Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Subchronic oral toxicity study of potassium pyrophosphate as a preliminary to long-term carcinogenicity studies in F344 rats
- Author:
- Shimoji N, Matsushima Y, Imaida K, Hasegawa R, Kurokawa Y and Hayashi Y.
- Year:
- 1 988
- Bibliographic source:
- ESKHA5 Eisei Shikenjo Horoku. Bulletin of the Institute of Hygienic Sciences. 106: 66-72
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Principles of method if other than guideline:
- A 13 week sub-chronic toxicity study of potassium pyrophosphate was carried out in male and female F344 rats at the dose levels of 10, 5, 2.5, 1.25, 0.6 and 0% in the diet. Sixty animals of both sexes were divided into the 6 dosage groups. The purpose of the study was to determine the maximumtolerable dose dose of test substance for use in rats in a long-term carcinogenicity study. Observations were limited to mortality, clinical abnormalities, body weights, food intake, haematology, clinical chemistry, gross pathology (incl. organ weight) and histopathology.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Tetrapotassium pyrophosphate
- EC Number:
- 230-785-7
- EC Name:
- Tetrapotassium pyrophosphate
- Cas Number:
- 7320-34-5
- IUPAC Name:
- tetrapotassium diphosphate
- Details on test material:
- - Name of test material (as cited in study report): potassium pyrophosphate.
- Substance type: Water soluble, colourless or white crystal powder.
- Physical state: Solid.
- Analytical purity: ≥ 95%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Ltd Japan.
- Age at study initiation: At least 6 weeks old.
- Fasting period before study: No. Fasting is recorded to have been carried out after the last dosing until the animals were sacrificed.
- Housing: 5 animals per plastic cage with soft chip on the floor which was changed every 2 weeks.
- Diet (e.g. ad libitum): CRF-1 (powder), Charles River Ltd. The test substance was mixed in the diet and provided ad libitum.
- Water (e.g. ad libitum): Mains water, ad libitum.
- Acclimation period: 1 week.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 - 25°C
- Humidity (%): 50 - 60%
- Air changes (per hr): 18 times per hour.
- Photoperiod (hrs dark / hrs light): 12 hours of light and 12 hours of darkness.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Up to 91 days.
- Frequency of treatment:
- Ad libitum during the exposure period.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: % (nominal in diet)
- Dose / conc.:
- 0.6 other: % (nominal in diet)
- Dose / conc.:
- 1.25 other: % (nominal in diet)
- Dose / conc.:
- 2.5 other: % (nominal in diet)
- Dose / conc.:
- 5 other: % (nominal in diet)
- Dose / conc.:
- 10 other: % (nominal in diet)
- No. of animals per sex per dose:
- 10 animals per sex per dose.
- Control animals:
- yes, plain diet
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily.
- Cage side observations checked: Mortality, general abnormalities.
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: Daily.
HAEMATOLOGY AND CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 92.
- Anaesthetic used for blood collection: Yes , ether.
- Animals fasted: Yes
- How many animals: All animals.
- Parameters checked: GOT, GPT, Alp, TTT, T-bil, T-cho, TG, beta-lipopro, T-pro, A/G, BUN, creatinine, uric acid, ZTT, Ca, erythrocyte, Ht, MCV, leukocyte and Hb. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Two males and one female from the 10% groups as a result of renal failure.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Two males and one female from the 10% groups as a result of renal failure.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Bodyweight gains of both male and female rats treated with 10% and of male rats treated with 5% were significantly decreased as compared with controls.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption was effected in the 10% and 5% groups. No further details are provided.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- There was a trend towards higher uric acid levels in both sexes at higher doses. There were significant changes of the hepato-related parameter levels in the dosed groups.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- There were significant deviations in organ weights.
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- KIDNEYS: In the 10% groups both sexes exhibited a mild to severe tubulorrhexis accompanied by calcification, interstitial fibrosis and mononuclear cell infiltration in the area of the cortico-medullary border.
