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EC number: 231-669-9 | CAS number: 7681-53-0
- 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:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2009-07-16 till 2009-09-16
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study (OECD 422 Guideline, EPA OPPTS 870.3650 Guideline)
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- other: audited draft study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EPA Guideline OPPTS 870.3650
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Sodium phosphinate
- EC Number:
- 231-669-9
- EC Name:
- Sodium phosphinate
- Cas Number:
- 7681-53-0
- Molecular formula:
- H3O2P.Na
- IUPAC Name:
- sodium phosphinate
- Reference substance name:
- Sodium hypophosphite
- IUPAC Name:
- Sodium hypophosphite
- Details on test material:
- - Name of test material: Sodium hypophosphite; tested in the form of monohydrate as the anhydrous form (CAS 7681-53-0) is highly hygroscopic and difficult to handle without specific precautions.
- Physical state: white crystalline solid
- Supplier: Rhodia UK-Oldbury
- Batch number: 90113D
- Expiry date: June 2010
- Storage condition of test material: room temperature, stored in a tightly closed container in a dry and well-ventilated place, opening of the container restricted to the minimum needs
- Disposal: incinerate the residues at an approved waste disposal site only
- Analytical purity: 99.5%
- Impurities (identity and concentrations):
Phosphite (Na2HPO3): 0.14%
Calcium (Ca): 21 ppm
Iron (Fe): 0.7 ppm
Sulphate (SO4): 8 ppm
Chloride (Cl): 64 ppm
- Certificate of analysis:
Analysis number: ITC/09/01/04
Analysis date: 2009-01-27
No more data available
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories France (l'Arbresle, France)
- Strain and Sanitary status: Sprague-Dawley Crl CD® (SD) IGS BR, Caesarian Obtained, Barrier Sustained-Virus Antibody Free (COBS-VAF®)
- Age at study initiation: males approx. 12 weeks old and females approx. 11 weeks old (both sexes sexually mature)
- Weight at study initiation:
males: mean body weight = 394 g (range: 353 g to 436 g)
females: mean body weight = 258 g (range: 238 g to 282 g)
- Identification: individual ear tattoo (unique CIT identity number)
- Housing: individually except during pairing in wire mesh cages; females housed in polycarbonate cages towards the end of the gestation period and with their litter during lactation. Autoclaved wood shavings were provided as nesting material a few days before delivery and during the lactation period
- Diet: ad libitum - SSNIFF R/M-H pelleted maintenance diet, batch No. 9361978 and 8632516 (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water: ad libitum - 0.22 µm filtered tap water
- Acclimation period: 5 days, one supplementary animal of each sex was acclimated to permit the selection and/or replacement of individuals if necessary
- Contaminant analyses:
batches of diet, wood shavings and sawdust analyzed by suppliers for composition and contaminant levels
bacterial and chemical analyses of water regularly by external laboratories (analyses included detection of possible contaminants such as pesticides, heavy metals and nitrosamines)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): approx. 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12 (7:00 - 19:00)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- DOSING:
- Dose-levels calculated in terms of sodium hypophosphite monohydrate (CAS 10039-56-2, MW 103.977).
- The test item was mixed with the required quantity of vehicle and concentrations prepared were 20.2, 61.8 and 215.9 mg/mL.
- Sodium hypophosphite dosage forms were prepared weekly (based on available stability data (CIT, Study N° 35771 AHS)) and stored in brown glass bottles at room temperature prior to use.
DIET PREPARATION
- Diet distributed weekly
VEHICLE:
- Vehicle used: water
- Amount of vehicle: 5 mL/kg/day - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Principle and validation of method used for chemical analysis of dosage forms:
Ion Chromatography with conductimetric detection (HPLC-IC) was used for the determination of sodium hypophosphite in dosage form samples
(method validated prior to dosage form analysis). Validation of the method was based on the ICH Q2(R1) guideline adopted in October 1994 and
accordingly the following parameters were checked: specificity, precision and accuracy, repeatability, linearity, Sensitivity Evaluation Test (SET) and
stability of the test item in working solutions.
The validation of the analytical method was conducted in CIT/Study No. 35770 VAA and precise details are documented in this report.
- Determination of sodium hypophosphite concentration in dosage forms
The dosage form samples were assayed using the above validated method. The test item concentration in samples of each control and test item
dosage form prepared for use in weeks 1, 4 and 7 was determined.
