The drinking water chlorination by-products 3,4-dichloro-5-hydroxy-2[5H]-furanone (mucochloric acid) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone do not induce preneoplastic or neoplastic intestinal lesions in F344 rats, Balb/cA mice or C57BL/6J-Min mice
Il. Steffensen et al., The drinking water chlorination by-products 3,4-dichloro-5-hydroxy-2[5H]-furanone (mucochloric acid) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone do not induce preneoplastic or neoplastic intestinal lesions in F344 rats, Balb/cA mice or C57BL/6J-Min mice, PHARM TOX, 85(2), 1999, pp. 56-64
Epidemiological studies indicate an association between exposure to chlorin
ated drinking water and risk of intestinal cancer. In order to study this e
xperimentally, we have examined the effects of 3,4-dichloro-5-hydroxy-2[5H]
-furanone (mucochloric acid, MCA) and 3-chloro-4-(dichloromethyl)-5-hydroxy
-2[5H]-furanone (MX), mutagenic and genotoxic compounds in drinking water,
on aberrant crypt foci and tumours in the intestines of male F344 rats and
Balb/cA mice, and C57BL/6J-Min (multiple intestinal neoplasia)/+ mice of bo
th sexes, in six independent experiments. In some experiments the effects o
f MCA and MX on aberrant crypt foci induced by the colon carcinogens 1,2-di
methylhydrazine or its metabolite azoxymethane were also studied. Neither M
CA nor MX alone induced aberrant crypt foci or intestinal rumours when give
n in drinking water. With this route of exposure neither MCA nor MX, when g
iven in combination with 1,2-dimethylhydrazine or azoxymethane, had any eff
ect on the induction or growth of the aberrant crypt foci. Drinking water e
xposure of MX did not affect the number or growth of aberrant crypt foci or
intestinal tumours in the Minl+ mice. When administered intrarectally MCA
had a weak inducing effect on aberrant crypt foci in the colons of Balb/cA
mice. Exposure to MCA and MX intrarectally apparently promoted the growth o
f aberrant crypt foci both in rats and mice, increasing the crypt multiplic
ity, aberrant crypts/aberrant crypt foci. Based on an overall evaluation of
these experiments, the intestinal tract, at least in rats and mice, seems
not to be a main target organ for effects of MCA or MX on preneoplastic or
neoplastic development.