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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.83 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):
5
Modified dose descriptor starting point:
NOAEC
Value:
79.13 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes. NOAEL rat 1820 mg/kg bw/day ÷1.15 m3/kgbw ÷20m3/rat NOAECrat 79.13 mg/m3
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.83 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):
5
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
79.13 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes. NOAEL rat 1820 mg/kg bw/day ÷1.15 m3/kgbw ÷20m3/rat NOAECrat 79.13 mg/m3

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.83 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.83 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.1 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):
5
Modified dose descriptor starting point:
NOAEL
Value:
45.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no dermal repeated studies available. For dermal exposure we taken that: -the average weight of rats is 250g (200-300g), -the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg corrected dermal NOAEL= oral NOAEL 1820 mg/kg bw/day x 0.025 kg = NOAELrat = 45.5 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200 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):
5
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.124 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.124 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEL

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Potassium oxide/ Dipotassium oxide

 

Workers

Humans differ in sensitivity due to a number of biological factors (such as age, gender, genetic composition and nutritional status). The intraspecies variation in humans is greater than in the more homogeneous experimental animal population.

The data from animal studies are the starting point for risk characterisation.The default assumption in general is that humans are more sensitive than experimental animals.The traditional default AF(Assessment factor) suggested for interspecies extrapolation is 5 for workers and 10 for general population should be applied to the concentration/dose descriptor.

A lower default factor is generally suggested for the worker population, because the very young and very old are not part of this population.

To cover the intra-species variation, the default AF (Assessment factor) of 5 for workers was applied to the concentration/dose descriptor (NOAEL or NOAEC).

 

The dose descriptor for dermal irritation/corrosion come from dermal repeated study. In this study, the dose is reported in the unit mg/kg of body weight/day. This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

We have taken that:

• the average weight of rats is 250g (200-300g), and the average weight of rabbit is 2.5 kg used by Merkel, D.J., N. 2000.

• the dose is applied over an area which is approximately 10% of the total body surface, and

• the total body surface of rats is on the average 445 cm2  (363 to 527 cm2) used by Merkel, D.J., N. 2000..

 

      

The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be

NOAELin mg/cm2 =     ((dose in mg/kg bw)x (average animal weight in kg)) / Treated surface in cm2)

 NOAELtest* 0.25/44.5= NOAELmodified

 

The highest dose not causing irritation/corrosion was 1000 mg/kg bw in dermal toxicity study in rats of Merkel, D.J., N. 2000.

 the modified dose descriptor would be

NOAELmodified =1000 mg/kg*0.25 kg/44.5cm2=5.62 mg/cm2

 

 

 

 

 

 

 

 

 

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.913 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:
79.13 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes. NOAEL rat 1820 mg/kg bw/day ÷1.15 m3/kgbw ÷20m3/rat NOAECrat 79.13 mg/m3
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.9 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
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
79.13 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes. NOAEL rat 1820 mg/kg bw/day ÷1.15 m3/kgbw ÷20m3/rat NOAECrat 79.13 mg/m3

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.913 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.913 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.55 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Value:
45.5 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 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):
10
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.562 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.562 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
other: NOAEL

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
182 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):
10
Modified dose descriptor starting point:
NOAEL
Value:
1 820 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
182 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):
10
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
1 820 mg/kg bw/day

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Potassium oxide/ Dipotassium oxide

General population

Humans differ in sensitivity due to a number of biological factors (such as age, gender, genetic composition and nutritional status). The intraspecies variation in humans is greater than in the more homogeneous experimental animal population

The data from animal studies are the starting point for risk characterisation.The default assumption in general is that humans are more sensitive than experimental animals.The traditional default AF (Assessment factor) suggested for interspecies extrapolation is 5 for workers and 10 for general population should be applied to the concentration/dose descriptor.

A lower default factor is generally suggested for the worker population, because the very young and very old are not part of this population.

To cover the intra-species variation, the default AF (Assessment factor) of 10 for general population was applied to the concentration/dose descriptor (NOAEL or NOAEC).

 

The dose descriptor for dermal irritation/corrosion come from dermal repeated study. In this study, the dose is reported in the unit mg/kg of body weight/day. This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

We have taken that:

• the average weight of rats is 250g (200-300g), and the average weight of rabbit is 2.5 kg used by Merkel, D.J., N. 2000.

• the dose is applied over an area which is approximately 10% of the total body surface, and

• the total body surface of rats is on the average 445 cm2  (363 to 527 cm2) used by Merkel, D.J., N. 2000..

 

      

The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be

NOAELin mg/cm2 =     ((dose in mg/kg bw)x (average animal weight in kg)) / Treated surface in cm2)

 NOAELtest* 0.25/44.5= NOAELmodified

 

The highest dose not causing irritation/corrosion was 1000 mg/kg bw in dermal toxicity study in rats of Merkel, D.J., N. 2000.

 the modified dose descriptor would be

NOAELmodified =1000 mg/kg*0.25 kg/44.5cm2=5.62 mg/cm2