Calcium (S)-2-hydroxypropionate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference Type:

review article or handbook

Title:

Calcium Chloride, SIDS Initial Assessment Report For SIAM 15

Author:

OECD

Year:

2002

Bibliographic source:

OECD SIDS Initial Assessment Report For SIAM 15, Boston, USA, 22-25th October 2002

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Calcium chloride

EC Number:

233-140-8

EC Name:

Calcium chloride

Cas Number:

10043-52-4

Molecular formula:

CaCl2

IUPAC Name:

calcium dichloride

Applicant's summary and conclusion

Conclusions:

Calcium and chloride are essential constituents and two of the most abundant ions in all animal species. In adult humans, the total calcium in the body is approx. 830-1100 g. Ninety-nine percent of the calcium is retained in skeletons. Hormonal systems maintain a relatively constant calcium concentration of about 100 µg/mL in the plasma by controlling the intestinal absorption of dietary calcium, the release of calcium from bones, and renal absorption/excretion. Excess calcium is excreted in the urine via glomerulal filtration. Chloride is the most abundant anion in all animal species. In adult humans, the total chloride in the body is approx. 70-95 g. Eighty percent of the chloride is located extracellularly. The intracellular concentration of chloride is approx. 100-140 µg/mL. The chloride concentration in plasma is maintained around 3.55-3.90 mg/mL although chloride is absorbed efficiently from the intestine. Chloride is excreted from the renal tubular lumen by active transport systems, and also by passive diffusion.

Executive summary:

In the published review document OECD SIDS (2002), the following information is provided on toxicokinetics, metabolism, mechanisms of action of calcium chloride:

Toxicokinetics, Metabolism and Distribution

Calcium chloride is easily dissociated into calcium and chloride ions in water. The absorption, the distribution and the excretion of the ions in animals are regulated separately. Calcium chloride exerts its irritating property to tissues directly in contact with the compound. Once calcium chloride is taken up, the effect of the substance on animals should be attributed to the effect of calcium ions, the effect of chloride ions, or both. The homeostasis and mechanisms of action of calcium and chloride ions are well reviewed in standard textbooks on pharmacology, physiology, biochemistry and nutritional science.

Metabolism, biotransformation and kinetics

Calcium is the most abundant inorganic constituent of all animal species and has an important role in the nutrition of animals. In adult humans, the total calcium in the body is approx. 830-1100 g. Ninety-nine percent of the calcium is retained in skeletons. Hormonal systems maintain a relatively constant calcium concentration of about 100 µg/mL in the plasma by controlling the intestinal absorption of dietary calcium, the release of calcium from bones, and renal absorption/excretion. Excess calcium is excreted in the urine via glomerulal filtration. The renal tubules are able to excrete as well as reabsorb calcium. Thus the tubules are able to produce efficiently a net excretion of calcium to achieve homeostasis when abnormally high levels of calcium are ingested. A significant increase in the calcium concentration in plasma will only occur after high calcium intake in conjunction with other disorders that alter calcium homeostasis, such as renal insufficiency and primary hyperthyroidism [1, 2, 3, 4].

Chloride is the most abundant anion in all animal species. In adult humans, the total chloride in the body is approx. 70-95 g. Eighty percent of the chloride is located extracellularly. The intracellular

concentration of chloride is approx. 100-140 µg/mL. The chloride concentration in plasma is maintained around 3.55-3.90 mg/mL although chloride is absorbed efficiently from the intestine.

Chloride is excreted from the renal tubular lumen by active transport systems, and also by passive diffusion [1, 2].

Mechanisms of action

Calcium is indispensable for the formation and maintenance of bones and teeth, and for the regulation of various physiological functions in all animal species. These include the regulation of neural transmission and muscle contraction, coagulation of the blood, cell membrane integrity, theactivity of several enzymes, and the regulation of the acid-base balance [1, 2, 3]. Chloride is important in the regulation of osmotic and acid-base balances of the body fluids. Chloride maintains electrochemical neutrality by anion exchange with bicarbonate (the chloride shift) in the CO2 transport in the blood red cells [1, 2].

Conclusion

Calcium chloride is easily dissociated into calcium and chloride ions in water. The absorption, the distribution and the excretion of the ions in animals are regulated separately. Calcium and chloride are essential constituents of the body of all animal species. Calcium is essential for the formation of skeletons and the regulation of neural transmission, muscle contraction and coagulation of the blood. Chloride is required for regulating intracellular osmotic pressure and buffering.

References:

(1) Ganong, W.F. (2001). Review of Medical Physiology, 20th ed., McGraw-Hill Medical Publishing Division, New York.

(2) Gomei, T. (chief ed.) (1998). Eiyougaku Handobukku (Handbook of Nutritional Science), 3rd ed., Gihoudou Publishing Co., Tokyo.

(3) Marcus, R. (2001). Agents affecting calcification and bone turnover: calcium, phosphate, parathyroid hormon, vitamin D, calcitonin, and other compounds. In Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. (Hardman, J.G. and Limbird, L.E., eds.), McGraw-Hill Medical Publishing Division, New York, pp. 1715-1743.

(4) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (1999). Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. National Academy Press, Washington, D.C.