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Toxicological information

Health surveillance data

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Administrative data

Endpoint:
health surveillance data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
no data available
Reliability:
other: high
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well-documented study on Ca supplementation to prevent the recurrence of colorectal adenomas. Under physiological conditions, the hydroxyl-ions released from lime following oral adminstration have been neutralised in the GI tract and are therefore not relevant for consideration of systemic toxicity. Therefore for assessment of any systemic effects of lime following administration via the oral route, the calcium ion Ca2+ is the chemical species of interest. In the current study, calcium was supplemented to humans in the form of calcium carbonate. The carbonate ion is released as CO2 following reaction with gastric juice and is therefore toxicologically not relevant. The objective of the study was the evaluation of any effects of calcium. In view of the the limited relevance of the anionic counter-ions discussed here, calcium released both from calcium hydroxide and calcium carbonate can be considered as structurally equivalent, and the results of the study can be used by read-across.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Calcium supplements for the preventation of colorectal adenomas
Author:
Baron, J.A.; et al.
Year:
1999
Bibliographic source:
New England J. Med., Vol. 340, No. 2, 101-107

Materials and methods

Study type:
medical monitoring
Endpoint addressed:
carcinogenicity
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Medical monitoring, double-blind placebo controlled trial for prevention of recurrence of colorectal adenomas
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Calcium carbonate
EC Number:
207-439-9
EC Name:
Calcium carbonate
Cas Number:
471-34-1
IUPAC Name:
calcium carbonate
Details on test material:
- Name of test material (as cited in study report): Calcium carbonate
No further details are given.

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
930 subjects (mean age, 61 years; 72 % men) with a recent history of colorectal adenomas were randomly assigned to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies 1 and 4 years after the qualifying examination. The primary endpoint was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas before the study, clinical center, and length of the surveillance period.

Results and discussion

Results:
The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 % CI: 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31%) and 159 subjects in the placebo group (38%); the adjusted risk ratio was 0.81 (95 % CI: 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 % CI: 0.6 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake.

Applicant's summary and conclusion

Conclusions:
Calcium supplementaion is associated with a significant - though moderate - reduction of the risk of recurrent colorectal adenomas.