Vincent F. Simmon

Study of Pesticide Genotoxicity

With a limited supply of arable land supporting an ever-increasing human population, the threat of crop loss to agricultural pests becomes continually more acute. Thus pesticides have become an essential component of modern agriculture. As competing organisms evolve resistance to commonly used agents, new and more effective poisons and repellants must constantly be developed. The fundamental problem in pesticide development is to produce chemicals that act specifically against certain organisms without adversely affecting others. Because of the similarities in the structural, metabolic and genetic components of all life forms, absolute species specificity is frequently difficult to attain. Furthermore, such toxic chemicals improperly used may engender biological effects beyond those for which they were originally manufactured.

An overview of short‐term tests for the mutagenic and carcinogenic potential of pesticides

In the last few years, marked progress has been made in the development of methods for evaluating the mutagenic and carcinogenic potential of pesticide chemicals. The correlation of genetic and related biological activity in short-term tests with carcinogenic activity in whole animals allows the utilization of short-term mutagenicity bioassays to prescreen chemicals for effects related to mutation induction and presumptive carcinogenicity. In addition, bioassays now available can measure directly the chemical transformation of normal cells in culture into cells capable of producing tumors when injected into animals. This paper will review briefly the major types of relevant short-term tests and will develop a rationale for a phased approach to the evaluation of the mutagenic and carcinogenic potential of environmental chemicals. This approach involves the sequential application of bioassays which are organized into a three-level matrix emphasizing first detection, then confirmation, and finally hazard assessment. Chemicals demonstrating positive results in the short-term detection systems and confirmatory bioassays are pursued in higher level whole animal define a negative result. The phased approach should facilitate a cost effective utilization of limited testing resources and provide protection for human health in proportion to the anticipated hazard. Results obtained in evaluating a series of thirty-eight pesticide chemicals according to the phased approach discussed in detail.

Mutagenic and carcinogenic potency of extracts of diesel and related environmental emissions: In vitro mutagenesis and DNA damage

The Saccharomyces cerevisiae D3 recombinogenic assay, the assay for forward mutagenesis in L5178Y mouse lymphoma cells, and the sister chromatid exchange (SCE) assay using Chinese hamster ovary cells were used to evaluate the in vitro mutagenic and DNA-damaging effects of eight samples of diesel engine emissions and related environmental emissions. The recombinogenic assay was not sufficiently sensitive for this evaluation, but mutagenicity was detected in the L5178Y mutagenesis assay following exposures of the cells to all of the emission samples, and DNA damage in the SCE assay was induced by most of the emission samples in the presence and absence of metabolic activation. The observation of positive results in the absence of activation indicated that the samples contained substances that were direct-acting mutagens and DNA-damaging agents.