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Diss Factsheets
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EC number: 201-132-3 | CAS number: 78-67-1
- 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:
- 0.14 mg/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1.76 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Corrected dose descriptor 1x1/0.38x6.7/10=1.76 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- This factor is applied because the dose-descriptor starting point is a NOAEC.
- AF for differences in duration of exposure:
- 1
- Justification:
- No uncertainty factor because the study is a rat prenatal developmental study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation because it is an oral to inhalation route.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor of 2.5 is applied for uncertainties
- AF for intraspecies differences:
- 5
- Justification:
- A factor of 5 is applied for workers
- AF for the quality of the whole database:
- 1
- Justification:
- The studies performed with AZDN are reliable studies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 199 mg/m³
- Most sensitive endpoint:
- acute toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 1 570 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Time extrapolation to the reference period of 15 minutes for acute effects, using the modified Haber's law (Cnx t = k) with ancoefficient of 3 for extrapolation from a longer to a shorter exposure duration : LOAEC (15 minutes) = 2489 mg/m3
- AF for dose response relationship:
- 1
- AF for interspecies differences (allometric scaling):
- 2.5
- AF for other interspecies differences:
- 1
- AF for intraspecies differences:
- 5
- Justification:
- A factor of 5 is applied for workers
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 194.17 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- A dermal penetration study is available. the mean penetrated amount is 0.0103% of human skin.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- No uncertainty factor because the study is a rat prenatal developmental study
- AF for interspecies differences (allometric scaling):
- 2.5
- AF for other interspecies differences:
- 4
- AF for intraspecies differences:
- 5
- Justification:
- A factor 5 is used for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Quality of the studies performed with AZDN are reliable.
- 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:
- hazard unknown (no further information necessary)
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
- Step 1: Selection of the relevant dose descriptor:
- Step 3: Assessment factors:
- Step 4: DNEL derivation:
- Corrected dermal NOAEL, route = oral NOAEL x (ABSoral-rat/ABSderm-rat) x (ABSderm-rat/ ABSderm-human)
- = oral NOAEL x (ABSoral-rat/ABSderm-human)
Worker Acute DNEL (inhalation, systemic)
The acute inhalation rat toxicity study using AZDN (Dupont., 1984, report unavailable (awaiting for Dupont), questionable validity(quoted K3), described in the SIDS 2002) was used for DNEL derivation. In this study, three concentrations were tested: 1.57, 3.40, and 7.78 mg/L during one hour exposure. Only one death was recorded 1 day after exposure to 1.57 mg/L. No other death was observed at any dose-level. Most rats exhibited moderate to severe weight losses 1 or 2 days after exposure, followed by a return to a normal weight gain rate. Most females exhibited sporadic weight losses during the 2-week observation period.
Step 1: Selection of the relevant dose descriptor:
LOAEC (1 hour) = 1.57 mg/L=1570 mg/m3
Step 2: Modification of the starting point:
Time extrapolation to the reference period of 15 minutes for acute effects, using the modified Haber's law (Cnx t = k) with ancoefficient of 3 for extrapolation from a longer to a shorter exposure duration :
LOAEC (15 minutes) = 2489 mg/m3
Step 3: Assessment factors:
- Interspecies differences: as massive exposure by inhalation is considered, no toxicokinetic assessment factor is applied. However, a factor of 2.5 to correct for differences other than differences in metabolic rate is applied.
- Intraspecies differences: the default assessment factor of 5 is applied.
- Severity: no additional safety factor taking into account the very low severity of effects
- Quality of whole database: a factor of 1 is applied based on the good quality of the whole database.
- Global assessment factor: 2.5 x 5 x 1 = 12.5
Step 4: DNEL derivation:
Worker DNEL (acute, systemic effects, inhalation) = 2489x1/12.5= 199 mg/m3
Worker Long term DNEL (inhalation, systemic)
-NOAEL (Maternal systemic toxicity) =1 mg/kg/day,
-The lowest NOAEL was recorded in the prenatal developmental study in rats (according to OECD 414) performed with the compound AZDN. In this study, the LOAEL was equal to 5 mg/kg/day based on transient effects of reduced body weight gain and reduced mean food intake while no effects were observed on foetal development.
The LOAEL of 1 mg/kg/day recorded for F1 generation in the extended one generation study was not taken for the calculation of the DNELs as it was based on kidneys effects in males considered as not relevant to Human as it was highly suggestive of hyaline droplet nephropathy, a male rat specific change of no relevance to human.
· Step 2: Modification of the starting point:
-Conversion into an inhalatory rat NOAEC by dividing by 0.38 m3/kg (8-hour respiratory volume in the rat).
-No correction for inhalatory and oral absorption rates (considered to be 100 %)
-Correction for activity driven differences in respiratory volume in workers compared to individuals at rest (6.7 m3/10 m3) .
-Corrected dose descriptor:NOAEC (worker, 8 h)= 1 x 1/0.38 x 6.7/10 =1.76 mg/m3
-Interspecies : no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed. However, a factor of2.5to correct for differences other than differences in metabolic rate is applied.
-Intraspecies : the default assessment factor of5is applied.
-Differences in exposure duration: none (as it is a prenatal developmental study)
-Dose-response relationship: a factor of1is applied due to the use of a NOAEL as dose descriptor and the low toxicity of the test substance.
-Quality of whole database: a factor of1is applied based on the good quality of the whole database.
-Global assessment factor: 2.5 x 5 x 1 x 1 x 1 =12.5
Worker DNEL (long term, systemic effects, inhalation)= 1.76 x 1/12.5 =0.14 mg/m3
2. Worker Long term DNEL (Dermal, systemic)
Occupational exposure to AZDN may also occur by dermal exposure. Although no dermal repeated dose toxicity studies are available, a dermal abosption study on human skin is available. We derived a dermal DNEL based on the Oral NOAEL selected for the derivation of the inhalation DNEL.
