Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29 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):
240
Modified dose descriptor starting point:
NOAEC
Value:
1 750 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
human to workers
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 111 mg/m³
Most sensitive endpoint:
acute 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:
NOAEC
Value:
3 500 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
human to worker

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:
8.3 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):
120
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
human to workers
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

1     Workers

Summary according to ECHA Guidance R.8

Exposure pattern

DNEL

 

workers

inhalation, systemic, long-term

29 mg/m³

inhalation, systemic, acute

1,111 mg/m³

inhalation, local, long-term

no data available

inhalation, local, acute

no data available

dermal, systemic, long-term

8.3 mg/kg

dermal, systemic, acute

100 mg/kg

dermal, local, long-term

no data available

dermal, local, acute

no data available

Hazard for the eyes

no

"Units for local effects are mg/m³for inhalation; and for dermal exposure: mg/cm² skin, mg/person/day (e.g., calculated based on the deposited amount per cm² times the actually exposed body area), or a measure of concentration (% or ppm)"

1.1  inhalation, systemic, long-term

Start value: NOAEL (sub-acute) = 1,000 mg/kg bw/day

 

Uncertainties

AF

Justification

route of exposure

2

oral to inhalation

Interspecies differences

4

rat to human

Intraspecies differences

5

human to workers

Exposure duration

6

sub-acute to chronic

Overall

240

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of NOAEC according to guideline R.8:

NOAEC (worker) = (1,000 mg/kg*70 kg) / (4*10 m³) = 1,750 mg/m³

 

Calculation of DNEL by taking into account the remaining AFs:

DNEL (inhalation, systemic, long-term) = 1750 mg/m³/ 60 =29 mg/m³

1.2  inhalation, systemic, acute

Start value: NOAEL (acute) = 2,000 mg/kg bw since LD50(oral) > 2,000 mg/kg bw

Uncertainties

AF

Justification

route of exposure

2

oral to inhalation

Interspecies differences

4

rat to human

Intraspecies differences

5

human to worker

Overall

40

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of NOAEC according to guideline R.8:

NOAEC (worker) = (2,000 mg/kg*70 kg) / (4*10 m³) = 3,500 mg/m³

 

Calculation of DNEL (4 hours) by taking into account the remaining AFs:

3,500 mg/m³/ 10 = 350 mg/m³

 

Correction for short term exposure (15 min) using modification of Haber's Law (ECHA guideline R.7a):

c = ((350 mg/m³)³*(8.0 h / 0.25 h))1/3= 1,111 mg/m³

DNEL (inhalation, systemic, acute) =1,111 mg/m³

1.3  dermal, systemic, long-term

Start value: NOAEL (sub-acute) = 1,000 mg/kg bw/day

Uncertainties

AF

Justification

route of exposure

1

oral to dermal

Interspecies differences

4

rat to human

Intraspecies differences

5

human to workers

Exposure duration

6

sub-acute to chronic

Overall

120

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of DNEL:

DNEL (dermal, systemic, long-term) = (1,000 mg/kg) / 120 =8.3 mg/kg

 

1.4  dermal, systemic, acute

Start value: NOAEL (acute) = 2,000 mg/kg bw since LD50(dermal) > 2,000 mg/kg bw

Uncertainties

AF

Justification

route of exposure

1

same route

Interspecies differences

4

rat to human

Intraspecies differences

5

human to worker

Overall

20

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of DNEL:

DNEL (dermal, systemic, acute) = (2,000 mg/kg) / 20 =100 mg/kg

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22 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):
480
Modified dose descriptor starting point:
NOAEC
Value:
2 612 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
human to general population
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
828 mg/m³
Most sensitive endpoint:
acute 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:
NOAEC
Value:
5 223 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
human to general population

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:
4.2 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
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
human to general population
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
same route
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
human to general population

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:
4.2 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
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
same route
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
human to general population
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

