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Toxicological information

Toxicity to reproduction

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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

Referenceopen allclose all

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

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:
H5O10P3.5Na
IUPAC Name:
pentasodium triphosphate
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

Applicant's summary and conclusion