Step 1) Relevant dose-descriptor
The NOAEL was selected based on the rat prenatal developmental study in rats (OECD 414).
-NOAEL, rats =(maternal toxicity) =1 mg/kg/day
Step 2) Modification of starting point:
Correction for oral to dermal absorption:
A dermal penetration study is available: The mean penetrated amount is 0.0103%of applied dose on human skin.No difference in dermal absorption is expected between rats and humans, no correction factor will be applied.
NOAEL corrected = 1 x (100 / 0.0103) = 9708.73 mg/kg bw
Step 3) Assessment factors
- Interspecies: 2.5 x 4
- Intraspecies : 5
- Exposure duration:none
- Dose response:1
- Quality of database:1
Global assessment factor = 50
DNEL Value (long term, systemic effects, dermal)= 9708.73 / 50 =194.17 mg/kg bw.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.07 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):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1.76 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Corrected dose descriptor 1x1/0.38x6.7/10=1.76 mg/m3
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- A factor of 1 is used as the key study is a rat developmental study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation because it is an oral to inhalation route.
- AF for other interspecies differences:
- 2.5
- Justification:
- as recommanded by ECHA guidance
- AF for intraspecies differences:
- 10
- Justification:
- A factor of 10 is used ofr the general population.
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 99.56 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 1 570 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Time extrapolation to the reference period of 15 minutes for acute effects, using the modified Haber's law (Cnx t = k) with ancoefficient of 3 for extrapolation from a longer to a shorter exposure duration : LOAEL (15 minutes) = 2489 mg/m3
- AF for dose response relationship:
- 1
- AF for interspecies differences (allometric scaling):
- 2.5
- AF for other interspecies differences:
- 1
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 97.08 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- A dermal penetration study is available. The mean penetrated amount is 0.0103% of human skin.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- based on a rat developmental study.
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- 10 is used for the general population
- 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:
- hazard unknown (no further information necessary)
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:
- 0.01 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- The rat developmental suty was performed by oral route, no extrapolation is needed.
- AF for dose response relationship:
- 1
- Justification:
- This factor is applied because the dose-descriptor starting point is a NOAEC.
- AF for differences in duration of exposure:
- 1
- Justification:
- No uncertainty factor because the study is a rat prenatal developmental study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- A factor of 4 is applied for the rat species
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor of 2.5 is applied for uncertainties
- AF for intraspecies differences:
- 10
- Justification:
- A factor of 10 is applied for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- The studies performed with AZDN are reliable studies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
- Corrected dermal NOAEL, route = oral NOAEL x (ABSoral-rat/ABSderm-rat) x (ABSderm-rat/ ABSderm-human)
- = oral NOAEL x (ABSoral-rat/ABSderm-human)
General population Acute DNEL (inhalation, systemic)
The acute inhalation rat toxicity study using AZDN (Dupont., 1984, report unavailable (awaiting for Dupont), questionable validity(quoted K3), described in the SIDS 2002) was used for DNEL derivation. In this study, three concentrations were tested: 1.57, 3.40, and 7.78 mg/L during one hour exposure. Only one death was recorded 1 day after exposure to 1.57 mg/L. No other death was observed at any dose-level. Most rats exhibited moderate to severe weight losses 1 or 2 days after exposure, followed by a return to a normal weight gain rate. Most females exhibited sporadic weight losses during the 2-week observation period.
Step 1: Selection of the relevant dose descriptor:
LOAEC (1 hour) = 1.57 mg/L=1570 mg/m3
Step 2: Modification of the starting point:
Time extrapolation to the reference period of 15 minutes for acute effects, using the modified Haber's law (Cnx t = k) with ancoefficient of 3 for extrapolation from a longer to a shorter exposure duration :
LOAEL (15 minutes) = 2489 mg/m3
Step 3: Assessment factors:
- Interspecies differences: as massive exposure by inhalation is considered, no toxicokinetic assessment factor is applied. However, a factor of 2.5 to correct for differences other than differences in metabolic rate is applied.
- Intraspecies differences: the default assessment factor of 10 is applied.
- Severity: no additional safety factor taking into account the very low severity of effects
- Quality of whole database: a factor of 1 is applied based on the good quality of the whole database.
- Global assessment factor: 2.5 x 10 x 1 = 25
Step 4: DNEL derivation:
Worker DNEL (acute, systemic effects, inhalation) = 2489x1/25= 99.56 mg/m3
General population Long term DNEL (Dermal, systemic)
Occupational exposure to AZDN may also occur by dermal exposure. Although no dermal repeated dose toxicity studies are available, a dermal absorption study on human skin is available. We derived a dermal DNEL based on the Oral NOAEL selected for the derivation of the inhalation DNEL.
Step 1) Relevant dose-descriptor
The lowest NOAEL was selected based on the rat prenatal developmental study in rats (OECD 414).
-NOAEL, rats =(maternal toxicity) =1 mg/kg/day
Step 2) Modification of starting point:
Correction for oral to dermal absorption:
A dermal penetration study is available: The mean penetrated amount is 0.0103%of applied dose on human skin.
NOAEL corrected = 1 x (100 / 0.0103) = 9708.73 mg/kg bw
Step 3) Assessment factors
- Interspecies: 2.5 x 4
- Intraspecies : 10
- Exposure duration:none
- Dose response:1
- Quality of database:1
Global assessment factor = 100
DNEL Value (long term, systemic effects, dermal)= 9708.73 / 100 =97.08 mg/kg bw.
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