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Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards with acceptable restrictions.

Data source

Reference
Reference Type:
publication
Title:
In Vivo Absorption of Calcium Carbonate and Magnesium Oxide from the Large Intestine in Rats
Author:
Ohta A, Baba S, Ohtsuki M, Takizawa T, Adachi T & Hara H
Year:
1997
Bibliographic source:
J. Nutr. Sci. Vitaminol., 43(1): 35-46

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was conducted to evaluate the ability of the large intestine to absorb calcium and magnesium from their sparingly water-soluble salts and also to determine whether fructooligosaccharides (FOS) stimulate the absorption of these minerals in rat large intestine in vivo. Rats were fed Ca- and Mg- free diets with and without 5% FOS. An aqueous suspension of CaCO3 and MgO was infused into the stomach via a gastric tube or into the caecum via an implanted catheter.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium carbonate
EC Number:
207-439-9
EC Name:
Calcium carbonate
Cas Number:
471-34-1
Molecular formula:
CH2O3.Ca
IUPAC Name:
calcium carbonate

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Clea Japan, Tokyo, Japan
- Age at study initiation: 4 weeks
- Mean weight at study initiation: 221 - 227 g
- Housing: Individually housed in stainless steel wire mesh cages
- Diet: Stock diet (MF, Oriental Yeast, Tokyo, Japan) available ad libitum
- Water: Deionised water available ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 °C
- Humidity (%): 55 %

Administration / exposure

Route of administration:
other: Direct implantation into the caecum and the stomach
Details on exposure:
A polyethylene tube was implanted directly into the caecum of each rat.
All rats were fed the Ca and Mg free diet. Two groups were subsequently fed a fructooligosaccharide (FOS) free diet (control diet) and the other two groups were fed a FOS-containing diet (50 g/kg diet). In half of the rats from each diet group, 0.3 mL of the suspension of CaCO3 and MgO, which contained 930 µmol of Ca and 136 µmol of Mg, was infused into the caecum via the implanted tube. In the remaining rats from each group, the same suspension was infused into the stomach by intubation. The suspension was infused twice per day (9:00 and 18:00) for 10 days. For the last 7 days, the rats were subjected to a Ca and Mg balance study and all faeces and urine were collected.
No. of animals per sex per dose / concentration:
7 animals/group
Control animals:
yes
Details on dosing and sampling:
The amounts of Ca, Mg and P in the diet, infusion, faeces, urine and femur of each rat were determined.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Ca BALANCE:
The apparent absorption of Ca infused into the stomach was higher than that absorbed into the caecum. FOS feeding increased the apparent absorption and retention of Ca irrespective of the infusion route. The apparent absorption and retention of Ca increased in the case of infusion into the stomach in the FOS fed groups.

Mg BALANCE:
The apparent absorption of Mg into the caecum in rats was equivalent to the Ca and Mg infusion into the stomach for both the control and FOS-feeding groups. FOS feeding increased the apparent absorption of Mg irrespective of the infusion route. However, the retention of Mg did not significantly differ among all of the groups.

P BALANCE:
The apparent absorption of P was higher in rats with Ca and Mg infusion into the caecum than in rats with Ca and Mg infusion into the stomach. On the other hand, the retention of P was lower in rats with Ca and Mg infusion into the caecum than in rats with Ca and Mg infusion into the stomach. The apparent absorption of P was decreased by FOS feeding.

APPARENT ABSORPTION EFFICIENCY OF Ca, Mg AND P:
The apparent absorption ratio of Ca in FOS fed rats with Ca and Mg infusion into the stomach was higher than in the other 3 groups. The apparent absorption ratio of Ca did not differ among these 3 groups. Regardless of FOS feeding, the apparent absorption efficiency of Mg infused into the caecum was similar to that of Mg infused into the stomach. The apparent absorption efficiency of P was higher in the case of infusion in the caecum than in infusion in the stomach.

RETENTION EFFICIENCY OF Ca, Mg AND P:
The retention ratio of Ca in FOS fed rats with Ca and Mg infusion into the stomach was higher than in the other 3 groups. The retention efficiency of Ca did not differ among these 3 groups. The retention efficiency of Mg was similar among all of the 3 groups. The retention efficiency of P was decreased by FOS feeding, being lower in rats with Ca and Mg infusion into the caecum than in rats with Ca and Mg infusion into the stomach.

Ca, Mg and P CONTENTS IN SERUM AND FEMUR:
The serum concentration of Ca in the FOS fed groups was higher when Ca was infused into the stomach than when Ca was infused into the caecum. The dry and ash weights of femur samples and the serum concentrations of Mg and P did not differ among the groups. The P content of the femur samples in the FOS fed groups with Ca and Mg infusion into the caecum was lower than that in the other 3 groups.

pH AND WEIGHT OF CAECAL CONTENTS:
The pH of the caecal contents was decreased by FOS feeding while the weight of the caecal contents was increased by FOS feeding.

Any other information on results incl. tables

The initial and final body weights did not significantly differ between the groups. FOS feeding decreased food intake.

Applicant's summary and conclusion

Conclusions:
The large intestine has the ability to absorb large amounts of Ca and Mg from CaCO3 and MgO, which are respectively very sparingly soluble in water and suggest that the stimulatory effect of FOS on the absorption of Mg takes place mainly in the large intestine.