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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.
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EC number: 216-036-7 | CAS number: 1478-61-1
- 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:
- 0.118 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:
- 10 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 8.82 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012).
To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8 h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8 h exposure period).
The corrected dose descriptor for inhalation is determined using the following equation:
Corrected Inhalatory NOAEC = 1/SRVrat x ABS(oral-rat)/ABS(inh-human) x sRVhuman/wRV
= [10 mg/kg bw/day] X [1/0.38 m3/kg bw/day] X [1/2] X [6.7 m3/10m3].
Thus, the corrected dose descriptor for inhalation is 8.82 mg/m3 for workers.
- AF for dose response relationship:
- 1
- Justification:
- The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default factor for a sub-acute study. Table R.8-5 ECHA REACH Guidance.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Table R.8-4 ECHA REACH Guidance. Assessment factor not to be used for inhalation route since the differences in the metabolic rate/bw has already been taken into account in the corrected dose descriptor.
- AF for other interspecies differences:
- 2.5
- Justification:
- Table R.8-4 ECHA REACH Guidance. Assessment factor not to be used for inhalation route since the differences in the metabolic rate/bw has already been taken into account in the corrected dose descriptor.
- AF for intraspecies differences:
- 5
- Justification:
- Default factor for worker. Table R.8-6 ECHA REACH Guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Default factor for good/standard quality of the database taken into account completeness of the standard information requirements for the tonnage band.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
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:
- 0.033 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:
- 10 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For systemic hazard assesment via the dermal route of exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. As no data on dermal penetration are available, dermal absorption is considered to be the same as oral absorption (i.e. 100 %). Therefore the oral NOAEL is considered the same as the dermal NOAEL (ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012)).
- AF for dose response relationship:
- 1
- Justification:
- The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default factor for a sub-acute study. Table R.8-5 ECHA REACH Guidance.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
- AF for intraspecies differences:
- 5
- Justification:
- Default factor for worker. Table R.8-6 ECHA REACH Guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Default factor for good/standard quality of the database taken into account completeness of the standard information requirements for the tonnage band.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
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:
- medium hazard (no threshold derived)
Additional information - workers
NOAEL (systemic toxicity) = 10 mg/kg bw/day; OECD 407; Umano (2012)
Long-term systemic hazard assessment for this substance is based on a subacute toxicity study conducted on rats in accordance with OECD 407 under GLP (Umano 2012). The substance was administered to 30 male and 30 female Sprague-Dawley rats by oral gavage at dose levels of 10, 30 and 100 mg/kg bw/day for up to 28 consecutive days. Although there was no recovery phase, this is not a guideline requirement. The key findings in this study were lower body weight gain at 100 mg/kg/day for males and at 30 and 100 mg/kg/day for females; lower white cell counts in males at 100 mg/kg/day; lower cholesterol levels in both sexes at 100 mg/kg/day; lower cholinesterase and higher bilirubin levels in females at 100 mg/kg/day; longer oestrous cycles in females at 100 mg/kg/day; lower absolute and relative prostate and seminal vesicles weights at 100 mg/kg/day, possibly reflecting the lower body weight; higher adrenal weight in males at 100 mg/kg/day; Leydig cell atrophy at 100 mg/kg/day in 5/10 males; hypertrophy of the adrenal zona fasciculata at 100 mg/kg/day in 8/10 males, 2/10 females; atrophy of mammary glands in 3/10 males at 100 mg/kg/day; decreased haematopoiesis in bone marrow and extramedullary haematopoiesis in spleen at 100 mg/kg/day in 4/10 and 2/10 males, respectively. Many findings were related to endocrine effects, but had not considered that some may have been secondary to the lower body weights. Without having the individual data, it is not possible to comment further. In conclusion, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was 10 mg/kg bw/day due to findings of reduced body weight gain and abnormal estrous cycles in the female rat treated at 30 mg/kg bw/day.
The hazard conclusion for reproductive and developmental toxicology were as follows (OECD 422, Anon., 2011):
NOAEL(fertility) = <30 mg/kg bw/day
NOAEL(development) = No hazard identified
Whilst these endpoints resulted in a classification of category 1B reproductive toxicant, the lower NOAEL of 10 mg/kg bw/day from the repeated dose toxicity study was used for long-term systemic hazard assessment, in accordance with the precautionary principle.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.029 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):
- 150
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 4.35 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Concerning absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012).
To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h).
The corrected dose descriptor for inhalation is determined using the following equation:
Corrected Inhalator NOAEC = 1/sRVrat x ABSoral-rat/ABSinh-rat x ABSinh-rat/ABSinh-human
= [10 mg/kg bw/day] x [1/1.15 m3/kg bw/ day] x [1/2].
