Report No DWI0112
MUTAGENIC ACTIVITY OF CONCENTRATED WATER EXTRACTS IN VIVO (EHT 9271) Final report to Department of the Environment DoE 2256-M/1
- To investigate the
ability of concentrated drinking water extracts to induce genotoxic
effects in cells of the gastro-intestinal tract.
- To investigate the binding of mutagens in drinking water to exogenous proteins and body fluids in vitro.
- To evaluate the
mutagenic activity of polar compounds in drinking water (those
recovered by XAD resin at low pH) using mammalian cell systems.
used for disinfection of drinking water reacts with naturally occurring
organic molecules to produce by-products that 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, gastro-intestinal tract or bladder. A
very slight increase of nuclear anomalies was seen in the non-glandular
stomach of some anim als 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 theglandular stomach but were 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.
- Mutagenicity to
mammalian cells in tissue culture was greatly reduced in the presence
of serum, albumin and glutathione suggesting that the activity of these
mutagens will be substantially ameliorated or abolished in higher
- 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.
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.
- 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
- 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.
- The absorption,
metabolism and excretion of MX and similar compounds should be further
studied in vivo using radiolabelled material.
- Consideration should
be given to the investigation of the mitogenic activity of extracts in
liver although this must be considered of lower priority than other
V SUMMARY OF CONTENTS
covered in this report concerns the evaluation of the potential risk to
consumers health of chlorination derived mutagens in drinking waters.
chlorinated drinking water concentrated at pH 2.0 have been shown to
produce chromosome aberrations in cells in tissue culture although the
toxicity of these extracts to the cells is greater than pH 7.0
extracts. In vitro studies have shown that the mutagens bind to serum
proteins and albumin and are inactivated by glutathione.
studies with extracts at the maximum tolerated dose indicate that these
are not genotoxic in bone marrow, gastro-intestinal tract, liver or
bladder. MX only produced marginal changes in jejunum/ileum, glandular
stomach and possibly lamina propria of bladder at doses approaching the
The implications of these findings are discussed and recommendations for further work presented.
Copies of this report may be available as an Acrobat pdf download under the 'Pre 2000 Reports' heading on the DWI website.