Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
61.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 70 mg/kg bw/d is corrected for breathing rate and activity level (/0.38 *0.67), the extent of oral absorption (50%) and inhalation absorption (100%)
AF for dose response relationship:
1
Justification:
The substance is classified as a reproductive toxin based on testicular effects seen in male rats at the highest dietary concentration of 10000 ppm (~700 mg/kg bw/d) in the 90-day toxicity study. No testicular effects were observed at the intermediate dose level of 5000 ppm (~350 mg/kg bw/d) and an overall NOAEL of 1000 ppm (70 mg/kg bw/d) was derived for this study based on bodyweight effects. The NOAEL of 70 mg/kg bw/d for this study is used as the starting point for the derivation of long-term DNEL values; the use of this dose level represents additional safety factors of 5 and 10 over the NOAEL and LOAEL (respectively) for testicular toxicity seen in the 90-day study and is considered to be an adequately conservative approach for the protection of workers. The use of an additional assessment factor is therefore not proposed.
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:
No adjustment for allometry required, addressed in the calculation to determine inhalation dose descriptor
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value (worker)
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:
DNEL (Derived No Effect Level)
Value:
3.5 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
44.1 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 50 mg/kg bw/d is corrected for breathing rate and activity level (1/0.38 *0.67), the extent of oral absorption (50%) and inhalation absorption (100%)
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
1
Justification:
No adjustment for allometry required, addressed in the calculation to determine inhalation dose descriptor
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value (worker)
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value

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:
7 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
Dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 70 mg/kg bw/d is corrected for the extent of oral absorption (50%) and dermal absorption (5%)
AF for dose response relationship:
1
Justification:
The substance is classified as a reproductive toxin based on testicular effects seen in male rats at the highest dietary concentration of 10000 ppm (~700 mg/kg bw/d) in the 90-day toxicity study. No testicular effects were observed at the intermediate dose level of 5000 ppm (~350 mg/kg bw/d) and an overall NOAEL of 1000 ppm (70 mg/kg bw/d) was derived for this study based on bodyweight effects. The NOAEL of 70 mg/kg bw/d for this study is used as the starting point for the derivation of long-term DNEL values; the use of this dose level represents additional safety factors of 5 and 10 over the NOAEL and LOAEL (respectively) for testicular toxicity seen in the 90-day study and is considered to be an adequately conservative approach for the protection of workers. The use of an additional assessment factor is therefore not proposed.
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat study)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value (worker)
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:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 50 mg/kg bw/d is corrected for the extent of oral absorption (50%) and dermal absorption (5%)
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat study)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value (worker)
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value

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:
no hazard identified

Additional information - workers

For repeated exposure, the critical study for BMBF is the 90-day rat oral toxicity which identifies a NOAEL of 70 mg/kg bw/d, based on bodyweight effects at the next highest dose level of 350 mg/kg bw/d. The highest dose level in this study (700 mg/kg bw/d) showed effects on the reproductive tract of male rats (testicular and epididymal spermatogenesis). This finding is consistent with those seen with other boron-containing substances such as boric acid and boric oxide. Findings with BMBF are also seen at dose levels comparable (following correction for boron content) to dose levels of boric acid and boric oxide also causing testicular effects. The dose level of 700 mg/kg bw/d BMBF is equivalent to a dose level of approximately 63 mg/kg bw/d boron; findings in a 90-day study with boric acid are seen at a dose level of 334 mg/kg bw/d, equivalent to approximately 59 mg/kg bw/d boron. A reproductive toxicity study performed with boric acid at the same dose level resulted in a marked reduction in fertility due to male sterility. It is a reasonable assumption, therefore, that the administration of BMBF would cause comparable reproductive effects. Testing of BMBF for reproductive toxicity is therefore not proposed. The substance is proposed to be classified for reproductive toxicity in Category 1B in line with boric acid and boric oxide. An SCL of 10.7% is proposed, in line with the SCL values agreed for boric acid (5.5%) and boric oxide (3.1%) and taking into account the lower boron content of BMBF.

For acute exposure, the critical study for BMBF is the acute neurotoxicity study in the rat, which identifies a NOAEL of 50 mg/kg bw based on behavioural effects apparent at dose levels of 100 mg/kg bw and higher.

The relevant starting points for the derivation of DNELs for BMBF are the NOAEL of 70 mg/kg bw/d from the 90-day rat study and the NOAEL of 50 mg/kg bw/d derived from the acute neurotoxicity study.

