Registration Dossier

Diss Factsheets

Toxicological information

Toxicological Summary

Currently viewing:

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.7 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
Modified dose descriptor starting point:
NOAEC
Value:
534 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation is justified in the absence of test data for repeated dose toxicity via the inhalation route. The dose descriptor has been corrected using the equations on the left-hand side of Example R.8-2 of and methodology described in the ECHA Guidance, Chapter R.8. The starting descriptor was first corrected for differences in molecular weight and stoichiometry between SAlP and phosphoric acid. 1 mole SAlP results in 8 moles H3PO4 thus the dose descriptor is calculated using the following equation: N(L)OAEL(H3PO4) = N(L)OAEL(SAlP)*8*([Mol.Weight(H3PO4)]/[Mol.Weight(SAlP)]). The molecular weight of SAlP in this instance is 1185.57, molecular formula = Na15Al3(PO4)8.
AF for dose response relationship:
1
Justification:
Dose-spacing is within the 2-4 range, response at the LOAEL is minimal. DNEL is based on NOAEL.
AF for differences in duration of exposure:
2
Justification:
The assessment factor reflects the extrapolation from sub-chronic to chronic.
Justification:
Not required as taken into account in the route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Additional AF accounts for remaining differences.
AF for intraspecies differences:
5
Justification:
Standard assessment factor for workers.
AF for the quality of the whole database:
2
Justification:
Modified based on the reliability of alternative data, to account for the use of read-across data.
Justification:
No further assessment factor required. Route to route extrapolation already accounted for.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: An appropriate OEL (8hr TWA) for phosphoric acid is in place and therefore a DNEL is not required.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: An appropriate OEL (15min STEL) for phosphoric acid is in place and therefore a DNEL is not required.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Choice of endpoint for DNEL derivation:

The following issues were taken into account when deciding on which study to base the DNEL:

1. Nephrocalcinosis (in the form of microconcretions) was observed in the renal tubules of animals investigated in the tests. In general, rats; particularly female rats, are known to be susceptible when administered high doses of dietary phosphate (typically 0.5 -1.0% in the diet). Occupational exposure is not considered to contribute to such exposures and in addition healthy humans are considered to be less sensitive to calcium phosphate precipitation when compared to laboratory rats.

 

2. Nephrocalcinosis and/or reduced bodyweight gain were the only toxic effects observed in any of the studies.

 

3. The ratio of sodium, aluminium and phosphate in the test material appears to be less relevant to the toxicity endpoint (NOAEL) than feed consumption, body weight and dose levels. In all rat studies the N(L)OAEL was based on nephrocalcinosis. In two of the studies performed on dogs (standard alternative test species) the N(L)OAEL is the highest dose level tested. In the other two studies minimal nephrocalcinosis and reduced bodyweight was observed at the highest does resulting in the NOAEL being set at the mid dose level.

