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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:
43.8 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
438 mg/m³
Explanation for the modification of the dose descriptor starting point:
As no inhalation study is available an reliable subchronic oral study is considered appropriate for the estimation of an inhalative DNEL.
AF for dose response relationship:
1
Justification:
true NOAEC applied
AF for differences in duration of exposure:
2
Justification:
correction for duration from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already considered in route correction
AF for intraspecies differences:
5
Justification:
ECHA default assessment factor
AF for the quality of the whole database:
1
Justification:
good quality for database
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
125 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal route is typically covered by oral route information in the absence of data for this administration route.
AF for dose response relationship:
1
Justification:
true NOAEL used
AF for differences in duration of exposure:
2
Justification:
correction for duration from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling rat to human
AF for intraspecies differences:
5
Justification:
default factor
AF for the quality of the whole database:
1
Justification:
good quality database
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

DNEL acute

A DNELacuteshould be established for substances if an acute hazard toxicity (leading to C&L) has been identified and a potential for high peak exposures exists.

RRR-(alpha-, beta-, gamma-, delta)-tocopherol does not have to be labelled for acute toxicity and therefore, a derivation of a DNELacuteis not necessary.

 

DNEL long-term systemic

RRR-(alpha-, beta-, gamma-, delta)-tocopherol isnot classified for any endpoint related to systemic toxicity.

For the DNEL-derivation a NOAEL of 500 mg/kg bw was used derived from the 90-day repeated dose oral, basedon hemorrhagic diathesis in males and females (an increase in APTT, PT and fibrinogen at 2000 mg/kg).

The dermal DNELfor long-term exposure - systemic effects for workers is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 500 mg/kg bw/day

Based on hemorrhagic diathesis in males and females

Step 2) Modification of starting point

 

x 50/5

 

 

50% for oral absorption, and 5% absorption is assumed for dermal absorption

Modified dose-descriptor

500 mg/kg bw/d x 50/5 = 5000 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

 

Allometric scaling for the rat, the additional factor of 2.5 is omitted.

Intraspecies

5

Default assessment factor

Exposure duration

2

A correction for duration from sub-chronic to chronic is required

Dose response

1

 NOAEL used

Quality of database

1

 good quality database

DNEL

Value

 5000 mg/kg bw/d/ (4 x 5 x 2 x 1 x 1)=125 mg/kg bw/d

The inhalative DNELfor long-term exposure - systemic effects for workers is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 500 mg/kg bw/d

Based on hemorrhagic diathesis in males and females

Step 2) Modification of starting point

/0.38 m3/kg bw

  

 x 6.7 m3/10 m3

 

 

 

 

x50/100

 

8 h respiratory volume for rat.

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.

 

 

Default 50% for oral absorption, and 100% absorption is assumed for inhalation.

Modified dose-descriptor

500 x 0.67 x 0.5 / 0.38 = 440 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1.0

 

The allometric scaling is already considered in the starting point correction. The additional factor of 2.5 is omitted.

Intraspecies

5

Default assessment factor

Exposure duration

2

A correction for duration from sub-chronic to chronic is required

Dose response

1

 NOAEL used

Quality of database

1

 good quality database

DNEL

Value

 

 440 mg/m3/ (1.0 x 5 x 2 x 1 x 1)=44 mg/m3

 

 

