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EC number: 202-619-3 | CAS number: 97-93-8
- 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:
- DNEL (Derived No Effect Level)
- Value:
- 3.59 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 27
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 33.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- LOAECcorr = LOAEC * (6.7 m³ (8h)/10 m³ (8h)) = 50 * 0.67 = 33.5 mg/m³
- AF for dose response relationship:
- 3
- Justification:
- Based on a LOAEC (ECHA Chapter R8, ECETOC (2010))
- AF for differences in duration of exposure:
- 1
- Justification:
- Adequate duration of exposure. No scaling necessary.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is not necessary as the mode of action is a portal-of-entry effect (overload) and adjustment for inhalatory volume has been carried out to modify the starting point; scientific evidence suggests rats are at greater susceptibility to overload than humans (Oberdorster, 1995; Pauluhn, 2010), therefore a factor of 2.5 for remaining effects was not considered appropriate.
- AF for other interspecies differences:
- 1
- AF for intraspecies differences:
- 3
- Justification:
- Eurometaux has adopted the ECETOC (2010) approach for intraspecies and interspecies assessment factors.
- AF for the quality of the whole database:
- 3
- Justification:
- The histopathological effects assessed are not the most sensitive endpoint. However, the relevance of the critical effect to the human lung is unclear as the effects are consistent with a rat overload response. Evidence suggests a greater susceptibility of rats to overload and the associated increase in lung retention and chronic pulmonary inflammation. Uncertainties exist with respect to particle dosimetry and toxicokinetics. As: (a) read-across has been used (based on the similar physicochemical properties of aluminium oxide (coat) and aluminium hydroxide) and the assumption that the aluminium component is the active moiety with respect to longer-term pulmonary effects when this substance is retained in the lung; (b) the limitations of the key study (lack of more sensitive endpoints); and (c) the limited nature of the existing database relevant for this substance (cross-sectional human studies of exposure to bauxite are available), overall the confidence in the database is moderate and a database adequacy factor of 3 is considered appropriate.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Additional information - workers
As described under 5 Environmental fate and pathways the test item decomposes rapidly with air or water. Thus no toxicological data can be found for the test item.
The resulting product is aluminium hydroxide. Therefore the toxicological data of aluminium hydroxide are given and discussed in the following.
Aluminium hydroxide
Assuming that the aluminium component is the active moiety with respect to any chemical–specific, long-term pulmonary effects on repeated exposure to aluminium hydroxide, read-across of the aluminium powder results from Gross et al. (1973) was used to derive a DNEL for aluminium hydroxide.
Key Study: Gross et al. (1973)
Dose Descriptor: 50 mg/m³, LOAEC
Test Animal: Rat
Test substance: aluminium powders - mean particle size diameters: 2.49, 2.22 and 4.85 μm
Doses used: 0, 15, 30, 50, 100 mg/m³
Duration of exposure in the experiment: 6 (for 50 and 100 mg/m³) and 12 months; 6 hours per day, 5 days per week; follow-up to 30 months.
Effects observed: lipid pneumonitis, granulomatous inflammation; collagenous scars but fibrosis was not evident.
Mode of Action: Threshold (see Aluminium powder)
Calculation of DNEL according to the ECHA guidance (ECHA guidance, Chapter R8, p27):
Modification of starting point to correct for differences in inhalation volume between the rats and lightly active humans –
LOAEC(corrected) = LOAEC * 6.7m³ (8h)/10m³ (8h)
= 50 * 6.7/10
= 33.5 mg/m³; corrected starting point
Assessment factors:
Interspecies: 1
Allometric scaling is not necessary as the mode of action is a portal-of-entry effect (overload) and adjustment for inhalatory volume has been carried out to modify the starting point; scientific evidence suggests rats are at greater susceptibility to overload than humans (Oberdorster, 1995; Pauluhn, 2010), therefore a factor of 2.5 for remaining effects was not considered appropriate.
