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EC number: 413-110-2 | CAS number: 135861-56-2
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.3 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:
- 358.3 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No experimental data available for the inhalation route.
- AF for dose response relationship:
- 1
- Justification:
- Experimental data show reliable dose-response relationship
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Rat to human correction undertaken during route-to route extrapolation of starting dose
- AF for other interspecies differences:
- 2.5
- Justification:
- Standard default value in ECHA guidance.
- AF for intraspecies differences:
- 5
- Justification:
- Standard default value in ECHA guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Data base is good
- AF for remaining uncertainties:
- 1
- Justification:
- No other uncertainties apparent
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.1 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:
- 406.4 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No experimental data available for the repeated dose dermal route.
- AF for dose response relationship:
- 1
- Justification:
- Experimental data show reliable dose-response relationship.
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Rat to human extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- Standard default value in ECHA guidance.
- AF for intraspecies differences:
- 5
- Justification:
- Standard default value in ECHA guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Data base is good
- AF for remaining uncertainties:
- 1
- Justification:
- No other uncertainties apparent
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
The DNEL for long-term inhalation exposure was derived from a NOAEL of 406.4 mg/kg bw/day for a sub-chronic dietary toxicity study in rats (Pharmakon Europe, 1993) . The corrected starting dose was calculated using the formula 406.4 mg/kg bw/day x 1/0.38 (rat standard breathing volume) x 0.5 (absorption differences) x 6.7/10 0 (light worker activity) = 358.3. mg/m3. An overall assessment factor of 25 was calculated, based on the ECHA guidance in R8, Figure R-6, May 2008, giving a DNEL of 14.3 mg/m3.
The DNEL for long-term dermal exposure was derived from a NOAEL of 406.4 mg/kg bw/day for a sub-chronic oral toxicity study in rats (Pharmakon Europe, 1993). The corrected starting dose was calculated using the formula 406.4 mg/kg bw/day x 1 (absorption difference) = 406.5 mg/kg bw/day. An allometric scaling factor of 4 was used (rat to human) and an overall assessment factor of 100 was calculated, based on the ECHA guidance in R8, Figure R-6, May 2008, giving a DNEL of 4.1 mg/kg bw/day.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.5 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:
- 176.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No experimental data available for the inhalation route.
- AF for dose response relationship:
- 1
- Justification:
- Experimental data show reliable dose-response relationship
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Rat to human correction undertaken during route-to route extrapolation of starting dose
- AF for other interspecies differences:
- 2.5
- Justification:
- Standard default value in ECHA guidance.
- AF for intraspecies differences:
- 10
- Justification:
- Standard default value in ECHA guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Data base is good
- AF for remaining uncertainties:
- 1
- Justification:
- No other uncertainties apparent
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 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:
- 406.4 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No experimental data available for the dermal route.
- AF for dose response relationship:
- 1
- Justification:
- Experimental data show reliable dose-response relationship
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Rat to human extrapolation.
- AF for other interspecies differences:
- 2.5
- Justification:
- Standard default value in ECHA guidance.
- AF for intraspecies differences:
- 10
- Justification:
- Standard default value in ECHA guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Data base is good
- AF for remaining uncertainties:
- 1
- Justification:
- No other uncertainties apparent
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 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:
- 406.4 ng/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Experimental data show reliable dose-response relationship
- AF for differences in duration of exposure:
- 2
- Justification:
- Sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Rat to human extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- Standard default value in ECHA guidance.
- AF for intraspecies differences:
- 10
- Justification:
- Standard default value in ECHA guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- Data base is good
- AF for remaining uncertainties:
- 1
- Justification:
- No other uncertainties apparent
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
The DNEL for long-term inhalation exposure was derived from a NOAEL of 406.5 mg/kg bw/day from a sub-chronic dietary toxicity study in rats (Pharmakon Europe, 1993). The corrected starting dose was calculated using the formula 406.4 mg/kg bw/day x 1/1.15 (rat standard breathing volume) x 0.5 (absorption differences) = 176.7 mg/m3. An overall assessment factor of 50 was calculated, based on the ECHA guidance given in R8, Figure R-6, May 2008, giving a DNEL of 3.5 mg/m3.
The DNEL for long-term dermal exposure was derived from a NOAEL of 406.5 mg/kg bw/day from a sub-chronic oral toxicity study in rats (Pharmakon Europe, 1993). The corrected starting dose was calculated using the formula 406.4 mg/kg bw/day x 1 (absorption difference) = 406.5 mg/kg bw/day. An allometric scaling factor of 4 was used (rat to human) and an overall assessment factor of 200 was calculated, based on the ECHA guidance given in R8, Figure R-6, May 2008, giving a DNEL of 2.0 mg/kg bw/day.
The DNEL for long-term oral exposure was derived from a NOAEL of 406.4 mg/kg bw/day from a sub-chronic dietary toxicity study in rats (Pharmakon Europe, 1993). Using an allometirc scaling factor of 4 (rat to human) and overall assessment factor of 200 was calculated, based on the ECHA guidance given in R8, Figure R-6, May 2008, giving a DNEL of 2.0 mg/kg bw/day.
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