The dermal DNELfor long term exposure - local effects for workers should be established for substances if a local toxicity (leading to C&L) has been identified and a potential for long term risks exists. RRR-(alpha-, beta-, gamma-, delta)-tocopherol does not have to be labelled for local toxicity, including irritation and skin sensitisation and therefore, a derivation of a DNELacute is not necessary.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.8 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):
20
Modified dose descriptor starting point:
NOAEC
Value:
217 mg/m³
Explanation for the modification of the dose descriptor starting point:
As no inhalation study is available an reliable subchronic oral study is considered appropriate for the estimation of a inhalative DNEL.
AF for dose response relationship:
1
Justification:
true NOAEL used
AF for differences in duration of exposure:
2
Justification:
correction fro duration from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already considered in rout correction
AF for intraspecies differences:
10
Justification:
default value
AF for the quality of the whole database:
1
Justification:
good quality databse
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 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):
40
Modified dose descriptor starting point:
LOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal route is typically covered by oral route information in the absence of data for this administration route.
AF for dose response relationship:
1
Justification:
true NOAEL used
AF for differences in duration of exposure:
2
Justification:
correction factor for duration from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling for the rat
AF for intraspecies differences:
10
Justification:
default value
AF for the quality of the whole database:
1
Justification:
good quality database
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.25 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not necessary as key study uses oral administration
AF for dose response relationship:
1
Justification:
true NOAEL used
AF for differences in duration of exposure:
2
Justification:
correction factor for duration from sub-chronic to chronic is required
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling for rat
AF for intraspecies differences:
10
Justification:
default value
AF for the quality of the whole database:
1
Justification:
good quality database
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

DNEL acute

ADNELacuteshould be established for substances if an acute hazard toxicity (leading to C&L) has been identifiedanda potential for high peak exposures exists. RRR-(alpha-, beta-, gamma-, delta)-tocopherol does not have to be labelled for acute toxicity and therefore, a derivation of a DNELacuteis not necessary.

DNEL long-term systemic

RRR-(alpha-, beta-, gamma-, delta)-tocopherol is not classified for systemic target organ toxicitity

For the DNEL-derivation a NOAEL of 500 mg/kg bw/d was used derived from the 90 -day repeated dose oral, based on hemorrhagic diathesis in males and females (an increase in APTT, PT and fibrinogen at 2000 mg/kg).

The dermal DNEL for long-term exposure - systemic effects for general population is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 500 mg/kg bw/d

Based on hemorrhagic diathesis

Step 2) Modification of starting point

 

x 50/5

 

 

50% for oral absorption and 5% absorption is assumed for dermal absorption.

Modified dose-descriptor

500 mg/kg bw/d x 50/5 = 5000 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

 

Allometric scaling for the rat

Intraspecies

10

Default assessment factor

Exposure duration

2

A correction for duration from sub-chronic to chronic is required

Dose response

1

 

Quality of database

1

 good quality database

DNEL

Value

5000 mg/kg bw/d/ (4 x 10 x 2 x 1 x 1)=62.5 mg/kg bw/d

The inhalation DNEL for long-term exposure - systemic effects for general population is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 500 mg/kg bw/d

Based on hemorrhagic diathesis

Step 2) Modification of starting point

/ 1.15 m3/kg bw

 

 

x 50/100

 

24 h respiratory volume for rats.

 

 

50% for oral absorption and 100% absorption is assumed for inhalation.

Modified dose-descriptor

500 / 1.15 x 0.5 = 217 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1.0

 

Allometric scaling already considered in starting point correction.

Intraspecies

10

Default assessment factor

Exposure duration

2

A correction for duration from sub-chronic to chronic is required.

Dose response

1

 

Quality of database

1

 

DNEL

Value

*DNEL using ECETOC AF

217 mg/m3/ (1.0 x 10 x 2 x 1 x 1)=10.8 mg/m3

The oral DNEL for long-term exposure - systemic effects for general public is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 500 mg/kg bw/d

Based on hemorrhagic diathesis

Step 2) Modification of starting point

Not required

 

 

 

 

 

Step 3) Assessment factors

 

 

Interspecies

4

 

Allometric scaling for the rat.

Intraspecies

10

Default assessment factor

Exposure duration

2

A correction for duration from sub-chronic to chronic is required

Dose response

1

 

Quality of database

1

 

DNEL

Value

500 mg/kg bw/d/ (4 x 10 x 2 x 1 x 1)=6.25 mg/kg bw/d

 

The dermal DNEL for long-term local effects should be established for substances if a local toxicity (leading to C&L) has been identified and a potential for long term risks exists. RRR-(alpha-, beta-, gamma-, delta)-tocopherol does not have to be labelled for local toxicity, including irritation and skin sensitisation and therefore, a derivation of a DNELacute is not necessary.