Acceptance criterion was measured concentration = nominal concentration ± 10%
- Determination of dosage form stability:
Suitability of the proposed preparation process was confirmed by analysis of the homogeneity and stability, as described in CIT/Study No. 35771 AHS. Results of this study indicated satisfactory stability of the dosage forms after 9 days storage at room temperature and no effect resulting from numerous openings of the flask containing the test item. - Duration of treatment / exposure:
- Males: 15 days before mating, during the mating period (up to 3 weeks) and until sacrifice (i.e. at least 5 weeks in total)
Females: 15 days before mating, during the mating period (up to 3 weeks), during pregnancy, during lactation until day 5 post-partum inclusive.
(day 1 = first day of treatment period) - Frequency of treatment:
- once a day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
101, 309, 1080 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: dose-levels were selected on the basis of a 2-week dose Range-Finding toxicity study (CIT, Study N° 35768 TSR) reported in chapter 7.5.1
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS:
- From arrival: once a day as part of routine examinations
- From the start of the treatment: once a day, at approximately the same time for the recording of clinical signs
MORBIDITY/MORTALITY:
Once a day during the acclimation period and at least twice a day during the treatment period
DETAILED CLINICAL OBSERVATIONS:
Once before the beginning of the treatment period and then once a week until the end of the study. Detailed clinical observations were performed outside the home cage in a standard arena.
Observations included (but were not limited to):
changes in the skin, fur, eyes and mucous membranes
occurrence of secretions and excretions
autonomic activity (e.g. lachrymation, piloerection, pupil size, unusual respiratory pattern)
Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypes (e.g. excessive grooming, repetitive circling) or bizarre behavior (e.g. self-mutilation, walking backwards) were also recorded.
BODY WEIGHT:
- Males: on the first day of treatment (day 1), then weekly until sacrifice
- Females: on the first day of treatment (day 1), then weekly until mated and on days 0, 7, 14 and 20 post-coitum and days 1 and 5 post-partum.
FOOD CONSUMPTION (FC):
- Males: recorded weekly over a 7 day period from the first day of treatment until sacrifice.
- Females: recorded weekly over a 7 day period from the first day of treatment through gestation (days 0-7, 7-14 and 14-20 post-coitum intervals) and lactation (days 1-5 post-partum intervals) until sacrifice.
- During the pairing period, food consumption was not recorded for males or females.
HAEMATOLOGY:
- Time schedule for collection of blood: On the day of sacrifice after food deprivation for an overnight period of at least 14 hours
- Anaesthetic used for blood collection: Yes, isoflurane
- Animals fasted: Yes
- How many animals: first 5 males and first 5 females to deliver from each group
- Parameters checked in table 1 were examined
CLINICAL CHEMISTRY:
- Time schedule for collection of blood: on the day of sacrifice
- How many animals:first 5 males and first 5 females to deliver from each group
- Parameters checked in table 1 were examined
URINALYSIS:
- Time schedule for collection of urine: on the day of sacrifice after food deprivation for an overnight period of at least 14 hours
- Animals fasted: Yes
- How many animals: first 5 males and first 5 females to deliver from each group
- Parameters checked in table 1 were examined
NEUROBEHAVIOURAL EXAMINATION:
- Time schedule for examinations: first 5 males and first 5 females to deliver from each group were evaluated at the end of the treatment period (for females, on day 5 post-partum after sacrifice of the pups)
- Dose groups that were examined: all, animals were randomized to ensure "blind" evaluation
- Observation: in the cage, in the hand and in the standard arena
- Battery of functions tested:
Detailed clinical examination
Measurement of reactivity to manipulation
Measurement of reactivity to different stimuli
Motor activity (measured once by automated infra-red sensor equipment over a 60-minute period)
- Parameters assessed and graded and parameter measurements, reflexes and responses recorded afterwards are given in table 2 - Sacrifice and pathology:
- SACRIFICE
males: after the end of the mating period (after at least 5 weeks of treatment)
females: on day 6 post-partum, or when not delivered by day 25 post-coitum sacrificed on this day (after body weight recording to check for a possible unnoticed delivery)
ORGAN WEIGHTS
- Organs listed in table 3 were weighted
GROSS PATHOLOGY / HISTOPATHOLOGY
1. Microscopic examination
* Preservation of tissues
The tissues listed in table 3 were preserved for the first 5 sacrificed-as-scheduled males, the first 5 females to deliver and be sacrificed on day 6 post-partum of each group, and for animals found dead unless otherwise specified.
