THE FATE AND SIGNIFICANCE OF MUTAGENIC BY-PRODUCTS OF CHLORINATION IN VIVO
Report No FR0105

J K Fawell

June 1990

SUMMARY

I OBJECTIVES

To assess the hazard of mutagens, produced as a by-product of chlorination, to consumers.

II REASONS

Chlorine used for disinfection of drinking water reacts with naturally occurring organic molecules to produce by-products which are mutagenic. The significance of these mutagens to the health of consumers is not clear.

III CONCLUSIONS

1. High doses of chlorinated drinking water extracts at pH 7.0 and pH 2.0 did not induce nuclear anomalies in bone marrow, gastrointestinal tract or bladder. A very slight increase of nuclear anomalies was seen in the non-glandular stomach of some animals treated with pH 7.0 extract.

2. Maximum tolerated doses of the potent bacterial mutagen MX induced only marginal increases in nuclear anomalies in the jejunum/ileum. A small increase in nuclear anomalies was seen in the glandular stomach but was not observed at lower than the maximum tolerated dose. No increase in nuclear anomalies was seen in bone marrow or transitional epithelium of bladder. A possible marginal increase in nuclear anomalies was observed in the lamina propria of bladder.

3. A clear and consistent increase in mitotic figures was seen in the liver of animals given extracts of chlorinated drinking water concentrated at pH 7.0. This was less marked with pH 2.0 extracts.

4. Substantial reassurance that mutagens from chlorinated drinking water do not pose a significant hazard to consumers can be gained from these findings. However, the limitations of the techniques available preclude absolute statements regarding hazard.

IV RECOMMENDATIONS

1. The adsorption, metabolism and excretion of MX and similar compounds should be further studied in vivo using radiolabelled materials.

2. Consideration should be given to further studies on the activity of chlorination derived mutagens in bladder.

3. Further attempts to characterise the mutagens present in pH 7.0 extracts should be made since little is known about the compounds contributing to this mutagenicity.

4. In the event of brominated derivatives of MX being detected in drinking water extracts these should be tested in higher test systems for genotoxicity and if appropriate in in vivo systems.

5. MX should be tested in a second in vivo test system when a suitable test system is adequately established.

6. Consideration should be given to the investigation of the mitogenic activity of extracts in liver.

V SUMMARY OF CONTENTS

The work covered in this report concerns the evaluation of the potential risk to consumers' health of chlorination derived mutagens in drinking waters.

In vivo studies with the nuclear anomaly assay using extracts of drinking water at the maximum tolerated dose indicate that these are not genotoxic in bone marrow, gastrointestinal tract, liver or bladder. The potent mutagen MX only produced marginal changes in jejunum/ileum, glandular stomach and possibly lamina propria of bladder at doses approaching the LD5O.

The implications of these fundings are discussed and recommendations for further work presented.

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