The 5% group exhibited a slight to mild tubulorrhexis accompanied by calcification in all animals.
The 2.5% group atrophy and deciduation of the uriniferous tubule epithelial cells was observed in 7/10 males and 8/10 females.
No other effects were reported at the lower doses.
TONGUE: Ulceration and/or granuloma formation was reported in the mucosal tissue at the root of the tongue for 8/8 males and 7/9 females in the 10% group; and for 6/10 males and 4/10 females the 5%.
SALIVARY GLAND: Hypertrophy and basophilisation of acinar cells of the sublingual gland and submandibular gland. Also noted was a compression/atrophy of the striated duct, intercalated duct and excretory duct. These effects were observed in 7/8 males and 4/9 females in the 10% group and in 2/10 males in the 5% group.
OTHER: Hyperplasia of RES cells and lymphoblasts was reported. A lesion in the submandibular lymph node is recorded in 2/10 males and 1/10 female in the 10% group. No other effects are reported for the other organs - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
Effect levels
open allclose all
- Key result
- Dose descriptor:
- LOEL
- Effect level:
- 0.6 other: %
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- haematology
- organ weights and organ / body weight ratios
- Key result
- Dose descriptor:
- LOEL
- Effect level:
- 308 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- haematology
- organ weights and organ / body weight ratios
- Remarks on result:
- other: Extrapolated from level of compound in diet assuming 0.35 kg rat eats 18 g food/day.
Target system / organ toxicity
- Key result
- Critical effects observed:
- not specified
Any other information on results incl. tables
Reduction in the body weight gain and the trend of higher uric acid levels may be due to the decreased food consumption and the effects in the kidneys. The effects in the tongue would be due to the high alkaline property of the test substance in the solution.
Table 1 - Serum chemistry and hematology results (male)
Dose |
10% |
5% |
2.5% |
1.25% |
0.6% |
control |
Effective No. |
7 |
10 |
10 |
10 |
10 |
8 |
GOT (KU) |
92.0±9.6a |
70.0±7.3 |
66.2±8.1 |
67.7±4.8 |
68.5±8.1 |
67.5±6.1 |
GPT (KU) |
39.5±9.0a |
27.9±1.4b |
26.2±1.9 |
25.8±2.8 |
24.3±2.8 |
25.8±2.0 |
Alp (KAU) |
21.1±2.0a |
13.3±1.2 |
11.3±1.2a |
11.8±0.9a |
11.8±1.3b |
13.3±1.0 |
TTT(SHU) |
0.99±0.54a |
0.40±0.16 |
