Pentapotassium triphosphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Acceptable well documented study report which meets basic scientific principles and is considered to sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Read across from pentasodium triphosphate to pentapotassium triphosphate is justified on the following basis: Both substances are ionic inorganic compounds containing a triphosphate anion and a group 1 alkali metal cation. Both the Na+ and the K+ cation have a similar biological function and therefore triphosphate 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 and therefore comparisons can be drawn to allow read-across.

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
In this instance, the substance similarities are as follows:
1. The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table; sodium/potassium and phosphate anion(s).
2. Both substances will ultimately dissociate into the common breakdown products; Na+ or K+ cations and PO43- anions. In biological systems, the triphosphate ion has been shown to undergo hydrolysis to form shorter phosphate chains and ultimately orthophosphate (PO43- anions).
3. Both substances have similar physicochemical and toxicological profiles. The ionic components of both the source and the target compounds are essential micronutrients and their uptake is tightly regulated.

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:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Pentasodium triphosphate

EC Number:

231-838-7

EC Name:

Pentasodium triphosphate

Cas Number:

7758-29-4

Molecular formula:

Na5P3O10 H5-xP3O10Nax (where x is approximately 5) 6H2O.Na5P3O10

IUPAC Name:

Pentasodium triphosphate

Details on test material:

- Name of test material (as cited in study report): FDA 71-46 Sodium tripolyphosphate
- Lot/batch No.: #3063

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Flow laboratories
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 280-350g
- Assigned to test groups randomly: yes
- Housing:1-5/cage, sanitary cages and bedding
- Diet (e.g. ad libitum): commercial 4% fat diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period:4-11 days

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

Acute study: 1 dose
Subacute study: 5 doses 24h apart

Frequency of treatment:

Acute study: 1 dose
Subacute study:daily

Post exposure period:

Acute study: 6, 24, 48 h
Subacute study: 6h

Doses / concentrations

Remarks:

Doses / Concentrations:
see table 1
Basis:

No. of animals per sex per dose:

5

Control animals:

yes

Positive control(s):

triethylenemelamine
- Route of administration: Oral (gavage)
- Doses / concentrations: 0.3 mg/kg

Examinations

Tissues and cell types examined:

Bone marrow cells

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
The highest dose was either a finite LD5 or 5000 mg/kg
The intermediate dose was either 1/10 of the finite LD5 or 2500 mg/kg
The low dose was either 1/100 of the finite LD5 or 30 mg/kg


DETAILS OF SLIDE PREPARATION:
Slides were stained using a 5% Giemsa solution, rinsed in acetone, 1:1 acetone:xylene and placed in fresh xylene for 30 min prior to mounting using Permount.

METHOD OF ANALYSIS:
The preparations were examined using brightfield optics microscopes with xenon light sources

Evaluation criteria:

Only diploid cells were analyzed. Scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with greater than then aberrations, polyploidy, pulverization and any other chromosomal aberrations.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Any other information on results incl. tables

Test 1: Metaphase summary

Compound	Dose (mg/kg)	No of animals	No of cells	Mitotic index	% cells with breaks	% cells with reunion	% cells other aber.	% cells with aber.
Negative control	Saline	3	150	10	4	0	0	4
Usage level	2.5	5	250	6	2	0	0	2
Intermediate level	25.0	5	250	7	4	0	0	4
LD5	250.0	5	25	8	3	1	0	4

Test 2: Subacute study. Metaphase summary

Compound	Dosage (mg/kg)	No of animals	No of cells	Mitotic index	No of cells w/breaks	no of cells w/reunion	No of cells w/other aber	No of cells w/aber
High level	1100	5	250	5.40	0	0	2	2
Negative control	Saline	3	150	7.67	0	0	1	1

Test 2: Acute study: metaphase summary

Compound	Dosage (mg/kg)	Time (hr)	No of animals	No of cells	Mitotic index	No of cells w/breaks	no of cells w/reunion	No of cells w/other aber	No of cells w/aber
High level	2500	6	5	250	4.10	0	0	0	0
		24	5	228	2.51	1	0	1	2
		48	5	250	4.96	0	1	1	2
Negative control	Saline	6	3	150	5.07	1	0	1	1
		24	3	150	4.20	0	0	1	1
		48	3	150	5.13	0	0	1	1
Positive control	0.3	48	5	250	2.92	17	25	>19	68

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
Sodium Tripolyphosphate is non mutagenic as measured by the cytogenetic test.