Pentasodium triphosphate

Toxicity to reproduction

Administrative data

Endpoint:

three-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Summaries of toxicological data

Author:

Hodge HC

Year:

1964

Bibliographic source:

Fd Cosmet, Toxicol (2)147-154

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1959

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Three generations of rats were reared on diets containing 0 and 0.5% sodium tripolyphosphate. Two litters were examined in each generation. Matingwas carried out between 16 females and 8 males of each group when the rats were 100 days old.

GLP compliance:

no

Remarks:

Study predates GLP

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:

H5O10P3.5Na

IUPAC Name:

pentasodium bis(phosphonatooxy)phosphinate

Details on test material:

- Name of test material (as cited in study report): Sodium tripolyphosphate
- Substance type: Anhydrous granular
- Physical state: solid
- Lot/batch No.: Lots 3561210 Lot D, Lot #195001-8 and Lot #5071018
- Stability under test conditions: Stable under test conditions

Test animals

Species:

rat

Strain:

other: Rochester Strain (Ex-Wistar 1923)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 60 g
- Diet: e.g. ad libitum
- Water :e.g. ad libitum

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

Exposure took place for 100 days prior to mating, 21 days of gestation and during lactation. For the F1, F2, F3-generations, offspring were weaned and exposed during an interim period of 10 days and then during a mating period of 7 days. Dams were exposed continually during gestation and lactation. Offspring of the second litter were again mated for 7 days after a 10 day interim period following weaning. The first litters (F1a, F2a, F3a) were sacrificed at 30 days of age. The second litters (F1b, F2b, F3b) were used to produce the succeeding generation.

Details on mating procedure:

Each male was caged with two females for 7 days until conception occurred.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure took place for 100 days prior to mating, 21 days of gestation and during lactation. For the F1, F2, F3-generations, offspring were weaned and exposed during an interim period of 10 days and then during a mating period of 7 days. Dams were exposed continually during gestation and lactation. Offspring of the second litter were again mated for 7 days after a 10 day interim period following weaning. The first litters (F1a, F2a, F3a) were sacrificed at 30 days of age. The second litters (F1b, F2b, F3b) were used to produce the succeeding generation.

Doses / concentrations

Remarks:

Doses / Concentrations:
0.5% in diet
Basis:
nominal in diet

No. of animals per sex per dose:

P1, F1, F2, F3: 16 females and 8 males

Control animals:

yes, concurrent vehicle

Examinations

Sperm parameters (parental animals):

Not evaluated

Litter observations:

number of pups, stillbirths, live births, weight gain per litter
Not Evaluated: sex of pups, presence of gross anomalies
physical or behavioural abnormalities, , no individual pup body weights

Postmortem examinations (offspring):

F3b generation groups of male (8/group) and female (16/group) rats were fed control diet or diet with 0.5% test material for 100 days (P1) generation. Body weights were measured weekly during the 100 day pre-mating exposure for each generation. Each male was caged with two females for 7 days until conception occurred. Pregnancy rates were determined. The first litter born of the parental animals was designated as the F1a litter. Upon delivery, offspring were counted and average litter weights determined. On day 5 pups were culled to 10 per litter. Body weights per litter were determined on day 21. Pup survival was determined on days 1-5 and days 6-21. The F1a litter was sacrificed at 30 days postnatally. Parental animals were mated again 10 days after the sacrifice of the F1a litter. Mating took place for 7 days. A second litter (F1b) was born after approximately 21 days of gestation. Upon delivery, offspring were counted and the average litter weights determined. On day 5 pups were culled to 10 per litter. Body weights per litter were determined on day 21. Pup survival was determined on days 1-5 and days 6-21. Following weaning of the F1b litter, 8 males and 16 females for the control group and the treated group were fed their respective diets for 100 days. Again two litters (F2a and F2b) were produced. Parental animals were mated for 7 days following 10 days after the sacrifice of the F2a litter (pups were 30 days old). Following birth of the F2b litter the same offspring and parental parameters were measured. Eight males and 16 females of the F2b litter were designated for continual exposure for another 100 days. Upon completion of the exposure of the F2b litter, animals were mated again to produce the F3a and F3b litters in the same manner described above. The ten males and ten females from final litter, the F3b litter, were evaluated for body weight, histopathology (liver, kidneys, gonads, lungs, brain, stomach, heart, spleen, adrenal, stomach, large and small intestines, bladder, nodes, marrow, pancreas) and organ weights (liver, kidneys, testes, lungs, brain, stomach, heart, spleen). Individual animal data were collected and recorded throughout the study.
Organ weights:
liver, kidneys, gonads, lungs, brain, stomach, heart, spleen on F2b offspring.
Not evaluated: Uterus, ovaries, epididymides (total and cauda), prostate, seminal vesicles, pituitary, thyroid, adrenal glands
Histopathology:
Kidneys, heart, brain, spleen, lungs, ovaries, testes, adrenal, bladder, lymph nodes, gut, bone marrow, pancreas on F3b animals.
Not Evaluated: Vagina, uterus with cervix, epididymis, seminal vesicle, prostate coagulating gland