* Microscopic examination was performed on:
All macroscopic lesions
All animals found dead
All tissues listed in table 3 for the first 5 sacrificed-as-scheduled males and the first 5 females to deliver and be sacrificed on day 6 post-partum of the control- and high-dose groups (1080 mg/kg/day)
The stomach with forestomach and the liver of the first 5 sacrificed-as-scheduled males and the first 5 females to deliver and be sacrificed on day 6 post-partum of the intermediate dose group (309 mg/kg/day)
2. A complete macroscopic post-mortem examination was performed on all animals, also those found dead. - Other examinations:
- No data
- Statistics:
- - Body weights, food consumption and reproductive data
Mean values were compared by one-way variance analysis and Dunnett test (mean values being considered as normally distributed, variances being
considered as homogeneous).
Percentage values were compared by Fisher exact probability test.
- Hematology and blood biochemistry
Citox software (version d.5) was used to perform the statistical analysis of hematology, blood biochemistry and urinalysis data
- Organ weights
PathData software (version 6.2b5) was used for the statistical analysis of organ weight data (level of significance: 0.05 or 0.01)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- Clinical signs:
No relevant clinical signs were observed during the study
- Mortality:
One female treated at 101 mg/kg/day was found dead after treatment on day 5 post-coitum, but the death was considered accidental. This female had jumped out of the weighing container before treatment and although alive at treatment, was found dead a short while later. At necropsy, a red
content in the thoracic cavity and an irregular red color of lungs which correlated histologically with hemorrhage and edema were observed. Hemorrhage was also observed in the heart and the mediastinum. These findings are probably related to injury sustained during the fall.
BODY WEIGHT AND WEIGHT GAIN (see table 1 in remarks on results)
There were no treatment-related effects.
FOOD CONSUMPTION AND COMPOUND INTAKE (see table 2 in remarks on results)
There were no treatment-related effects.
HAEMATOLOGY
No remarkable differences between control and test item-treated animals
CLINICAL CHEMISTRY
A statistically significant decrease in creatinine in females treated at 1080 mg/kg/day was observed (see table 3 in remarks on results). This was
considered incidental as a similar pattern was not observed in males and no concomittant parameters were affected.
URINALYSIS
- Protein levels: All test item-treated male groups had higher levels of protein in the urine than the controls (see table 4 in remarks on results) but the incidence and the protein level were not dose-related. No female showed protein in the urine so the significance of this observation is unclear.
- Blood: One male treated at 101 mg/kg/day had blood in the urine but the isolated nature of this finding indicates that it is not related to treatment
with the test item.
NEUROBEHAVIOUR
- Functional Observation Battery (abnormal responses/observations) ans motor activity:
No dose-relationship was observed in the abnormal responses and often one animal was concerned in several tests. As no relevant clinical signs were noted during the study, these abnormal responses were considered not indicative of an effect of treatment with the test item
The abnormal responses/observations noted during the study are presented in table 5 (see remarks on results)
ORGAN WEIGHTS
- Thymus (see table 6 in remarks on results)
There was a lower absolute and relative weight of the thymus in females given 309 or 1080 mg/kg/day, reaching a statistically significant level at
1080 mg/kg/day. This was not associated with any histopathological change at 1080 mg/kg/day.
- Kidneys
The absolute and relative weights of kidneys were greater in females given 1080 mg/kg/da, reaching a statistically significant level for the relative
weight (P<0.05). In the absence of any treatment-related changes in biochemistry or urinary parameters and at the histopathological examination,
this variation was considered to be incidental.
- Other changes in the mean organ weights were considered to reflect normal individual variations and were considered to be unrelated to treatment.
GROSS PATHOLOGY
No macroscopic changes were noted that were considered to be associated with treatment.
HISTOPATHOLOGY: NON-NEOPLASTIC
- Forestomach:
Minimal thickening of the limiting ridge of the forestomach associated in most cases with minimal increased exocytosis of inflammatory cells, was
observed in 5/5 males and 3/5 females given 1080 mg/kg/day and in one male given 309 mg/kg/day. This was considered to be related to treatment with the test item. However, due to the minimal degree of severity of this change compared with the dose-level (more than 1000 mg/kg/day), this
effect was considered to be non-adverse and in the absence of a similar structure in the stomach from human beings, this change was not
considered relevant for human health.
- Liver:
In the liver of females, minimal foci of hepatocellular necrosis were observed in the subcapsular area of 1/5 females given 309 mg/kg/day and 3/5
females given 1080 mg/kg/day. This change characterized by the presence of aggregates of macrophages, occasionally with pigment and some fibroblasts, was not acute and was considered to reflect the healing of previous necrotic areas. Subcapsular hepatocellular necrosis may be occasionally
seen in rats of this strain and age. Therefore, despite the apparent dose-related increased incidence, this observation was considered to be probably
incidental, because of its low magnitude, the location restricted to the subcapsular area as well as the absence of change in males, in liver weights andbiochemical parameters.
