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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.99 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):
45
Dose descriptor starting point:
NOAEL
Value:
18.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
44.68 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 18.1 mg/kg bw/day for rats based on salivation and slight effects on the body weight at the next higher dose level of 86 mg/kg bw/day in male rats only.

The NOAEL of 18.1 mg/kg bw/day thus was considered appropriate as point of departure for DNEL derivation. This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the “Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the exposure duration of 5 days per week in comparison to 7 days per week, the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 5/7 x 1/0.38 m³/kg/day x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 44.68 mg/m³.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
6
Justification:
Default value: subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
3
Justification:
Systemic effects in the repeated dose study with rats were minimal and restricted to general systemic toxicity (effects on body weight, food consumption, salivation) and only present in males (LOAEL: 86 mg/kg bw/day) at the next higher dose level. Therefore an intraspecies factor of 3 is considered to be sufficient.
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 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):
180
Dose descriptor starting point:
NOAEL
Value:
18.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
253.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following dermal application. The NOAEL for general, systemic toxicity of the test substance was 18.1 mg/kg bw/day for rats based on salivation and slight effects on the body weight at the next higher dose level of 86 mg/kg bw/day in male rats only.

The NOAEL of 18.1 mg/kg bw/day thus was considered appropriate as point of departure for DNEL derivation. This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the “Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the dermal human NOAEL corrected for differences between the exposure duration of 5 days per week in comparison to 7 days per week, and for differences between the oral and dermal absorption rate (calculated with DermWin as "very low"; furthermore no clinical signs were observed in the acute dermal toxicity study in comparison to the acute oral toxicity study), by multiplying with the corresponding factors (x 5/7 x 100/10). The resulting corrected starting point for dermal DNEL derivation for workers is equal to 253.4 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
6
Justification:
Default value: subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
3
Justification:
Systemic effects in the repeated dose study with rats were minimal and restricted to general systemic toxicity (effects on body weight, food consumption, salivation) and only present in males (LOAEL: 86 mg/kg bw/day) at the next higher dose level. Therefore an intraspecies factor of 3 is considered to be sufficient.
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.209 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:
NOAEL
Value:
18.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
15.74 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 18.1 mg/kg bw/day for rats based on salivation and slight effects on the body weight at the next higher dose level of 86 mg/kg bw/day in male rats only.

The NOAEL of 18.1 mg/kg bw/day thus was considered appropriate as point of departure for DNEL derivation. This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the “Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24 -hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg/day). The resulting corrected starting point for inhalation DNEL derivation for general population is equal to 15.74 mg/m³.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
6
Justification:
Default value: subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Systemic effects on the repeated dose study with rats were minimal and restricted to general systemic toxicity (effects on body weight, food consumption, salivation) and only present in males (LOAEL: 86 mg/kg bw/day) at the next higher dose level. Therefore, an intraspecies factor of 5 is considered to be sufficient.
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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:
NOAEL
Value:
18.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
181 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following dermal application. The NOAEL for general, systemic toxicity of the test substance was 18.1 mg/kg bw/day for rats based on salivation and slight effects on the body weight at the next higher dose level of 86 mg/kg bw/day in male rats only.

The NOAEL of 18.1 mg/kg bw/day thus was considered appropriate as point of departure for DNEL derivation. This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the “Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the dermal human NOAEL corrected for differences between the oral and dermal absorption rate (calculated with DermWin as "very low", furthermore no clinical signs were observed in the acute dermal toxicity study in comparison to the acute oral toxicity study), by multiplying with the corresponding factor (x 100/10). The resulting corrected starting point for dermal DNEL derivation for general population is equal to 181.0 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Systemic effects on the repeated dose study with rats were minimal and restricted to general systemic toxicity (effects on body weight, food consumption, salivation) and only present in males (LOAEL: 86 mg/kg bw/day) at the next higher dose level. Therefore, an intraspecies factor of 5 is considered to be sufficient.
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.06 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:
NOAEL
Value:
18.1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
18.1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following oral administration. The NOAEL for general, systemic toxicity of the test substance was 18.1 mg/kg bw/day for rats based on salivation and slight effects on the body weight at the next higher dose level of 86 mg/kg bw/day in male rats only.

The NOAEL of 18.1 mg/kg bw/day thus was considered appropriate as point of departure for DNEL derivation.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Systemic effects on the repeated dose study with rats were minimal and restricted to general systemic toxicity (effects on body weight, food consumption, salivation) and only present in males (LOAEL: 86 mg/kg bw/day) at the next higher dose level. Therefore, an intraspecies factor of 5 is considered to be sufficient.
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population