Aluminium metaphosphate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

The source substance and the target substance are considered to be similar enough to facilitate read-across for the following reasons:
(1) Both substances are inorganic salts containing a trivalent aluminium cation and phosphoric acid. Thus, they all share the Al3+ cation and the PO43- anion as common functional groups.
(2) Both substances will ultimately dissociate into the common breakdown products of the Al3+ cations and the PO43- anion. The addition of the sodium ion in the source substance is not considered to have an impact on the toxicological profile since Na+ is a common physiological ion.
(3) In general, independently of the cation under consideration, the water solubility of phosphates decreases with increasing degree of phosphate condensation (orthophosphate > diphosphate > triphosphate > polyphosphate). The source substance in this case is more soluble than the target substance and as such the results are considered to be relevant as a worst-case.
In accordance with the provisions set out in Annex XI, Section 1.5, the results of the studies used for assessment and read-across are adequate for the purpose of classification and labelling and/or risk assessment; have adequate and reliable coverage of the key parameters addressed in the corresponding test method; cover an exposure duration comparable to or longer than the corresponding test method; and adequate and reliable documentation of the applied method is provided in the technical dossier.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The kidneys of group 3 animals were found to have large and more numerous renal concretions as compared to the controls and other treatment groups. As such these were attributed to the test material.

Histopathological findings: neoplastic:

no effects observed

Other effects:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY: No untoward behavioural reactions were recorded during the investigation and no fatalities occurred.


BODY WEIGHT AND WEIGHT GAIN: No significant deviations from normally expected body weight gains for dogs of this age were noted.


FOOD CONSUMPTION AND COMPOUND INTAKE : There is no significant difference between the untreated control group and the three test groups.


HAEMATOLOGY: No significant abnormalities were noted at any level tested.


CLINICAL CHEMISTRY: There is no significant difference between the untreated control group and the three test groups.


URINALYSIS: Urinalysis revealed no significant abnormalities at any of the levels tested.


ORGAN WEIGHTS: No significant abnormalities were noted among any levels tested.


GROSS PATHOLOGY: All of the findings noted are attributed to spontaneous disease. All tissues and organs not mentioned were normal.

HISTOPATHOLOGY: NON-NEOPLASTIC: The kidneys of animals tested in group 3 were found to have large and more numerous renal concretions thought to be as a result of test material consumption. All other findings noted were attributed to spontaneous disease.

Dose descriptor:

NOAEL

Effect level:

322.88 mg/kg bw/day (nominal)

Based on:

other: test material, calculated based on food consumption

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

Dose descriptor:

NOAEL

Effect level:

492.77 mg/kg bw/day (nominal)

Based on:

other: test material, calculated based on food consumption

Sex:

female

Basis for effect level:

histopathology: non-neoplastic

Critical effects observed:

yes

Lowest effective dose / conc.:

322.88 mg/kg bw/day (nominal)

System:

urinary

Organ:

kidney

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

The 90-day oral administration of KASAL to purebred beagle dogs at dietary levels of 0.3, 1.0 and 3.0% revealed in three of the Group T-III animals renal concretions which were unusually large and more numerous than those normally observed in untreated dogs. The few other calcified microconcretions present in the lumen of renal tubules located at the corticomedullary junction and/or medulla of the kidney were attributed to normally occurring disease.
No significant other changes were noted. Thus the dieatry level of 1% can be considered as NOAEL (this is equivalent to 322.88 mg/kg bw/day).

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified