In vivo genotoxicity studies with 3-monochloropropan-1,2-diol.
3-Monochloropropan-1,2-diol (3-MCPD) is a contaminant of polyamine flocculants used in the production of drinking water, but more significantly for human exposure it can arise also in certain foodstuffs containing acid-hydrolysed vegetable protein. It is carcinogenic in the rat, producing tumours in males in the testes, mammary gland and the preputial gland and also kidney tumours in both sexes. It has given positive results in in vitro mutagenicity studies, but there have been no satisfactorily conducted in vivo studies in somatic cells published in the peer reviewed literature. As a result, and because of the absence of appropriate in vivo evidence, several international regulatory agencies had previously judged it prudent to assume that 3-MCPD possessed mutagenic activity in vivo and considered 3-MCPD to be a genotoxic carcinogen. We present in this paper results from two in vivo mutagenicity studies with 3-MCPD, namely a bone marrow micronucleus test in the rat and unscheduled DNA synthesis in the rat liver, both conducted in accordance with relevant OECD protocols. These studies show that 3-MCPD does not possess genotoxic activity in vivo in the tissues examined. On the basis of these findings, and along with evidence that tumours may be induced by mechanisms involving either hormonal disturbances or sustained cytotoxicity, we believe that 3-MCPD may now be considered to be carcinogenic to rodents via a non-genotoxic mechanism.
Robjohns
Stephen
S
Public Health Group, Department of Health, Skipton House, 80 London Road, London SE1 6LH, UK. stephen.robjohns@doh.gsi.gov.uk
Marshall
Richard
R
Fellows
Michael
M
Kowalczyk
George
G
D000818:Animals; D021461:Animals, Outbred Strains; D001854:Bone Marrow Cells / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005990:Glycerol / Q000031:analogs & derivatives / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D051381:Rats; D000517:alpha-Chlorohydrin
D004247:DNA; D000517:alpha-Chlorohydrin; D005990:Glycerol