Inhalation DNELs

Systemic DNELs

A long-term inhalation systemic DNEL is derived from the NOAEL of 70 mg/kg bw/d from the 90-day rat study.  A corrected (inhalation) starting point of 61.7 mg/m3derived, taking into account breathing rate (1/0.38*0.67) and the relative extent of oral (50%) and inhalation absorption (100%).

Applying 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) results in an overall assessment factor of 25. Applying the assessment factor of 25 to the corrected starting point gives a DNEL of 2.5 mg/m3.

BMBF is classified for reproductive toxicity based on effects seen in the 90-day study at a dose level of 700 mg/kg bw/d; the NOAEL for this effect is 350 mg/kg bw/d, whereas the overall study NOAEL is 70 mg/kg bw/d. Derivation of the DNEL from the overall study NOAEL therefore represents additional margins of safety of 5 and 10 over the NOAEL and LOAEL for testicular effects, respectively. This approach is considered to be adequately conservative for the protection of workers from the reproductive toxicity of BMBF. The use of additional assessment factors is therefore not proposed.

A short-term inhalation systemic DNEL is derived from the NOAEL of 50 mg/kg bw/d from the acute neurotoxicity rat study. A corrected (inhalation) starting point of 44.1 mg/m3is derived, taking into account breathing rate (1/0.38*0.67), and the relative extent of oral absorption (50%) and inhalation absorption (100%). 

Applying assessment factors of 1 (for dose-response relationship), 1 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 12.5. Applying the assessment factor of 12.5 to the corrected starting point gives a DNEL of 3.5 mg/m3.

Local inhalation DNEL values are not derived in the absence of any identified hazard.

Dermal DNELs

Systemic DNELs

A long-term dermal systemic DNEL is derived from the NOAEL of 70 mg/kg bw/d from the 90-day rat study. A corrected (dermal) starting point of 700 mg/kg bw/d derived taking into account the relative extent of oral absorption (50%) and dermal absorption (5%).

Applying 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) results in an overall assessment factor of 100. Applying the assessment factor of 100 to the corrected starting point gives a DNEL of 7 mg/kg bw/d. BMBF is classified for reproductive toxicity based on effects seen in the 90-day study at a dose level of 700 mg/kg bw/d; the NOAEL for this effect is 350 mg/kg bw/d, whereas the overall study NOAEL is 70 mg/kg bw/d. Derivation of the DNEL from the overall study NOAEL therefore represents additional margins of safety of 5 and 10 over the NOAEL and LOAEL for testicular effects, respectively. This approach is considered to be adequately conservative for the protection of workers from the reproductive toxicity of BMBF. The use of additional assessment factors is therefore not proposed.

A short-term dermal systemic DNEL is derived from the NOAEL of 50 mg/kg bw/d from the acute neurotoxicity rat study. A corrected (dermal) starting point of 500 mg/kg bw/d derived taking into account the relative extent of oral absorption (50%) and dermal absorption (5%).

Applying assessment factors of 1 (for dose-response relationship), 4 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 50. Applying the assessment factor of 50 to the corrected starting point gives a DNEL of 10 mg/kg bw/d.

Local dermal DNELs are not derived in the absence of any hazard.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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
Dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
30.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 70 mg/kg bw/d is corrected for breathing rate (/1.15), the extent of oral absorption (50%) and inhalation absorption (100%)
AF for dose response relationship:
1
Justification:
The substance is classified as a reproductive toxin based on testicular effects seen in male rats at the highest dietary concentration of 10000 ppm (~700 mg/kg bw/d) in the 90-day toxicity study. No testicular effects were observed at the intermediate dose level of 5000 ppm (~350 mg/kg bw/d) and an overall NOAEL of 1000 ppm (70 mg/kg bw/d) was derived for this study based on bodyweight effects. The NOAEL of 70 mg/kg bw/d for this study is used as the starting point for the derivation of long-term DNEL values; the use of this dose level represents additional safety factors of 5 and 10 over the NOAEL and LOAEL (respectively) for testicular toxicity seen in the 90-day study and is considered to be an adequately conservative approach for the protection of the general population. The use of an additional assessment factor is therefore not proposed.
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No adjustment for allometry required, addressed in the calculation to determine inhalation dose descriptor
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
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:
DNEL (Derived No Effect Level)
Value:
0.9 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
21.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 50 mg/kg bw/d is corrected for breathing rate (/1.15), the extent of oral absorption (50%) and inhalation absorption (100%)
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
1
Justification:
No adjustment for allometry required, addressed in the calculation to determine inhalation dose descriptor
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value