1     General population

Summary according to ECHA Guidance R.8

Exposure pattern

DNEL

 

general population

inhalation, systemic, long-term

22 mg/m³

inhalation, systemic, acute

828 mg/m³

inhalation, local, long-term

no data available

inhalation, local, acute

no data available

dermal, systemic, long-term

4.2 mg/kg

dermal, systemic, acute

50 mg/kg

dermal, local, long-term

no data available

dermal, local, acute

no data available

oral, systemic, long-term

4.2 mg/kg

oral, systemic, acute

50 mg/kg

Hazard for the eyes

no

Units for local effects are mg/m³for inhalation; and for dermal exposure: mg/cm²skin, mg/person/day (e.g., calculated based on the deposited amount per cm² times the actually exposed body area), or a measure of concentration (% or ppm).

1.1  inhalation, systemic, long-term

Start value: NOAEL (sub-acute) = 1,000 mg/kg bw/day

 

Uncertainties

AF

Justification

route of exposure

2

oral to inhalation

Interspecies differences

4

rat to human

Intraspecies differences

10

human to general population

Exposure duration

6

sub-acute to chronic

Overall

480

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of NOAEC according to guideline R.8:

NOAEC (worker) = (1,000 mg/kg*70 kg) / (4*6.7 m³) = 2,612 mg/m³

 

Calculation of DNEL by taking into account the remaining AFs:

DNEL (inhalation, systemic, long-term) = 2612 mg/m³/ 120 =22 mg/m³

1.2  inhalation, systemic, acute

Start value: NOAEL (acute) = 2000 mg/kg bw since LD50(oral) > 2000 mg/kg bw

Uncertainties

AF

Justification

route of exposure

2

oral to inhalation

Interspecies differences

4

rat to human

Intraspecies differences

10

human to general population

Overall

80

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of NOAEC according to guideline R.8:

NOAEC (worker) = (2,000 mg/kg·70 kg) / (4*6.7 m³) = 5,223 mg/m3

 

Calculation of DNEL (4 hours) by taking into account the remaining AFs:

5,223 mg/m³/ 20 = 261 mg/m³

 

Correction for short term exposure (15 min) using modification of Haber's Law (ECHA guideline R.7a):

c = ((261 mg/m³)*(8.0 h / 0.25 h))1/3= 828 mg/m³

DNEL (inhalation, systemic, acute) =828 mg/m³

1.3  dermal, systemic, long-term

Start value: NOAEL (sub-acute) = 1,000 mg/kg bw/day

Uncertainties

AF

Justification

route of exposure

1

oral to dermal

Interspecies differences

4

rat to human

Intraspecies differences

10

human to general population

Exposure duration

6

sub-acute to chronic

Overall

240

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of DNEL:

DNEL (dermal, systemic, long-term) = (1,000 mg/kg) / 240 = 4.2 mg/kg

1.4  dermal, systemic, acute

Start value: NOAEL (acute) = 2,000 mg/kg bw since LD50(dermal) > 2,000 mg/kg bw

Uncertainties

AF

Justification

route of exposure

1

same route

Interspecies differences

4

rat to human

Intraspecies differences

10

human to general population

Overall

40

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of DNEL:

DNEL (dermal, systemic, acute) = (2,000 mg/kg) / 40 =50 mg/kg

1.5  oral, systemic, long-term

Start value: NOAEL (sub-acute) = 1,000 mg/kg bw/day

Uncertainties

AF

Justification

route of exposure

1

same route

Interspecies differences

4

rat to human

Intraspecies differences

10

human to general population

Exposure duration

6

sub-acute to chronic

Overall

240

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of DNEL:

DNEL (oral, systemic, long-term) = (1,000 mg/kg) / 240 = 4.2 mg/kg

1.6  oral, systemic, acute

Start value: NOAEL (acute) = 2,000 mg/kg bw since LD50(oral) > 2,000 mg/kg bw

Uncertainties

AF

Justification

route of exposure

1

same route

Interspecies differences

4

rat to human

Intraspecies differences

10

human to general population

Overall

40

 

AFs according to ECETOC Technical Report No. 110

 

Calculation of DNEL:

DNEL (oral, systemic, acute) = (2,000 mg/kg) / 40 =50 mg/kg