Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.76 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
132.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
It is assumed that the oral absorption rate is 50% of that of the inhalation absorption. ABSoral/rat=oral absorption rate in rats, ABSinh./human=inhalation absorption rate in humans. NOAEC: Workers Inhalatory NOAECcorr=NOAELoral*(1/0.38 m3/kg/d)*(ABSoral-rat/ABSinhhuman)*(6.7 m3 (8h)/10 m3 (8h)) = 150mg/kg/d*(1/0.38 m3/kg/d)*(0.5*1)*0.67=132.2mg/m3
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
Justification:
not used for inhalation
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
300
Modified dose descriptor starting point:
NOAEL
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Workers corrected Dermal NOAEC= oral NOAEL*(ABS oral/ABS dermal) It is assumed that the oral absorption rate is 10% of that of the dermal absorption. ABS oral /ABS dermal = 10 Workers Corrected DERMAL NOAEC= 150 mg/kg bw/day * 10 = 1500 mg/kg bw/day See it OECD document: ENV /JM/MONO(2011)36 GUIDANCE NOTES ON DERMAL ABSORPTION Series on Testing Assessment No 156 18 -Aug-2011

Workers Corrected Dermal NOAEC= 150 mg/kg bw/day *10 = 1500 mg/kg bw/ day

See it Se

See it OECD document: ENV/JM/MONO(2011)36 GUIDANCE NOTES ON DERMAL ABSORPTION Series on Testing and Assessment No. 156 18-Aug-2011

Workers Corrected Dermal NOAEC= 150 mg/kg bw/day * 10 = 1500 mg/kg bw/day

See it OECD document:

ENV/JM/MONO(2011)36 GUIDANCE NOTES ON DERMAL ABSORPTION Series on Testing and Assessment No. 156 18-Aug-2011

Workers Corrected Dermal NOAEC = oral NOAEL * (ABS oral/ ABS dermal)

It is assumed that the oral absorption rate is10% of thatof the dermal absorption. ABS oral/ ABS dermal =10

Workers Corrected Dermal NOAEC = oral NOAEL * (ABS oral/ ABS dermal)

It is assumed that the oral absorption rate is10% of thatof the dermal absorption. ABS oral/ ABS dermal =10

Workers Corrected Dermal NOAEC = oral NOAEL * (ABS oral/ ABS dermal)

It is assumed that the oral absorption rate is10% of thatof the dermal absorption. ABS oral/ ABS dermal =10

Workers Corrected Dermal NOAEC = oral NOAEL * (ABS oral/ ABS dermal)

It is assumed that the oral absorption rate is10% of thatof the dermal absorption. ABS oral/ ABS dermal =10

 

Workers Corrected Dermal NOAEC = 150 mg/kg bw/day*10=1500mg/kg bw /day

See it OECD document: ENV/JM/MONO(2011)36 GUIDANCE NOTES ON DERMAL ABSORPTION Series on Testing and Assessment No. 156 18-Aug-2011

II

It is assumed that the oral absorption rate is10% of thatof the dermal absorption. ABS oral/ ABS dermal =10

10% dermal absorption was assumed

AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
It is assumed that the oral absorption rate is 10% of that of the dermal absorption. ABS oral / dermal =10
AF for intraspecies differences:
5
Justification:
worker
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.43 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
65.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
It is assumed that the oral absorption rate is 50% of that of the inhalation absorption. AB ABSoral/rat=oral absorption rate in rats, ABSinh./human=inhalation absorption rate in humans NOAEC: General population inhalatroy NOAECcorr=NOAELoral*(1/1.15 m3/kg/d)*(ABSoral-rat/ABSinh-human) = 150 mg/kg/d*(1/1.15 m3/kg/d)*(0.5*1)=65.2 mg/m3
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general population
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:
2.5 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

General population Corrected Dermal NOAEC = oral NOAEL * (ABS oral/ ABS dermal) It is assumed that the oral absorption rate is 100% of that of the dermal absorption. ABS oral/ ABS dermal = 1 General population Corrected Dermal NOAEC = 150 mg/kg bw/day *10= 1500mg/kg bw /day

Workers corrected Dermal NOAEC= oral NOAEL*(ABS oral/ABS dermal) It is assumed that the oral absorption rate is 10% of that of the dermal absorption. ABS oral /ABS dermal = 10 Workers Corrected DERMAL NOAEC= 150 mg/kg bw/day * 10 = 1500 mg/kg bw/day See it OECD document: ENV /JM/MONO(2011)36 GUIDANCE NOTES ON DERMAL ABSORPTION Series on Testing Assessment No 156 18 -Aug-2011
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general population
AF for remaining uncertainties:
1
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to oral no need extrapolation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population