Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.25 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
122.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
303.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in male and female animals in a sub-chronic oral repeated dose toxicity study in rats (OECD 408) with the structural analogue substance melamine. The NOAEL (72 mg/kg bw/day) found for melamine was corrected for the test substance by molecular weight (corrected NOAEL = 122.8 mg/kg bw/day) as melamine is the toxic species in the test substance. To correct the interspecies difference between rat and human the NOAEL has to be corrected as follows:

Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVrat) × (ABSoral-rat ÷ ABSinh-human) × (sRVhuman ÷ wRV) × (days of exposure in the study ÷ days of exposure worker)

= 122.8 mg/kg bw/day × (1 ÷ 0.38 m³/kg bw) × (1 ÷ 1) × (6.7 m³ ÷ 10 m³) × (7 days ÷ 5 days) = 303.1 mg/m³

sRV = standard respiratory volume; wRV = respiratory volume light activity for worker (8 h); ABS = absorption

No adjustment is made for oral /inhalation absorption. The oral route is considered the most favourable one for uptake because melaminephosphate disintegrates to melamine and phosphate in stomach acid.

Thus, the corrected starting point for workers is 303.1 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on the NOAEL of a sub-chronic study. Since the chronic study did not reveal a lower NOAEL but was even higher no AF is considered.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.44 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):
50
Dose descriptor starting point:
NOAEL
Value:
122.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
171.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in male and female animals in a sub-chronic oral repeated dose toxicity study in rats (OECD 408) with the structural analogue substance melamine. The NOAEL (72 mg/kg bw/day) found for melamine was corrected for the test substance by molecular weight (corrected NOAEL = 122.8 mg/kg bw/day) as melamine is the toxic species in the test substance. To correct the interspecies difference between rat and human the NOAEL has to be corrected as follows:

 Corrected dermal NOAEL = NOAEL(oral) × (ABSoral-rat ÷ ABSdermal-human) × (days of exposure in the study ÷ days of exposure worker) = 122.8 mg/kg bw/day × (1 ÷ 1) × (7 ÷ 5) = 171.9 mg/kg bw/day

ABS = absorption

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on the NOAEL of a sub-chronic study. Since the chronic study did not reveal a lower NOAEL but was even higher no AF is considered.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rats according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.27 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):
25
Dose descriptor starting point:
NOAEL
Value:
122.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
106.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in male and female animals in a sub-chronic oral repeated dose toxicity study in rats (OECD 408) with the structural analogue substance melamine. The NOAEL (72 mg/kg bw/day) found for melamine was corrected for the test substance by molecular weight (corrected NOAEL = 122.8 mg/kg bw/day) as melamine is the toxic species in the test substance. To correct the interspecies difference between rat and human the NOAEL has to be corrected as follows:

 Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVrat) × (ABSoral-rat ÷ ABSinh-human)

= 122.8 mg/kg bw/day × (1 ÷ 1.15 m³/kg bw) × (1 ÷ 1) = 106.8 mg/m³

sRV = standard respiratory volume; ABS = absorption

No adjustment is made for oral /inhalation absorption. The oral route is considered the most favourable one for uptake because melaminephosphate disintegrates to melamine and phosphate in stomach acid.

Thus, the corrected starting point for workers is 106.8 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on the NOAEL of a sub-chronic study. Since the chronic study did not reveal a lower NOAEL but was even higher no AF is considered.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.23 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):
100
Dose descriptor starting point:
NOAEL
Value:
122.8 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
122.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in male and female animals in a sub-chronic oral repeated dose toxicity study in rats (OECD 408) with the structural analogue substance melamine. The NOAEL (72 mg/kg bw/day) found for melamine was corrected for the test substance by molecular weight (corrected NOAEL = 122.8 mg/kg bw/day) as melamine is the toxic species in the test substance. To correct the interspecies difference between rat and human the NOAEL has to be corrected as follows:

 Corrected dermal NOAEL = NOAEL(oral) × (ABSoral-rat ÷ ABSdermal-human) = 122.8 mg/kg bw/day × (1 ÷ 1) = 122.8 mg/kg bw/day

ABS = absorption

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on the NOAEL of a sub-chronic study. Since the chronic study did not reveal a lower NOAEL but was even higher no AF is considered.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.23 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):
100
Dose descriptor starting point:
NOAEL
Value:
122.8 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on the NOAEL of a sub-chronic study. Since the chronic study did not reveal a lower NOAEL but was even higher no AF is considered.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population