Pesticide dose-response relationship

Heptachlor, chlordane, and endosulfan (another cyclodiene pesticide) were shown to inhibit hepatocyte gap junctional intercellular communication (Ruch et al. 1990). All three pesticides showed similar dose-response relationships. Further testing with chlordane and heptachlor indicated that inhibition of the cytochrome P-450 system had no effect on this response. These results suggest that the interference with intercellular communication is not directly tied into the effects of these cyclodienes on the P-450 system. 

One principle that is central to the understanding of toxicology is the dose-response relationship, which implies that there is a threshold level below which no toxic effects are observed. This level can be approximated in studies in which animals are dosed with the pesticide the maximum dose tested at which there are no detectable differences between treated and untreated control animals is called the no observed effect level (NOEL). The dosage slightly in excess of the NOEL at which toxic effects are observed is referred to as the lowest observed effect level (LOEL). These two dosages should be relatively close together in order to clearly define the threshold level. 

Other studies evaluated for interspecies dose-response relationships by these workers, primarily between rats and humans, included metals (Evans et al. 1944, as cited in Dourson and Stara 1983), pesticides (Hayes 1967, as cited in Dourson and Stara 1983), arsenic and fluorine (Lehman and Fitzhugh 1954). Dourson and Stara (1983) concluded that although separate factors of 10-fold for interspecies and intraspecies response adjustments for chronic data appeared reasonable, more experimental data were needed. They believed that intermediate UFs of less than 10-fold for individual factors or less than 100-fold for combined factors could be used to estimate the ADI and may be developed on a logarithmic scale (e.g., 31.6 being halfway between 10 and 100 on a logarithmic scale). 

A major source of confusion contributing to the debate on the safety of pesticide residues in food, and low-level exposure to environmental chemicals, is the relationship between a chemical exposure or dose and the observed effect. Some pesticides to which we are exposed in our fruit and vegetables are capable of causing harm to humans if given in high enough quantities. This is usually limited to occupational exposure where high toxic doses may actually be encountered. If the need for statistical analysis to rule out chance effects is the first scientific tenet that forms the cornerstone of our modern science-based medicine, the dose-response relationship is the second. 

Due to seasonal use of these compounds, human exposure is often transient, lasting only 3-6 months per year for some occupationally-exposed groups (such as farmers and sprayers). Intermediate studies in humans and animals or evaluations of workers using these agents would contribute greatly to the database concerning systemic and other health effects. These studies might also aid in the identification of dose-response relationships for effects from exposures to these pesticides. 

Epidemiological studies in occupationally-exposed pesticide workers typically involve exposure to a wide variety of pesticides. Therefore, it is impossible to ascribe the observed effects solely to maneb or mancozeb exposure. Additional epidemiological studies are necessary to more fully define the potenhal spectrum of systemic effects associated with these specific pesticides and to build a database from which dose-response relationships can be more fully defined. 

Cl 1.6-2.8) (Table II) (12). A dose-response relationship was demonstrated by years of exposure. However it was not possible to link the increased lung cancer risk to any particular pesticide or group of pesticides. A random sample of study subjects did not smoke more than a general population sample. 

Based on these principles, quantitative and qualitative toxicology data on pesticides are generated from animal studies and extrapolated to sian. The extrapolation, however, is usually not direct and stay include several assumptions. Species susceptibility, species metabolism differences, and extrapolations of dose response relationships below the experimental range should be considered (7 ). In a work situation, the husian body burden is determined by the exposure, absorption, and excretion rates. The same is true in animal studies, although continuous exposure is usually incorporated in the study design. Absorption is usually considered relatively complete. Excretion rates are usually specific to the physico-chemical properties of the chemical and the species however differences in excretion rates are not usually incorporated into extrapolations to man ( ). 

Keywords-. Toxins, dose-response relationship, endocrine disruption, pesticides, chemical resistance, epigenetics, chemical regulation, persistent organic pollutants (POPs),... 

Assess the basic data base, identify the need and type of additional testing for pesticide registration Human health and ecological exposures of new chemicals and consumer products Fate and aquatic toxicity of new chemicals Aquatic toxicity testing of new chemicals utilizes dose-response relationship to predict evaluation of new chemical s impact. 

It is possible to use chemicals such as DDT effectively and responsibly, as has been illustrated, and this particular substance has been of enormous benefit to humans. A little more care and respect for the chemical when it was introduced would have improved the risk-benefit balance. The example of DDT again illustrates that recognition of the principle of Paracelsus is vital in the use of chemicals, especially those intended as pesticides. We know also that the relationship between the dose and the effect is different in insects and in other species. Therefore using less DDT would still have been effective but have caused fittle, if any, harm to other species. 

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