The LOAEL based on nephrocalcinosis (oral study, 90 days, rat) is lower than any of the reported NOAELs and as such this is used to derive the oral DNEL. As nephrocalcinosis is assumed to be relevant for dietary exposure the endpoints derived on the basis of this effect have not been taken into account for the inhalation route. In the studies where nephrocalcinosis was observed, there were no other forms of toxicity noted and as such it is considered acceptable to base the inhalation DNEL on the lowest NOAEL. In this instance the NOAEL is taken from 90 day and 6 month studies in the dog and is based on reduced bodyweight gain at the highest dose.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.57 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
Modified dose descriptor starting point:
NOAEC
Value:
457.42 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation is justified in the absence of test data for repeated dose toxicity via the inhalation route. The dose descriptor has been corrected using the equations on the left-hand side of Example R.8-1 of and methodology described in the ECHA Guidance, Chapter R.8. The standard human bosyweight ised was 60kg to represent the general population. The starting descriptor was first corrected for differences in molecular weight and stoichiometry between SAlP and phosphoric acid. 1 mole SAlP results in 8 moles H3PO4 thus the dose descriptor is calculated using the following equation: N(L)OAEL(H3PO4) = N(L)OAEL(SAlP)*8*([Mol.Weight(H3PO4)]/[Mol.Weight(SAlP)]). The molecular weight of SAlP in this instance is 1185.57, molecular formula = Na15Al3(PO4)8.
AF for dose response relationship:
1
Justification:
Dose-spacing is within the 2-4 range, response at the LOAEL is minimal.
AF for differences in duration of exposure:
2
Justification:
Key study is a 90-day Sub-chronic investigation. The assessment factor reflects the extrapolation from sub-chronic to chronic.
Justification:
Not applicable - allometric scaling performed when deriving the starting dose.
AF for other interspecies differences:
2.5
Justification:
Additional AF accounts for remaining differences.
AF for intraspecies differences:
10
Justification:
Standard assessment factor for general population.
AF for the quality of the whole database:
2
Justification:
Modified based on the reliability of alternative data, to account for the use of read-across data.
Justification:
No further assessment factor required. Route to route extrapolation already accounted for.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.36 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: OEL used as starting point for derivation of an exposure limit for the general population. An additional factor is applied to take into account the differences in weekly exposure (worker = 5 days, consumer = 7 days).
Overall assessment factor (AF):
2
Dose descriptor:
other: OEL (8hr TWA)
Justification:
Not applicable - starting point is OEL
Justification:
Not applicable - starting point is OEL and exposure time was accounted in the calculation
Justification:
Not applicable
Justification:
Not application
AF for intraspecies differences:
2
Justification:
Worker to general population - The value indicated for derivation of DNELs from a dataset is normally 10 however since the starting point is an occupational exposure limit for a local effect based on the P2O5 concentration unlikely to cause irritation in workers a factor of 10 would be considered unnecessarily restrictive. A factor of 2 is selected on the basis that the normal factor for the general population is twice that of the worker population.
Justification:
Not applicable
Justification:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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):
1 200
Modified dose descriptor starting point:
LOAEL
Value:
155.36 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable. The starting descriptor was first corrected for differences in molecular weight and stoichiometry between SAlP and phosphoric acid. 1 mole SAlP results in 8 moles H3PO4 thus the dose descriptor is calculated using the following equation: N(L)OAEL(H3PO4) = N(L)OAEL(SAlP)*8*([Mol.Weight(H3PO4)]/[Mol.Weight(SAlP)]). The molecular weight of SAlP in this instance is 897.82, molecular formula = Na3H15Al2(PO4)8.
AF for dose response relationship:
3
Justification:
Starting dose is an LOAEL
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Standard allometric scaling - rat to human
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining circumstances
AF for intraspecies differences:
10
Justification:
Standard assessment factor for general population
AF for the quality of the whole database:
2
Justification:
Modified to 2 to account for use of read-across data
AF for remaining uncertainties:
1
Justification:
Completeness and consistency of available data
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

In addition when considering the hazard for consumer products of phosphoric acid containing 10 <25% of phosphoric acid; the resultant classification according to the harmonised classification is: Skin irrit. 2 and Eye irrit. 2 (labelled with Hazard Statements H315 and H319) thus resulting assignment as a ‘low hazard’ in accordance with Table E.3-1 and a qualitative assessment that may be less strict than that performed for a moderate hazard.

 

However, although the likelihood of volatilisation is low as a precautionary measure knowing that volatilisation is possible and inhalation may occur (e.g. if solutions are heated) a classification of respiratory irritation 2 could be applied; thus resulting in the hazard being bumped up to moderate as all three (skin, eye and resp. irrit.) occur simultaneously. As such a worst-case approach based on a moderate hazard will be considered for products containing 10 <25% w/w of phosphoric acid.

Choice of endpoint for DNEL derivation:

The following issues were taken into account when deciding on which study to base the DNEL:

1. Nephrocalcinosis (in the form of microconcretions) was observed in the renal tubules of animals investigated in the tests. In general, rats; particularly female rats, are known to be susceptible when administered high doses of dietary phosphate (typically 0.5 -1.0% in the diet). Occupational exposure is not considered to contribute to such exposures and in addition healthy humans are considered to be less sensitive to calcium phosphate precipitation when compared to laboratory rats.

 

2. Nephrocalcinosis and/or reduced bodyweight gain were the only toxic effects observed in any of the studies.

 

3. The ratio of sodium, aluminium and phosphate in the test material appears to be less relevant to the toxicity endpoint (NOAEL) than feed consumption, body weight and dose levels. In all rat studies the N(L)OAEL was based on nephrocalcinosis. In two of the studies performed on dogs (standard alternative test species) the N(L)OAEL is the highest dose level tested. In the other two studies minimal nephrocalcinosis and reduced bodyweight was observed at the highest does resulting in the NOAEL being set at the mid dose level.

The LOAEL based on nephrocalcinosis (oral study, 90 days, rat) is lower than any of the reported NOAELs and as such this is used to derive the oral DNEL. As nephrocalcinosis is assumed to be relevant for dietary exposure the endpoints derived on the basis of this effect have not been taken into account for the inhalation route. In the studies where nephrocalcinosis was observed, there were no other forms of toxicity noted and as such it is considered acceptable to base the inhalation DNEL on the lowest NOAEL. In this instance the NOAEL is taken from 90 day and 6 month studies in the dog and is based on reduced bodyweight gain at the highest dose.