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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:
0.04 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:
0.88 mg/m³
Explanation for the modification of the dose descriptor starting point:
It is assumed that oralabsorption rate is 50%of that inhalation absorption.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral 90 day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
for workers
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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):
12.5
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
0.88 mg/m³
Explanation for the modification of the dose descriptor starting point:
It is assumed that oralabsorption rate is 50%of that inhalation absorption.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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
Modified dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral and dermal absorption rates are equal.
AF for differences in duration of exposure:
2
Justification:
based on an oral 90 day study
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
for workers
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 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):
50
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral and dermal absorption rates are equal.
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
for workers

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

DNEL - long term, worker

Inhalation systemic long term. Route-to-route extrapolation:

The calculations for the long term DNELs for workers are based on a 90 day oral feeding study performed in Fischer 344 rats. The NOAEL value in this study was found to be 1 mg/kg bw/d. This value was used as basis for DNEL calculation. Route-to-route extrapolation (oral to inhalative) was performed according to the ECHA Guidance Document on information requirements and chemical safety assessment Chapter R.8. It was assumed that oral absorption rate is 50% of that of inhalation absorption.

Starting point (worker, inhalation)= NOAEL oral*(1/sRVrat)*(sRVhuman/wRV)*(ABSoral-rat/ABSinh-human)= 1mg/kg/d*(1/0.38m3/kg/d)*(6.7m3(8h)/10m3(8h))*0.5=0.88mg/m3

It was assumed that oral and dermal absorption rates are equal.

Starting point (worker,dermal)= 1mg/kg/d

Assessment factors for DNEL derivations

Inhalation

Overall AF = 25

Dermal

Overall AF = 100

Taken above information

DNEL inhalation, long term, sytemic effects = 0.88/25=0.035 mg/m3

DNEL dermal, long term,systemic effects = 1/100=0.01 mg/kg bw/d

DNEL - short term, worker

Inhalation systemic effects acute.

DNELacute extrapolated from long term DNEL

Starting point (worker, inhalation, acute)=0.88 mg/m3

Assessment factors for DNEL derivations

Inhalation, worker,acute

Overall AF = 12.5

Dermal systemic effects acute.

DNELacute extrapolated from long term DNEL

It was assumed that oral and dermal absorption rates are equal.

Starting point (worker,dermal)= 1mg/kg/d

Dermal

Overall AF = 50

Taken above information:

DNEL inhalation, short term, sytemic effects = 0.88/12.5=0.07 mg/m3

DNEL dermal, short term,systemic effects = 1/50=0.02 mg/kg bw/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
0.43 mg/m³
Explanation for the modification of the dose descriptor starting point:
It is assumed that oralabsorption rate is 50%of that inhalation absorption.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral 90 day study
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 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
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
0.43 mg/m³
Explanation for the modification of the dose descriptor starting point:
It is assumed that oralabsorption rate is 50%of that inhalation absorption.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
AF for the quality of the whole database:
1

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral and dermal absorption rates are equal.
AF for differences in duration of exposure:
2
Justification:
based on an oral 90 day study
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral and dermal absorption rates are equal.
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
AF for the quality of the whole database:
1

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:
0.01 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:
1 mg/kg bw/day
AF for differences in duration of exposure:
2
Justification:
based on an oral 90 day study
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
for general population
AF for the quality of the whole database:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNEL - long term, general population

Inhalation systemic long term. Route-to-route extrapolation:

The calculations for the long term DNELs for workers are based on a 90 day oral feeding study performed in Fischer 344 rats. The NOAEL value in this study was found to be 1 mg/kg bw/d. This value was used as basis for DNEL calculation. Route-to-route extrapolation (oral to inhalative) was performed according to the ECHA Guidance Document on information requirements and chemical safety assessment Chapter R.8. It was assumed that oral absorption rate is 50% of that of inhalation absorption.

Starting point (general population, inhalation)= NOAEL oral*(1/1.15 m3/kg/d)*(ABSoral-rat/ABSinh-human)= 1mg/kg/d*(1/1.15m3/kg/d)*0.5=0.43mg/m3

It was assumed that oral and dermal absorption rates are equal.

Starting point (general population,dermal)= 1mg/kg/d

Assessment factors for DNEL derivations

Inhalation

Overall AF = 50

Dermal

Overall AF = 200

Taken above information

DNEL inhalation, long term, sytemic effects = 0.43/50=0.0086 mg/m3

DNEL dermal, long term,systemic effects = 1/200=0.005 mg/kg bw/d

DNEL - short term, general population

Inhalation systemic effects acute.

DNELacute extrapolated from long term DNEL

Starting point (general population, inhalation, acute)=0.43 mg/m3

Assessment factors for DNEL derivations

Inhalation, general population,acute

Overall AF = 25

Dermal systemic effects acute.

DNELacute extrapolated from long term DNEL

It was assumed that oral and dermal absorption rates are equal.

Starting point (general population,dermal)= 1mg/kg/d

Dermal

Overall AF = 100

Taken above information:

DNEL inhalation, short term, sytemic effects = 0.43/25=0.02 mg/m3

DNEL dermal, short term,systemic effects = 1/100=0.01 mg/kg bw/d

The DNEL oral is the same as the DNEL dermal.