Magnesium bis(dihydrogenorthophosphate)

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

Remarks:

Scientifically sound study. However, as the study was only conducted for 14 days it is not sufficient for use as a key study for the endpoint repeated dose toxicity and therefore the data is only submitted as a supporting study to show that calcium phosphates are not considered to be systemically toxic.

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. Both substances are inorganic salts of a monovalent cation from Group 2 of the periodic table, calcium or magnesium, and phosphoric acid. Thus, they all share the Ca2+ or Mg2+ cation and the PO43- anion as common functional groups.
2. Both substances will ultimately dissociate into the common breakdown products of the Ca2+ or Mg2+ cations and the PO43- anion.
3. Calcium and magnesium orthophosphates have been shown to have a similar toxicological profile and physicochemical nature and therefore this data is considered to be adequate and reliable for use in read-across. 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. Orthophosphates are not considered to be genotoxic and are essential micronutrients. As such the acute inhalation toxicty of the target substance will be predominantly determined by the presence of the Mg2+ cation.

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:

no guideline followed

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

Limit test:

yes

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:

CaHPO4

IUPAC Name:

calcium hydrogen phosphate

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

Dose / conc.:

214 mg/kg bw/day (actual dose received)

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):

No signs of toxicity were reported for either dicalcium phosphate sample.

Mortality:

no mortality observed

Description (incidence):

0/10 animals died during the study

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 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

clinical signs

gross pathology

mortality

Target system / organ toxicity

Critical effects observed:

no

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 under the conditions of the study.