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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.5 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):
34.3
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
523.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction for rat standard breathing volume, 8 hrs = 0.38 m3/kg (ECHA R.8, 2012)

Correction for activity driven differences of respiratory volumes in workers compared to workers = 10 m3/6.7 m3 (ECHA R.8, 2012)

Default AF for oral to inhalation extrapolation = 2 (ECHA R.8, 2012)

AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
AF 6 for extrapolation from sub-acute to chronic (ECHA R.8, 2012)
AF for interspecies differences (allometric scaling):
5
Justification:
Default value for workers (ECHA R.8, 2012)
AF for other interspecies differences:
1
Justification:
No other interspecies differences
AF for intraspecies differences:
1
Justification:
No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)
AF for the quality of the whole database:
1
Justification:
The key study is of high quality, being rated K1. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
No remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
120
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

AF for oral to dermal extrapolation = 1 (ECHA R.8, 2012).

AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
AF 6 for extrapolation from sub-acute to chronic (ECHA R.8, 2012)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans (ECHA R.8, 2012)
AF for other interspecies differences:
1
Justification:
No other interspecies differences.
AF for intraspecies differences:
5
Justification:
Default value for workers (ECHA R.8, 2012)
AF for the quality of the whole database:
1
Justification:
The key study is of high quality, being rated K1. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Sytemic effects, long term

Calculation from the oral repeated dose/ repro screening study (OECD 422) study with BPMA in rats

 

DNEL inhal worker long-term

Description

Value/ factor

Remark

Step 1) Relevant dose-descriptor

NOAEL:600 mg/kg bw/d 

NOAEL determined by the highest dose tested in an OECD 422 study in rats by oral gavage

Step 2) Modification of starting point

0.38 m³/kg

 

6.7 m3/10 m3

Correction for rat standard breathing volume, 8 hrs (ECHA R.8, 2012)

-Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3) is required(ECHA R.8, 2012)

 

Route-to-Route extrapolation

2

Oral to inhalation extrapolation (ECHA R.8, 2012)

NAEC worker

523.4 mg/m3

 

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)

Intraspecies

5

Default value for workers (ECHA R.8, 2012)

Exposure duration

6

The NOAEL is based on a subacute study of approx. 50 d for the relevant sex (males). AF 6 for extrapolation from sub-acute to chronic (ECHA 2012) represents a conservative approach as this study period exceeds the duration of a normal subacute study almost by a factor of two and long term data from metabolites indicate a lower exposure duration effect as used here.

Dose response

1

The NOAEL is reliable. No adjustment is required.

Quality of database

1

The key study is of high quality, being rated K1. No adjustment is required.

Remaining uncertainties

1

No remaining differences

DNEL

 

Based upon a NOAEL of 600 mg/kg bw/d for male rats, for 50 d by the oral route.

17.5 mg/m3

Using a total factor (POD modifier and AF) of 34.3 (/ 0.38 x 10/6.7 m³ x 2 x 1 x 5 x 6 x 1 x 1 x 1) a DNELlong-term, inhal, workerof 17.5 mg/m³ is derived.

 

DNEL dermal worker long-term

Description

Value/ factor

Remark

Step 1) Relevant dose-descriptor

NOAEL:600 mg/kg bw/d

NOAEL determined by the highest dose tested in an OECD 422 study in rats by oral gavage

Step 2) Modification of starting point

1

Oral to dermal extrapolation (ECHA R.8, 2012).

NAEL worker

600 mg/kg bw/d

 

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling rat to humans (ECHA R.8, 2012)

Intraspecies

5

Default value for workers (ECHA R.8, 2012)[KK5] 

Exposure duration

6

The NOAEL is based on a subacute study of approx. 50 d for the relevant sex (males). AF 6 for extrapolation from sub-acute to chronic (ECHA 2012) represents a conservative approach as this study period exceeds a normal subacute study and long term data from metabolites indicate a lower exposure duration effect as used here.

Dose response

1

The NOAEL is reliable. No adjustment is required.

Quality of database

1

The key study is of high quality, being rated K1. No adjustment is required.

Remaining uncertainties

1

No remaining uncertainties

DNEL

 

Based upon a NOAEL of 600 mg/kg bw/d for male rats, for 50 d by the oral route.

5.0 mg/kg bw/d

Using a total factor (POD modifier and AF) of 120 (1 x 4 x 5 x 6 x 1 x 1) a DNELlong-term, dermal, workerof 5.0 mg/kg bw/d is derived.

 

ylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of3/5is sufficiently conservative. (ECETOC, 2010)

 [KK5]In Absprache mit Harald 2017-12-06 auf Standardwerte (5/10) gesetzt, da Metabolismusdaten für BPMA fehlen)

Die Begründung für niedrigere ECETOC-Werte wäre gese dann wäre gewesen:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of3/5is sufficiently conservative. (ECETOC, 2010)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 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):
138
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
199.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction for rat standard breathing volume, 24 hrs = 1.15 m3/kg (ECHA R.8, 2012) 

Default AF for oral to inhalation extrapolation = 2 (ECHA R.8, 2012)

AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
AF 6 for extrapolation from sub-acute to chronic (ECHA R.8, 2012)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)
AF for other interspecies differences:
1
Justification:
No other interspecies differences
AF for intraspecies differences:
10
Justification:
Default value for general poulation (ECHA R.8, 2012)
AF for the quality of the whole database:
1
Justification:
The key study is of high quality, being rated K1. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
240
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default AF for oral to dermal extrapolation (ECHA R.8, 2012).

AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
AF 6 for extrapolation from sub-acute to chronic (ECHA R.8, 2012)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans (ECHA R.8, 2012)
AF for other interspecies differences:
1
Justification:
No other interspecies differences
AF for intraspecies differences:
10
Justification:
Default value for general population (ECHA R.8, 2012)
AF for the quality of the whole database:
1
Justification:
The key study is of high quality, being rated K1. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
240
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation required.

AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
AF 6 for extrapolation from sub-acute to chronic (ECHA R.8, 2012)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans (ECHA R.8, 2012)
AF for other interspecies differences:
1
Justification:
No other interspecies differences.
AF for intraspecies differences:
10
Justification:
Default value for workers (ECHA R.8, 2012)
AF for the quality of the whole database:
1
Justification:
The key study is of high quality, being rated K1. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Sytemic effects, long term

Calculation from the oral repeated dose/ repro screening study (OECD 422) study with BPMA in rats

DNEL inhal gen pop long-term

Description

Value/ factor

Remark

Step 1) Relevant dose-descriptor

NOAEL:600 mg/kg bw/d

NOAEL determined by the highest dose tested in an OECD 422 study in rats by oral gavage

Step 2) Modification of starting point

1.15 m³/kg

Correction for rat standard breathing volume, 24 hrs (ECHA R.8, 2012)

Route-to-Route extrapolation

2

Oral to inhalation extrapolation (ECHA R.8, 2012).

NAEC general population

199.8 mg/m3

 

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)

Intraspecies

10

Default value for general population (ECHA R.8, 2012)

Exposure duration

6

The NOAEL is based on an subacute study of approx. 50 d for the relevant sex (males). AF 6 for extrapolation from sub-acute to chronic (ECHA 2012) represents a conservative approach as this study period exceeds a normal subacute study and long term data from metabolites indicate a lower exposure duration effect as used here.

Dose response

1

The NOAEL is reliable. No adjustment is required.

Quality of database

1

The key study is of high quality, being rated K1. No adjustment is required.

Remaining uncertainties

1

No remaining uncertainties

DNEL

 

Based upon a NOAEL of 600 mg/kg bw/d for male rats, for 50 d by the oral route.

4.35 mg/m3

Using a total factor (POD modifier and AF) of 138 (/ 1.15 m³ x 2 x 1 x 10 x 6 x 1 x 1 x 1) a DNELlong-term,inhal, gen. pop.of 4.35 mg/m³ is derived.

 

 

DNEL dermal general population long-term

Description

Value/ factor

Remark

Step 1) Relevant dose-descriptor

NOAEL:600 mg/kg bw/d

NOAEL determined by the highest dose tested in an OECD 422 study in rats by oral gavage

Step 2) Modification of starting point

1

Oral to dermal extrapolation (ECHA R.8, 2012).

NAEL general population

600 mg/kg bw/d

 

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling rat to humans (ECHA R.8, 2012)

Intraspecies

10

Default value for general population (ECHA R.8, 2012)

Exposure duration

6

The NOAEL is based on an subacute study of approx. 50 d for the relevant sex (males). AF 6 for extrapolation from sub-acute to chronic (ECHA 2012) represents a conservative approach as this study period exceeds a normal subacute study and long term data from metabolites indicate a lower exposure duration effect as used here.

Dose response

1

The NOAEL is reliable. No adjustment is required.

Quality of database

1

The key study is of high quality, being rated K1. No adjustment is required.

Remaining uncertainties

1

No remaining uncertainties

DNEL

 

Based upon a NOAEL of 600 mg/kg bw/d for male rats, for 50 d by the oral route.

2.5 mg/kg bw/d

Using a total factor (POD modifier and AF) of 240 (1 x 4 x 10 x 6 x 1 x 1) a DNELlong-term,dermal, gen.pop.of 2.5 mg/kg bw/d is derived.

 

 

DNEL oral general population long-term

Description

Value/ factor

Remark

Step 1) Relevant dose-descriptor

NOAEL:600 mg/kgbw/d

NOAEL determined by the highest dose tested in an OECD 422 study in rats by oral gavage

Step 2) Modification of starting point

1

No route-to-route extrapolation required.

NAEL general population

600 mg/kg bw/d

 

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling rat to humans (ECHA R.8, 2012)

Intraspecies

10

Default value for general population (ECHA R.8, 2012)

Exposure duration

6

The NOAEL is based on an subacute study of approx. 50 d for the relevant sex (males). AF 6 for extrapolation from sub-acute to chronic (ECHA 2012) represents a conservative approach as this study period exceeds a normal subacute study and long term data from metabolites indicate a lower exposure duration effect as used here.

Dose response

1

The NOAEL is reliable. No adjustment is required.

Quality of database

1

The key study is of high quality, being rated K1. No adjustment is required.

Remaining uncertainties

1

No remaining uncertainties

DNEL

 

Based upon a NOAEL of 600 mg/kg bw/d for male rats, for 50 d by the oral route.

2.5 mg/kg bw/d

Using a total factor (POD modifier and AF) of 240 (1 x 4 x 10 x 6 x 1 x 1) a DNELlong-term,oral, gen.pop.of 2.5 mg/kg bw/d is derived.