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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
705.26 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no relevant reliable long-term inhalation study available
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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

Long-term - systemic - inhalation

The hazard assessment of the target substance is based on the read-across substance, thermocracked kerosene (CAS 68333-23-3). The NOAEL for systemic effects is established from the dermal subacute (28-D; 5d/wk.) study in rats (Koschier, F.J., 1992).

Relevant dose descriptor NOAEL = 400 mg/kg/day, subacute, dermal exposure, rat (BP, 1992).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 3.

100 % dermal absorption for rats

100 % inhalation absorption regardless of species

Corrected inhalatory NOAEC = dermal NOAEL * (1/ sRVrat 8h) * (ABSdermal-rat/ ABSinh-human) * (sRVhuman8h/ wRV) ABS – absorption

sRVrat – respiratory volume under standard conditions = 0.38 m3/kg/d

sRVhuman- respiratory volume under standard conditions = 6.7 m3 (8h)

wRV - respiratory volume light activity for worker = 10 m3 (8h)

Corrected inhalatory NOAEC= 400 * (1/0.38) * (100/100) * (6.7 / 10)

Corrected inhalatory NOAEC = 705.26 mg/m3

Assessment factors according to ECHA 2012 Guidance R.8 Characterization of dose response to human health

Interspecies - remaining differences 2.5

Intraspecies differences for workers 5

Exposure duration - subacute to chronic 6

Issues related to dose responses - the starting point for the DNEL calculation is a derived NOAEL - default assessment factor 1 Quality of whole database - default assessment factor 1

Overall AF 2.5 * 5 * 6 * 1 * 1 = 75

DNEL worker inhalation= 705.26 mg/m3/ 75 = 9.40 mg/m3

Long-term - systemic - dermal

The hazard assessment of the target substance is based on the read-across substance, thermocracked kerosene (CAS 68333-23-3). The NOAEL for systemic effects is established from the dermal subacute (28-D; 5d/wk.) study in rats (Koschier, F.J., 1992).

Relevant dose descriptor NOAEL = 400 mg/kg/day, subacute, dermal exposure, rat by BP, 1992.

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 2.

100 % dermal absorption is assumed for both species

Corrected dermal NOAEL = dermal NOAEL * (ABSdermal-rat/ ABSdermal-human)

Corrected dermal NOAEL = 400 * (100/100)

Corrected dermal NOAEL = 400 mg/kg bw/day

Assessment factors according to ECHA 2012 Guidance R.8 Characterization of dose response to human health

Interspecies - allometric scaling - rat 4

Interspecies - remaining differences 2.5

Intraspecies differences – worker 5

Exposure duration - subacute to chronic 6

Issues related to dose responses - the starting point for the DNEL calculation is a derived NOAEL- default assessment factor 1 Quality of whole database - default assessment factor 1

Overall AF 4 * 2.5 * 5 * 6 * 1 * 1 = 300

DNEL worker by dermal route = 400 mg/kg bw/day / 300 = 1.30 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
1 052.63 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no relevant reliable long-term inhalation study available
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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:
0.67 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no relevant reliable long-term oral study available
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

Long-term - systemic - inhalation

The hazard assessment of the target substance is based on the read-across substance, thermocracked kerosene (CAS 68333-23-3). The NOAEL for systemic effects is established from the dermal subacute (28-D; 5d/wk.) study in rats (Koschier, F.J., 1992).

Relevant dose descriptor

NOAEL = 400 mg/kg/day, subacute, dermal exposure, rat by (Koschier, F.J., 1992).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 3.

100 % dermal absorption for mouse

100 % inhalation absorption regardless of species

 

Corrected inhalatory NOAEC = dermal NOAEL * (1/ sRVrat 8h) * (ABSdermal-rat/ ABSinh-human)

ABS – absorption

sRVrat – respiratory volume under standard conditions = 0.38 m3/kg/d

Corrected inhalatory NOAEC= 400 * (1/0.38) * (100/100)

Corrected inhalatory NOAEC = 1052.63 mg/m3

 

Assessment factors according to ECHA 2012 Guidance R.8 Characterization of dose response to human health

Interspecies - remaining differences 2.5

Intraspecies differences - general population 10

Exposure duration - subacute to chronic 6                                      

Issues related to dose responses - the starting point for the DNEL calculation is a derived NOAEL - default assessment factor 1

Quality of whole database - default assessment factor 1

 

Overall AF 2.5*10*6*1*1 = 150

DNEL general population inhalation= 1052.63 mg/m3/ 150 = 7.02 mg/m3

Long-term - systemic - dermal

The hazard assessment of the target substance is based on the read-across substance, thermocracked kerosene (CAS 68333-23-3). The NOAEL for systemic effects is established from the dermal subacute (28-D; 5d/wk.) study in rats (Koschier, F.J., 1992).

Relevant dose descriptor

NOAEL = 400 mg/kg/day, subacute, dermal exposure, rat byKoschier, F.J., 1992.

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 2.

100 % dermal absorption regardless of species.

 Corrected dermal NOAEL = dermal NOAEL * (ABSdermal-rat/ ABSdermal-human)

Corrected dermal NOAEL = 400 * (100/100)

Corrected dermal NOAEL = 400 mg/kg bw/day

 

Assessment factors according to ECHA 2012 Guidance R.8 Characterization of dose response to human health

Interspecies - allometric scaling - rat 4

Interspecies - remaining differences 2.5

Intraspecies differences – general population 10

Exposure duration - subacute to chronic 6

Issues related to dose responses - the starting point for the DNEL calculation is a derived NOAEL- default assessment factor 1

Quality of whole database - default assessment factor 1

 

Overall AF 4 * 2.5 * 10 * 6 * 1 * 1 = 600

DNEL general population by dermal route = 400 mg/kg bw/day / 600 = 0.67 mg/kg bw/day

Long-term - systemic - oral

The hazard assessment of the target substance is based on the read-across substance, thermocracked kerosene (CAS 68333-23-3). The NOAEL for systemic effects is established from the dermal subacute (28-D; 5d/wk.) study in rats (Koschier, F.J., 1992).

Relevant dose descriptor

NOAEL = 400 mg/kg/day, subacute, dermal exposure, rat byKoschier, F.J., 1992.

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 6.

100 % oral absorption regardless of species

100 % dermal absorption for mouse

 

Corrected oral NOAEL = dermal NOAEL * (ABSdermal-rat/ ABSoral-human)

Corrected oral NOAEL = 400 * (100/100)

Corrected oral NOAEL = 400 mg/kg bw/day

 

Assessment factors according to ECHA 2012 Guidance R.8 Characterization of dose response to human health

Interspecies - allometric scaling - rat 4

Interspecies - remaining differences 2.5

Intraspecies differences – general population 10

Exposure duration - subacute to chronic 6

Issues related to dose responses - the starting point for the DNEL calculation is a derived NOAEL- default assessment factor 1

Quality of whole database - default assessment factor 1

 

Overall AF 4 * 2.5 * 10 * 6 * 1 * 1 = 600

DNEL general population by oral route = 400 mg/kg bw/day / 600 = 0.67 mg/kg bw/day