Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

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.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.7 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:
other: NOEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
352.63 mg/m³
Explanation for the modification of the dose descriptor starting point:

Allometric scaling is applied as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/0.38 * 6.7/10 = mg/m3 inhalation NOAEC for workers.

AF for dose response relationship:
1
Justification:
The default assessment factor for NOEL is 1.
AF for differences in duration of exposure:
6
Justification:
ECHA guidance indicates a factor of 6 for extrapolation from subacute to chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
No substance specific data is available.
AF for intraspecies differences:
5
Justification:
ECHA guidance indicates a default assessment factor of 5 for workers.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.7 mg/m³
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:
0.67 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:
other: NOEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:
1
Justification:
The default assessment factor for NOEL is 1.
AF for differences in duration of exposure:
6
Justification:
ECHA guidance indicates a factor of 6 for extrapolation from subacute to chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for rat to human is 4.
AF for other interspecies differences:
2.5
Justification:
No substance specific data is available.
AF for intraspecies differences:
5
Justification:
ECHA guidance indicates a default assessment factor of 5 for workers.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 mg/kg bw/day
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

As basis for DNEL derivation the result from a 28-day oral toxicity study with rats was used, in which test item-related findings were generally restricted to salivation during daily observation and elevated liver weights and slight centrilobular hepatocellular hypertrophy after 4 weeks, in both sexes at the high dose level of 1000 mg/kg bw/day (no treatment related findings at 50 and 200 mg/kg bw/day). All these findings were reversible during the recovery period and histopathological findings in males and females treated with 1000 mg/kg/day, in the absence of commensurate changes in clinical biochemistry parameters, were considered to be metabolic adaptation. Therefore, 200 mg/kg bw/day was considered to be the NOEL and 1000 mg/kg bw/day was considered to be the NOAEL in this study. No factor was introduced in the route to route extrapolation based on toxicokinetic assessment of absorption. Allometric scaling is applied as described in ECHA technical guidance the oral NOEL in the rat mg/kg/day *1/0.38 * 6.7/10 = mg/m3 inhalation NOEC for workers. Based on toxicokinetic assessment, the absorption rate from dermal route is considered to be same as oral route. The NOELcorr for dermal therefore remains unchanged. The local effects are with low hazard (no threshold derived) due to the lack of significant response observed in available studies. The hazard for eyes are also considered to be low (no threshold derived) based on slightly effects observed in rabbit eye irritation study.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 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:
other: NOEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
173.91 mg/m³
Explanation for the modification of the dose descriptor starting point:

Allometric scaling is applied as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/1.15 = mg/m3 inhalation NOAEC for general population.

AF for dose response relationship:
1
Justification:
The default assessment factor for NOEL is 1.
AF for differences in duration of exposure:
6
Justification:
ECHA guidance indicates a factor of 6 for extrapolation from subacute to chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
No substance specific data is available.
AF for intraspecies differences:
10
Justification:
ECHA guidance indicates a default assessment factor of 10 for general population.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 mg/m³
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:
0.33 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:
other: NOEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:
1
Justification:
The default assessment factor for NOEL is 1.
AF for differences in duration of exposure:
6
Justification:
ECHA guidance indicates a factor of 6 for extrapolation from subacute to chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for rat to human is 4.
AF for other interspecies differences:
2.5
Justification:
No substance specific data is available.
AF for intraspecies differences:
10
Justification:
ECHA guidance indicates a default assessment factor of 10 for general population.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/kg bw/day
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:
0.33 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:
other: NOEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
other: NOEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation is applied.

AF for dose response relationship:
1
Justification:
The default assessment factor for NOEL is 1.
AF for differences in duration of exposure:
6
Justification:
ECHA guidance indicates a factor of 6 for extrapolation from subacute to chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for rat to human is 4.
AF for other interspecies differences:
2.5
Justification:
No substance specific data is available.
AF for intraspecies differences:
10
Justification:
ECHA guidance indicates a default assessment factor of 10 for general population.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

As basis for DNEL derivation the result from a 28-day oral toxicity study with rats was used, in which test item-related findings were generally restricted to salivation during daily observation and elevated liver weights and slight centrilobular hepatocellular hypertrophy after 4 weeks, in both sexes at the high dose level of 1000 mg/kg bw/day (no treatment related findings at 50 and 200 mg/kg bw/day). All these findings were reversible during the recovery period and histopathological findings in males and females treated with 1000 mg/kg/day, in the absence of commensurate changes in clinical biochemistry parameters, were considered to be metabolic adaptation. Therefore, 200 mg/kg bw/day was considered to be the NOEL and 1000 mg/kg bw/day was considered to be the NOAEL in this study. No factor was introduced in the route to route extrapolation based on toxicokinetic assessment of absorption. Allometric scaling is applied as described in ECHA technical guidance the oral NOEL in the rat mg/kg/day *1/1.15 = mg/m3 inhalation NOEC for general population. Based on the toxicokinetic assessment, the absorption rate from dermal route is considered to be same as oral route. The NOELcorr for dermal therefore remains unchanged. The local effects are with low hazard (no threshold derived) due to the lack of significant response observed in available studies. The hazard for eyes are also considered to be low (no threshold derived) based on slightly effects observed in rabbit eye irritation study.