Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
44 mg/m³
Explanation for the modification of the dose descriptor starting point:

Long-term inhalation DNEL worker

According to ECHA guidance 2012 Chapter R.8, p57 (example shown on p59):

Assume 100% absorption for the oral and the inhalative route for rats and humans.

25 mg/kg/d oral NOAEL in rats can be converted to a NOAEC in workers of 44 mg/m3, as the starting point.

 

             ÷4 (allometric scaling, interspecies differences)

 

             X 70 kg

 

             ÷10 m3/person (Respiratory volume light activity for worker (wRV), 8h exposure)

 

 

AFs:

Remaining interspecies difference: 2.5

Intraspecies (worker): 5

Exposure duration (sub-acute to chronic): 6

Total: 75

Therefore, long-term inhalation DNEL for workers: 44/75=0.6 mg/m3

AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
interspecies difference rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
worker exposure
AF for the quality of the whole database:
1
Justification:
OECD study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
32 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
1 600 mg/m³
AF for interspecies differences (allometric scaling):
4
Justification:
standard AF assessment factor rat to human
AF for other interspecies differences:
2.5
Justification:
standard
AF for intraspecies differences:
5
Justification:
rat to human

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:
0.8 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
OECD study
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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

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:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL general population, lactation effects

NOAEL of 25 mg/kg/d

AFs:

Interspecies difference: 2.5 x 4

Intraspecies difference: 10

Total: 100

Therefore, DNEL for general population, lactation effects: 25/100= 0.25 mg/kg/d

Assuming a body weight of baby for 3kg, then it would be 0.25x 3=0.75 mg/baby/d

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