Magnesium bis(dihydrogenorthophosphate)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20/8/1984 - 7/11/1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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 containing an alkali metal cation and a phosphate anion.
(2) Both substances will ultimately dissociate into the similar breakdown products of the M2+ cations and the PO43- anion.
(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).
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. Orthophosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity. In addition, both salts have been shown to be of similar low toxicity in acute oral studies. These studies are supported by a number of acute oral studies on similar compounds which all show magnesium and calcium orthophosphates to possess low systemic toxicity via the oral route (See section 7.2.1.) and therefore comparisons can be drawn to allow read-across for the acute dermal endpoint. Regarding the nature of the substances in question; inorganic, Molecular weight >100, the absorption through the dermal layer will be considerably less than via the gastro-intestinal tract (a route which has shown low systemic toxicity). This approach is considered to be reliable and justified and no further testing for sodium dihydrogenorthophosphate is required.

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 1

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

details on bodyweight observations during and at the end of the test period were not reported

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

occlusive dressing was used, skin was abraded, exposure duration 72 hours

Principles of method if other than guideline:

Study states protocols were consitent with or exceeded the requirements of EPA and OECD guidelines at the time of the study.

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium bis(dihydrogenorthophosphate)

EC Number:

231-837-1

EC Name:

Calcium bis(dihydrogenorthophosphate)

Cas Number:

7758-23-8

Molecular formula:

CaH4O8P2

IUPAC Name:

calcium dihydrogen phosphate

Details on test material:

- Name of test material (as cited in study report): monocalcium phosphate anhydrous
- Physical state: solid; white powder
- Analytical purity: no data
- Lot/batch No.: 525

Test animals

Species:

rabbit

Strain:

other: Stauffland albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Phillips Rabbitry, Soquel, California
- Weight at study initiation: 1.642 - 2.146 kg

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdominal skin
- % coverage: no data
- Type of wrap if used: gauze binder

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: no

Duration of exposure:

72 hr

Doses:

0, 2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

other: sham-treated

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: :no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

no data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

A single dermal dose of 2000 mg/kg bw produced no mortalities in a mixed group of albino rabbits (5 male and 5 female).

Clinical signs:

other: All rabbits in the test group and the sham-exposed control group appeared normal throughout the 14-day test.

Gross pathology:

10 rabbits from the test material exposed group and 4 rabbits from the sham-exposed group were necropsied on day 14 and appeared normal.

Other findings:

- Other observations: local effects: Local dermal effects in the test material group included darkened dose sites, severe erythema, mild edema and the skin at the abrasion marks was separated and filled with reddish fluid and pus-like material. There were no apparent local dermal effects following a 24 hour sham-treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Calcium bis(dihydrogenorthophosphate) was found to have a dermal LD50 of >2000 mg/kg bw, therefore, calcium bis(dihydrogenorthophosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation EC (No.) 1272/2008 (EU CLP).