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EC number: 476-670-7 | CAS number: -
- 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:
- 3.05 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 37.5
- Dose descriptor starting point:
- NOAEL
- Value:
- 64.97 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 114.55 mg/m³
- Explanation for the modification of the dose descriptor starting point:
No data available for repeated dose toxicity by inhalation route.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3
- Justification:
- DNEL is based on sub-chronic study (61 days).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable, AF not used for inhalation route
- AF for other interspecies differences:
- 2.5
- 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
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
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:
- 2.16 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):
- 150
- Dose descriptor starting point:
- NOAEL
- Value:
- 64.97 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 324.85 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No data available for repeated dose toxicity by dermal route.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3
- Justification:
- DNEL is based on sub-chronic study (61 days).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The study was conducted on rats.
- AF for other interspecies differences:
- 2.5
- 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
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
The calculation of the DNELs is performed in accordance with the principles given in ECHA (2012) “Guidance of Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health”.
Available dose descriptors:
The target substance Fe(III)IDHA is not acutely toxic by oral route of exposure because LD50 was > 2000 mg/kg bw (Szefczyk, 2007). Therefore a long-term DNEL for systemic effects is needed for oral route for general public. The substance is not toxic by dermal route of exposure (LD50 > 2000 mg/kg bw; Szefczyk, 2007) and inhalation is not relevant route of exposure due to the low vapour pressure of the substance (3.84 x E-18 Pa at 25°C). The target substance is non-volatile (in microgranulated form) and therefore no risk of irritation or sensitisation of respiratory tract exists, but the substance is classified as skin sensitiser category 1B. Therefore, no DNELs for acute/short term exposures (systemic and local effects) and for long-term exposures (local effects for both inhalation and dermal routes) need to be derived.
For the long-term exposure–systemic effects (inhalation and dermal DNEL), the NOAEL of 64.97 mg/kg bw established in the repeated dose toxicity study in rats (Appel, 2001) was used as the starting point (please see TK statement IUCLID 7.1.).
The DNELs for inhalation and dermal routes can be derived by route-to-route extrapolation applying appropriate assessment factors.
For the other non-threshold endpoints (mutagenicity, eye and skin irritation/corrosion) no DNELs can be derived because a No-Observed-Effect-Level could not be established from the relevant studies.
Modification of the starting point:
From all available data on the target and read-across substances it is clear that these substances exert their effects by a threshold mode of action. Thus, DNELs can be calculated for the threshold endpoints based on the most relevant dose descriptors per endpoint. DNELs are derived based on the available toxicity data for the target substance and reflecting the routes, the duration and the frequency of exposure. DNELs are derived for workers and the general population. The general population includes consumers and humans exposed via the environment (please see below).
Bioavailability (absorption):
There is no substance-specific experimental information on absorption by the oral, dermal and inhalation
routes available. The absorption rates are assessed based on the physico-chemical properties and on the
effects observed in treated animals in the available studies.
Oral absorption:
A moderate direct absorption across the gastrointestinal tract epithelium will occur when Fe(III)IDHA is applied orally. The complex Fe(III)IDHA is expected to dissociate at very high acidic conditions of stomach (pH below 2). In the upper intestines, iron cation will tend to be complexed again with free ligand IDHA because pH reaches the optimum (about 5) for complex formation. Therefore, the absorbed fraction will result from intact Fe(III)IDHA and its released components: Fe3+ ions and free IDHA. Intestinal uptake of released Fe3+ ions (after reduced to the ferrous Fe2+ state) is low, 1 to 10%, while intestinal uptake of sodium IDHA is at least 37 % comparing to 5 % of sodium EDTA. Therefore, oral absorption of intact iron IDHA chelates is expected to be somewhat higher than oral absorption of iron of EDTA complexes or free EDTA.
In conclusion, taking into account low absorption potential based on physico-chemical properties of chelate Fe(III)IDHA, its instability at low pH values, absorption of 10 % for iron and 37% for free IDHA, 50 % oral absorption (as worst-case) for Fe(III)IDHA is considered appropriate in case of hazard assessment (DNEL derivation).
Dermal absorption:
No significant dermal absorption is expected for the target substance. The log Pow of -7.51 is below the
optimal logPow range (0 - 4) values favourable for dermal absorption. High water solubility of 733.33 g/L points
also to a low absorption potential through the skin. The molecular weight of 323.89 g/mol indicates that a
certain potential to penetrate the skin (< 500) exists. However, in case of such a hydrophilic substance
dermal penetration is rather unlikely.
Dermal absorption is considered to be negligible and equal to 10 % (worst-case) as established for
substances which meet criteria of low dermal absorption potential mentioned in ECHA guidance R7c.
