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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.411 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):
30
Modified dose descriptor starting point:
NOAEC
Value:
12.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated dose toxicity study by inhalation is available. Therefore a oral-to-inhalation extrapolation is done. The default factor of 2 was included.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
default value for time extrapolation from subacute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default value for correction for differences in metabolic rate (rat to humans)
AF for intraspecies differences:
5
Justification:
default value (worker)
AF for the quality of the whole database:
1
Justification:
GLP Guideline study
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
0.233 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):
120
Modified dose descriptor starting point:
NOAEL
Value:
28 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated dose toxicity study with dermal application is available. Therefore a oral-to-dermal extrapolation is done. A dermal absorption potential of 50% is assumed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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:
medium hazard (no threshold derived)

Additional information - workers

Worker:

Inhalation long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (RCC, 1998) 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 10 mg/kg bw/day for rats based on a reduction in thymus weights (females), thymical atrophy (females), alpha-2-microglobulin nephropathy and seminiferous tubular atrophy of the testes at the next higher dose level of 50 mg/kg bw/day.

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. 20 f.":

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between 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 and by adjusting the time of exposure (rats were exposed 7 days/week and worker is exposed 5 days per week) (x 1/0.38 m³/kg/d x 6.7 m³/10 m³ x 7/5). Furthermore, it is proposed, thus, in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation. The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 12.3 mg/m³.

Dermal long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study (28 days) with rats conducted according to OECD TG 407 (RCC, 1998) 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 10 mg/kg bw/day for rats based on a reduction in thymus weights (females), thymical atrophy (females), alpha-2-microglobulin nephropathy and seminiferous tubular atrophy of the testes at the next higher dose level of 50 mg/kg bw/day.

This point of departure was modified to get the corrected starting point for DNEL derivation based on the assumption of a limited dermal absorption compared to oral absorption which is supported by the fact that in an acute dermal toxicity study in rats a LD50 of > 2000 mg/kg was observed (BASF SE, 2012) compared to a LD50 of 1770 mg/kg after oral administration in rats via gavage (BASF AG, 1989). Therefore, a route-to-route (oral -> dermal) extrapolation factor of 0.5 is used. The starting point was further corrected by a factor of 1.4 since rats were exposed 7 days per week and the worker is exposed 5 days per week (7/5). This results in a corrected starting point of 28 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.072 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):
60
Modified dose descriptor starting point:
NOAEC
Value:
4.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated dose toxicity study by inhalation is available. Therefore a oral-to-inhalation extrapolation is done. The default factor of 2 was included.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
0.083 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):
240
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated dose toxicity study with dermal application is available. Therefore a oral-to-dermal extrapolation is done. A dermal absorption potential of 50% is assumed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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:
0.042 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):
240
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Consumer

Inhalation long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (RCC, 1998) 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 10 mg/kg bw/day for rats based on a reduction in thymus weights (females), thymical atrophy (females), alpha-2-microglobulin nephropathy and seminiferous tubular atrophy of the testes at the next higher dose level of 50 mg/kg bw/day.

This point of departure was modified to get the correct 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. 20 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/d). Furthermore, it is proposed, thus, in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation.

The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 4.3 mg/m³.

Dermal long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study (28 days) with rats conducted according to OECD TG 407 (RCC, 1998) 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 10 mg/kg bw/day for rats based on a reduction in thymus weights (females), thymical atrophy (females), alpha-2-microglobulin nephropathy and seminiferous tubular atrophy of the testes at the next higher dose level of 50 mg/kg bw/day.

This point of departure was modified to get the corrected starting point for DNEL derivation based on the assumption of a limited dermal absorption compared to oral absorption which is supported by the fact that in an acute dermal toxicity study in rats a LD50 of > 2000 mg/kg was observed (BASF SE, 2012) compared to a LD50 of 1770 mg/kg after oral administration in rats via gavage (BASF AG, 1989). Therefore, a route to route (oral -> dermal) extrapolation factor of 0.5 is used. This results in a corrected starting point of 20 mg/kg bw/day.

 

Oral long-term exposure – systemic effects:

In addition, the DNEL for oral long-term exposure was derived from the no observed adverse effect level obtained in a gavage study conducted with the substance in rats according to OECD TG 407 (RCC, 1998).The NOAEL for general, systemic toxicity of the test substance was 10 mg/kg bw/d for rats based on a reduction in thymus weights (females), thymical atrophy (females), alpha-2-microglobulin nephropathy and seminiferous tubular atrophy of the testes at the next higher dose level of 50 mg/kg bw/day.

A correction of the starting point is not necessary since an oral study is available.