Registration Dossier

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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

Constituent 1
Chemical structure
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.