Report No FR0411

TOXIC MECHANISMS OF DISINFECTION BY-PRODUCTS -
A PRELlMlNARY REPORT

FR0411

Sept 1993

SUMMARY

I BENEFITS

As the toxic mechanisms of disinfection by-products are better understood, less uncertainty is involved in the risk assessment process, possibly leading to standards that are less conservative (ie. less stringent) than previously established but which still afford adequate protection to consumers. This in turn could have a significant impact on water treatment costs and the ease of achieving standards, and may also influence the selection of disinfection processes.

II OBJECTIVES

  1. To keep up to date on recent work on MX and bromate.
  2. To review practical work undertaken as part of this contract to determine the effect of dichloroacetic acid (DCA) and trichloroacetic acid (TCA) on intercellular communication in rat hepatocyte couplets.
  3. To review recent studies on the mechanisms of carcinogenicity of DCA and TCA
  4. To suggest possible work to be carried out to elucidate these mechanisms.

III REASONS

There is international concern over the possible health effects of by-products of disinfection. The chlorinated acetic acids, bromate and MX are receiving considerable attention from researchers and regulators. Bromate, DCA and TCA have been shown to cause an increase in tumours in laboratory animals and MX is an extremely potent mutagen in bacterial test systems. Inappropriate regulation could compromise water treatment as currently practised.

IV CONCLUSIONS

  1. MX has recently been shown to cause sister chromatid exchanges in rat peripheral lymphocytes in vivo.
  2. Neither DCA nor TCA affect gap junction intercellular communication (GJIC) in rat hepatocytes.
  3. DCA and TCA are both carcinogenic but act through different mechanisms.
  4. TCA appears to act as a peroxisome proliferator, while DCA may be acting by an enzymatic mechanism.

V RESUME OF CONTENTS

The latest study on MX from Finland is summarised and indicates that MX is potentially systemically genotoxic in vivo, although the effects have been confined to sister chromatid exchanges (SCE) in rat peripheral lymphocytes. Further work on the potential carcinogenicity of MX is expected from Finland in the near future and will be monitored.

It is suggested that further information on the mechanism of carcinogenicity of bromate could be obtained by investigating lipid peroxidation in vivo. Several groups in the US are working on bromate and these will be contacted.

There appear to be no effects on gap junction intercellular communication (GJIC) due to either DCA or TCA in rat hepatocyte couplets in vivo without evidence of cytotoxicity within the population of cells. TCA has previously been shown to inhibit GJIC i n cultures of B6C3F1 mouse hepatocytes and, it is suggested that effects on GJIC may be dependent on factors specific to species and strain.

It is postulated that TCA may act as a peroxisome proliferator, leading indirectly to DNA damage via increased levels of free radicals. DCA however, is considered to act via an enzymatic pathway involving glycogen synthetase stimulation.

Several gaps in the database are identified and future work suggested.

Copies of the report are available from FWR, price 15.00, less 20% to FWR Members.