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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 283-041-9 | CAS number: 84539-53-7
- 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:
- 8.8 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):
- 10
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 88 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Systemic effects
- AF for dose response relationship:
- 1
- Justification:
- the NOAEL was at least 50 mg/kg bw
- AF for differences in duration of exposure:
- 2
- Justification:
- subchronic exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- has aleardy been done at the correction in sRV
- AF for other interspecies differences:
- 1
- Justification:
- hardly absorbed and not metabolized
- AF for intraspecies differences:
- 5
- Justification:
- standard for workers
- AF for the quality of the whole database:
- 1
- Justification:
- several repeated dose studies available
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.83 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- not applicable; dermal study is used for setting dermal DNEL. In this study both local and systemic effects were observed
- AF for dose response relationship:
- 1
- Justification:
- the NOAEL was at least 100 mg/kg bw
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- allometric scaling
- AF for other interspecies differences:
- 1
- Justification:
- hardly any absorption, not metabolized
- AF for intraspecies differences:
- 5
- Justification:
- workers
- AF for the quality of the whole database:
- 1
- Justification:
- several repeated dose studies available
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
Acute/short-term exposure - systemic effects
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified.
Referring to the available data on acute toxicity, EDDHMA-Fe displays low acute toxicity as evidenced by LD50 values of >2000 mg/kg bw determined in rats for both the oral and the dermal route, and a 4 -h LC50 value of >1240 mg/m³ (technically highest attainable concentration). Therefore, EDDHMA-Fe is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, and consequently the derivation of worker DNELs for acute/short-term exposure - systemic effects is not required.
Acute/short-term and long-term exposure - local effects
Based on the available toxicological information, EDDHMA-Fe is not subject to classification for skin, eye and/or respiratory irritation and skin sensitisation and no worker DNEL for local effects following acute/short-term or long-term exposure is derived.
This is in line with the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-repsonse for human health".
Long-term exposure - systemic effects
Using a conservative approach, the NOELs determined in the repeated dose toxicity studies for the oral and dermal routes are also identified as NOAELs.
For the dermal route, the NO(A)EL of 100 mg/kg bw/day from the key subacute repeated dose dermal toxicity study with the structurally related substance EDDHA-FeNa (CIBA-GEIGY Limited, 1996b) is regarded as the relevant dose descriptor for systemic effects associated with long-term dermal exposure to EDDHMA-Fe. Dermal treatment with the test item resulted in no mortality, no relevant clinical signs, no changes in food consumption, no effects on haematology and clinical chemistry parameters and no gross findings. A transient slight body weight loss was noted in females at 1000 mg/kg bw/day during the first week of treatment. There was an increase in adrenal weight in males at 1000 mg/kg bw/day. Microscopically, the skin application sites of females at 1000 mg/kg bw/day revealed epidermal hyperkeratosis associated with an increased severity of acanthosis. In 2/5 males at 1000 mg/kg bw/day centrilobular hypertrophy of hepatocytes was noted.
For the inhalation route, the NOAEL of 50 mg/kg bw/day from the key subchronic oral toxicity study (Schoenmakers, 1996) is considered to represent the appropriate dose descriptor for systemic effects related to long-term inhalation exposure to EDDHMA-Fe.
In this study, treatment with the test item resulted in slight haematological changes and a slightly increased relative liver weight in male rats treated at 100 mg/kg bw/day. The slight increase in relative kidney weight was, however, not corroborated by histopathological renal effects, and was not seen in female rats at this level (NOEL 100 mg/kg bw). Histopathological kidney effects were observed in both male and female rats at the next higher level of 500 mg/kg bw.
Estimation of NOAEL: A more realistic NOAEL was estimated from the LOAEL of 100 mg/kg bw/day in males applying an assessment factor of 2. This is scientifically justified for this test, as only slight slight adverse effects were observed at 100 mg/kg bw/day in males only (see above). To take the relatively large concentration gap between 20 (clear NOEL) and 100 mg/kg bw/day into account, 20 mg/kg bw/day was not taken as NOAEL, but extrapolated from the LOAEL in males. An assessment factor of 2 seems to be approprate and conservative enough for the current study as only slight effects were observed at the LOAEL of 100 mg/kg bw/day in males. Also in the oral one-generation test (Rejinders, 1997), applying a treatment period of at least 13 weeks, a parental NOAEL of 50 mg/kg was established. The NOAEL in an oral 4 -week study (Banks, 1988) was 200 mg/kg bw; in a second oral 4 -week study (Korn, 1990) 200 mg/kg bw was a LOAEL, the only change observed at that level consisted of
slight fatty degenerations of renal tubular epithelial cells; no increase in relative kidney weight was observed at that level.
Consequently a NOAEL of 50 mg/kg bw/day is calculated for the 90 -day study and used for DNEL and PNEC(oral) derivation.