(the value used for hazard assessment: DNEL derivation). Dermal absorption in rats, and in humans is assumed to be the same since no information for dermal absorption of the target substance in humans is available.
Inhalation absorption
Absorption by inhalation is considered to be negligible due to the low vapour pressure of 3.84 x 10-18 Pa at
25°C and that the substance is in microgranulated form with particles with aerodynamic diameter higher
than 100μm. It means that 100 % of inhaled substance (in case of dust forming) will be deposited in the upper respiratory tract, which will finally be taken up orally. Of this, 50 % will be absorbed in the GI tract and
become systemic available: 1 x 0.5 = 0.5 will be the total absorption factor for inhalation (or 50 %). Absorption by inhalation is considered to be equal in rats and in humans since no substance specific information is available.
Route-to-route extrapolation:
Oral-to-inhalation extrapolation is performed to obtain long-term inhalation NOAEC for systemic effects. The
following formula was used:
Corrected inhalatory NOAEC = oral NOAEL x (1/sRVrat) x (ABS oral-rat/ABS inh-human) x (6.7 m3/10 m3)
where sRV is the standard respiratory volume of rats during 8 hours (= 0.38 m3/kg/day); ABS-absorption and
6.7 m3and 10 m3are standard respiratory volumes for workers under normal conditions and by light activity.
Oral-to-dermal extrapolation is performed to obtain dermal NOAEL for systemic effects. The following
formula was used (as described in the Example B.5 of the Appendix R.8 -2, ECHA REACH Guidance R8):
Corrected dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS derm-rat) x (ABS derm-rat/ABS derm-human)
= oral NOAEL x (ABS oral-rat/ABS derm-human).
Exposure conditions:
No modification of the starting points for exposure conditions was necessary since the systemic dose after
oral administration of the test material was already assessed in respiratory volume taken for rats during 8
h (0.38 m3). Differences in the respiratory volumes between experimental animals and humans were used
when an oral rat NOAEL from the oral repeated dose toxicity study in rats was used to assess inhalation
exposure in humans. 0.38 m3/kg/day is the standard respiratory volumes in rats during 8h exposure. 6.7
and 10 m3are standard respiratory volumes for workers under normal conditions and by light activity,
respectively.
Applying of assessment factors and calculation of DNELs:
The assessment factors have been applied to the corrected starting point to obtain the endpoint specific
DNELs. Assessment factors (AFs) correct uncertainties and variability within and between species in the
effect data.
Interspecies differences:
The species-specific default assessment factor of 4 for allometric scaling for rats was applied in the case of
employment of the oral NOAEL from the oral repeated dose toxicity study in rats, which was used to derive
the dermal long-term DNEL. No allometric scaling factor was applied when the oral NOAEL was used for
the derivation of inhalation long-term DNEL.
An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between
rat and human in all cases.
Intraspecies differences:
An assessment factor of 5 was applied for workers for all endpoints and for all exposure routes.
Extrapolation of duration:An assessment factor of 3 was applied for duration of exposure (sub-chronic to chronic; the study was 61days instead of 90 days).
Quality of whole data base: A default assessment factor of 1 was used.
Issues related to dose response: An assessment factor of 1 was applied.
Calculation of DNELs:
Long-term exposure–systemic effects (inhalation DNEL):
The oral rat NOAEL of 64.97 mg/kg bw (In the sub-chronic oral repeated dose toxicity study (31 to 61 days of exposure) the NOAEL value was established > 11.2 mg Fe/kg bw/day (Appeal M.J. et al., 2001, publication), what corresponds with 64.97 mg Fe(III)IDHA (11.2 mg Fe x 323.98 Fe(III)IDHA /55,85 g Fe).) was converted into the inhalation NOAEL:
Corrected inh. NOAEL = oral NOAEL x [1/sRV(rat) ] x [absorption (oral-rat) / absorption (inh-human) ]. This
will be: 64.97 x 1/0.38 m3 (8h) x 50/50 = 170.97 mg/m3; sRV = respiratory volume rat in 8 h. Further correction:
x [sRV(human) / wRV]. This will be: 170.97 mg/m3 x [6.7 m3 (8h) / 10 m3 (8h) = 114.55 mg/m3 sRV(human)
= respiratory volume in 8 h (with a factor 4 for allometric scaling) wRV = worker respiratory volume (light
work). Next the following assessment factors were used: Interspecies: difference in BW (allometric scaling):
in this case not applicable as this has already been done at the correction in sRV; remaining differences: 2.5
(in case of systemic effects), Intraspecies worker: 5, Exposure duration: 3 (sub-chronic to chronic; please
note that study was 61 days instead of 90 days). This results in a total assessment factor of 2.5 x 5 x 3 =
37.5, so the DNEL will be: 114.55/37.5= 3.05 mg/m3.
