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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.3 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):
37.5
Dose descriptor starting point:
LOAEL
Value:
126 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
310.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Melamine is absorbed rapidly and almost completely after oral dosing and there is apparently no metabolism in rats. A similar toxicokinetic profile is expected for melamine phosphate. A transformation of the LOAEL oral to LOAEC inhalation is therefore justified, taking the default absorption rate for inhalation of 100 %, and setting also the oral absorption rate to 100 %. 


The LOAEC rat, inhalation calculated from the LOAEL oral, 2 years of 126 mg/kg bw/d (carcinogenicity study) and the standard respiratory volume sRV for the rat of 0.38 m³/kg bw for an 8 hour exposure.


The LOAEC was further adjusted for an increased respiratory volume of 10 m³/8h for workers, compared to 6.7 m³/8h for the general public. 


The exposure conditions for the orally dosed rats were 7d/w compared to the inhalation exposure of workers of 5d/w. 


126 x 1 x 2.63 x 0.67 x 1.4 =  310.8 mg/m³


 

AF for dose response relationship:
3
Justification:
LOAEL as a starting point and a steep dose-response curve
AF for differences in duration of exposure:
1
Justification:
Default for a chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already applied via modification of the starting point
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
5
Justification:
Default factor for the worker
AF for the quality of the whole database:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
AF for remaining uncertainties:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low 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:
11.8 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):
150
Dose descriptor starting point:
LOAEL
Value:
126 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 764 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal absorption is estimated to be 10 % as a worst-case assumption. The LOAEL of the original study has further been modified to account for the differences in exposure duration (7d/week for oral rat dosing vs. 5d/week for the worker).

AF for dose response relationship:
3
Justification:
LOAEL as a starting point
AF for differences in duration of exposure:
1
Justification:
Default for a chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Default for a rat study
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for the worker
AF for the quality of the whole database:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
AF for remaining uncertainties:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
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:
low hazard (no threshold derived)

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:
DNEL (Derived No Effect Level)
Value:
4.2 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:
LOAEL
Value:
126 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 260 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

LOAEC has been corrected to account for dermal absorption (10% assumed as a worst case approach).

AF for dose response relationship:
3
Justification:
Default factor for LOAEC as starting point
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rat study
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for the general population
AF for the quality of the whole database:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
AF for remaining uncertainties:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
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:
0.42 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:
LOAEL
Value:
126 mg/kg bw/day
AF for dose response relationship:
3
Justification:
Default for LOAEL as a starting point
AF for differences in duration of exposure:
1
Justification:
Default for a chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rat study
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
Justification:
several studies for melamine in several species available. No factor for read-across needed, as the toxicologically relevant compound is melamine; using a melamine study as a starting point is a worst-case approach for melamine phosphate.
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