- Thymus:
At necropsy no histopathological changes which correlated with the lower weight of the thymus were noted.
- Testes
Careful examination did not reveal any treatment-related changes
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 080 mg/kg bw/day (actual dose received)
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
- No contaminants were present in the diet, drinking water, wood shavings or sawdust at levels which could be expected to interfere with, or prejudice, the outcome of the study.
- Chemical analysis of the dosage forms
Test item concentrations in the administered dosage forms were analyzed in weeks 1, 4 and 7 of treatment and remained within an acceptable range of -0.8% to +3.0% of variation compared to the nominal values.
- Table 1: Mean body weight (g) and body weight gain (g) for male and female rats of all treatment groups are presented in the table below
Sex |
Male |
Female |
||||||
Dose-level (mg/kg/day) |
0 |
101 |
309 |
1080 |
0 |
101 |
309 |
1080 |
Pre-mating |
||||||||
Day 1 |
396 |
394 |
393 |
392 |
257 |
260 |
255 |
259 |
Day 15 |
452 |
448 |
448 |
445 |
275 |
272 |
272 |
278 |
Day 36 |
499 |
499 |
507 |
499 |
/ |
/ |
/ |
/ |
Days 1-15 |
+56 |
+55 |
+56 |
+53 |
+18 |
+12 |
+17 |
+19 |
Days 1-36 |
+103 |
+105 |
+115 |
+107 |
/ |
/ |
/ |
/ |
Gestation |
||||||||
Day 0 p.c. |
/ |
/ |
/ |
/ |
283 |
276 |
275 |
283 |
Day 20 p.c. |
/ |
/ |
/ |
/ |
427 |
418 |
416 |
440 |
Days 0-20 p.c. |
/ |
/ |
/ |
/ |
+144 |
+142 |
+142 |
+157 |
Lactation |
||||||||
Day 1 p.p. |
/ |
/ |
/ |
/ |
325 |
327 |
312 |
332 |
Day 5 p.p. |
/ |
/ |
/ |
/ |
345 |
354 |
333 |
354 |
Days 1-5 p.p. |
/ |
/ |
/ |
/ |
+20 |
+27 |
+21 |
+22 |
/: not recorded,p.c.:post-coitum,p.p.:post-partum
- Table 2: Mean food consumption (g/day) for male and female rats of all treatment groups are presented in the table below
Sex |
Male |
Female |
||||||
Dose-level (mg/kg/day) |
0 |
101 |
309 |
1080 |
0 |
101 |
309 |
1080 |
Pre-mating |
||||||||
Day 1-8 |
34 |
32 |
31 |
31 |
20 |
21 |
20 |
20 |
Days 8-15 |
35 |
33 |
32 |
32 |
22 |
21 |
22 |
21 |
Gestation |
||||||||
Day 0 -7 p.c. |
/ |
/ |
/ |
/ |
26 |
25 |
27 |
27 |
Days 7-14 p.c. |
/ |
/ |
/ |
/ |
28 |
27 |
28 |
29 |
Days 14-20 p.c. |
/ |
/ |
/ |
/ |
31 |
30 |
30 |
32 |
Lactation |
||||||||
Days 1-5 p.p. |
/ |
/ |
/ |
/ |
43 |
48 |
44 |
46 |
/: not recorded,p.c.:post-coitum,p.p.:post-partum
- Table 3: Clinical chemistry. Overview of creatine concentrations in blood for all treatment groups for both sexes
Sex |
Male |
Female |
||||||
Dose-level (mg/kg/day) |
0 |
101 |
309 |
1080 |
0 |
101 |
309 |
1080 |
Creatinine (μmol/L) |
46 |
50 |
50 |
49 |
49 |
49 |
47 |
45* |
Statistically significant, *: p<0.05
- Table 4: Urinalysis. Occurence and levels of proteins for both sexes and all treatment groups are presented as well as the occurence of blood in urine.
