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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
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
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 1A of the periodic table, and triphosphoric acid. Thus, they share the Na+ or K+ cation and P3O105- anion.
2. 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.
3. 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. Therefore it is not considered to be scientifically justified to perform any further in vivo studies.

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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1956
Report date:
1956
Reference Type:
publication
Title:
Summaries of toxicological data
Author:
Hodge HC
Year:
1964
Bibliographic source:
Fd Cosmet, Toxicol (2)147-154

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
One dog was fed a diet containing 0.1g/kg bw/day of the test material for a period of 28 days. A second dog received increasing doses from 1.0g up to 4.0 g/kg bw/ day for 5 months, doses were increased after approximately a week or so without any deleterious effects being observed. Observations were limited to bodyweights, at autopsy macroscopic and microscopic organ changes were noted.
GLP compliance:
no
Remarks:
Predates GLP
Limit test:
no

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): Sodium tripolyphosphate, Curafos (TPP)
- Code No EE22
- Lot No L 1019

Test animals

Species:
dog
Strain:
other: The dog fed increasing doses (up to 4 gm/kg bw/day) is desrcibed as a female beagle mongrel. the dog fed 0.1 g/kg bw/ day is described as a male mongrel terrier.
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult dogs.
- Weight at study initiation:
See results tables for weight changes throughout study.

ENVIRONMENTAL CONDITIONS
- No data

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: No vehicle
Details on oral exposure:
No data.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
28 days (0.1g/kg bw/ day)
and
up to 20 weeks (increasing doses up to 4.0 g/ kg bw/ day)
Frequency of treatment:
daily in diet.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.1 g /kg
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
Increasing dose 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 g/kg
Basis:
nominal in diet
No. of animals per sex per dose:
One animal per dose.
The male was treated with 0.1g/kg bw/day for 28 days.
The female was treated with up to 4.0g/kg bw/ day for up to 20 weeks.
Control animals:
no
Details on study design:
MAXIMUM DOSE VOLUME APPLIED:
In the one month study: 0.1g/kg/day; the maximum dose applied was 1g in one day, based on an intial 10 kg bw.
In the 20 week exposure: 4.0g/kg/day the maximum dose applied is not reported by the author, however, given a final bodweight of 11.3 kg the dose is expected to be approximately 45.2g in the daily diet.

Rationale for dose selection.
up to 4.0g/kg/day:
The dog(s) is given a daily dose of the material. If there is no response then the dose is upped after a period of a week or two, and then again until some evidence of a toxic effect is obtained. At an effect level the dog is maintained for a period of atleast four weeks.
0.1g/kg/day:
A second dog is maintained for four weeks on a daily dose much lower; 1/10th - 1/100th of the hightest tolerated dose.
Positive control:
no data.

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood:
- Low dose: Day -2 and 27
- High dose study: day -6 and day 153
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked: Total red blood count, hemoglobin values, total white cell count, differential counts and observations of a number of characteristics of the red blood cells

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
- Time schedule for collection of urine:
- low dose study: at -2 days then every 7 days following dosing
- High dose study: twice during study, two weeks and 5 months after start of dosing
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters checked: Sugar and protein

NEUROBEHAVIOURAL EXAMINATION: No

ORGAN WEIGHTS: Yes, kidneys, heart, lung, spleen, liver, kidney and brain
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
No data.
Statistics:
No data.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
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:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
No mortalities

BODY WEIGHT AND WEIGHT GAIN
Weight loss was observed in the dog receiving 4000mg/kg bw/day of the test material. No significant effect was seen for the dog fed 100 mg/ kg bw/ day.

HAEMATOLOGY
Blood samples taken initially and near the end of the experiment yielded expected hematological values (almost without exception).

URINALYSIS
Urine analysis for sugar and protein were as expected for both dose groups.

ORGAN WEIGHTS
Organ weights lay in the normal ranges except for an increased heart weight in the dog fed the high dose (up to 4000 mg) of sodium tripolyphosphate. Kidney weights were normal.

GROSS PATHOLOGY
The only gross abnormality was the hypertrophy of the left ventricles in the heart of the dogs given the high dose. No effect was seen in the animal treated with 100 mg/kg bw/day.

HISTOPATHOLOGY: NON-NEOPLASTIC
A thorough histological examination revealed for the most part normal appearing tissues. In the kidneys of the dog receiving up to 4000 mg/kg, tubular changes were observed.

Effect levels

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: At this dosing level there were no changes in organ weights

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Please see attachments as results are too large to fit in free-text field.

Applicant's summary and conclusion

Conclusions:
When the test material was administered at a dose of 100 mg/kg bw/day the test subject did not demonstrate any adverse effects.
At the highest dose tested, up to 4000 mg/kg bw/ day, the major findings were limited to; an enlarged heart, tubular changes in the kidneys and a loss in bodyweight.

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