0.27±0.11 |
0.45±0.16 |
0.42±0.29 |
0.34±0.17 |
T-bil.(mg/dL) |
0.55±0.08b |
0.47±0.08 |
0.51±0.07 |
0.52±0.08 |
0.48±0.06 |
0.46±0.07 |
T-cho.(mg/dL) |
96.3±5.5a |
51.0±5.4 |
49.9±2.7 |
54.2±2.7 |
50.1±3.8 |
51.7±3.8 |
TG(mg/dL) |
69.1±16.8 |
77.6±17.6 |
77.5±14.3 |
116.0±18.6a |
94.7±30.7 |
85.3±17.5 |
β lipo-pro.(mg/dL) |
131.4±26.8 |
117.5±20.8 |
106.0±27.1 |
195.1±147.1 |
132.4±36.8 |
127.2±19.8 |
T-pro.(g/dL) |
6.25±0.22b |
6.54±0.13 |
6.57±0.18 |
6.65±0.16b |
6.5±0.12 |
6.48±0.10 |
A/G |
1.70±0.19 |
1.75±0.05 |
1.81±0.07 |
1.85±0.07 |
1.89±0.09 |
1.93±0.08 |
BUN(mg/dL) |
34.6±2.1a |
22.7±1.8a |
17.9±2.1 |
17.6±1.4 |
17.0±1.3 |
17.5±1.1 |
Creatine(mg/dL) |
0.85±0.21 |
0.65±0.25 |
0.84±0.23 |
0.94±0.15 |
0.72±0.45 |
0.91±0.35 |
Uric acid(mg/dL) |
2.00±0.037a |
1.19±0.29 |
1.01±0.20 |
1.29±0.56 |
1.47±0.63 |
0.98±0.29 |
ZTT(KU) |
2.79±1.02a |
1.62±0.32a |
1.24±0.19b |
1.41±0.36b |
1.07±0.23 |
1.08±0.12 |
Ca(mg/dL) |
9.2±0.4a |
10.5±0.3a |
10.7±0.2 |
10.8±0.4 |
11.1±0.6 |
10.9±0.3 |
Erythrocytes(x104/mm2) |
706.6±43.7a |
893.1±17.3a |
926.1±24.0 |
953.4±33.0 |
942.8±15.1 |
949.0±22.4 |
Ht.(%) |
375.0±16.4a |
443.6±9.1a |
454.6±11.8 |
468.4±15.6 |
465.1±9.5 |
465.5±10.8 |
MCV(µ2) |
53.3±1.1a |
49.7±0.7b |
49.1±0.3 |
49.2±0.4 |
49.0±0.5 |
49.0±0.0 |
Leukocyte(x102/mm2) |
71.9±14.5 |
59.9±10.5 |
85.7±38.5 |
146.6±41.4a |
98.9±14.2a |
59.3±15.5 |
Hb.(g/dL) |
121.1±20.7a |
154.0±3.7a |
153.8±15.1 |
160.3±6.1 |
159.9±3.2 |
161.3±3.6 |
ap<0.01;bp<0.05
Table 1 continued - Serum chemistry and hematology results (female)
Dose |
10% |
5% |
2.5% |
1.25% |
0.6% |
control |
Effective No. |
8 |
9 |
10 |
10 |
9 |
10 |
GOT (KU) |
90.3±3.6a |
69.0±3.9a |
70.7±5.8a |
68.8±8.7 |
69.0±5.2b |
63.3±4.1 |
GPT (KU) |
35.2 ±9.0a |
26.5±4.2b |
24.1±2.8 |
23.4±1.4 |
23.0±2.6 |
23.1±2.0 |
Alp (KAU) |
15.0±1.8a |
8.6±1.1 |
8.6±0.8 |
10.0±1.7 |
9.0±1.2 |
8.5±1.4 |
TTT(SHU) |
0.43±0.17 |
0.39±0.14 |
0.45±0.22 |
0.48±0.19 |
0.31±0.09b |
0.44±0.16 |
T-bil.(mg/dL) |
0.47±0.16 |
0.53±0.12 |
0.62±0.06 |
0.55±0.11 |
0.59±0.07 |
0.57±0.11 |
T-cho.(mg/dL) |
112.0±10.0a |
83.9±9.2 |
85.0±5.5 |
86.4±8.5 |
80.8±5.1b |
87.7±6.2 |
TG(mg/dL) |
65.0±26.2 |
53.2±9.7 |
59.0±10.3 |
57.0±12.2 |
54.3±4.6 |
58.3±9.4 |
β lipo-pro.(mg/dL) |
79.0±30.7b |
52.9±13.7a |
93.3±16.4 |
92.6±21.8 |
90.4±8.5 |
102.8±16.9 |
T-pro.(g/dL) |
6.01±0.20a |
6.19±0.18b |
6.41±0.24 |
6.45±0.09 |
6.32±0.19 |
6.37±0.16 |
