Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.117 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):
300
Modified dose descriptor starting point:
other: NAEC
Value:
35 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC= ((20 / 4) x 70) /10; NOAEL = 20 mg/kg on young rat (Koizumi et al., 2001); 4 = allometric scaling factor rat; 70 kg/bw= standard human body weight; 10 m^3/person= default human breathing volume for workers in 8 h.
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
6
Justification:
from subacute (28 days) to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC) has just been corrected for the human evaluation.
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
other: NAEC
Value:
1 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC= ((20 / 1.4) x 70) /(10 x 100); LD50 = 20 mg/kg on dog (NRC, 1981); 1.4 = allometric scaling factor dog; 70 kg/bw = standard human body weight; 10 m^3/person= default human breathing volume for workers in 8 h; 100 = additional default AF to correct the LD50 starting point.
AF for dose response relationship:
1
Justification:
A default AF of 100 has been taken into account to correct the LD50 starting point
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC) has just been corrected for the human evaluation.
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed

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:
0.017 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No modification necessary.
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
6
Justification:
from subacute (28 days) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 500
Modified dose descriptor starting point:
other: LD20
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No modification necessary.
AF for dose response relationship:
10
Justification:
The 10 AF has been chosen for uncertainties
AF for interspecies differences (allometric scaling):
3
Justification:
guinea pig
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed

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:
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:
0.029 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):
600
Modified dose descriptor starting point:
other: NAEC
Value:
17.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC= ((20 / 4) x 70) /20; NOAEL = 20 mg/kg on young rat (Koizumi et al., 2001); 4 = allometric scaling factor rat; 70 kg/bw= standard human body weight; 20 m^3/person= default human breathing volume for general population 24h.
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
6
Justification:
from subacute (28 days) to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC) has just been corrected for the human evaluation.
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.005 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
other: NAEL
Value:
0.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC= ((20 / 1.4) x 70) /(20 x 100); LD50 = 20 mg/kg on dog (NRC, 1981); 1.4 = allometric scaling factor dog; 70 kg/bw = standard human body weight; 20 m^3/person= default human breathing volume for general population in 24 h; 100 = additional default AF to correct the LD50 starting point.
AF for dose response relationship:
1
Justification:
A default AF taken into account the dose response relationship to correct the LD50 starting point has just been used
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC) has just been corrected for the human evaluation.
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed

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:
0.008 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):
2 400
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no modification necessary
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
6
Justification:
from subacute (28 days) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
3 000
Modified dose descriptor starting point:
other: LD20
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No modification necessary.
AF for dose response relationship:
10
Justification:
The 10 AF has been chosen for uncertainties
AF for interspecies differences (allometric scaling):
3
Justification:
guinea pig
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
No scaling needed.
AF for remaining uncertainties:
1
Justification:
No scaling needed

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:
0.008 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):
2 400
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no modification necessary
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
6
Justification:
from subacute (28 days) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.014 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
other: LD50
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no modification necessary
AF for dose response relationship:
10
Justification:
The 10 AF has been chosen. This precautionary AF has been applied due to the serious and irreversible effects observed in human occupational exposure literaturereports, despite a quantitative assessment was not recorded.
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog
AF for other interspecies differences:
10
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
No scaling needed
AF for remaining uncertainties:
1
Justification:
No scaling needed

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Toxicity on eye is the main reason 2,4-DNP was banned from use for weight control by the Food and Drug Administration.

A a clinical study of Hitch JM, Schwartz WF, 1933 showed that 2,4-dinitrophenol at dose of 1.86 mg/kg/day caused cataracts in patients who were at an age when senile cataracts do not occur. The patient developed blurred vision which was attributed to bilateral cataracts.

Generally, cataracts developed also in a small percentage of patients who took 2,4-DNP or sodium 2,4-DNP as a weight reduction aid for acute, intermediate, and chronic durations (Horner, 1942).