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Participants at the meeting endorsed five recommendations:
Preliminary registration, registration, and reregistration of pesticides is
frequently, if not exclusively, based on the evaluation of comprehensive
animal data. To enhance and improve assessment of risk to human
health, more use should be made of information based on human
exposure and health effects.
In addition to generating hypotheses, epidemiological studies should
be designed and used to verify hypotheses. Particular attention should
be paid to verification of specific exposures, selection of controls, and
occurrence of mixed exposure. Whenever possible, prospective records
on the use of pesticides should be kept, preferably linked to individuals
or groups of individuals.
Various techniques and methods for assessment of exposure, such as
analyses of data on use, measurement of external exposure, and biological
monitoring, each have a specific contribution to make. Combining
the various techniques and methods will increase the accuracy of an
assessment.
Data on early biological effects may serve as indicators of possible health
effects. Case-by-case evaluation will be helpful in assessing the clinical
significance of a biological effect.
Data on health or biological effects, obtained in situations with multiple
exposures, should be used to stimulate measures to reduce pesticide
exposure.
General discussion during the meeting highlighted several points. In assessment
of toxicological risk of pesticides, the experimental model by which
single compounds are tested is limiting. In practice, agricultural workers are
commonly exposed to formulations and mixtures of pesticides. Although it is
not feasible to test all possible mixtures or associations of compounds encountered
by users, when there is reason to suspect that an interaction between two
pesticides can occur (e.g., based on the mechanism of action), specific experiments
with mixtures should be carried out. However, in most cases, mixed
exposure in real life will remain an unprecedented experiment, emphasizing
the importance of human observations and epidemiology in detecting additive
or synergistic effects.
Because of lack of statistical power or other methodological flaws, experiments
to investigate carcinogenicity in humans may produce false-negative
results. On the other hand, animal experiments to investigate carcinogenicity
of chemicals are carried out in extreme conditions, i.e., a very high dose is
administered over a prolonged period. This method is appropriate to detect
the carcinogenic potential of a molecule even through testing a limited number
of animals, but it generates information that is more qualitative than quantitative.
For pesticide users, who are exposed to doses four or five orders of
magnitude smaller than those used on experimental animals, the assessment
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