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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:
0.176 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
17.632 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC = NOAEL oral * (1/SRVrat) * (sRVhuman/wRV)*(ABS oral-rat /ABS inh-human) = 5*1/0.38*0.67*0.5 = 4.407 mg/m3

sRV human = standard respiratory volume human= 6.7 m3 (8h)

wRV = worker respiratory volume =10 m3 (8h)

sRVrat = standard respiratory volume rat = 0.38 m3/kg/d

ABS = Absorption

Oral default absorption rate: 100% (50% if oral-to-inhalation extrapolation)

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
expert judgement
AF for interspecies differences (allometric scaling):
1
Justification:
default value systemic effect
AF for other interspecies differences:
2.5
Justification:
default value systemic effect or for effects on skin, eye and GI tract via local metabolism, for effects on respiratory tract
AF for intraspecies differences:
5
Justification:
default value worker
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
69.444 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:
6 944.44 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity had been used for the calculation of margin of

safety by SCCS, and is the same value conisdered for DNEL calculation.

Absorption oral versus dermal are calculated, taking into account the dermal penetration rate of 0.072% . Oral absorption is assumed to be 100%

NOAEL dermal = 5 mg/kg bw/d x (100/0.072) = 6944.44 mg/kg bw/d

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
expert judgement
AF for interspecies differences (allometric scaling):
4
Justification:
allometric value (rat)
AF for other interspecies differences:
2.5
Justification:
default value systemic effect or for effects on skin, eye and GI tract via local metabolism, for effects on respiratory tract
AF for intraspecies differences:
5
Justification:
default value worker
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.33 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor:
other: EC3
Value:
260 µg/m³
AF for dose response relationship:
3
Justification:
the EC3 is considered as a LOAEL
AF for differences in duration of exposure:
1
Justification:
default value
AF for interspecies differences (allometric scaling):
1
Justification:
default value - local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1)
AF for other interspecies differences:
1
Justification:
default value. In terms of dynamics, one might assume that animals and humans will respond to the insult in the same way. In this case, the default
factor for remaining uncertainties of 2.5 could be reduced to 1
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
reliability 2
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.33 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor starting point:
other: EC3
Value:
260 µg/m³
AF for dose response relationship:
3
Justification:
the EC3 is considered as a LOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
default value - local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1)
AF for other interspecies differences:
1
Justification:
default value. In terms of dynamics, one might assume that animals and humans will respond to the insult in the same way. In this case, the default factor for remaining uncertainties of 2.5 could be reduced to 1
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
reliability 2
AF for remaining uncertainties:
1
Justification:
not concerned

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium 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:
0.055 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2.74 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity had been used for the calculation of margin of safety by SCCS, and is the same value conisdered for DNEL calculation.

NOAEC (dose descriptor calculation).

NOAEL oral * (1/SRVrat) * (ABS oral-rat/ABS inh-human)= NOAEL oral*1/1.15*(50/100) = 5*1/1.15*0.5= 2.174 mg/m3

Oral rat default absorption rate: 100% (50% if oral-to-inhalation extrapolation)

Inhalation human default absorption rate : 100%

sRVrat = standard respiratory volume rat = 1.15 m3/kg/d  

ABS = Absorption

Oral default absorption rate: 100% (50% if oral-to-inhalation extrapolation)

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
expert judgement
AF for interspecies differences (allometric scaling):
1
Justification:
default value systemic effect
AF for other interspecies differences:
2.5
Justification:
default value systemic effect
AF for intraspecies differences:
10
Justification:
default value general population
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
138.88 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):
50
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 944.44 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity had been used for the calculation of margin of safety by SCCS, and is the same value conisdered for DNEL calculation.

Absorption oral versus dermal are calculated, taking into account the dermal penetration rate of 0.072% . Oral absorption is assumed to be 100%

NOAEL dermal = 5 mg/kg bw/d x (100/0.072) = 6944.44 mg/kg bw/d

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
expert judgement
AF for interspecies differences (allometric scaling):
1
Justification:
default value
AF for other interspecies differences:
2.5
Justification:
default value systemic effect
AF for intraspecies differences:
10
Justification:
default value general population
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.666 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Dose descriptor:
other: EC3
Value:
260 µg/m³
AF for dose response relationship:
3
Justification:
EC 3 is considered as LOAEL
AF for differences in duration of exposure:
1
Justification:
default value
AF for interspecies differences (allometric scaling):
1
Justification:
default value - local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1)
AF for other interspecies differences:
1
Justification:
default value. In terms of dynamics, one might assume that animals and humans will respond to the insult in the same way. In this case, the default factor for remaining uncertainties of 2.5 could be reduced to 1
AF for intraspecies differences:
10
Justification:
default value genearl population
AF for the quality of the whole database:
1
Justification:
reliability 2
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.666 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Dose descriptor starting point:
other: EC3
Value:
260 µg/m³
AF for dose response relationship:
3
Justification:
EC 3 is considered as LOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
default value - local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1)
AF for other interspecies differences:
1
Justification:
default value. In terms of dynamics, one might assume that animals and humans will respond to the insult in the same way. In this case, the default factor for remaining uncertainties of 2.5 could be reduced to 1
AF for intraspecies differences:
10
Justification:
default value genearl population
AF for the quality of the whole database:
1
Justification:
reliability 2
AF for remaining uncertainties:
1
Justification:
not concerned

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.025 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):
200
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
expert judgement
AF for interspecies differences (allometric scaling):
4
Justification:
default value
AF for other interspecies differences:
2.5
Justification:
default value systemic effect
AF for intraspecies differences:
10
Justification:
default value genearl population
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
other: DL0
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default value
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is also not appropriate for acute lethal effects as these effects, which are accomplished by an immediate and intolerable level of damage to some critical homeostatic processes, may be independent of caloric demand and related physiological processes which affect toxicity
AF for other interspecies differences:
2.5
Justification:
default value systemic effect
AF for intraspecies differences:
10
Justification:
default value general population
AF for the quality of the whole database:
2
Justification:
expert judgment.
AF for remaining uncertainties:
1
Justification:
not concerned

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population