Thus, the corrected dose descriptor for inhalation is 0.0290 mg/m3 for the general population.
- AF for dose response relationship:
- 1
- Justification:
- The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default factor for a sub-acute. Table R.8-5 ECHA REACH Guidance.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Table R.8-4 ECHA REACH Guidance. Assessment factor not to be used for inhalation route since the differences in metabolic rate/bw has already been taken into account for the corrected dose descriptor.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
- AF for intraspecies differences:
- 10
- Justification:
- Default factor for general population. Table R.8-6 ECHA REACH Guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Default factor for good/standard quality of the database taken into account completeness of the standard information requirements for the tonnage band.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
- Explanation for the modification of the dose descriptor starting point:
In accordance with Annex VIII, Section 8.5.2, Column 2 of REACH, testing by the inhalation route was waived due to low vapour pressure and a use pattern resulting in exposure to humans being considered negligible. No acute toxicity hazard (leading to classification & labelling) has been identified for the substance following oral and dermal exposure. No acute inhalation hazard is therefore identified for this substance.
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:
- 0.017 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For systemic hazard assesment via the dermal route of exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. As no data on dermal penetration are available, dermal absorption is considered to be the same as oral absorption (i.e. 100 %). Therefore the oral NOAEL is considered the same as the dermal NOAEL (ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012)).
- AF for dose response relationship:
- 1
- Justification:
- The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default factor for a sub-acute study. Table R.8-5 ECHA REACH Guidance.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
- AF for intraspecies differences:
- 10
- Justification:
- Default factor for general population. Table R.8-6 ECHA REACH Guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Default factor for good/standard quality of the database taken into account completeness of the standard information requirements for the tonnage band.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
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:
- 0.017 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No modification of the dose descriptor starting point is required. The endpoint used to derive the DNEL uses the oral route for exposure.
- AF for dose response relationship:
- 1
- Justification:
- The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default factor for a sub-acute study. Table R.8-5 ECHA REACH Guidance.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
- AF for intraspecies differences:
- 10
- Justification:
- Default factor for good/standard quality of the database taken into account completeness, consistency and the standard information requirements for the tonnage band.
- AF for the quality of the whole database:
- 1
- Justification:
- Default factor for good/standard quality of the database taken into account completeness of the standard information requirements for the tonnage band.
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
NOAEL (systemic toxicity) = 10 mg/kg bw/day; OECD 407; Umano (2012)
Long-term systemic hazard assessment for this substance is based on a subacute toxicity study conducted on rats in accordance with OECD 407 under GLP (Umano 2012). The substance was administered to 30 male and 30 female Sprague-Dawley rats by oral gavage at dose levels of 10, 30 and 100 mg/kg bw/day for up to 28 consecutive days. Although there was no recovery phase, this is not a guideline requirement. The key findings in this study were lower body weight gain at 100 mg/kg/day for males and at 30 and 100 mg/kg/day for females; lower white cell counts in males at 100 mg/kg/day; lower cholesterol levels in both sexes at 100 mg/kg/day; lower cholinesterase and higher bilirubin levels in females at 100 mg/kg/day; longer oestrous cycles in females at 100 mg/kg/day; lower absolute and relative prostate and seminal vesicles weights at 100 mg/kg/day, possibly reflecting the lower body weight; higher adrenal weight in males at 100 mg/kg/day; Leydig cell atrophy at 100 mg/kg/day in 5/10 males; hypertrophy of the adrenal zona fasciculata at 100 mg/kg/day in 8/10 males, 2/10 females; atrophy of mammary glands in 3/10 males at 100 mg/kg/day; decreased haematopoiesis in bone marrow and extramedullary haematopoiesis in spleen at 100 mg/kg/day in 4/10 and 2/10 males, respectively. Many findings were related to endocrine effects, but had not considered that some may have been secondary to the lower body weights. Without having the individual data, it is not possible to comment further. In conclusion, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was 10 mg/kg bw/day due to findings of reduced body weight gain and abnormal estrous cycles in the female rat treated at 30 mg/kg bw/day.
The hazard conclusion for reproductive and developmental toxicology were as follows (OECD 422, Anon., 2011):
NOAEL(fertility) = <30 mg/kg bw/day
NOAEL(development) = No hazard identified
Whilst these endpoints resulted in a classification of category 1B reproductive toxicant, the lower NOAEL of 10 mg/kg bw/day from the repeated dose toxicity study was used for long-term systemic hazard assessment, in accordance with the precautionary principle.
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.
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