Intraspecies: 3
Eurometaux has adopted the ECETOC (2010) approach for intraspecies and interspecies assessment factors. Therefore, the client indicated that this value should be inserted here
Duration of exposure: 1 (The duration of exposure was adequate.)
Dose response extrapolation: 3 (Based on a LOAEC)
Adequacy of database: 3
The histopathological effects assessed are not the most sensitive endpoint. However, the relevance of the critical effect to the human lung is unclear as effects are consistent with an overload response. Evidence suggests a greater susceptibility of rats to overload and the associated increase in lung retention and chronic pulmonary inflammation. Uncertainties remain with respect to particle dosimetry and toxicokinetics. As: (a) read-across has been used (based on the similar physicochemical properties of aluminium oxide (coat) and aluminium hydroxide) and the assumption that the aluminium component is the active moiety with respect to longer-term pulmonary effects when this substance is retained in the lung; (b) the limitations of the key study (lack of more sensitive endpoints); and (c) the limited nature of the existing database relevant for this substance (cross-sectional human studies of exposure to bauxite are available), overall the confidence in the database is moderate and a database adequacy factor of 3 is considered appropriate.
Total assessment factor = 27
Calculated DNELlong-term, worker= 33.5/27 = 1.24 mg Al/m³, respirable, 8 hour TWA
= 3.54 mg Al(OH)3/m³, respirable, 8 hour TWA.
As the calculated value is slightly higher than, but similar to, general dust limits used in setting Occupational Exposure Limits and the weight of evidence supports behavior of aluminium hydroxide dust as a low cytotoxic, poorly soluble particulate,the general dust limits are considered appropriate for exposure scenarios with exposure to aluminium hydroxide dust.
Proposed DNELlong-term,workerfor aluminium hydroxide = 3 mg Al(OH)3/m³
These DNEL values are supported by the NOAECof 3 mg/m³ observed in the 28 day sub-acute study by Pauluhn (2009a) for aluminium oxyhydroxide particulates with a finer particle size distribution that employed a more sensitive set of endpoints.
At present, the available evidence supports a lack of substance specific effects in the lungs on inhalation exposure to the target substances. The ECHA Guidance (Chapter R8, p144) specifies that a registrant can use a health-based national OEL when the scientific basis of the national OEL has been evaluated and the method validated against the REACH DNEL derivation method.
The adoption of a health-based OEL may be considered for the aluminium oxide component of welding fume, given that the existing evidence does not support a chemical-specific effect of this exposure.
Summary DNEL derivation:
Gross (1973) | ||
Effect: | Pulmonary Toxicity (Repeated Dose) | |
Target Substance: | Aluminium hydroxide | |
Target Population: | Workers (exposed to the powder or dust) | |
Exposure Route: | Inhalation | |
Exposure Duration: | Repeated Dose | |
Effect type: | Local/Chronic | |
KEY REFERENCE: | Gross P, Harley R, de Treville RTP. 1973. Pulmonary reaction to metallic aluminium powders. Arch Environ Health.26:227-236. | |
TEST ANIMAL: | Rats | |
TEST SUBSTANCE: | Aluminium powder | |
EXPOSURE ROUTE/MEDIUM/ CONCENTRATION/DURATION | Inhalation/ dust, powder - mean particle size diameters: 2.49, 2.22 and 4.85μm/ 0, 15, 30, 50, 100 mg/m3/6 hours per day, 5 days a week for either 6(for 50 and100 mg/m3)or 12 months. | |
CRITICAL EFFECT: | Lipid pneumonitis, granulomatous inflammation; collagenous scars | |
MODE OF ACTION: | Threshold (portal of entry - overload) | |
RELEVANT DOSE-DESCRIPTOR: | 50 | mg/m3 |
MODIFYING FACTORS: | ||
Adjustment for differences in exposure conditions and respiratory rates | ||
Inhalation volume (experiment) | 6.7 | Inhalation volume (rat resting): 6.7 m3(8h). |
Inhalation volume (target population) | 10 | Inhalation volume (human light activity): 10 m3(8h) |
Ratio of bioavailabilities between test and target species: | 1 | There is no evidence suggesting that there would be a difference between animal species with respect to actual bioavailability. |
