The carcinogenicity of the biocide ortho-phenylphenol.
The biocides ortho-phenylphenol and its sodium salt (OPP and SOPP) are widely used as fungicides and antibacterial agents for commercial and consumer purposes. The carcinogenicity of OPP/SOPP toward the urinary bladder was demonstrated when rats were chronically fed concentrations of 0.5%-4% in their diet. Other species tested so far did not develop tumours. Understanding the mechanisms underlying OPP/SOPP-induced bladder carcinogenesis is critical to determine whether risks observed at high doses in rats are of relevance to humans exposed at much lower levels. This overview details experimental studies of carcinogenicity, genotoxicity as well as metabolism/toxicokinetics and other mechanistic studies which bear on cancer hazard and risk evaluation of exposure to humans. Based on the presently available knowledge, it is concluded that reactive quinoid metabolites exhibiting redox cycling activities are the crucial factors. At certain concentration levels, these metabolites are able to produce cytotoxic events with concomitant enhanced cell proliferation of the target tissue. Further important risk factors are probably promutagenic lesions induced by oxidative stress and a higher urinary pH. Supposed that these mechanisms are the basis for the tumourigenicity observed, then suitable low doses of OPP/SOPP will practically pose no cancer risk.
Appel
K E
KE
Division for Plant Protection Products and Pesticides, Federal Institute for Health Protection of Consumers and Veterinary Medicine, Berlin, Germany.
D000818:Animals; D001713:Biphenyl Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000473:pathology; D004249:DNA Damage; D005260:Female; D005659:Fungicides, Industrial / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D008297:Male; D009153:Mutagens / Q000633:toxicity; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology
D001713:Biphenyl Compounds; D002273:Carcinogens; D005659:Fungicides, Industrial; D009153:Mutagens; C004369:2-phenylphenol