Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9 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):
50
Dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
452 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for phosphonic acid which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422) used for read-across. The NOAEL was established to 250 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 366 mg/kg bw/day. (MW phosphonic acid = 82, Mw phosphonic acid calcium salt (1:1) = 120; 250 x 120/82= 366 mg/kg bw/day.

Therefore the corrected NOAEC is : NOAEL*(1/0.38)*(1/2)*(6.7/10)*1.4 = 452 mg/m3.

1.4 is representating the correction for differences between human and experimental exposure conditions (workers) .

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for workers
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
no additional factor.
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:
2.56 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):
200
Dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
512 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for phosphonic acid which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422) used for read-across. The NOAEL was established to 250 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 366 mg/kg bw/day. (MW phosphonic acid = 82, Mw phosphonic acid calcium salt (1:1) = 120; 250 x 120/82= 366 mg/kg bw/day).

When applying the correction for differences between human and experimental exposure conditions (workers) , the corrected NOAEL is : 366 x 1.4 = 512 mg/kg/day.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No additional factor
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.66 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):
100
Dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
159 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for phosphonic acid which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422) used for read-across. The NOAEL was established to 250 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 366 mg/kg bw/day. (MW phosphonic acid = 82, Mw phosphonic acid calcium salt (1:1) = 120; 250 x 120/82= 366 mg/kg bw/day). Therefore the corrected NOAEC is : NOAEL*(1/1.15)*(1/2)= 159 mg/kg/day.

AF for dose response relationship:
1
Justification:
Starting poing is a NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6 and a factor of 2 for a 90-day study. In an OECD 422 study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No additional factor.
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:
0.92 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):
400
Dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for phosphonic acid which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422) used for read-across. The NOAEL was established to 250 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 366 mg/kg bw/day. (MW phosphonic acid = 82, Mw phosphonic acid calcium salt (1:1) = 120; 250 x 120/82= 366 mg/kg bw/day). Therefore the corrected NOAEC is : NOAEL* (1/1) = 366 mg/kg/day.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6 and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study
AF for remaining uncertainties:
1
Justification:
no additional factor
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:
0.92 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):
400
Dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
366 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for phosphonic acid which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422) used for read-across. The NOAEL was established to 250 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 366 mg/kg bw/day. (MW phosphonic acid = 82, Mw phosphonic acid calcium salt (1:1) = 120; 250 x 120/82= 366 mg/kg bw/day). Therefore the corrected NOAEC is : NOAEL* (1/1) = 366 mg/kg/day.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use of 6 and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
A defeult factor for allometric scaling is 4 for rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No additional factor.
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