Pentapotassium triphosphate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Comparable to OECD guideline 414 with acceptable restrictions. 1. There were not 20 female animals with implantation sites at necropsy in each dose group as described in OECD414. 2. Dosing was carried out from day 6-18, OECD 414 recommends from day 5-28 (the day prior to caesarean section) 3. No data on assessment of gravid uteri.

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

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Version / remarks:

1. There were not 20 female animals with implantation sites at necropsy in each dose group as described in OECD414. 2. Dosing was carried out from day 6-18, OECD 414 recommends from day 5-28 (the day prior to caesarean section) 3. No data on assessment of gravid uteri.

Deviations:

yes

Remarks:

See remarks

GLP compliance:

not specified

Limit test:

no

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; anhydrous)
- Physical state: Solid

Test animals

Species:

rabbit

Strain:

Dutch

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENT
- The animals were housed in temperature and humidty controlled rooms.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not applicable.

Details on mating procedure:

- On day 0 the doe's pretreated with human chorionic gonadotrophin were, 3h later, artificially inseminated with sperm from proven buck.

Duration of treatment / exposure:

On day 6 and continuing through to day 18 the females were dosed with the test material.

Frequency of treatment:

Daily through treatment period.

Duration of test:

13 days of treatment.

No. of animals per sex per dose:

15 - sham treated control; 13 - positive control; 16 - 2.5 mg/kg; 15 - 11.6 mg/kg; 16 - 54 mg/kg; 13 - 250 mg/kg.

Control animals:

yes, concurrent vehicle

other: Positive control fed 2.5 mg/kg of 6-aminonicotinamide, dosed on day 9

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes, for appearance and behaviour.
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 12, 18 and 29 of gestation

POST-MORTEM EXAMINATIONS: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Food consumption was monitored to rule out abnormalities as a result of anorexic effects.

Ovaries and uterine content:

The urogenital tract of each animal was examined.
(and included:)
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes

Fetal examinations:

- External examinations: Yes: gross examination - all per litter
- Pup survival - Following caesarean section the pups were placed in an incubator for 24 hours to assess neonatal survival.

The pups were then sacrificed and examined as follows:

- visceral exminations.
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: No data
- Bodyweight of live pups also recorded.

Statistics:

No data

Indices:

No data.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects. Remark: please see below.

Details on maternal toxic effects:
Cage-side observations and periodic recording of bodyweight suggested no signs of toxicity. There were no discernible effects on nidation.

Effect levels (maternal animals)

Dose descriptor:

NOEC

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: no effects observed

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The number of abnormalities seen in either soft or skeletal tissues of the test group did not differ from the number occurring spontaneously in the sham treated control.

Effect levels (fetuses)

Dose descriptor:

NOEC

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects observed

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Any other information on results incl. tables

Table 1 - Reproduction data

Dose (mg/kg)	0	Positive control*	2.5	11.6	54	250
Pregnancy
Total no	15	13	16	15	16	13
Died or aborted	5	2	1	3	8	1
To term	10	11	15	12	14	12
Total corpora lutea	216	166	227	242	263	200
Average corpora lutea	10.8	9.76	11.4	12.1	12.0	9.52
Total live litters	8	8	14	12	14	10
Average implant site no	6.20	4.91	5.13	6.08	5.71	5.33
Resorptions
Percent partial resorptions	50.0	72.7	26.7	16.7	50.0	50.0
Percent complete resorptions	10.0	27.3	6.67	-	-	16.7
Average live foetus	4.7	3.73	4.27	5.42	5.07	4.42
Sex ratio (m/f)	1.35	1.16	1.29	1.16	1.29	0.83
Dead foetuses	6	1	4	-	1	-
Percent partial dead	10.0	9.09	13.3	-	7.14	-
percent all dead	10.0	-	-	-	-	-
Average foetus weight (g)	37.2	33.5	41.8	39.7	41.0	38.9

*2.5 mg/kg 6-aminonicotinamide dosed on day 9

Table 2 - Summary of skeletal findings

Dose (mg/kg)	0	Positive control	2.5	11.6	54.0	250
Sternebrae
Incomplete oss	-	6/2	-	-	4/3	-
Bipartite	-	-	-	-	1/1	-
Fused	-	10/5	6/3	1/1	2/2	1/1
Extra	2/2	1/1	-	2/2	3/3	2/1
missing	-	1/1	-	-	1/1	-
Ribs
Fused/split	-	13/6	-	-	-	-
Vertebrae
Scrambled	-	16/6	-	-	-	-
Scoliosis	-	13/6	-	-	-	-
Tail defects	1/1	35/8	-	-	1/1	-
Skull
Incomplete closure	-	1/1	-	-	-	-

(number of foetuses effected/number of litters)

Soft tissue abnormalities were only observed in the positive control group.

Applicant's summary and conclusion

Conclusions:

Under the conditions of the study, the test material administered to pregnant rabbits for 13 days up to a dose level of 250 mg/kg bw showed no maternal or developmental toxicity. The NOAEL for both maternal and fetoxicity is > 250 mg/kg bw. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham treated controls.

This study is considered to be of adequate reliability and relevance to be submitted as the key study for this endpoint.