Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.821 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):
75
Dose descriptor starting point:
NOAEL
DNEL value:
35.2 mg/kg bw/day
Modified dose descriptor starting point:
other: NAEC
DNEL value:
61.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Inhalation should not be a preferred route for absorption. Original value is NOAEL 35.2 mg/kg bw/day, subacute toxicity in rat by oral administration. Allometric scaling from rat to human is 4. The result is multiplied by 70 kg considered as the average weight of a human being (bw) and divided by 10 m3/person considered as the average volume that is breathed in a 8 h exposure.

NAEC = [(35.2 mg/kg bw/ 4)*70 kg bw]/10 m3/person= 61.6 mg/m3 bw

AF for dose response relationship:
1
Justification:
Not necessary
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered (4)
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
5
Justification:
Worker population
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
No further uncertainties
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:
1.173 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:
NOAEL
DNEL value:
35.2 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
352 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Skin absorption can be considered as negligible and never higher 10 % than oral absorption. A starting value of 10x the NOAEL measured in a oral study is considered.

AF for dose response relationship:
1
Justification:
Not necessary
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
From rat to human
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
No further uncertainties
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

Calcium hypophosphite is classified H302 (acute oral toxicity cat.4) and H319 (eye irritation cat.2).

The assessment is done based on repeated dose toxicity studies (NOAEL 28 days rat = 35.2 mg/kg bw/day).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.205 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):
150
Dose descriptor starting point:
NOAEL
DNEL value:
35.2 mg/kg bw/day
Modified dose descriptor starting point:
other: NAEC
DNEL value:
30.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Inhalation should not be a preferred route for absorption. Original value is NOAEL 35.2 mg/kg bw, subacute toxicity in rat by oral administration. Allometric scaling from rat to human is 4. The result is multiplied by 70 kg considered as the average weight of a human being (bw) and divided by 20 m3/person considered as the average volume that is breathed by general population.

NAEC = [(35.2 mg/kg bw / 4)*70 kg bw]/20 = 30.8 mg/m3 bw

AF for dose response relationship:
1
Justification:
not necessary
AF for differences in duration of exposure:
6
Justification:
From subacute to subchronic
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered (4)
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME.
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Original data from GLP study performed on the substance itself.
AF for remaining uncertainties:
1
Justification:
No other concern derived from other studies.
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:
0.587 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):
600
Dose descriptor starting point:
NOAEL
DNEL value:
35.2 mg/kg bw/day
Modified dose descriptor starting point:
other: modified starting point
DNEL value:
352 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Skin absorption can be considered as negligible and never higher 10 % than oral absorption. A starting value of 10x the NOAEL measured in a oral study is considered.

AF for dose response relationship:
1
Justification:
not necessary
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
From rat to human.
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME.
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Original data from a GLP study performed on the substance itself.
AF for remaining uncertainties:
1
Justification:
No other concerm from other studies.
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:
0.058 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):
600
Dose descriptor starting point:
NOAEL
DNEL value:
35.2 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Not necessary
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
From rat to human.
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME.
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Original data from a GLP study performed on the substance itself.
AF for remaining uncertainties:
1
Justification:
No other concerm from other studies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.352 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
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
DNEL value:
35.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No extrapolation.

AF for dose response relationship:
1
Justification:
Not necessary
AF for interspecies differences (allometric scaling):
4
Justification:
not necessary
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME.
AF for intraspecies differences:
10
Justification:
General population.
AF for the quality of the whole database:
1
Justification:
Original data from a GLP study performed on the substance itself.
AF for remaining uncertainties:
1
Justification:
No other concerm from other studies.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Exposure of general population is not expected due to the peculiar use of the substance. Calcium hypophospite will not be available to general population as it is only included in polymeric matrices.

DNELs were derivied for precautionary principle.

Even though calcium may have an effect for acute exposure, there is no concern for repeated dose exposure at lower concentration as both calcium and hypophosphiye ions have a very low toxicological profile.