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOEC

Effect level:

0.5 other: %

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

This study included only one dose level of the test material, 0.5% in the diet. There were occasional fluctuations in the fertility index.  The lower fertility index in the F2a, F3a and F3b litters is considered spurious and not treatment-related.  The fertility indices of the treated group were greater than the control group for some litters (F1a, F2b); the same as the control group for the F1b litter, and less than the control group for other litters (F2a, F3a, F3b).  These variations are not considered to show a treatment-related effect on fertility.  The duration of pregnancy, live birth index, litter size, litter weights, survival index, viability index and lactation index were all comparable between control and treated groups.  Organ weights were similar between control and treated groups.  There were no treatment-related histopathological findings.

Parameter			Control		High dose
		Generation	M	F	M	F
Mortality	Incidence	P	0	0	0	0
		F1	0	0	0	0
		F2	0	0	0	0
		F3	0	0	0	0
Food consumption	% of control		NA	NA	NA	NA
Body weight gain	% of control		100	100	100	100
Clinical Observations specify effects	Incidence		NA	NA	NA	NA
Organ weights (F3b)	% of control		95 -103	95 -103	95 -103	95 -103
Pathology
Histopathologic examination: F3b Immature testes Renal cyst Parasites in intestine Focal pulmonary hemorrhage Parasites in renal pelvis	Incidence		10 - - - -	- - 1 1 -	10 1 1 1 -	- - - - 2
Reproductive Performance
Mating index: P			-	NA		NA
F1			-	NA	-	NA
F2			-	NA	-	NA
F3			-	NA	-	NA
Fertility index: P, la			-	87.5	-	93.8
F1b			-	75	-	75
F2a			-	82.3	-	68.8
F2b			-	76.5	-	81.3
F3a				81.3	-	68.8
F3b				80	-	62.5
Number of implantation sites	Mean		-	NA	-	NA
Duration of pregnancy: P, 1a	Mean days			24.7		24.06
F1b				25.1	-	25.25
F2a				23.36	-	24.91
F2b				25	-	24.4
F3a				25.8	-	25.1
F3b				25.2	-	25
Birth index
Live birth index: P, 1a			-	93.8	-	100
F1b				93.8	-	100
F2a				100	-	100
F2b				100	-	93.8
F3a				93.8	-	100
F3b				100		87.5
Gestation index
Litter size: P, 1a	Mean		-	8.9	-	9.2
F1b				11	-	13
F2a				9.2	-	9.5
F2b				10.7	-	10.2
F3a				10.4	-	10.2
F3b				8.4	-	10.5
Litter weight: P, 1a	Mean, day 21, g		-	307	-	283
F1b				348	-	392
F2a				279	-	341
F2b				379	-	325
F3a				270		349
F3b				319	-	388
Pup weight, 1a	Mean: day 21, g			36.8	-	37.8
F1b				42.2	-	40.5
F2a				42.9	-	42.1
F2b				40.3	-	41.5
F3a				41.4	-	43.7
F3b				45.6	-	41.9
Sex ratio	Male/female			NA		NA
Survival index: P, 1a	Day 5			91.4	-	95.6
F1b				91.6	-	97.4
F2a				93.3	-	88.6
F2b				96.7	-	93.4
F3a				82.4	-	85.2
F3b				74.8	-	98.8
Viability index: P, 1a	Day 21		-	86.2	-	81.1
F1b				75	-	74.3
F2a				74.2	-	84.8
F2b				85	-	77
F3a				72.8	-	72
F3b				76.2	-	88
Lactation index: P, 1a	Day 21			86.2	-	81.1
F1b				75	-	74.3
F2a				74.2	-	84.8
F2b				85	-	77
F3a				72.8	-	72
F3b				76.2	-	88
Sperm characterization				NA		NA
Number	% of control			NA		NA
Deformations	% of control			NA		NA