a mass comparison basis, the respirable fraction of occupational aerosols is on average 20% of the total aerosol. A DNEL for a respirable aerosol would most likely be congruent with an inhalable limit approximately five-fold larger. Thus, a respirable DNEL of 0.052 mg/m3 would be comparable to an inhalable measurement of 0.263 mg/m3.
The relatively coarse nature of occupational aerosols observed here is typical of that observed for other nonferrous metal sectors and is reflective of factors such as the relatively coarse nature of sulfidic feed materials for smelters and particle agglomeration in occupational aerosols (Spears et al. 1998; Battersby and Boreiko, 2004). Moreover, granulometry studies performed for different antimony compounds indicate that diantimony trioxide has a significantly smaller particle size distribution than materials such as antimony metal powder or diantimony trisulfide.
A scaling factor of 5 thus likely significantly overestimates the respirable fraction of the aerosols that would be associated with antimony metal powder.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 28 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 686 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 409 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Selection of the relevant dose-descriptor
In accordance with the diantimony trioxide CSR, theNOAEL of 1686 mg/kg bw/dfrom a subchronic oral toxicity study in rats is selected as being the most relevant for estimating systemic effects that might be associated with dermal uptake of antimony metal or antimony (III) compounds. In the absence of studies defining systemic toxicity from dermal exposure, route-to-route extrapolation is required.
Modification of the dose descriptor to the correct starting point
Because the route of exposure in animal toxicity studies (oral) is not the same for which extrapolations to humans are to be made (dermal), an evaluation must be undertaken to determine if there is a need to adjust the animal NOAEL starting point. In principle this entails evaluation of whether different rates of uptake are to be expected via the two different exposure routes.
In the specific case of the antimony compounds under consideration, uptake rates after oral or dermal exposure are quite limited and can, for the purpose of DNEL derivation, be presumed to be the same: the absorption of antimony compounds such from the gastrointestinal tract after oral exposure is, based upon studies in rodents, very low and on the order of 0.05 to 0.3%. In vivo dermal uptake studies are lacking, but in vitro percutaneous absorption studies suggest that dermal uptake does not exceed 0.1%. Dermal uptake rates are thus comparable to, or less than, oral uptake rates. Indeed, dermal uptake will likely be lower than oral uptake, building additional conservatism into calculated DNELs that impart an extra margin of safety.
Since the effects of diantimony trioxide are presumed to be mediated by release and subsequent dermal uptake of the Sb (III) oxyanion, read across to other antimony (III) compounds is possible. The NOAEL can thus be adjusted for the antimony content of diantimony trioxide yielding a NOAEL indexed to antimony content of 1409 mg/kg bw/d.
- AF for dose response relationship:
- 1
- Justification:
- Adequate vdata available
- AF for differences in duration of exposure:
- 2
- Justification:
- Subchronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Correction for differences in metabolic rate (AS)
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining differences (e.g. toxicokinetics/-dynamics)
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- No need for a further assessment factor
- AF for remaining uncertainties:
- 1
- Justification:
- Route extrapolation: oral to dermal
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
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 28 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 686 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 409 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Selection of the relevant dose-descriptor
As noted by the EU RAR (2008) on diantimony trioxide"Two repeated dose oral studies suggest that diantimony trioxide may be toxic to the liver based on a 10% increase in liver weight, supported by significantly elevated ALP and ASAT levels(Sunagawa, 1981; Hext et al., 1999).However, in the absence of histological changes or any clinical signs of antimony intoxication to support that the liver findings are adverse, the findings are regarded as adaptive or incidental to treatment with diantimony trioxide and a NOAEL of 1686 mg/kg bw/d for repeated dose toxicity is derived from these studies.”
In accordance with the EU RAR, the NOAEL of 1686 mg/kg bw/dfrom a subchronic oral toxicity study in rats is used as starting point for DNEL derivation for antimony III compounds. The effects of diantimony trioxide are presumed to be mediated by release and subsequent uptake of the Sb (III) oxyanion, and read across to other antimony (III) compounds releasing such oxyanion, is thus assumed possible. The NOAEL can thus be adjusted for the antimony content of diantimony trioxide yielding a NOAEL indexed to antimony content of 1409 mg/kg bw/d
Modification of the dose descriptor to the correct starting point
Because the route of exposure is identical in animals and in humans, no correction of the starting point is necessary.
- AF for dose response relationship:
- 1
- Justification:
- Adequate data available
- AF for differences in duration of exposure:
- 2
- Justification:
- Subchronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Correction for differences in metabolic rate (AS)
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining differences (e.g. toxicokinetics/-dynamics)
- AF for intraspecies differences:
- 10
- Justification:
- General population
- AF for the quality of the whole database:
- 1
- Justification:
- No need for a further assessment factor
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.2 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 30 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Adequate data available
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Correction for differences in metabolic rate
- AF for other interspecies differences:
- 1
- Justification:
- Remaining differences (e.g. toxicokinetics/-dynamics)
- AF for intraspecies differences:
- 10
- Justification:
- General population
- AF for the quality of the whole database:
- 1
- Justification:
- No need for a further assessment factor
- AF for remaining uncertainties:
- 2
- Justification:
- Subchronic to chronic
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
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.
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