Indirect mutagenicity test

The dangerous properties of acute toxicity, irritation, corrosivity, sensitisation, repeated-dose toxicity and CMR are evaluated in terms of their potential toxic effects to workers, consumers and man exposed indirectly via the environment, based on the use for each stage in the lifecycle of the substance from which exposure can occur. Risk assessment is also required if there are reasonable grounds for concern for potential hazardous properties, e.g., from positive in vitro mutagenicity tests or structural alerts. The risk assessment involves comparing the estimated occupational or consumer exposure levels with the exposure levels at which no adverse effects are anticipated. This may be a quantitative risk assessment, based on the ratio between the two values, or a qualitative evaluation. The principles of human health risk assessment are covered in detail by Illing (a.30) and more briefly in Chapter 7 of (73). 

The question is, is there something like a mutagenicity test, direct acting or indirect acting, whereby we can test and determine the risk and set an acceptable level for our drinking water supply I would consider an acceptable level toward humans and an acceptable ecological level. Maybe there is a single test or maybe a battery of simple tests. 

The crude holothurins from Philippine sea cucumbers belonging to Holothuriidae family have indirect mutagenic and clastogenic activity. Although no activity was noted in vitro (Rec- assay and Ames test) after metabolic activation, these holothurins produced aberration scores in Swiss albino mice (micronuclear test) when administered intraperitoneally [29]. Nevertheless, at peroral injection, they exhibited a 35-fold reduction in activity, which indicates inactivation in the alimentary canal [29]. On the contrary, Polycarpova et al. showed the absence of mutagenic activity of cucumarioside - triterpene glycoside from the sea cucumber Cucumaria Japonica [27]. 

In addition to structure-activity relationships, dozens of useful tests have been developed for mutagenicity to germ cells and somatic cells and inferred carcinogenicity. The most straightforward means of testing for effects on DNA is an examination of DNA itself. This is normally difficult to do, so indirect tests are used. One useful test measures the activity of DNA repair mechanisms (unscheduled DNA synthesis) a higher activity is indicative of prior damage to DNA. 

A thorough review of markers of DNA repair and susceptibility to cancer in humans from 2000 [64] has summarized the results from 64 epidemiologic studies that addressed the association of cancer susceptibility with a putative defect in DNA repair capacity. The authors concluded that the vast majority of studies showed a difference between cancer case subjects and although this observation is compatible with a chromosomal instability due to the cancer itself, it was notable that impaired mutagen sensitivity was also observed in healthy relatives of cancer subjects. There were a variety of functional tests used that only indirectly addressed DNA repair and these showed high variability in their expression. Finally, the issue of confounding was almost totally unexplored. 

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