In order to derive a worker DNEL and under the assumption of a daily exposure period of 8 hours, the oral NOAEL is converted into an inhalation NOAEC according to the following formula:
inhalation NOAEC = oral NOAEL × 1/sRV(rat) × ABSoral(rat)/ABSinhalation(human) × sRV(human)/wRV(human) with:
oral NOAEL: 50 mg/kg bw/day
sRV(rat): 0.38 m³/kg bw (8 hours) [standard respiratory volume of the rat]
ABSoral(rat)/ABSinhalation(human): 1 [ratio of oral absorption in the rat to inhalative absorption in the human]. See also section 7.1: based on physical-chemical characteristics, particularly water solubility, octanol-water partition coefficient and vapour pressure, no or only limited absorption by the dermal and inhalation routes is expected, which is further supported by the dermal and inhalation acute toxicity studies results. For the oral route uptake is more likely compared to the other routes. As such no higher absorption for inhalation should have to be taken into account.
sRV(human)/wRV(human): 6.7 m³/10 m³ [ratio of human standard respiratory volume to worker respiratory volume]
Accordingly, the oral NOAEL of 50 mg/kg bw/day is transformed in an inhalation NOAEC of 88 mg/m³.
The following assessment factors are used for the derivation of worker DNEL LT systemic for inhalation exposure to EDDHMA-Fe:
Interspecies factor (rat to human): 1 (inhalation exposure)
Remaining differences (systemic effects): 1 (EDDHMA-Fe is hardly absorbed and not metabolized, as such no differences in toxicokinetics expected)
Intraspecies factor (worker): 5
Exposure duration factor: 2 (subchronic to chronic)
Dose-response factor: 1
Quality of whole database factor: 1
Total assessment factor: 10
The resulting worker DNEL LT inhalation systemic is:
worker DNEL (inhalation exposure) = 88 mg/m³ / 10 = 8.8 mg/m³
The following assessment factors are used for the derivation of worker DNEL LT systemic/local for dermal exposure to EDDHMA-Fe:
Interspecies factor (rat to human): 4
Intraspecies factor (worker): 5
Exposure duration factor: 6 (subacute to chronic)
Dose-response factor: 1
Quality of whole database factor: 1
Total assessment factor: 120
The resulting worker DNEL LT dermal local/systemic is:
worker DNEL (dermal exposure) = 100 mg/kg bw/day / 120 = 0.83 mg/kg bw/day, rounded to 0.8 mg/kg bw/day
This is in line with the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-response for human health".
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.2 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):
- 20
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 43.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Systemic effects
- AF for dose response relationship:
- 1
- Justification:
- the NOAEL was at least 50 mg/kg bw
- AF for differences in duration of exposure:
- 2
- Justification:
- subchronic exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- has already been done at the correction in sRV
- AF for other interspecies differences:
- 1
- Justification:
- hardly absorbed and not metabolized
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- several repeated dose toxicity studies available
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.42 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 240
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Not applicable, dermal study used
- AF for dose response relationship:
- 1
- Justification:
- the NOAEL is at least 100 mg/kg bw
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- allometric scaling
- AF for other interspecies differences:
- 1
- Justification:
- hardly absorbed and not metabolized
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- several repeated studies available
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
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:
- 0.62 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):
- 80
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- not applicable, oral study used
- AF for dose response relationship:
- 1
- Justification:
- the NOAEL is at least 50 mg/kg bw
- AF for differences in duration of exposure:
- 2
- Justification:
- subchronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- allometric scaling
- AF for other interspecies differences:
- 1
- Justification:
- hardly absorbed and not metabolized
- AF for intraspecies differences:
- 10
- Justification:
- general population
- AF for the quality of the whole database:
- 1
- Justification:
- several repeated studies available
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
Acute/short-term exposure - systemic effects
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified.
Referring to the available data on acute toxicity, EDDHMA-Fe displays low acute toxicity as evidenced by LD50 values of >2000 mg/kg bw determined in rats for both the oral and the dermal route, and a 4 -h LC50 value of > 1.24 mg/L (technically highest attainable concentration) determined in rats for the inhalation route. Therefore, EDDHMA-Fe is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, and consequently the derivation of general population DNELs for acute/short-term exposure - systemic effects is not required.
Acute/short-term and long-term exposure - local effects
Based on the available toxicological information, EDDHMA-Fe is not subject to classification for skin, eye and/or respiratory irritation and skin sensitisation and no general population DNEL for local effects following acute/short-term or long-term exposure is derived.
This is in line with the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-repsonse for human health".
Long-term exposure - systemic effects
Using a conservative approach, the NOELs determined in the repeated dose toxicity studies for the oral and dermal routes are also identified as NOAELs.
