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.
Epidemiological studies indicate an association between exposure to chlorinated drinking water and risk of intestinal cancer. In order to study this experimentally, 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 both sexes, in six independent experiments. In some experiments the effects of MCA and MX on aberrant crypt foci induced by the colon carcinogens 1,2-dimethylhydrazine or its metabolite azoxymethane were also studied. Neither MCA nor MX alone induced aberrant crypt foci or intestinal tumours when given in drinking water. With this route of exposure neither MCA nor MX, when given in combination with 1,2-dimethylhydrazine or azoxymethane, had any effect on the induction or growth of the aberrant crypt foci. Drinking water exposure 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 of aberrant crypt foci both in rats and mice, increasing the crypt multiplicity, 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.
Steffensen
I L
IL
National Institute of Public Health, Department of Environmental Medicine, Oslo. inger-lise.steffensen@folkehelsa.no
Paulsen
J E
JE
Engeset
D
D
Kronberg
L
L
Alexander
J
J
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D005663:Furans / Q000633:toxicity*; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014881:Water Supply / Q000032:analysis*; D015430:Weight Gain / Q000187:drug effects
D002273:Carcinogens; D005663:Furans; D009153:Mutagens; C014117:mucochloric acid; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D019813:1,2-Dimethylhydrazine