Ratio of inhalation bioavailabilities between test and target substances: | 1 | |
TOTAL MODIFICATION FACTOR: | 0.67 | |
Corrected Starting Point: | 33.50 | mg/m3(50 x 6.7/10) |
ASSESSMENT FACTORS | ||
Interspecies: | 1 | Allometric scaling is not necessary as the mode of action is a portal-of-entry effect (overload) and adjustment for inhalatory volume has been carried out to modify the starting point; scientific evidence suggests rats are at greater susceptibility to overload than humans (Oberdorster, 1995; Pauluhn, 2010), therefore a factor of 2.5 for remaining effects was not considered appropriate. |
Intraspecies: | 3 | ECETOC (2010) gives a value of 3 for the worker population. A value of 5 would be inserted for the general population. Note: Eurometaux has adopted the ECETOC (2010) approach for intraspecies and interspecies assessment factors. Therefore, the client indicated that these values should be inserted here. |
Duration of exposure: | 1 | Adequate duration of exposure. No scaling necessary. |
Dose-response extrapolation: | 3 | Based on a LOAEC (ECHA Chapter R8, ECETOC (2010)) |
Adequacy of database: | 3 | The histopathological effects assessed are not the most sensitive endpoint. However, the relevance of the critical effect to the human lung is unclear as the effects are consistent with a rat overload response. Evidence suggests a greater susceptibility of rats to overload and the associated increase in lung retention and chronic pulmonary inflammation. Uncertainties exist with respect to particle dosimetry and toxicokinetics. As: (a) read-across has been used (based on the similar physicochemical properties of aluminium oxide (coat) and aluminium hydroxide) and the assumption that the aluminium component is the active moiety with respect to longer-term pulmonary effects when this substance is retained in the lung; (b) the limitations of the key study (lack of more sensitive endpoints); and (c) the limited nature of the existing database relevant for this substance (cross-sectional human studies of exposure to bauxite are available), overall the confidence in the database is moderate and a database adequacy factor of 3 is considered appropriate. |
TOTAL ASSESSMENT FACTOR: | 27 | |
1.24 | mg/m3as Al, daily 8 hour TWA (respirable) | |
DNEL inhalation-workers-long-term: | 3.59 | mg/m3as Al(OH)3, daily 8 hour TWA (respirable) |
Short-term DNEL
According to REACH guidance (ECHA, 2008, Chapter 8, p.106), there is no generally accepted methodology for the establishment of an acute toxicity DNEL for effects occurring after a single exposure of a few minutes up to 24 hours. In most cases it may be unnecessary to derive an acute DNEL, as the long-term DNEL is usually sufficient to ensure that these effects do not occur. In summary, according to ECHA, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures, for example, connecting or disconnecting vessels.
The weight of evidence suggests that these substances behave as poorly soluble low cytotoxicity particulates. A chemical-specific acute toxicity hazard leading to C&L was not identified for the target substances. The long-term DNEL should ensure that these effects do not occur.
General Population - Hazard via inhalation route
Systemic effects
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.37 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 40
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 94.8 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- NOAELcorr = NOAEL * 3.16 = 30 * 3.16 = 94.80 mg Al/kg bw/day (Modification of starting point, to adjust ratios of the whole body fractional uptake for Al-citrate (0.079%) to the whole body fractional uptakes of Al metal (<0.025%).)
- AF for dose response relationship:
- 1
- Justification:
- Based on NOAEL (ECHA, 2008).
- AF for differences in duration of exposure:
- 1
- Justification:
- The study exposed the animals until they were 1 year of age.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- 4 for allometric scaling (rats to humans)[ECHA default, 2008].
