INDEX genotoxicity

Environment Canada recently developed an evaluation system based on effluent toxicity testing, capable of ranking the environmental hazards of industrial effluents [185]. This so-called Potential Ecotoxic Effects Probe (PEEP) incorporates the results of a variety of small-scale toxicity tests into one relative toxicity index to prioritize effluents for sanitation. In the index no allowance has been made for in-stream dilution, therefore the acmal risk for environmental effects is not modeled. The tests performed on each effluent are the following bacterial assay [V.fisheri (P. phosphoreum), Microtox], microalgal assay S. capricornutum) crustacean assay (C. dubiay, and bacterial genotoxicity test E. coli, SOS-test). 

In applying the PEEP index concept to sets of industrial effluents thus far, wastewater samples have been filtered prior to bio-analysis (see Section 5.1). Hence, only their soluble toxicity potential is taken into consideration. This is certainly a drawback at this time as toxic and genotoxic potential linked to suspended matter of some industrial plant effluents, for example, have been shown to be important (White et ah, 1996 Pardos and Blaise, 1999). Particulate toxicity in effluent samples should certainly be addressed in future PEEP applications, as soon as reliable small-scale toxicity tests are developed and available to estimate it. Indeed, the issue of soluble and particulate toxicity is especially relevant in relation to technology-based reduction of hazardous liquid emissions. 

Gold LS, Zeiger E,. Handbook of Carcinogenic Potency and Genotoxicity Databases. New York, NY CRC Press 1997. See also The Carcinogenic Potency Database. Retrieved from http //potency.berkeley.edu/index.html. Accessed March 18, 2009... 

A detailed discussion of the test procedures employed is contained within Galloway et al. (1994). Detectable levels of chromosome aberrations are often found only at doses that induce some evidence of cytotoxicity, and consequently most current recommended protocols require that the maximum test concentration should induce >50% reduction in cell number or culture confluency for cell lines, or an inhibition of mitotic index by >50% for lymphocytes. However, there are growing concerns as to the relevance of genotoxic effects that are found only at highly cytotoxic concentrations (Galloway 2000), and this may be reflected by the poor specificity of mammalian cells tests (Kirkland et al. 2005). 

Different types of tests for genotoxicity of peroxisomicine Ai (T514), such as inhibition of mitotic index, lymphocyte proliferation kinetics, frequency of sister chromatid interchange, and frequency of chromosomic aberrations, have yielded negative results [75]. 

The effect of NDGA on the production of sister-chromatid exchanges and on the level of the mitotic index in cultured human lymphocytes and in mouse bone marrow cells in vivo was evaluated by Madrigal Bujaidar et al. [311], and they observed that in both models NDGA produced genotoxic and cytotoxic effects. In a later study [312], the same author observed... 

This value. Maximum Positive Total (MP), is divided into the AS for the test material to obtain an index (expressed as percent) of what portion of the maximum genotoxic effect was obtained in the evaluations (% MP). 

This scoring scheme, then, takes the actual test results from a multitest battery through to a specific action recommendation based on an index of the maximum genotoxic effect for that group of assays. It should facilitate the interpretation and decision making process which follow the actual testing program. 

Pasqual, M.S., C.P. Lauer, P. Moyna, and J.A.P. Henriques. 1993. Genotoxicity of the isoquinoBne alkaloid berberine in prokaryotic and eukaryotic organisms. Mutat. Res. 286(2) 243-252. Price, C.J., and J.D. George. 2003. Final study report on the developmental toxicity evaluation for berberine chloride dihydrate (CAS No. 5956-60-5) administered in the feed to Swiss (CD-1 ) mice on gestational days 6 through 17. Gov. Rep. Announce. Index No. 20 112. 

Conversely, NDGA exhibited protective activity against genotoxic damage induced by the compound norgestrel. Study parameters included sister-chromatid exchanges, chromosomal aberrations, mitotic index, and replication index (Siddique et al. 2006). 

Fig. 4.3 Nanoparticle and nanotoxicology citations from 1980 to 2013. The number of scientific articles published each year on toxicity of nanoparticles (pink) and all nanotechnology topics (yellow), as indexed by ISI Web of Knowledge. The bottom inset shows an expanded view. The top inset shows the proportion (in %) of nanotoxicology articles to total nanotechnology articles per year, and indicates that this propoition has been growing significantly over the last decade. Values in yellow were determined by a topic search string of nano OR ultrafine particles" and values in pink were determined by a search string of (nano OR ultrafine particles) AND (toxic OR cytotoxic OR genotoxic ) ...

D. Eke and A. Celik, Genotoxicity of thimerosal in cultured human lymphocytes with and without metabolic activation sister chromatid exchange analysis proliferation index and mitotic index, Toxicol. In Vitro, 2008, 22, 927-934. 

---