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:
3.5 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 70 mg/kg bw/d is corrected for the extent of oral absorption (50%) and dermal absorption (5%)
AF for dose response relationship:
1
Justification:
The substance is classified as a reproductive toxin based on testicular effects seen in male rats at the highest dietary concentration of 10000 ppm (~700 mg/kg bw/d) in the 90-day toxicity study. No testicular effects were observed at the intermediate dose level of 5000 ppm (~350 mg/kg bw/d) and an overall NOAEL of 1000 ppm (70 mg/kg bw/d) was derived for this study based on bodyweight effects. The NOAEL of 70 mg/kg bw/d for this study is used as the starting point for the derivation of long-term DNEL values; the use of this dose level represents additional safety factors of 5 and 10 over the NOAEL and LOAEL (respectively) for testicular toxicity seen in the 90-day study and is considered to be an adequately conservative approach for the protection of the general population. The use of an additional assessment factor is therefore not proposed.
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat study)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
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:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 50 mg/kg bw/d is corrected for the extent of oral absorption (50%) and dermal absorption (5%)
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat study)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value

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:
0.4 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required - oral study used as starting point
AF for dose response relationship:
1
Justification:
The substance is classified as a reproductive toxin based on testicular effects seen in male rats at the highest dietary concentration of 10000 ppm (~700 mg/kg bw/d) in the 90-day toxicity study. No testicular effects were observed at the intermediate dose level of 5000 ppm (~350 mg/kg bw/d) and an overall NOAEL of 1000 ppm (70 mg/kg bw/d) was derived for this study based on bodyweight effects. The NOAEL of 70 mg/kg bw/d for this study is used as the starting point for the derivation of long-term DNEL values; the use of this dose level represents additional safety factors of 5 and 10 over the NOAEL and LOAEL (respectively) for testicular toxicity seen in the 90-day study and is considered to be an adequately conservative approach for the protection of the general population. The use of an additional assessment factor is therefore not proposed.
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (Rat)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
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:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required - oral study used as starting point
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat study)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
AF for the quality of the whole database:
1
Justification:
Default value
AF for remaining uncertainties:
1
Justification:
Default value

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

For repeated exposure, the critical study for BMBF is the 90-day rat oral toxicity which identifies a NOAEL of 70 mg/kg bw/d, based on bodyweight effects at the next highest dose level of 350 mg/kg bw/d. The highest dose level in this study (700 mg/kg bw/d) showed effects on the reproductive tract of male rats (testicular and epididymal spermatogenesis). This finding is consistent with those seen with other boron-containing substances such as boric acid and boric oxide. Findings with BMBF are also seen at dose levels comparable (following correction for boron content) to dose levels of boric acid and boric oxide also causing testicular effects. The dose level of 700 mg/kg bw/d BMBF is equivalent to a dose level of approximately 63 mg/kg bw/d boron; findings in a 90-day study with boric acid are seen at a dose level of 334 mg/kg bw/d, equivalent to approximately 59 mg/kg bw/d boron. A reproductive toxicity study performed with boric acid at the same dose level resulted in a marked reduction in fertility due to male sterility. It is a reasonable assumption, therefore, that the administration of BMBF would cause comparable reproductive effects. Testing of BMBF for reproductive toxicity is therefore not proposed. The substance is proposed to be classified for reproductive toxicity in Category 1B in line with boric acid and boric oxide. An SCL of 10.7% is proposed, in line with the SCL values agreed for boric acid (5.5%) and boric oxide (3.1%) and taking into account the lower boron content of BMBF.

For acute exposure, the critical study for BMBF is the acute neurotoxicity study in the rat, which identifies a NOAEL of 50 mg/kg bw based on behavioural effects apparent at dose levels of 100 mg/kg bw and higher.

The relevant starting points for the derivation of DNELs for BMBF are the NOAEL of 70 mg/kg bw/d from the 90-day rat study and the NOAEL of 50 mg/kg bw/d derived from the acute neurotoxicity study.

