THE FATE AND SIGNIFICANCE OF MUTAGENIC BY-PRODUCTS OF CHLORINATION IN VIVO
Report No FR0105
J K Fawell
To assess the hazard of mutagens, produced as a by-product of
chlorination, to consumers.
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.
- 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.
- 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
- 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.
- 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.
- The adsorption, metabolism and excretion of MX and similar
compounds should be further studied in vivo using radiolabelled
- Consideration should be given to further studies on the activity
of chlorination derived mutagens in bladder.
- 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.
- 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.
- MX should be tested in a second in vivo test system when a
suitable test system is adequately established.
- 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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