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Administrative data

Endpoint:
acute toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING

Study is not scientifically necessary.

In chronic toxicity study (Raheja et. al., 1977, Toxicology, 8: 115--119), the NOAEL of disodium beta-Glycerophosphate was found to be >1900 mg/kg bw, after oral exposure during 33 weeks. Since no adverse toxic effect was observed after daily exposition of 1900 mg/kg bw, it can safely be expected that a single exposition to 2000 mg/kg bw (only approx. 5% higher dosis) would not be toxic.

Moreover, on a patent record for the use of glycerophosphate salt solution for IV solutions from 1977, an LD50 dosis of 3400 mg/kg bw is reported for rats (probably IV exposure).
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to other study
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
Exposure duration 33 weeks instead of 12 weeks
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 220-225 g
- Fasting period before study: not specified
- Housing: individual wire cages
- Diet: ad libitum plain ground Purina rat chow
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- air-conditioned laboratory
- Photoperiod: 12 : 12 h light-dark cycle

Route of administration:
oral: feed
Details on oral exposure:
- DIET PREPARATION :
- ground Purina rat chow containing 2.5% beta-glycerophosphate.


Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
33 weeks
Frequency of treatment:
daily
Dose / conc.:
1 900 mg/kg bw/day (actual dose received)
Remarks:
The daily intake of beta-glycerophosphate was calculated from food consumption
No. of animals per sex per dose:
9
Control animals:
yes, plain diet
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations: not specified, recorded throughout the experiment

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
-yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY and CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of 33 weeks
- Anaesthetic used for blood collection: Yes, Nembutal
- Animals fasted: Not specified
- How many animals: all
- Blood was drawn from the femoral vein
- Parameters checked haematology: total blood counts, differential blood count and hematocrit and hemoglobin determinations.
- Parameters checked clinical Chemistry: cholesterol, triglycerides and phospholipids, serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT) and serum alkaline phosphatase.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No

OTHER:
- Bile was collected under nembutal anaestetic from cannulated bile duct for two 1-h collection periods. During the two hours of bile collection the rats were infused with isotonic saline at the rate of 1 ml/h through a catheter placed in the femoral vein in order to replace the volume of collected bile.
- Parameters analyzed: cholesterol, bile acids and phospholipids.

- Cholesterol, phospholipids and triglycerides were also determined in frozed portions of Liver.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes. Liver, spleen, kidneys, testes, heart and brain were
removed and weighed.

HISTOPATHOLOGY: Yes. Parts of the liver and kidneys were preserved in buffered formaline. Hematoxylin-eosin staining.
Statistics:
Student's t-test
Clinical signs:
not specified
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Control: 2/9
Treated: 1/9

Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Kidneys which were significantly larger in the /3-glycerophosphate-fed group (0.686 + 0.027) compared to control group (0.569 + 0.020). Attributed to hyperplasia.
Heart, brain, testes and spleen were similar in the treated and control groups.
Gross pathological findings:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Beta-glycerophosphate significantly increased the phospholipid concentrations (4.79 + 0.20 vs. 3.55 + 0.20 mtmol/ml) without
affecting the cholesterol and bile acid concentrations or the volumes of bile collections.
Liver phospholipids were significantly higher in the beta-glycerophosphate-fed rats compared to control rats (5117.0 +/- 169.6 vs. 4180.8 +/- 132.5
mg/100 g, respectively)
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 900 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical biochemistry
gross pathology
haematology
histopathology: non-neoplastic
mortality
organ weights and organ / body weight ratios
Key result
Critical effects observed:
no
Conclusions:
Beta-glycerophosphate when given in a high dose for a prolonged period of time has no detrimental effect in rats.
Executive summary:

Toxic effects of a high dose of orally administered disodium beta-glycerophosphate to the rat for a period of 33 weeks was determined.

Beta-glycerophosphate administration had no effect on either survival rate, body weight, hematological and liver function tests or on serum and liver lipids concentrations. All organ weights were similar in the control and experimental rats except for the kidneys which were significantly heavier in the beta-glycerophosphate-fed rats. The biliary phospholipids concentrations was significantly increased in the treated group. Histological examination of liver and kidneys did not reveal any pathological findings. These results suggest that long-term administration of beta-glycerophosphate did not induce any

toxic manifestations. The observed hyperplasia of the kidneys was attributed to the effect of the sodium content of beta-glycerophosphate.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: other routes
Remarks:
route not specified, presumed intravenous
Type of information:
other: information reported on a patent record
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
unspecified
Vehicle:
not specified
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 400 mg/kg bw
Conclusions:
An acute toxicity test on rats was performed to determine the safety of using glycerophosphate salt for IV solutions (administration type not specified, but it could be presumed it was IV).
Beta-Glycerophosphate (CAS 819-83-0) is not toxic to rats. The LD50 was determined to be 3400 mg/kg bw for rats.
Executive summary:

An acute toxicity test on rats was performed to determine the safety of using glycerophosphate salt for IV solutions (administration type not specified, but it could be presumed it was IV)

Beta-Glycerophosphate (CAS 819-83-0) is not toxic to rats. The LD50 was determined to be 3400 mg/kg bw for rats.

Alpha-Glycerophosphate was also tested. The LD50 was determined to be 3800 mg/kg bw in rats.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion