Summary, Conclusions, and Future Developments - Pesticide Biotransformation and Disposition - page 207

Given the ready availability of hepatocytes, cell fractions, cell lines, and recombinant
xenobiotic-metabolizing enzymes (XMEs), all derived from humans, ethical human
studies have been relatively easy to conduct since the beginning of the 21st century.
Such studies are essential if variation within the human population is part of the risk
assessment paradigm, and if subpopulations and individuals at increased risk are to be
identified.
Finally, since pesticides are, more often than not, used in mixtures or in temporal
proximity that is so close as to have the same implications for risk analysis as mixtures,
the question of interactions between the pesticides in mixtures and between pesticides
and endogenous metabolites is beginning to be addressed, at the metabolic and other
levels.
CONTINUING NEED FOR PESTICIDE METABOLISM STUDIES
In view of the needs outlined above it is clear first, that metabolic studies must con-
tinue and second, that new techniques need to be brought to bear on the various
problems involved. Although production of food and fiber without the use of pesti-
cides (“green agriculture”) may be a worthy goal, it seems unlikely, in the short and
intermediate future, that advances in that direction can produce the food and fiber
necessary to care for a world population of over 6 billion and growing.
Given the emerging changes in risk assessment ( National Research Council, 2007;
Hodgson, 2010a,b; Kullman et al., 2010 ) that rely heavily on human cell lines and
the techniques of genomics, proteomics, metabolomics, QSAR, and bioinformatics,
the nature of human studies will doubtless change, but their importance will increase.
Examination for potential toxicity of the very large number of chemicals in general
use, using high-throughput genomic, proteomic, and metabolic methods, will go far to
make practical a task that currently, because of the huge number of chemicals involved,
is not feasible. Experience would suggest, however, that both false positives and false
negatives will occur and that detailed studies of single chemicals will still be needed. In
the specific case of pesticides. Because of the regulatory requirements for registration
and use, it is likely that the detailed studies of both single chemicals and the mixtures
actually used in the field will continue alongside the new techniques. Detailed studies
on the pesticide mixtures commonly in use and PBPK studies of one pesticide in the
presence of another will be an essential starting point.
Improved human health risk analysis is vital when, although it is becoming increas-
ingly clear that the risks to human health from pesticides are minimal to the general
population when the pesticides are properly evaluated and used, there are significant
risks to applicators and other users. By some statistical measures, agriculture is now the
most hazardous occupation in the United States ( U.S. Bureau of Labor Statistics, 2011 ).