Hexacalcium hexaoxotris[sulphato(2-)]dialuminate(12-)

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

other: Reliability assignment for regulatory purposes is not applicable

Data source

Reference

Reference Type:

publication

Title:

Calcium , magnesium and nitrate in drinking water and gastric cancer mortality.

Author:

Yang C-Y, Cheng M-F, Tsai S-S & Hsieh Y-L

Year:

1998

Bibliographic source:

Jpn. J. Cancer Res 89: 124 - 130.

Materials and methods

Study type:

case control study (retrospective)

Endpoint addressed:

carcinogenicity

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The possible association between the risk of gastric cancer and the levels of calcium, magnesium and nitrate in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Records of gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on calcium, magnesium and nitrate levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The municipality of cases and controls was assumed to be the source of the subjects calcium, magnesium and nitrate exposure via drinking water. The subjects were divided into tertiles according to the levels of calcium, magnesium and nitrate in their drinking water.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material: Calcium in drinking water

Method

Type of population:

general

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED : The risk of gastric cancer in relation to the levels of calcium, magnesium, and nitrate in drinking water.

METHOD OF DATA COLLECTION
- Type: Record review
- Details: Data on all deaths of Taiwan residents from 1987 through 1991 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health which is responsible for the death registration system in Taiwan. For each death, detailed demographic information, including sex, year of birth, year of death, cause of death, place of death (municipality) and residential district (municipality), recorded on computer tapes.

STUDY PERIOD: 1987-1991

SETTING: Taiwan

STUDY POPULATION
- Selection criteria: Eligible gastric cancer deaths (ICD 151) were selected for the study. Controls were selected for all other deaths excluding those which were associated with gastrointestinal problems (i.e., malignant neoplasm of small intestine (ICD 152-154), gastric ulcer (ICD 531), duodenal ulcer (ICD 532), peptic ulcer, site unspecified (ICD 533), gastrojejunal ulcer (ICD 534) and gastrointestinal haemorrhage (578). Subjects who died from prostate, bladder, lung, oesophageal, and head and neck cancer were also excluded from the control group because of previously reported associations with nitrate or N-nitroso compounds exposures. Subjects who died from cardiovascular and cerebrovascular diseases were also excluded from the control group because of previously reported associations with hardness levels (calcium and magnesium) in drinking water. 30 aboriginal townships and 9 islets which have different life-styles and living environments were excluded from the study. Amongst the 322 municipalities, 70 were excluded as they were supplied by more than one water works and the exact population served by each could not be determined.
- Total number of subjects participating in study: 6766
- Sex/age: 4480 males mean age 2286 females with a mean age of 65.2 ± 13.0
- Matching criteria: Controls were pair-matched to the cases by sex, year of birth and year of death. Each matched control was selected randomly from the set of possible controls for each case. Each case and its matched control had residence and place-of death in the same municipality.

COMPARISON POPULATION
- Type: Control or reference group
- Details: Controls were pair-matched with the subjects and were selected on the cause of death that did not fall into the exclusion criteria.

HEALTH EFFECTS STUDIED
- Disease(s): Gastric cancer deaths
- ICD No.: 151
- Year of ICD revision: 9th revision 1997
- Diagnostic procedure: Death certificate

Exposure assessment:

estimated

Details on exposure:

TYPE OF EXPOSURE: Oral, present in drinking water

EXPOSURE LEVELS : Please refer to table 1. The final data set consisted of drinking water quality data from 252 municipalities. Hardness (calcium and magnesium) remains reasonably constant for long periods of time and is a quite stable characteristic of a municipality's water supply. Data collected included the mean levels of calcium for the year 1990. The municipality of residence for all cases and controls was identified from the death certificate and was assumed to be the source of the subject's calcium exposure via drinking water. The level of calcium in that municipality were used as the indicator of that individual's exposure to those substances. Information on the levels of calcium in each municipality's treated drinking water supply were obtained from the Taiwan Water Supply Corporation to whom each water works is required to submit drinking water quality data including the levels of calcium. Four finished water samples were collected for each season were collected for each water works.

Statistical methods:

Conditional logic regression was used to estimate the relative risk in relation to the nitrate levels in drinking water. Odds ratios and their 95 % confidence intervals (95 % CIs) were calculated using the group with the lowest exposure as the reference group. Coefficients with P values < 0.05 were considered statistically significant.

Results and discussion

Results:

FINDINGS:
A total of 6766 gastric cancer cases with complete records were collected for the period of 1987 - 1991. Of the 6766 cases, 4480 were males and 2286 were females. The mean calcium concentrations for the gastric cancer cases was 30.4 mg/L (SD = 19.2). Controls had a mean calcium exposure of 34.3 mg/L (SD 19.0). Both cases and controls had a mean age of 65.2. Cases lived in municipalities in which 89.8 % of the population was served by a water-works. For controls, this number was 89.4 %. Cases had a slightly higher rate (42.0 %) of living in metropolitan municipalities than the controls (36.9 %).

The odds ratios in relation to calcium levels in drinking water for death from gastric cancer were significantly lower for the two groups with high levels of calcium in their drinking water. Adjustment for possible confounders only slightly altered the odds ratios (95 % CI) were 0.77 (0.69 - 0.88) for the group with water calcium levels between 22.0 and 38.7 mg/L and 0.70 for (0.62 - 0.80) the group with calcium levels of 39.5 mg/L or more.

The results show a significant protective effect of calcium intake from drinking water on the risk of gastric cancer, when the groups with the highest and the lowest were compared

Confounding factors:

A number of major risk factors for gastric cancer in Taiwan include cigarette smoking and consumption of alcohol, green tea, salted or cured meat, smoked or fried food and fermented beans, which should be taken into account when investigating the possible role of drinking water quality. There risk factors present possible confounders in the study. There is no information available of these factors for individual study subjects and could not be adjusted for directly in the analysis.

Strengths and weaknesses:

Not reported

Any other information on results incl. tables

Table 2: Odds ratios (ORs) and 95 % CIs for gastric cancer dath by calcium levels in drinking water, 1987 - 1991:

	Calcium, mg/L (median)
	≤ 20.2 (7.5)	22.0 – 38.7 (32.8)	39.5 – 81 (53.4)
No. of cases	2523	2142	2101
No. of controls	1914	2277	2575
Crude odds ratio	1.0	0.71 (0.65 – 0.77)^a	0.61 (0.57 – 0.66)
Adjusted odds ratio^b	1.0	0.77 (0.69 – 0.88)	0.70 (0.62 – 0.80)

a) 95 % confidence intervals in parentheses

b) adjusted for urbanisation level of residence, nitrate and magnesium levels in drinking water.

Applicant's summary and conclusion

Conclusions:

The study suggests that there is a significant protective effect of calcium intake from drinking water on the risk of gastric cancer.

Executive summary:

This dstudy summary was provided for the registration of calcium sulfate.