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EC number: 204-809-1 | CAS number: 126-86-3
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.76 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
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 132 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- 28 day subacute study to chronic study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- there is no need for the species-specific allometric scaling factor for inhalation exposures (ECHA, 2010, table R.8-4)
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 5
- Justification:
- individual variability
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no others
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5.28 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):
- 0.33
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 132 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- One simple and well-established method used to estimate an acute threshold limit value (TLV) is multiplication of the long-term DNEL by a factor of 3 (Guidance R.8, Appendix R.8.8, 2010)
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- there is no need for the species-specific allometric scaling factor for inhalation exposure
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 5
- Justification:
- individual variability
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no others
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 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
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- 28 day subchronic study to chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rats to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 5
- Justification:
- individual variability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.5 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):
- 0.33
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rats to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 5
- Justification:
- individual variability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
The overall assessment factor for chronic oral/dermal exposure for workers is 300, which is divided into the NOAEL of 150 mg/kg bw/day, for a final value of 0.5 mg/kg bw/day. The overall workers assessment factors is comprised of 4 independent AFs: - allometric scaling scaling factor of 4, - remainder factor of 2.5, - intraspecies factor of 5, - study duration factor of 6. It is dived into the NOEL of 150 mg/kg Bw/day from the following study: Envirogem AD01, H-104, in a 28-day gavage study in Hsd:WISnrats, at dose concentrations of 0, 15, 150, and 1000 mg/kg bw/d. The NOAEL in this study was 150 mg/kg bw/day.
For the longterm inhalation DNEL route-to-route extrapolation is used.
The NOAEL from the H-104 28 day repeated dose toxicity study in rats is chosen (150 mg/kg bw/d). The NOAEL is multiplied by an absorption factor of 0.5 (gastric absorption from the oral route is half that of inhalation exposure, as per an ECHA default value), and a modifier (0.75) to convert from a 6 h/day exposure to the 8 h/day exposure of a worker’s shift. This is also multiplied by another modifier (0.67) to reflect an increased respiratory volume (10.0 m3) during light exertion of a worker compared to the resting level typical of animal exposure (6.7 m3). This results in the dose descriptor being reduced to to 132.26 mg/ m3. There is no need for the species-specific allometric scaling factor for inhalation exposures (ECHA, 2010, Table R.8-4). The overall AF is 75, divided into the modified dose descriptor, resulting in a DNEL of 1.76 mg/ m3.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.43 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
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 150 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- 28 day subacute study to chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rats to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 10
- Justification:
- individual varability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.29 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):
- 0.33
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 150 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- existing long term test on rats (oral)
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rats to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 10
- Justification:
- individual varability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 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
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- 28 day subacute study to chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rats to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 10
- Justification:
- individual varability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.75 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):
- 0.33
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rats to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 10
- Justification:
- individaual varability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Local effects
Long term exposure
- Hazard assessment conclusion:
- DMEL (Derived Minimum Effect Level)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 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
- Modified dose descriptor starting point:
- NOAEL
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- 28 day subacute study to chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 10
- Justification:
- individual variability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.75 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):
- 0.33
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- long term 28 day repeated dose toxicity is chosen
- AF for dose response relationship:
- 1
- Justification:
- not a LOAEL
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remainder
- AF for intraspecies differences:
- 10
- Justification:
- individual variability in response
- AF for the quality of the whole database:
- 1
- Justification:
- full data set
- AF for remaining uncertainties:
- 1
- Justification:
- no other
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
The overall assessment factor for chronic oral/dermal exposure for the population is 600, which is divided into the NOAEL of 150 mg/kg bw/day, for a final value of 0.25 mg/kg bw/day. The overall population assessment factor is comprised of 4 independent AFs: - allometric scaling scaling factor of 4, - remainder factor of 2.5, - intraspecies factor of 10, - study duration factor of 6. It is dived into the NOEL of 150 mg/kg Bw/day from the following study: Envirogem AD01, H-104, in a 28-day gavage study in Hsd:WISnrats, at dose concentrations of 0, 15, 150, and 1000 mg/kg bw/d. The NOAEL in this study was 150 mg/kg bw/day.
For the longterm inhalation DNEL route-to-route extrapolation is used. The NOAEL from the H-104 28 day repeated dose toxicity study in rats is chosen (150 mg/kg bw/d). The NOAEL is multiplied by an absorption factor of 0.5 (gastric absorption from the oral route is half that of inhalation exposure, as per an ECHA default value), and a modifier (0.87) to convert from a 6 h/day exposure to the 24 h/day exposure for the population. The final dosedescriptor is 64.22 mg/m³. Three AFs are applied: remainder 2.5, intraspecies 10, duration 6. There is no need for the species-specific allometric scaling factor. The overall AF is 150, divided into the modified dose descriptor, resulting in a DNEL of 0.43 mg/ m3.
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