Inhalation DNELs

Systemic DNELs

A long-term inhalation systemic DNEL is derived from the NOAEL of 70 mg/kg bw/d from the 90-day rat study.  A corrected (inhalation) starting point of 30.4 mg/m3is derived, taking into account breathing rate (*1/1.15) and the relative extent of oral (50%) and inhalation absorption (100%).

Applying 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) results in an overall assessment factor of 50. Applying the assessment factor of 50 to the corrected starting point gives a DNEL of 0.6 mg/m3.

BMBF is classified for reproductive toxicity based on effects seen in the 90-day study at a dose level of 700 mg/kg bw/d; the NOAEL for this effect is 350 mg/kg bw/d, whereas the overall study NOAEL is 70 mg/kg bw/d. Derivation of the DNEL from the overall study NOAEL therefore represents additional margins of safety of 5 and 10 over the NOAEL and LOAEL for testicular effects, respectively. This approach is considered to be adequately conservative for the protection of workers from the reproductive toxicity of BMBF. The use of additional assessment factors is therefore not proposed.

A short-term inhalation systemic DNEL is derived from the NOAEL of 50 mg/kg bw/d from the acute neurotoxicity rat study. A corrected (inhalation) starting point of 21.7 mg/m3is derived, taking into account breathing rate (*1/1.15), and the relative extent of oral absorption (50%) and inhalation absorption (100%). 

Applying assessment factors of 1 (for dose-response relationship), 1 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 25. Applying the assessment factor of 25 to the corrected starting point gives a DNEL of 0.9 mg/m3.

Local inhalation DNEL values are not derived in the absence of any identified hazard.

Dermal DNELs

Systemic DNELs

A long-term dermal systemic DNEL is derived from the NOAEL of 70 mg/kg bw/d from the 90-day rat study. A corrected (dermal) starting point of 700 mg/kg bw/d derived taking into account the relative extent of oral absorption (50%) and dermal absorption (5%).

Applying 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) results in an overall assessment factor of 200. Applying the assessment factor of 200 to the corrected starting point gives a DNEL of 3.5 mg/kg bw/d. BMBF is classified for reproductive toxicity based on effects seen in the 90-day study at a dose level of 700 mg/kg bw/d; the NOAEL for this effect is 350 mg/kg bw/d, whereas the overall study NOAEL is 70 mg/kg bw/d. Derivation of the DNEL from the overall study NOAEL therefore represents additional margins of safety of 5 and 10 over the NOAEL and LOAEL for testicular effects, respectively. This approach is considered to be adequately conservative for the protection of workers from the reproductive toxicity of BMBF. The use of additional assessment factors is therefore not proposed.

A short-term dermal systemic DNEL is derived from the NOAEL of 50 mg/kg bw/d from the acute neurotoxicity rat study. A corrected (dermal) starting point of 500 mg/kg bw/d derived taking into account the relative extent of oral absorption (50%) and dermal absorption (5%).

Applying assessment factors of 1 (for dose-response relationship), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 100. Applying the assessment factor of 100 to the corrected starting point gives a DNEL of 5 mg/kg bw/d.

Local dermal DNELs are not derived in the absence of any hazard.

 

Oral DNELs

Systemic DNELs

A long-term oral systemic DNEL is derived from the NOAEL of 70 mg/kg bw/d from the 90-day rat study. Correction of the starting point is not required.

Applying 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) results in an overall assessment factor of 200. Applying the assessment factor of 200 to the starting point gives a DNEL of 0.4 mg/kg bw/d. BMBF is classified for reproductive toxicity based on effects seen in the 90-day study at a dose level of 700 mg/kg bw/d; the NOAEL for this effect is 350 mg/kg bw/d, whereas the overall study NOAEL is 70 mg/kg bw/d. Derivation of the DNEL from the overall study NOAEL therefore represents additional margins of safety of 5 and 10 over the NOAEL and LOAEL for testicular effects, respectively. This approach is considered to be adequately conservative for the protection of workers from the reproductive toxicity of BMBF. The use of additional assessment factors is therefore not proposed.

A short-term oral systemic DNEL is derived from the NOAEL of 50 mg/kg bw/d from the acute neurotoxicity rat study. Correction of the starting point is not required.

Applying assessment factors of 1 (for dose-response relationship), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 100. Applying the assessment factor of 100 to the corrected starting point gives a DNEL of 0.7 mg/kg bw/d.