Genotoxic contaminants

Reactive chemicals are used to manufacture drugs and a proportion of these are geno-toxic. A draft guideline has been issued by the Europe and CHMP that seeks to control patient exposure to most genotoxic contaminants to below a Threshold of Toxicological concern of 1.5 xg/day. This is based on modelling data on known human carcinogens where such concentrations for specific compoimds would not be expected to increase human cancer above 1 per 10 exposed individuals. ... 

Methods for Detecting Individual-Level Effects of Genotoxic Contaminants in Organisms... 

Nitro polycyclic aromatic hydrocarbons are environmental contaminants which have been detected in airborne particulates, coal fly ash, diesel emission and carbon black photocopier toners. These compounds are metabolized Tn vitro to genotoxic agents through ring oxidation and/or nitroreduction. The details of these metabolic pathways are considered using 4-nitrobiphenyl, 1- and 2-nitronaphthalene, 5-nitro-acenaphthene, 7-nitrobenz[a]anthracene, 6-nitro-chrysene, 1-nitropyrene, 1,3-, 1,6- and 1,8-dinitro-pyrene, and 1-, 3- and 6-nitrobenzo[a] pyrene as examples ... 

Genotoxicity is one of the most important characteristics of toxic compounds in waste. For studying genotoxicity of waste, contaminated soil, sewage sludge, and sediments the conventional Ames test with Salmonella is usually used together with SOS-Chromotest and Mutatox [11,19,50-52,165-167]. 

Increased use of liquid chromatography/mass spectrometry (lc/ms) for structural identification and trace analysis has become apparent. Thermo-spray lc/ms has been used to identify by-products in phenyl isocyanate precolumn derivatization reactions Liquid chromatography/thermospray mass spectrometric characterization of chemical adducts of DNA formed during in vitro reaction lias been proposed as an analytical technique to detect and identify those contaminants in aqueous environmental samples which have a propensity to be genotoxic, t.e.. to covalently bond to DNA. 

The outputs from risk assessment will normally include information about the relationship between dose and risk and estimates of levels of doses and thus risks in the population. For contaminants that have a toxicological threshold the Provisional Tolerable Weekly Intake (PTWI) might be defined and the number of consumers who have the potential to exceed this level of intake quantified. If a PTWI cannot be established (such as for genotoxic carcinogens) then it may be possible to quantify the proportion of a population exposed to a given level of risk by using QRA methods. If QRA methods cannot be applied then a qualitative assessment can be made such as to reduce intake levels to as low as is reasonably practicable. In either case it is the function of risk management to identify an optimal course of action to minimise the risk to consumers. 

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