Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 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):
60
Modified dose descriptor starting point:
NOAEC
DNEL value:
12.72 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral route is the worst case because melamine cyanurate is soluble in stomach acid and should therefore be taken up more easily than after inhalation. Allometric scaling factor for pigs = 1.1
AF for dose response relationship:
1
Justification:
Renal crystal formation is identified as the most sensitive marker.
AF for differences in duration of exposure:
6
Justification:
28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
already included in route to route extrapolation
AF for other interspecies differences:
1
Justification:
Mode of action has been described for rats, mice, cats, dogs and fish.
AF for intraspecies differences:
5
Justification:
ECHA guidance
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
Data is mostly used from co-exposure to melamine and cyanuric acids. Experimental data on inhalation not available.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.6 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):
240
Modified dose descriptor starting point:
NOAEL
DNEL value:
4 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Absorption data available for rat (oral) and human (dermal)
AF for dose response relationship:
1
Justification:
most sensitive endpoint assessed (renal crystal formation)
AF for differences in duration of exposure:
6
Justification:
subacute exposure
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
Justification:
Same mode of action reported over many species (rat, cat, mouse, fish, dog)
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
Data is mostly used from co-exposure to melamine and cyanuric acids.
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The DNEL is derived from the 28 -day feeding study in pigs. This study is considered to be the most relevant one in regard to the risk assessment for humans. For the dermal exposure, the study in rats is used because bioavailability data is available for rat (oral) and skin (human).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.053 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):
120
Modified dose descriptor starting point:
NOAEC
DNEL value:
6.36 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
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:
DNEL (Derived No Effect Level)
Value:
8.3 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):
480
Modified dose descriptor starting point:
NOAEL
DNEL value:
4 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Absorption data available for rat (oral) and human (dermal)
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
Justification:
kidney effects described in several species.
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
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:
15 µg/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):
132
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not needed
AF for dose response relationship:
1
Justification:
Renal crystal formation is the most sensitive parameter
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1.1
Justification:
pig
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
general population default.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
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