Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 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):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
100 mg/kg/day x (1/0.38 m3/kg/day) x 6.7 m3/10 m3 x (10/100 oral absorption in rats/inhalation absorption in humans) = 17.6 mg/m3
AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default value for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
default value for remaining differences
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.3 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
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:
The same extent for dermal and oral absorption (i.e. 10%) has been set for risk assessment purposes
AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default value for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default value - rat
AF for other interspecies differences:
2.5
Justification:
default value for remaining differences
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
no hazard identified

Additional information - workers

Based on the available acute toxicity data (oral, dermal), BPA-DA is not expected to be an acute toxicant. In addition, based on available irritation and sensitization data, BPA-DA would not be considered an irritant or sensitizer. Therefore, derivation of DNEL long-term will be sufficient to control potential risks associated with short-term exposures.

Although the NOAEL from the 28 -day oral study was > 2750 mg/kg/day as no adverse effects were reported in the study, a lower NOAEL at 100 mg/kg/day for systemic toxicity was obtained in an OECD 421 study, mainly based on effects on body weight/body weight gain. This is also supported by results of pre-natal developmental toxicity studies in rats and rabbits, both conducted at the limit dose of 1000 mg/kg bw/day and both determining the NOAEL for maternal toxicity to be lower than 1000 mg/kg/day, again mainly based on effects on body weight/body weight gains. As a conservative estimate, the long-term DNELs for systemic toxicity are derived using the lowest NOAEL of 100 mg/kg/day.

Route-to-route extrapolation

Long-term systemic DNELs for workers are derived for the dermal and inhalation routes of exposure. However, the only repeat dose toxicity studies available for BPA-DA are on the oral route of exposure. Therefore, route-to-route extrapolation from the oral route to the dermal and inhalation routes is required.

Dermal DNEL starting dose

Both oral and dermal absorption are set at 10 %. The starting dose for setting the long-term dermal systemic DNEL is therefore 100 mg/kg/day.

Inhalation starting dose

The oral NOAEL needs to be converted to an inhalation NOAEL. The worst-case assumption is that absorption is limited for the starting (oral) route, and maximal for inhalation. Oral absorption is set at 10 % for risk assessment purposes and absorption via inhalation is set at 100 % although it is noted that the substance is too large for being inhaled or taken up by macrophages. The starting dose for setting the long-term systemic inhalation DNEL is therefore 100 mg/kg/day x (1/0.38 m³/kg/day) x 6.7 m³/10 m³ x (10/100 oral absorption in rats/inhalation absorption in humans) = 17.6 mg/m³.

Assessment factor for Interspecies

Per page 30 of ECHA Guidance R.8, interspecies assessment factor should include an allometric scaling (AS) factor plus an additional factor of 2.5. In the case of the rat, a factor 4 is recommended in the ECHA Guidance R.8. So the interspecies AF is equal to 4 x 2.5 = 10. Per page 68 of the ECHA Guidance R.8, an allometric scaling factor is not used when extrapolating from an oral NOAEL to an inhalation exposure. Therefore, for inhalation, only an interspecies factor of 2.5 is used.

Assessment factor for Intraspecies

Per page 33 -34 of ECHA Guidance R.8, intraspecies AF should be 5 for workers.

Assessment factor for duration differences

Per page 35 of ECHA Guidance R.8, the AF for extrapolation from a subacute toxicity study to a chronic is 6.

Assessment factor for issues related to dose response

No additional assessment factor is required since a NOAEL was used (i.e. assessment factor = 1).

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:
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

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The substance is used (and transported) as intermediate under strictly controlled conditions; no exposure to the general population will occur.