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additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Insufficient documentation on environmental conditions and test animals.
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:
Acute effects on soft drink intake on calcium and phosphate metabolism in immature and adult rats
Amato D
Bibliographic source:
Rev Invest Clin 50: 158-189

Materials and methods

Type of study / information:
Acute effects of the intake of phosphoric acid containing soft drink on acid-base balance and on calcium and phosphate metabolism were studied in 14 young adult male Sprague-Dawley rats aged 90 days, and 14 immature animals aged 30 days.
Principles of method if other than guideline:
Seven animals in each group were randomly assigned as controls to receive tap water ad libitum; the rest of the animals received Coca-Cola ad libitum, instead of water, for seven days.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Orthophosphoric acid
EC Number:
EC Name:
Orthophosphoric acid
Cas Number:
Molecular formula:
phosphoric acid
Details on test material:
- Name of test material (as cited in study report): Phosphoric acid

Results and discussion

Any other information on results incl. tables

Rats received soft drink increased significantly their liquid intake from 34 ± 3 mL/24h in the adult control group to 143 ± 4 (p< 0.05) and from 13 ± 2 mL/24h in the immature control group to 55 ± 3 (p < 0.05). body weight did not show significant differences within groups: 308 ± 4.9 g in the adult controls vs 305± 6.8 g in the adult experimental group, and 114 ± 6.1 g in the immature control group vs 116 ± 4.9 g in the immature experimental group.

Urinary excretion of calcium and phosphorus:

Both adult and immature animals receiving soft drink developed a significant hypercalciuria and hyperphosphaturia. In immature animals, ionized calcium significantly dropped from 1.06 ± 0.04 mEq in the control group to 0.80 ± 0.06 in the experimental group (p<0.05). In adult animals, ionized calcium showed a trend to reduction from 1.40 ± 0.04 to mEq/L to 0.95 ± 0.05 without reaching statistical significance. Immature animals developed metabolic acidosis, i.e. pH dropped from 7.45 ± 0.04 to 7.33 ± 0.02 (p< 0.05), and total CO22 from 22.7 ± 2.2 to 19.3 ± 1.4 mEq/L (NS); also non-significant were the data in adult animals: pH (7.40 ± 0.02 to 7.39 ±0.03) and CO2 (21.6 ± 1.3 to 22.3 ± 1.5 mEq/L).

Values of total calcium, phosphorus, PTH, 1a, 25 (OH)2 D3 and 25 OH D3:

The immature animals developed a significant reduction of 1a, 25 (OH)2 D3 and 25 OH D3, and the adult animals developed a secondary hyperparathyroidism. Phosphorus content of the soft drink was 18.7 ± 0.4 mg/dL and pH 2.35 ± 0.08 (mean ± SEM).

Applicant's summary and conclusion

The results in this paper support the hypothesis that the intake of soft drinks with phosphoric acid may be related to the development of hypocalcemia. We also confirmed suspected age related effect. Young individuals may be at a higher risk of sufferin disorders of calcium phosphorus and vitamin D metabolism, but since adult individuals seem to prevent hypocalcemia with the development of hyperparathyroidism, they may be at a higher risk for urolithiasis and osteoporosis.