Sex |
Male |
Female |
||||||
Dose-level (mg/kg/day) |
0 |
101 |
309 |
1080 |
0 |
101 |
309 |
1080 |
Protein |
||||||||
Negative |
4/5 |
2/5 |
|
2/5 |
5/5 |
5/5 |
5/5 |
5/5 |
0.3 g/L |
1/5 |
2/5 |
4/5 |
2/5 |
|
|
|
|
1 g/L |
|
|
1/5 |
1/5 |
|
|
|
|
3 g/L |
|
1/5 |
|
|
|
|
|
|
Blood |
||||||||
negative |
5/5 |
4/5 |
5/5 |
5/5 |
5/5 |
5/5 |
5/5 |
5/5 |
moderate |
|
1/5 |
|
|
|
|
|
|
- Table 5: Neurobehaviour. Abnormal responses/observations noted at the end of the treatment of male (M) and female (F) rats of all treatment groups
Dose-level (mg/kg/day) |
0 |
101 |
309 |
1080 |
Difficulty in removal from cage |
|
1M |
|
|
Difficulty in handling |
|
1M |
|
|
Hypoactivity |
|
|
|
1F |
Bizarre response to touching; aggressiveness, vocalization or biting |
1M |
1M |
|
|
Bizarre response to touching; freezing or withdrawal |
|
|
|
1M |
Freezing or withdrawal during visual stimulus |
|
2M |
|
|
No response to tail pinch |
1M |
|
|
1M |
Hyperactivity, aggressiveness or biting at tail pinch |
1M |
1M |
1M |
1M |
Slight difficulty during righting reflex test |
1M, 1F |
1M |
1F |
|
Fall on back during righting reflex test |
|
|
1M |
|
Moderate decrease in forelimb grip strength |
1M |
1M |
1M |
2M |
Increase in forelimb grip strength |
2M |
1M |
1F |
2M, 1F |
No forelimb grip |
|
1M |
|
|
- Table 6: The differences between the control and the treated group (expressed in %) are shown for body weight and absolute and relative weight of the thymus.
Sex |
Male |
Female |
||||
Dose-level (mg/kg/day) |
101 |
309 |
1080 |
101 |
309 |
1080 |
Body weight |
-2% |
+2% |
+1% |
+3% |
-4% |
+1% |
Thymus |
||||||
absolute |
+3% |
+4% |
+4% |
-7% |
-27% |
-36% * |
relative |
+7% |
+1% |
+2% |
-7% |
-22% |
-36% * |
* p<0.05 (Organ weight value statistically significant from control; not the percentage)
Applicant's summary and conclusion
- Conclusions:
- Under these experimental conditions, no noteworthy toxic effects were observed related to the repeated oral administration of the test item sodium hypophosphite.
- Executive summary:
The potential toxicity of sodium hypophosphite was evaluated following repeated oral administration to rats according to OECD Guideline 422 and EPA guideline OPPTS 870.3650. The study was conducted in compliance with the principles of Good Laboratory Practice regulations on the monohydrated form of the test item as the anhydrous form is highly hygroscopic and difficult to handle without specific precautions.
Three groups of 10 males and 10 females were administered the test substance once daily by gavage for 2 weeks before mating, during mating (up to 3 weeks), and, for the females, through gestation until day 5 post-partum at dose-levels of 101, 309 and 1080 mg/kg/day. A concurrent vehicle control group received purified water.
Clinical signs and mortality were checked daily and detailed clinical observations were performed weekly. Body weight and food consumption were recorded weekly until mating and then at designated intervals throughout gestation and lactation. A Functional Observation Battery including touch response, forelimb grip strength, pupillary reflex, visual stimulus response, auditary startle reflex, tail pinch response, righting reflex, landing foot splay, rectal temperature and motor activity was performed at the end of the study. Blood and urine samples were taken for analysis of haematology, clinical chemistry and urinalysis at the end of the study.
Males were sacrificed after completion of the mating period and females on day 6 post-partum. Afterwards the designated organs were weighed and gross pathology as well as histopathology were performed.
There were no treatment-related unscheduled deaths during the study and no relevant clinical signs were observed. There were no treatment-related effects on body weight, body weight gain or food consumption at any dose-level. The functional observation battery assessment and hematology and blood biochemistry revealed no treatment-related effects but males from all groups had protein in the urine at a non-dose-related incidence.
There were no treatment-related macroscopic findings and the only effect on organ weights was a lower thymus weight in females treated at 309 or 1080 mg/kg/day which, in the absence of histopathological changes was considered to be of low toxicological significance. Microscopic examination revealed minimal increased epithelial thickness of the forestomach, in males treated at 309 mg/kg/day and in both sexes treated at 1080 mg/kg/day.
This change was considered to be related to treatment with the test item. However, due to the minimal degree of severity of this change compared with the administered dose-level (more than 1000 mg/kg/day), this effect was considered to be non-adverse and in the absence of a similar structure in the stomach from human beings, this change was not considered relevant for human health.
Under these experimental conditions the No Observed Adverse Effect Level (NOAEL) is 1080 mg/kg/day.
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