Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.3 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:
132 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study is available. The overall NOAEL of 150 mg/kg bw/d is corrected for breathing rate (/0.38), activity (*0.67/10) and assuming that inhalation absorption is twice the level of oral absorption. The corrected inhalation NOAEC is therefore 132 mg/m3.
AF for dose response relationship:
1
Justification:
Default assessment factor
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Already taken into account in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default assessment factor (rat study)
AF for intraspecies differences:
5
Justification:
Default assessment factor
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor.
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:
1.5 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:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal study is available. As a worst case default assumption, dermal absorption is assumed to be the same as oral absorption. A corrected dermal NOAEL of 150 mg/kg bw/d is therefore derived.
AF for dose response relationship:
1
Justification:
Default assessment factor
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic suudy to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor (rat study)
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor (workers)
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor
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

Endpoint selection

BEPD is of low acute oral and dermal toxicity, is not a skin irritant or skin sensitiser, but is classified as an eye irritant. Repeated dose toxicity studies with BEPD identified renal toxicity specific to male rats. Based on the findings of these studies and the structural similarity of BEPD to substances know to cause male rat-specific nephropathy secondary to the deposition of alpha-2 -microglobulin, an overall NOAEL of 150 mg/kg bw/d is derived. Non-renal findings in male rats and findings in female rats were relatively minor and were seen only at the limit dose level. The developmental toxicity study with BEPD did not identify any adverse effects; a maternal NOAEL of 150 mg/kg bw/d was derived, based on effects at the limit dose. Based on the results of the 28 -day, 90-day and developmental toxicity studies, a starting point of 150 mg/kg bw/d is used for DNEL derivation.

Inhalation DNELs

Systemic Inhalation DNELs

The oral NOAEL of 150 mg/kg bw/d from the rat studies is corrected for breathing rate (/0.38), activity (*0.67) and assuming that inhalation absorption is twice the level of oral absorption. The corrected inhalation NOAEC is therefore 132 mg/m3.

Long-term systemic inhalation DNEL

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 25. Application of the overall assessment factor to the corrected inhalation NOAEC results in a DNEL of 5.3 mg/m3.

Short-term systemic inhalation DNEL

A DNEL is not derived in the absence of any identified hazard. There is no indication of short-term or acute toxicity from other studies and the substance is not classified for acute toxicity.

Local Inhalation DNELs

DNELs are not derived in the absence of any evidence of respiratory irritation.

Dermal DNELs

Systemic Dermal DNELs

As a worst case default assumption, dermal absorption is assumed to be the same as oral absorption. A corrected dermal NOAEL of 150 mg/kg bw/d is therefore derived.

Long-term systemic dermal DNEL

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 100. Application of the overall assessment factor to the corrected dermal NOAEL results in a DNEL of 1.5 mg/kg bw/d.

Short-term systemic dermal DNEL

A DNEL is not derived in the absence of any identified hazard. There is no indication of short-term or acute toxicity from other studies and the substance is not classified for acute toxicity.

Local Dermal DNELs

Local long-term and short-term dermal DNEL values are not derived, in the absence of an identified hazard. The substance is not a skin irritant or skin sensitiser.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
65 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation studies are available. The oral NOAEL of 150 mg/kg bw/d from the rat developmental toxicity study is corrected for breathing rate (/1.15) and assuming that inhalation absorption is twice the level of oral absorption. The corrected inhalation NOAEC is therefore 65 mg/m3.
AF for dose response relationship:
1
Justification:
Default assessment factor
AF for differences in duration of exposure:
2
Justification:
Extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Already taken into account
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor (general population)
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor
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:
0.75 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:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal study is available. As a worst case default assumption, dermal absorption is assumed to be the same as oral absorption. A corrected dermal NOAEL of 150 mg/kg bw/d is therefore derived.
AF for dose response relationship:
1
Justification:
Default assessment factor
AF for differences in duration of exposure:
2
Justification:
Extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor (rat study)
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor (general population)
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor
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:
0.75 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:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required; the starting point is derived from an oral study
AF for dose response relationship:
1
Justification:
Default assessment factor
AF for differences in duration of exposure:
2
Justification:
Extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor
AF for other interspecies differences:
2.5
Justification:
Default assessment factor (rat study)
AF for intraspecies differences:
10
Justification:
Default assessment factor (general population)
AF for the quality of the whole database:
1
Justification:
Default assessment factor
AF for remaining uncertainties:
1
Justification:
Default assessment factor
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

Endpoint selection

BEPD is of low acute oral and dermal toxicity, is not a skin irritant or skin sensitiser, but is classified as an eye irritant. Repeated dose toxicity studies with BEPD identified renal toxicity specific to male rats. Based on the findings of these studies and the structural similarity of BEPD to substances know to cause male rat-specific nephropathy secondary to the deposition of alpha-2 -microglobulin, an overall NOAEL of 150 mg/kg bw/d is derived. Non-renal findings in male rats and findings in female rats were relatively minor and were seen only at the limit dose level. The developmental toxicity study with BEPD did not identify any adverse effects; a maternal NOAEL of 150 mg/kg bw/d was derived, based on effects at the limit dose. Based on the results of the 28 -day, 90-day and developmental toxicity studies, a starting point of 150 mg/kg bw/d is used for DNEL derivation.

Inhalation DNELs

Systemic Inhalation DNELs

The oral NOAEL of 150 mg/kg bw/d from the rat studies is corrected for breathing rate (/1.15) and assuming that inhalation absorption is twice the level of oral absorption. The corrected inhalation NOAEC is therefore 65 mg/m3.

Long-term systemic inhalation DNEL

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 50. Application of the overall assessment factor to the corrected inhalation NOAEC results in a DNEL of 1.3 mg/m3.

Short-term systemic inhalation DNEL

A DNEL is not derived.. There is no indication of short-term or acute toxicity; BEPD is not classified for acute toxicity.

Local Inhalation DNELs

A DNEL is not derived in the absence of any indication of respiratory irritation.

Dermal DNELs

Systemic Dermal DNELs

As a worst case default assumption, dermal absorption is assumed to be the same as oral absorption. A corrected dermal NOAEL of 150 mg/kg bw/d is therefore derived.

Long-term systemic dermal DNEL

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 200. Application of the overall assessment factor to the corrected dermal NOAEL results in a DNEL of 0.75 mg/kg bw/d.

Short-term systemic dermal DNEL

A DNEL is not derived.  There is no indication of short-term or acute toxicity and the substance is not classified for acute toxicity.

Local Dermal DNELs

Local long-term and short-term dermal DNEL values are not derived, in the absence of an identified hazard. The substance is not a skin irritant or skin sensitiser.

Oral DNELs

Systemic Oral DNELs

Correction of the starting point is not required.

Long-term systemic oral DNEL

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 200. Application of the overall assessment factor to the oral NOAEL results in a DNEL of 0.75 mg/kg bw/d.

Short-term systemic oral DNEL

A separate DNEL for acute/short-term exposure not derived. There is no indication of short-term or acute toxicity and the substance is not classified for acute toxicity.