Polychlorinated biphenyls mutagenicity

Hayes, M.A. 1987. Carcinogenic and mutagenic effects of PCBs. Pages 77-95 in S. Safe (ed.). Polychlorinated Biphenyls (PCBs) Mammalian and Environmental Toxicology. Environ. Toxin Ser. 1. Springer-Verlag, New York. 

In 1985 it was published [1] that stevioside was completely safe but that metabolically activated steviol was mutagenic in a "Forward Mutation Test". Steviol had to be applied together with the microsomal fraction of liver of animals treated with carcinogenic compounds (polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone). This publication has led to a confusing discussion between advocates and opponents of the use of Stevia or stevioside. To unravel the problem we must consider the opinion of authoritative international organisations such as OECD (Organisation for Economic Co-Operation and Development) and ICH (International Council of Harmonisation). To accept new substances as food three different mutagenesis tests are accepted and required by the OECD as well as by the ICH. These can be seen in Table 1. 

Kalina I, Sram RJ, Konecna H, et al. 1991. Cytogenetic analysis of peripheral blood lymphocytes in workers occupationally exposed to polychlorinated biphenyls. Teratog Carcinog Mutagen 11 77-82. 

Safe S. 1989b. Polychlorinated biphenyls (PCBs) mutagenicity and carcinogenicity. Mutat Res 220 31 7. 

If a test compound significantly increases the number of observed colonies relative to a control for spontaneous reversion, which always occurs to some extent, that compound must have caused mutation that resulted in reversion. Each type of strain, of which five are normally used for the full test and two for more limited versions, detects a specific type of mutation TA98 detects frameshift mutations while TAIOO picks up base pair substitutions. Since the mutagenic abilities of compounds often depend on metabolic activation, as it does for aflatoxin Bl, the test can be run in the presence of S9 liver fraction from rats whose CYPs have been induced by the polychlorinated biphenyl Aroclor 1254. An increase in reversion only in the presence of S9 shows that the mutagen must be a metabolite. 

Most wastewater streams contain significant amounts of carcinogenic, toxic, mutagenic, or genotoxic substances in addition to conventional pollutants. These harmful compounds originate from industrial processes and households. Some of these toxic chemicals may also exhibit endocrine-disrupting effects. Therefore, organic micropollutants such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), nonylphenol, xenobiotics, dioxins, pesticides, and heavy metals create important environmental health risks [3-7]. 

Mouse Liver microsomes Demethylation induced by polychlorinated biphenyls kinetics of demethylation and activation to a mutagen compared 90... 

Generally speaking, no marked difference has been found in the preparation of S-9 Mix from these different species of rodents. However, phenacetin, which has been suspected of producing human cancer, is mutagenic only with S-9 Mix from the liver of hamsters treated with polychlorinated biphenyls... 

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