Long-term exposure–systemic effects (dermal DNEL):
Dermal absorption is estimated to be 10% (based on the physico-chemical properties and ECHA guidance R7c); oral absorption is 50%. Corrected dermal NOAEL = oral NOAEL x [absorption (oral-rat) / absorption (dermal-human)] This will be: 64.97 x 50/10 = 324.85 mg/kg. Next the following assessment factors were used Interspecies: difference
in BW (allometric scaling): 4 and remaining differences: 2.5 (in case of systemic effects), Intraspecies
worker: 5, Exposure duration: 3 (sub-chronic to chronic). This results in a total assessment factor of 4 x 2.5
x 5 x 3 = 150, indicating that the DNEL dermal will be 324.85 / 150 = 2.16 mg/kg
Selected DNELs
DNEL systemic inhalation =3.05 mg/m3
DNEL systemic dermal (long-term) =2.16 mg/kg bw
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.75 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 64.97 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 56.49 mg/m³
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3
- Justification:
- DNEL is based on sub-chronic study (61 days).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable, AF not used for inhalation route
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- 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
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
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:
- 1.08 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):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 64.97 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 324.85 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Dermal absorption is 10%; oral absorption 50%. Corrected dermal
NOAEL = oral NOAEL x [absorption (oral-rat) / absorption (dermal-human)]. This will be: 64.97 x 50/10 = 324.85 mg/kg.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3
- Justification:
- DNEL is based on sub-chronic study (61 days).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- 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
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.22 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):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 64.97 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3
- Justification:
- DNEL is based on sb-chronic study (61 days).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute 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
The principles of the DNEL calculation for the general population are the same as already described for workers. However, there are additional considerations or deviations for:
Modification of the starting point:
Bioavailability (absorption by oral route)
The oral absorption in rats and in humans is assumed to be the same since no information for oral absorption for target chemical in rats and in humans is available.
Respiratory volumes:
No differences in the respiratory volumes under normal conditions and by light activity in humans were taken into account.
Applying of assessment factors:
A higher assessment factor of 10 (in place of 5 for workers) for intraspecies variation/differences of human
population was used.
Calculation of endpoint-specific DNEL for general population
Long-term exposure–systemic effects (inhalation DNEL):
The oral rat NOAEL of 64.97 mg/kg bw was converted into the inhalation NOAEC:
Corrected inh NOAEC = oral NOAEL x [1/sRV(rat) ] x [absorption (oral-rat) / absorption (inh-human) ] This
will be: 64.97 x 1/1.15 m3 (24h) x 50/50 = 56.49 mg/m3. sRV = respiratory volume rat in 24 h. Next the following
assessment factors were used: Interspecies: difference in BW (allometric scaling): in this case not applicable
as this has already been done at the correction in sRV; remaining differences: 2.5 (in case of systemic
effects), Intraspecies consumer: 10, Exposure duration: 3 (sub-chronic to chronic). This results in a total
assessment factor of 2.5 x 10 x 3 = 75, thus the DNEL will be: 56.49/75 = 0.75 mg/m3
Long-term exposure–systemic effects (dermal DNEL):
Dermal absorption is 10%; oral absorption 50%. Corrected dermal NOAEL = oral NOAEL x [absorption
(oral-rat) / absorption (dermal-human)]. This will be: 64.97 x 50/10 = 324.85 mg/kg. Next the following
assessment factors were used: Interspecies: difference in BW (allometric scaling): 4, remaining differences:
2.5 (in case of systemic effects), Intraspecies general population: 10, Exposure duration: 3 (sub-chronic to
chronic). This results in a total assessment factor of 4 x 2.5 x 10 x 3 = 300, indicating that the DNEL dermal
will be 324.85 / 300 = 1.08 mg/kg
Long-term exposure–systemic effects (oral DNEL):
Assuming that absorption is similar for rats and humans: NOAEL = 64.97 mg/kg bw (31/61 day study). Next the
following assessment factors were used: Interspecies: difference in BW (allometric scaling): 4, remaining
differences: 2.5 (in case of systemic effects), Intraspecies general population: 10, Exposure duration: 3
(sub-chronic to chronic). This results in a total assessment factor of 4 x 2.5 x 10 x 3 = 300, indicating that
the DNEL oral will be 64.97 / 300 = 0.22 mg/kg
Selected DNELs
DNEL systemic inhalation =0.75 mg/m3
DNEL systemic dermal (long-term) =1.08 mg/kg bw
DNEL systemic oral (long-term) =0.22 mg/kg bw
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