reaction mass of calcium bis(dihydrogenorthophosphate) and calcium hydrogenorthophosphate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

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

(1) All salts are inorganic phosphates, composed of a phosphate anion and a calcium cation.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Ca2+ cation and the PO43-anion.
(3) A number of studies are provided to show that monovalent calcium and/or magnesium inorganic orthophosphates exhibit low acute oral toxicity. These data are provided in Section 7.2.1 of this dossier. The information provided in these records is considered to be of suitable relevance and reliability to underpin the read across for the acute dermal and inhalation endpoints. All substances are ionic and will readily dissociate to their ionic forms in aqueous environments. The orthophosphate ion can undergo ionisation with loss of H+ from each of the three –OH groups and therefore can occur in the -1, -2 or -3. The degree of ionisation is dependent upon the associated cation and the ambient pH (if in solution). Calcium and phosphate are key elements in various cellular processes their import and export over cell membranes is regulated via pore systems and usually tightly regulated. Orthophosphate salts of these types are not considered to differ in their systemic toxicity profiles. Differences arise in their local effects profile due differences in pH and buffering capacities. This does not have an effect on systemic toxicity.

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’.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Report date:

1970

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: no data

Deviations:

not applicable

Principles of method if other than guideline:

The test material was administered to male rats by means of a stomach tube daily for 14 days. 24 hours after the final dose animals were autopsied and observed for pathological changes.

GLP compliance:

no

Remarks:

Study pre-dates GLP

Test material

Test material information

Constituent 1

Reference substance name:

Calcium hydrogenorthophosphate

EC Number:

231-826-1

EC Name:

Calcium hydrogenorthophosphate

Cas Number:

7757-93-9

Molecular formula:

Ca.H3O4P

IUPAC Name:

calcium hydrogen phosphate

Details on test material:

- Name of test material (as cited in study report): Dicalcium phosphate
- Other: test material was made from PCI superphosphoric acid
- Analytical purity: no data
- Lot/batch No.: MK 1.5 9-29-70 w/PCI SPA

- Name of test material (as cited in study report): Dicalcium phosphate reagent grade
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 220-240 g
- Fasting period before study: 24 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
214 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The dose level of 214 mg/kg bw is equivalent to the 0.15 lb/head/day level fed to cattle as a food additive.

Positive control:

No

Examinations

Observations and examinations performed and frequency:

No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

0/10 animals died during the study and nosigns of toxicity were reported for either dicalcium phosphate sample.

Mortality:

no mortality observed

Description (incidence):

0/10 animals died during the study and nosigns of toxicity were reported for either dicalcium phosphate sample.

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Description (incidence and severity):

All animals appeared grossly normal when necropsied following termination of the experiment

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Effect levels

Dose descriptor:

NOAEL

Effect level:

214

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: Mortality

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No adverse effects of administration of dicalcium phosphate (reagent grade and PIC SPA derived) were noted at a dose level of 214 mg/kg bw in rats and under the conditions of the study.