A/G |
2.00±0.18 |
1.90±0.26 |
1.88±0.09 |
1.84±0.33 |
2.02±0.10 |
1.93±0.12 |
BUN(mg/dL) |
35.6±5.3a |
25.8±2.3a |
19.4±1.4a |
18.3±1.4a |
16.8±1.1 |
16.1±1.2 |
Creatine(mg/dL) |
0.66±0.14 |
0.70±0.25 |
0.76±0.34 |
0.91±0.22 |
0.86±0.31 |
0.64±0.33 |
Uric acid(mg/dL) |
1.75±0.32 |
1.71±0.35 |
1.66±0.22 |
1.73±0.29 |
1.74±0.37 |
1.78±0.26 |
ZTT(KU) |
0.80±0.38a |
1.67±0.71 |
2.18±0.39 |
2.37±1.58 |
1.56±0.47 |
1.98±0.82 |
Ca(mg/dL) |
9.5±0.5a |
10.8±1.1 |
10.4±0.9 |
9.8±0.4a |
10.0±0.2a |
10.4±0.4 |
Erythrocytes(x104/mm2) |
685.8±34.9a |
862.2±25.6 |
861.1±23.0 |
856.6±23.4 |
846.6±21.4 |
876.9±32.6 |
Ht.(%) |
372.1±15.5a |
445.4±14.1 |
444.8±13.5 |
441.1±14.3 |
448.3±10.1 |
452.7±16.4 |
MCV(µ2) |
54.1±0.8a |
51.6±0.5 |
51.8±0.6 |
51.6±0.7 |
51.9±0.3 |
51.7±0.7 |
Leukocyte(x102/mm2) |
66.8±8.3a |
127.9±64.8 |
207.5±51.1a |
239.0±33.6a |
160.3±55.3 |
116.5±23.3 |
Hb.(g/dL) |
116.9±24.5a |
159.3±5.3 |
160.1±5.6 |
157.8±5.4 |
158.8±4.7 |
159.5±4.0 |
ap<0.01;bp<0.05
Table 2 - Absolute and relative organ weights (male)
Relative organ weights are shown in parenthesises (%)
Dose |
10% |
5% |
2.5% |
1.25% |
0.6% |
Control |
Effective No. |
8 |
10 |
10 |
10 |
10 |
10 |
Brain |
1.86±0.04a(1.1)a |
1.98±0.06 (0.7)b |
2.01±0.06 (0.6) |
1.98±0.05 (0.6)b |
2.02±0.04 (0.6)b |
2.02±0.08 (0.6) |
Pituitary |
0.007±0.003 (0.004) |
0.011±0.004 (0.003) |
0.008+0.003 (0.002) |
0.008±0.003 (0.002) |
0.007±0.002 (0.002) |
0.011±0.006 (0.003) |
Saliv. Glds. |
0.79±0.21b(0.48)a |
0.82±0.28b(0.28)b |
0.68±0.12 (0.20) |
0.60±0.06 (0.18) |
0.62±0.05 (0.19) |
0.59±0.06 (0.19) |
Thymus |
0.12±0.05a(0.07) |
0.20±0.04 (0.07) |
0.23±0.03 (0.07) |
0.22±0.03 (0.07) |
0.26±0.04 (0.08)
|
0.23±0.05 (0.07) |
Lung (R) |
0.48±0.03a(0.29)a |
0.71±0.07 (0.24) |
0.77±0.04 (0.24) |
0.77±0.07 (0.23) |
0.77±0.10 (0.23) |
0.75±0.11 (0.24) |
Lung (L) |
0.26±0.03a(0.15)a |
0.36±0.04 (0.12) |
0.39±0.03 (0.11) |
0.38±0.03 (0.12) |
0.41±0.06 (0.12) |
0.37±0.03 (0.12) |
Heart |
0.58±0.05a (0.36)a |
0.87±0.14 (0.30) |
1.01±0.06 (0.31) |
0.96±0.06 (0.29) |
1.01±0.08 (0.30) |
0.95±0.12 (0.30) |
Spleen |
0.40±0.05a(0.25)a |
0.61±0.05 (0.21)b |
0.64±0.04 (0.19) |
0.61±0.04 (0.19) |
0.65±0.06 (0.19) |
0.62±0.05 (0.20) |
Liver |
4.13±0.37a(2.5)a |
7.00±0.58 (2.4)a |
7.62±0.60 (2.3) |
7.77±0.47b (2.4)b |
7.67±0.45 (2.3) |
7.22±0.54 (2.3) |
Adrenal (R)
|
0.019±0.002b (0.012)a |
0.21±0.006 (0.007) |
0.022±0.001 (0.006) |
0.020±0.005 (0.006) |
0.021±0.005 (0.006) |
0.024±0.004 (0.008) |
Adrenal (L)
|
0.021±0.005 (0.012)a |
0.021±0.003 (0.007) |
0.023±0.001 (0.007) |
0.023±0.001 (0.007) |
0.023±0.003 (0.007) |
0.023±0.008 (0.007) |
Kidney (R) |
0.78±0.05a (0.48)a |
1.09±0.05a (0.38)a |
1.03±0.07 (0.31) |
0.99±0.09 (0.30) |
1.02±0.05 (0.31) |
0.99±0.06 (0.31) |
Kidney (L) |
0.84±0.08a (0.52)a |
1.10±0.06a (0.37)a |
1.04±0.08 (0.32) |
1.00±0.07 (0.30) |
1.02±0.06 (0.31) |
0.99±0.05 (0.31) |
Testis (R) |
1.17±0.07a (0.71)a |
1.41±0.08 (0.49)b |
1.48±0.06 (0.45) |
1.43±0.10 (0.44) |
1.48±0.09 (0.44) |
1.42±0.07 (0.45) |
Testis (L) |
1.22±0.06a (0.75)a |
1.44±0.08 (0.50)a |
1.50±0.05 (0.46) |
1.47±0.06 (0.45) |
1.52±0.05 (0.46)b |
1.49±0.07 (0.47) |
ap<0.01;bp<0.05
Table 2 continued - Absolute and relative organ weights (female)
Relative organ weights are shown in parenthesises (%)
Dose |
10% |
5% |
2.5% |
1.25% |
0.6% |
Control |
Effective No. |
9 |
10 |
10 |
10 |
10 |
10 |
Brain |
1.75±0.07a (1.5)a |
1.84±0.05 (1.0) |
1.86±0.06 (1.0) |
1.84±0.05 (1.0) |
1.89±0.05b(1.1) |
1.86±0.05 (1.0) |
Pituitary |
0.006±0.002a (0.005) |
0.010±0.003 (0.006) |
0.012±0.003 (0.007) |
0.011±0.003 (0.006) |
0.010±0.003 (0.006) |
0.010±0.003 (0.005) |
Saliv. Glds. |
0.61±0.18a (0.54)a |
0.44±0.04b (0.25)a |
0.40±0.05 (0.22) |
0.43±0.08 (0.23) |
0.41±0.05 (0.23) |
0.40±0.03 (0.22) |
Thymus |
0.13±0.04a (0.12) |
0.17±0.03 (0.09) |
0.17±0.06 (0.09) |
0.20±0.05 (0.11) |
0.20±0.04 (0.11) |
0.19±0.03 (0.10) |
Lung (R) |
0.40±0.04a (0.35)a |
0.57±0.07 (0.32)b |
0.54±0.04 (0.30) |
0.56±0.06 (0.30) |
0.54±0.04 (0.30) |
0.54±0.06 (0.29) |
Lung (L) |
0.21±0.03a(0.19)a |
0.29±0.03 (0.16) |
0.27±0.03 (0.15) |
0.28±0.03 (0.15) |
0.27±0.02 (0.15) |
0.29±0.03 (0.16) |
Heart |
0.48±0.04a (0.43)a |
0.63±0.03 (0.35)a |
0.65±0.07 (0.35)b |
0.60±0.05 (0.32) |
0.60±0.04 (0.33) |
0.61±0.04 (0.33) |
Spleen |
0.34±0.06a (0.30)a |
0.48±0.06b (0.27)a |
0.43±0.03 (0.24) |
0.43±0.04 (0.23) |
0.42±0.05 (0.23) |
0.43±0.03 (0.23) |
Liver |
3.16±0.24a (2.8)a |
4.07±0.34b (2.3)a |
3.97±0.16 (2.2)b |
3.94±0.17 (2.1) |
3.77±0.25 (2.1) |
3.77±0.28 (2.0) |
Adrenal (R)
|
0.018±0.002b (0.016)a |
0.022±0.005 (0.012) |
0.024±0.004 (0.01) |
0.023±0.005 (0.012) |
0.024±0.004 (0.013) |
0.23±0.005 (0.012) |
Adrenal (L)
|
0.020±0.003a (0.018)b |
0.25±0.003 (0.014) |
0.025±0.006 (0.014) |
0.024±0.005 (0.013) |
0.027±0.004 (0.015) |