For the dermal route, the NO(A)EL of 100 mg/kg bw/day from the key subacute repeated dose dermal toxicity study with the structurally related substance EDDHA-FeNa (CIBA-GEIGY Limited, 1996b) is regarded as the relevant dose descriptor for systemic effects associated with long-term dermal exposure to EDDHMA-Fe. Dermal treatment with the test item resulted in no mortality, no relevant clinical signs, no changes in food consumption, no effects on haematology and clinical chemistry parameters and no gross findings. A transient slight body weight loss was noted in females at 1000 mg/kg bw/day during the first week of treatment. There was an increase in adrenal weight in males at 1000 mg/kg bw/day. Microscopically, the skin application sites of females at 1000 mg/kg bw/day revealed epidermal hyperkeratosis associated with an increased severity of acanthosis. In 2/5 males at 1000 mg/kg bw/day centrilobular hypertrophy of hepatocytes was noted.
For the inhalation route, the NOAEL of 50 mg/kg bw/day from the key subchronic oral toxicity study (Schoenmakers, 1996) is considered to represent the appropriate dose descriptor for systemic effects related to long-term inhalation exposure to EDDHMA-Fe.
In this study, treatment with the test item resulted in slight haematological changes and a slightly increased relative liver weight in male rats treated at 100 mg/kg bw/day. The slight increase in relative kidney weight was, however, not corroborated by histopathological renal effects, and was not seen in female rats at this level (NOEL 100 mg/kg bw). Histopathological kidney effects were observed in both male and female rats at the next higher level of 500 mg/kg bw.
Estimation of NOAEL: A more realistic NOAEL was estimated from the LOAEL of 100 mg/kg bw/day in males applying an assessment factor of 2. This is scientifically justified for this test, as only slight slight adverse effects were observed at 100 mg/kg bw/day in males only (see above). To take the relatively large concentration gap between 20 (clear NOEL) and 100 mg/kg bw/day into account, 20 mg/kg bw/day was not taken as NOAEL, but extrapolated from the LOAEL in males. An assessment factor of 2 seems to be approprate and conservative enough for the current study as only slight effects were observed at the LOAEL of 100 mg/kg bw/day in males. Also in the oral one-generation test (Rejinders, 1997), applying a treatment period of at least 13 weeks, a parental NOAEL of 50 mg/kg was established. The NOAEL in an oral 4 -week study (Banks, 1988) was 200 mg/kg bw; in a second oral 4 -week study (Korn, 1990) 200 mg/kg bw was a LOAEL, the only change observed at that level consisted of
slight fatty degenerations of renal tubular epithelial cells; no increase in relative kidney weight was observed at that level.
Consequently a NOAEL of 50 mg/kg bw/day is calculated for the 90 -day study and used for DNEL and PNEC(oral) derivation.
For the oral route, the NO(A)EL of 50 mg/kg bw/day from the key subchronic oral toxicity study and the one-generation study is used as the dose descriptor for systemic effects after long-term exposure to EDDHMA-Fe.
In order to derive a general population DNEL and under the assumption of a daily exposure period of 8 hours, the oral NOAEL is converted into an inhalation NOAEC according to the following formula:
inhalation NOAEC = oral NOAEL × 1/sRV(rat) × ABSoral(rat)/ABSinhalation(human) × sRV(human)/wRV(human)with:
oral NOAEL: 50 mg/kg bw/day
sRV(rat): 1.15 m³/kg bw/day [standard respiratory volume of the rat]
ABSoral(rat)/ABSinhalation(human): 1 [ratio of oral absorption in the rat to inhalative absorption in the human] See also section 7.1: based on physical-chemical characteristics, particularly water solubility, octanol-water partition coefficient and vapour pressure, no or only limited absorption by the dermal and inhalation routes is expected, which is further supported by the dermal and inhalation acute toxicity studies results. For the oral route uptake is more likely compared to the other routes. As such no higher absorption for inhalation should have to be taken into account
Accordingly, the oral NOAEL of 50 mg/kg bw/day is transformed in an inhalation NOAEC of 43.5 mg/m³.
The following assessment factors are used for the derivation of general population DNELs for oral, dermal or inhalation exposure to EDDHMA-Fe:
Interspecies factor (rat to human): 4 [used for the oral and dermal routes only]
Intraspecies factor (general population): 10
Exposure duration factor: 6 (subacute to chronic) [for the dermal route], 2 (subchronic to chronic) [for the oral and inhalation routes]
Dose-response factor: 1
Quality of whole database factor: 1
The resulting general population DNELs are:
general population DNEL (dermal exposure) = 100 mg/kg bw/day / (4 × 10 × 6 × 1 × 1) = 100/240 = 0.42 mg/kg bw/day
general population DNEL (inhalation exposure) = 43.5 mg/m³ / (10 × 2 × 1 × 1) = 43.5/20 = 2.2 mg/m³
general population DNEL (oral exposure) = 50 mg/kg bw/day / (4 × 10 × 2 × 1 × 1) = 50/80 = 0.62 mg/kg bw/day
This is in line with the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-response for human health".
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.