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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.12 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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
52.89 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC = NOAEL oral x (1/SRVrat) x (sRVhuman/wRV) x (ABS oral rat/ABS inhalation human)

NOAEC = 5 x (1/0.38) x 0.67 x 1.0

NOAEC = 52.89 mg/m3

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

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

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

ABS = absorption

Oral absorption rate = 100%

Inhalation absorption rate = 100%

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:
52.63 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:
5 263.2 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL was set at 30 mg/kg bw/day.

NOAEL for maternal and developmental toxicity of 30 mg/kg bw/day was determined in a study performed to OECD guideline 414 (most sensitive endpoint).

The NOAEL for maternal and developmental toxicity has been used for the calculation of margin of safety by SCCS in the Opinion on Hydroxyethyl-p-phenylenediamine sulfate (SCCS/1310/10).

Absorption oral vs dermal are calculated taking into account the dermal absorption of 0.57%.

Oral absorption is assumed to be 100%.

NOAEL dermal : 30 x (100/0.57) = 5263.2 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:
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:
9.5 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:
142.5 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:
9.5 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:
142.5 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:
0.261 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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
13.04 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL was set at 30 mg/kg bw/day.

NOAEL for maternal and developmental toxicity of 30 mg/kg bw/day was determined in a study performed to OECD guideline 414 (most sensitive endpoint).

The NOAEL for maternal and developmental toxicity has been used for the calculation of margin of safety by SCCS in the Opinion on Hydroxyethyl-p-phenylenediamine sulfate (SCCS/1310/10).

NOAEC = NOAEL oral x (1/SRVrat) x (ABS oral rat/ABS inhalation human)

NOAEC = 30 x (1/1.15) x (50/100)

NOAEC = 13.04 mg/m3

ABS = absorption

Oral absorption rate = 100% (50% if oral to inhalation extrapolation)

Inhalation default absorption rate = 100%

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

AF for dose response relationship:
1
Justification:
Defaul 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:
105.26 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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 263 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL was set at 30 mg/kg bw/day.

NOAEL for maternal and developmental toxicity of 30 mg/kg bw/day was determined in a study performed to OECD guideline 414 (most sensitive endpoint).

The NOAEL for maternal and developmental toxicity has been used for the calculation of margin of safety by SCCS in the Opinion on Hydroxyethyl-p-phenylenediamine sulfate (SCCS/1310/10).

Absorption oral vs dermal are calculated taking into account the dermal absorption of 0.57%.

Oral absorption is assumed to be 100%.

NOAEL dermal : 30 x (100/0.57) = 5263.2 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):
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:
4.75 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:
142.5 µg/m³
AF for dose response relationship:
3
Justification:
EC3 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 general 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:
4.75 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:
142.5 µg/m³
AF for dose response relationship:
3
Justification:
EC3 is consideredas 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 general 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:
0.15 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:
30 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 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:
DNEL (Derived No Effect Level)
Value:
0.72 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:
36 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is 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 judgement
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

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