0.026±0.004 (0.014) |
Kidney (R) |
0.64±0.05a (0.57)a |
0.98±0.06a (0.55)a |
0.72±0.06a (0.40)a |
0.63±0.05b (0.34)b |
0.59±0.03 (0.33)a |
0.57±0.04 (0.31) |
Kidney (L) |
0.67±0.05a (0.59)a |
0.97±0.04a (0.56)a |
0.71±0.05a (0.39)a |
0.62±0.05 (0.33) |
0.60±0.03 (0.33) |
0.60±0.04 (0.32) |
Testis (R) |
0.020±0.005b (0.018) |
0.033±0.010 (0.019) |
0.041±0.019 (0.023) |
0.042±0.020 (0.023) |
0.040±0.009 (0.022) |
0.042±0.022 (0.023) |
Testis (L) |
0.012±0.003 (0.011) |
0.040±0.020 (0.022) |
0.046±0.021 (0.025) |
0.039±0.022 (0.021) |
0.045±0.016 (0.025)b |
0.033±0.009 (0.18) |
ap<0.01;bp<0.05
Table 3 - Summary of histopathological findings in F344 rats (both sexes) after 13 weeks treatment.
Findings |
Concentration of potassium pyrophosphate in diet |
|||||
10% |
5% |
2.5% |
1.25% |
0.6% |
0% |
|
Kidney Tubular necrosis, with calcification and interstitial fibrosis |
+++ |
++ |
± |
- |
- |
- |
Tongue Ulceration and/or granuloma formation |
+ |
+ ~ ± |
- |
- |
- |
- |
Salivary glands (serous) hypertrophy |
+ |
± ~ - |
- |
- |
- |
- |
+++ severe, ++ moderate, + mild, ± slight
Applicant's summary and conclusion
- Conclusions:
- LOEL = 0.6%
- Executive summary:
- A 13 week sub-chronic toxicity study of potassium pyrophosphate was carried out in male and female F344 rats at the dose levels of 10, 5, 2.5, 1.25, 0.6 and 0% in the diet. Sixty animals of both sexes were divided into the 6 dosage groups. The purpose of the study was to determine the maximum tolerable dose of test substance for use in rats in a long-term carcinogenicity study. Observations were limited to mortality, clinical abnormalities, body weights, food intake, haematology, clinical chemistry, gross pathology (incl. organ weight) and histopathology. By the end of the test, two male and one female from the 10% dosage group had died of renal failure. Bodyweight gains of both male and female rats treated with 10% and of male rats treated with 5% were significantly decreased as compared with controls. On histological examination, necrosis and calcification in renal tubules, ulceration and/or granuloma formation in tongue mucosa and hypertrophy of salivary glands were observed at high incidence. Based on these findings, a concentration of 5% in diets was considered to be the maximum tolerable dose for use in a long-term carcinogenicity study.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.