THE FATE OF THE CHLORINATION-DERIVED MUTAGEN MX IN VIVO
Report No FR0235

H Horth, J K Fawell, C P James and W F Young

Sept 1991

SUMMARY

I OBJECTIVES

To investigate the fate of the chlorination-derived drinking water mutagen MX in vivo.

II REASONS

Chlorine which is used for disinfection of drinking water reacts with naturally occurring organic substances to form mutagenic by-products, including the potent bacterial mutagen MX. MX explains a significant proportion of the mutagenicity of UK drinking waters, but the significance to the health of consumers is not clear.

III CONCLUSIONS

MX was rapidly absorbed and widely distributed within the animal body. Absorbed material was rapidly metabolised and eliminated, mainly in the urine, in the form of very polar metabolites. There was evidence of binding of radioactive material to red blood cells in vivo; this appeared to be 'metabolised MX'.

IV RECOMMENDATIONS

Further work is required to determine the mutagenicity and identity of the metabolites of MX. Attempts should be made to confirm whether absorption of MX is primarily through the stomach as opposed to the small and large intestine, and the possibility of biliary excretion of MX should be investigated. The significance of the binding of 'metabolised MX' to red blood cells should be identified.

V SUMMARY OF CONTENTS

Carbon-14 labelled MX was synthesised and its disposition in the mouse was investigated. Plasma kinetics, excretion kinetics and tissue distribution of total radioactivity were examined following a single oral administration to mice. Plasma protein binding was examined in vivo and in vitro, and metabolite profiling of key urine samples was undertaken. The results showed that MX was rapidly absorbed and was widely distributed within the animal body. Absorbed material was rapidly metabolised and eliminated, mainly in the urine, in the form of very polar metabolites. There was evidence of binding of radioactive material to red blood cells in vivo; this appeared to be 'metabolised MX'.

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