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EC number: 204-289-6 | CAS number: 118-96-7
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.04 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:
- 0.88 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oralabsorption rate is 50%of that inhalation absorption.
- AF for differences in duration of exposure:
- 2
- Justification:
- DNEL is based on an oral 90 day study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation route
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- Justification:
- for workers
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.1 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):
- 12.5
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 0.88 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oralabsorption rate is 50%of that inhalation absorption.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation route
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- Justification:
- workers
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- irritation (respiratory tract)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.01 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):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oral and dermal absorption rates are equal.
- AF for differences in duration of exposure:
- 2
- Justification:
- based on an oral 90 day study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- experimental animal was rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- Justification:
- for workers
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.02 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):
- 50
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oral and dermal absorption rates are equal.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- experimental animal was rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- Justification:
- for workers
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
DNEL - long term, worker
Inhalation systemic long term. Route-to-route extrapolation:
The calculations for the long term DNELs for workers are based on a 90 day oral feeding study performed in Fischer 344 rats. The NOAEL value in this study was found to be 1 mg/kg bw/d. This value was used as basis for DNEL calculation. Route-to-route extrapolation (oral to inhalative) was performed according to the ECHA Guidance Document on information requirements and chemical safety assessment Chapter R.8. It was assumed that oral absorption rate is 50% of that of inhalation absorption.
Starting point (worker, inhalation)= NOAEL oral*(1/sRVrat)*(sRVhuman/wRV)*(ABSoral-rat/ABSinh-human)= 1mg/kg/d*(1/0.38m3/kg/d)*(6.7m3(8h)/10m3(8h))*0.5=0.88mg/m3
It was assumed that oral and dermal absorption rates are equal.
Starting point (worker,dermal)= 1mg/kg/d
Assessment factors for DNEL derivations
Inhalation
Overall AF = 25
Dermal
Overall AF = 100
Taken above information
DNEL inhalation, long term, sytemic effects = 0.88/25=0.035 mg/m3
DNEL dermal, long term,systemic effects = 1/100=0.01 mg/kg bw/d
DNEL - short term, worker
Inhalation systemic effects acute.
DNELacute extrapolated from long term DNEL
Starting point (worker, inhalation, acute)=0.88 mg/m3
Assessment factors for DNEL derivations
Inhalation, worker,acute
Overall AF = 12.5
Dermal systemic effects acute.
DNELacute extrapolated from long term DNEL
It was assumed that oral and dermal absorption rates are equal.
Starting point (worker,dermal)= 1mg/kg/d
Dermal
Overall AF = 50
Taken above information:
DNEL inhalation, short term, sytemic effects = 0.88/12.5=0.07 mg/m3
DNEL dermal, short term,systemic effects = 1/50=0.02 mg/kg bw/d
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.01 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):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 0.43 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oralabsorption rate is 50%of that inhalation absorption.
- AF for differences in duration of exposure:
- 2
- Justification:
- DNEL is based on an oral 90 day study
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- for general population
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.02 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
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 0.43 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oralabsorption rate is 50%of that inhalation absorption.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation route
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- for general population
- AF for the quality of the whole database:
- 1
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- irritation (respiratory tract)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.01 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):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oral and dermal absorption rates are equal.
- AF for differences in duration of exposure:
- 2
- Justification:
- based on an oral 90 day study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- experimental animal was rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- for general population
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.01 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):
- 100
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- It is assumed that oral and dermal absorption rates are equal.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- experimental animal was rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- for general population
- AF for the quality of the whole database:
- 1
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
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:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- AF for differences in duration of exposure:
- 2
- Justification:
- based on an oral 90 day study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- experimental animal was rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- for general population
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.01 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):
- 100
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 mg/kg bw/day
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- experimental animal was rat
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- Justification:
- for general population
- AF for the quality of the whole database:
- 1
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
DNEL - long term, general population
Inhalation systemic long term. Route-to-route extrapolation:
The calculations for the long term DNELs for workers are based on a 90 day oral feeding study performed in Fischer 344 rats. The NOAEL value in this study was found to be 1 mg/kg bw/d. This value was used as basis for DNEL calculation. Route-to-route extrapolation (oral to inhalative) was performed according to the ECHA Guidance Document on information requirements and chemical safety assessment Chapter R.8. It was assumed that oral absorption rate is 50% of that of inhalation absorption.
Starting point (general population, inhalation)= NOAEL oral*(1/1.15 m3/kg/d)*(ABSoral-rat/ABSinh-human)= 1mg/kg/d*(1/1.15m3/kg/d)*0.5=0.43mg/m3
It was assumed that oral and dermal absorption rates are equal.
Starting point (general population,dermal)= 1mg/kg/d
Assessment factors for DNEL derivations
Inhalation
Overall AF = 50
Dermal
Overall AF = 200
Taken above information
DNEL inhalation, long term, sytemic effects = 0.43/50=0.0086 mg/m3
DNEL dermal, long term,systemic effects = 1/200=0.005 mg/kg bw/d
DNEL - short term, general population
Inhalation systemic effects acute.
DNELacute extrapolated from long term DNEL
Starting point (general population, inhalation, acute)=0.43 mg/m3
Assessment factors for DNEL derivations
Inhalation, general population,acute
Overall AF = 25
Dermal systemic effects acute.
DNELacute extrapolated from long term DNEL
It was assumed that oral and dermal absorption rates are equal.
Starting point (general population,dermal)= 1mg/kg/d
Dermal
Overall AF = 100
Taken above information:
DNEL inhalation, short term, sytemic effects = 0.43/25=0.02 mg/m3
DNEL dermal, short term,systemic effects = 1/100=0.01 mg/kg bw/d
The DNEL oral is the same as the DNEL dermal.
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