reaction mass of calcium bis(dihydrogenorthophosphate) and calcium hydrogenorthophosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Objective of study:

other: Disposition and relative bioavailability

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

yes (incl. QA statement)

Remarks:

FDA GLP'S (FR, vol.43, No.247, part 58, 12/22/78)

Test material

Test material information

Constituent 1

Reference substance name:

Calcium bis(dihydrogenorthophosphate)

EC Number:

231-837-1

EC Name:

Calcium bis(dihydrogenorthophosphate)

Cas Number:

7758-23-8

Molecular formula:

Ca.2H3O4P

IUPAC Name:

calcium dihydrogen phosphate

Details on test material:

- Name of test material (as cited in study report): 45Ca- Monocalcium phosphate monohydrate
- Molecular formula (if other than submission substance): 45Ca (H2PO4)2.H20
- Physical state: White Power
- Lot/batch No: ERC-8486-50H
- Specific activity (if radiolabelling): 5.58 µCi/ mg
- Locations of the label (if radiolabelling): 45Ca
- Expiration date of radiochemical substance (if radiolabelling): 11/9/85
- Other: Source: Stauffer Chemical Company, ERC, Dobbs Ferry, N.Y.

Radiolabelling:

yes

Remarks:

45Ca-Monocalcium phosphate monohydrate

Test animals

Species:

rat

Strain:

other: Sprague-Dawley [CR Crl: CD SD BR]

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 195-264 g
- Fasting period before study: Food was withheld for at least 8 hours prior to dosing. Food was also withheld for the first 4 hours on study.
- Housing: The animals were housed in individual Nalgene metabolism cages equipped with urine/feces separators.
- Individual metabolism cages: yes
- Diet : Certified Purina Chow was allowed ad libitum throughout the study.
- Water : Tap water was allowed ad libitum throughout the study.
- Acclimation period: Animals were acclimatised in individual Nalgene metabolism cages with tap water and Certified Purina Chow #5002 ad libitum for at least 4 days in the metabolism laboratory.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2
- Humidity (%): 50±5
- Air changes (per hr): Room air flow was approximately 15 exchanges/ hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle


IN-LIFE DATES: From: 4/8/1982 To:25/03/1985

Administration / exposure

Route of administration:

oral: gavage

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Dose solution were prepared for the calcium chloride liquid intravenous and oral dose groups by mixing the proper amount of 45Ca- calcium chloride and nonlabeled calcium chloride anhydrous and dissolving them in sterile physiological saline. Aliqouts of the dose solution were analysed for radioactive content and weights of the dosing apparatus before and after administration were used for dose verification.

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:


VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Lot/batch no. (if required):
- Purity:


HOMOGENEITY AND STABILITY OF TEST MATERIAL:

Duration and frequency of treatment / exposure:

Single oral tablet

Doses / concentrations

Remarks:

Doses / Concentrations:
The calcium salt (Monocalcium phosphate) was administered such that each animal received a single dose of 3 mg/kg dose of calcium containing approximately 25µCi of 45Ca.

No. of animals per sex per dose / concentration:

At least 12 animals were used per dose group

Control animals:

other: Yes. Results were compared to those from a water soluble stnadard, calcium chloride, after a single intravenous liquid, oral liquid or oral tablet dose.

Details on study design:

- Dose selection rationale:
- Justification for route of administration: The test compound is used as an excipient and vitamin supplement and oral administration is the most common route of exposure
- Rationale for animal assignment (if not random): Sprague-Dawley rats are commonly used in bioavailability and disposition studies

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : urine, faeces, blood, plasma and serum
- Time and frequency of sampling: Excreta and blood samples were collected over a 5 day period before the animals were sacrificed and tissues were collected. Urine and feces samples were collected at twenty four hour intervals. Blood samples from the tail vein were collected using heparinised microhematocrit tubes at 5, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours after dosing. At 120 hours after dose administration, the animals were sacrificed and the tissues collected were skin, eviscerated organs and remaning carcass.
- Other: All animals were allowed ad libitum access to food foloowing the four hour blood collection.

Statistics:

For the deposition data, the percent recoveries of the administered dose in various organs, excreta and washes were determined. These recoveries and the total percent recovered were compared by Duncan's multiple range test using the SAS statistics program.
For the bioavailability data, the area under the plasma concentration versus time curves (AUCs) were calculated using trapezoidal rule and computer generated equations. The computer generated equations were obtained using the CSTRIP and NONLIN 84 pharmacokinetic programs. The AUCs and other pharmacokinetic parameters were compared by Duncan's multiple range test using the SAS statistics program.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No data

Details on distribution in tissues:

No data

Details on excretion:

No data

Metabolite characterisation studies

Details on metabolites:

No data

Any other information on results incl. tables

No data

Applicant's summary and conclusion

Conclusions:

No conclusions can be drawn from the study as the results section was missing from the report.