- AF for other interspecies differences:
- 1
- AF for intraspecies differences:
- 5
- Justification:
- ECETOC (2010) gives a value of 5 for the general population.
- AF for the quality of the whole database:
- 2
- Justification:
- Evidence for differences in toxicokinetics of Al when complexed with citrate (Jouhanneau et al., 1997); uncertainty as to the critical period of exposure and lack of information on food consumption in the ToxTest-TEH113 study.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Summary DNEL derivation:
Oral DNEL Derivation Summary | ||
TEH-113 | ||
Effect: | Repeated Dose - neurotoxicity | |
Target Substance: | Al(OH)3 | |
Target Population: | Adults | |
Exposure Route: | Oral exposure | |
Effect type: | Long-term, systemic | |
KEY REFERENCE: | Developmental and One-Year Chronic Neurotoxicity Study of Aluminium Citrate in Rats. ToxTest, Alberta Research Council Inc. Project No. TEH-113. | |
TEST ANIMAL: | Sprague-Dawley male and female rats | |
TEST SUBSTANCE: | Aluminium citrate (CAS# 31142-56-0) | |
EXPOSURE ROUTE/MEDIUM/ CONCENTRATION/DURATION | Pregnant females were exposed to Al-citrate at dose levels 30, 100 and 300 mg Al/kg bw/day from GD6 to GD21 and from PND 1 to PND 21. Pups were exposed to Al-citratein uteroand with maternal milk from PND 1 to PND 21, 64, 120 or 364. | |
EFFECTS: | A deficit in fore- and hind-limb grip strength in the mid-dose group, supported by evidence of dose response for this endpoint | |
ENDPOINT- CONCENTRATION: | LOAEL - 100 mg Al/kg bw/day; NOAEL - 30 mg Al/kg bw/day | |
MODE OF ACTION: | Threshold | |
RELEVANT DOSE-DESCRIPTOR: | 30 | mg Al/kg bw/day; NOAEL |
MODIFYING FACTORS | ||
Route-to-route: | 1 | Oral to oral extrapolation with the same units (ECHA, 2008) |
Bioavailability differences between animal species: | 1 | Evidence suggests no difference between animal species for oral exposure (Priest, 2010). |
Ratio of bioavailability between test and target substance: | 3.16 | Priest (2010): ratios of the whole body fractional uptake for Al-citrate (0.079%) to the whole body fractional uptakes of Al metal (<0.015%), Al-oxide (0.018%), and Al-hydroxide (0.025%). Note: The whole body fractional uptake (f) of Al metal powder was g |
TOTAL MODIFICATION FACTOR: | 3.16 | |
Corrected Starting Point: | 94.80 | mg Al/kg bw/day |
ASSESSMENT FACTORS | ||
Interspecies: | 4 | 4 for allometric scaling (rats to humans)[ECHA default, 2008]. Note: Eurometaux has adopted the ECETOC (2010) approach for intraspecies and interspecies assessment factors. Therefore, the client indicated that an additional factor of 2.5 was not necessary |
Intraspecies: | 5 | ECETOC (2010) gives a value of 5 for the general population. A value of 3 would be inserted for the worker population. Note: Eurometaux has adopted the ECETOC (2010) approach for intraspecies and interspecies assessment factors. Therefore, the client ind |
Duration of exposure: | 1 | The study exposed the animals until they were 1 year of age. |
Dose-response extrapolation: | 1 | Based on NOAEL (ECHA, 2008) |
Adequacy of database: | 2 | Evidence for differences in toxicokinetics of Al when complexed with citrate (Jouhanneau et al., 1997); uncertainty as to the critical period of exposure and lack of information on food consumption in the ToxTest-TEH113 study. |
TOTAL ASSESSMENT FACTOR: | 40 | |
DNEL: general population | 2.37 | mg Al/kg bw/day |
6.85 | mg substance/kg bw/day |
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