Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22.2 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:
555 mg/m³
AF for dose response relationship:
1
Justification:
NOAEL is starting point (default factor)
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure (default factor)
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable
AF for other interspecies differences:
2.5
Justification:
remaining differences in interspecies variability
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required, data base considered of high quality
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
6.49 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
Value:
450 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
649 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

According to ECHA Guidance R.8, the route to route extrapolation based on the assumption that the dermal uptake is equal to oral uptake.

AF for dose response relationship:
1
Justification:
NOAEL is starting point (default factor)
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure (default factor)
AF for interspecies differences (allometric scaling):
4
Justification:
interspecies conversion metabolism, allometric scaling factor rat - human (default factor)
AF for other interspecies differences:
2.5
Justification:
default factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required, data base considered of high quality
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute DNELs:

- Local effects: Derivation of DNELs not applicable, as no significant skin or eye irritating effects were observed in the acute in vivo studies. Furthermore no data on respiratory irritation are available.

- Systemic effects: Dermal DNEL derivation not applicable, as no significant systemic toxic effects were observed in the acute in vivo skin toxicity study. Inhalation DNEL derived from long-term inhalation DNEL.

Long-term DNELs:

- Local effects: Derivation of DNELs not applicable, as no significant skin or eye irritating effects were observed in the acute in vivo studies. Long term dermal toxicity studies without significant irritating effects. Furthermore no data on respiratory irritation are available.

- Systemic effects: Dermal DNEL derived from NOAEL observed on the oral 90-days repeated dose toxicity study (route to route extrapolation, assuming dermal uptake to be equal to oral uptake). Inhalation DNEL derived from NOAEL observed in the oral 90 -days repeated dose toxicity study. This value was converted into a NOAEC for human inhalation exposure according to ECHA Guidance R.8 taking into account allometric scaling, exposure duration, human breathing volume for workers and body weight. Route to route extrapolation from oral to inhalation includes furthermore a factor of 2 (worst case assumption).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
2.25 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:
450 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

According to ECHA Guidance R.8, the route to route extrapolation based on the assumption that the dermal uptake is equal to oral uptake.

AF for dose response relationship:
1
Justification:
NOAEL is starting point (default factor)
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure (default factor)
AF for interspecies differences (allometric scaling):
4
Justification:
interspecies conversion metabolism, allometric scaling factor rat - human (default factor)
AF for other interspecies differences:
2.5
Justification:
default factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required, data base of high quality
AF for remaining uncertainties:
1
Justification:
not required
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:
2.25 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:
450 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

not applicable

AF for dose response relationship:
1
Justification:
NOAEL is starting point (default factor)
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure (default factor)
AF for interspecies differences (allometric scaling):
4
Justification:
interspecies conversion metabolism, allometric scaling factor rat - human (default factor)
AF for other interspecies differences:
2.5
Justification:
default factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required, data base of high quality
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Acute DNELs:

- Local effects: Derivation of DNELs not applicable, as no significant skin or eye irritating effects were observed in the acute in vivo studies. Furthermore no data on respiratory irritation are available.

- Systemic effects: Dermal DNEL derivation not applicable, as no significant systemic toxic effects were observed in the acute in vivo skin toxicity study. Inhalation DNELs not applicable to the general population, as BMBDM only is being used in consumer products as sun screens or other cosmetic products, without significant exposure to aerosols. Handling of BMDBM powder limited to industrial formulation sites, thus no consumer exposure to BMDBM dust particles possible. Acute oral DNEL not derived as no hazard identified.

Long-term DNELs:

- Local effects: Derivation of DNELs not applicable, as no significant skin or eye irritating effects were observed in the acute in vivo studies. Long term dermal toxicity studies without significant irritating effects. Furthermore no data on respiratory irritation are available.

- Systemic effects: Dermal and oral DNEL derived fom NOAEL observed on the oral 90-days repeated dose toxicity study (route to route extrapolation, assuming dermal uptake to be equal to oral uptake). Inhalation DNELs not applicable to the general population, as BMBDM only is being used in consumer products as sun screens or other cosmetic products, without significant exposure to aerosols. Handling of BMDBM powder limited to industrial formulation sites, thus no consumer exposure to BMDBM dust particles possible.