Antagonism and Synergism

Chronic experiments using combined exposures to multiple carcinogenic metals, such as would occur most frequently in human exposures (Waalkes and Oberdorster 1990), have not been carried out with cadmium. However, cadmium can both enhance and antagonize the carcinogenic effects of several organic carcinogens (Harrison and Heath 1986 Kurokawa et al. 1985 Wade et al. 1987 Waalkes et al. 1991c). The incidence of diethyl- 

One compound may be toxic when used alone, and another may not. If a combination of the two is more toxic than the insecticidal compound alone, synergism is said to occur, and the nontoxic compound is the synergist. Several important synergists that can increase the toxicity of insecticides contain the active moiety methylendioxyphenyl (MDP)  

Examples of these include sesamin and sesamolin, both active principles of sesame oil, and piperonyl butoxide (PBO) and sesamex, both synthetic products. Although initially developed for use with pyrethrins, they have since been observed to synergize some, but not all, carbamates, organophosphates, pyrethroids, and organochlorines. In addition to the MDP compounds, another type of synergist called MGK 264 was developed to synergize the toxicity of pyrethroids and rotenone. The structure of piperonyl butoxide and MGK 264 are as follows  

It is now known that these compounds act by inhibiting cytochrome P450 monooxygenases (detoxification enzymes), which metabolize insecticides, resulting in the accumulation 

Parathion to paraoxon 218X Phorate to phorate sulfoxide 6X Phorate to phorate sulfone 21X Aldicarb to aldicarb sulfoxide 76X Aldicarb to aldicarb sulfone 17X 

Insecticide Alone (A) LCW (% w/v) With 1% sesamex (B) Synergistic ratio (A/B) 

Chemical modifiers of the action of selected herbicides can interact with the respective herbicides either outside or inside the target or nontarget plant species. Interactions may also occur before application while herbicides are mixed with other herbicides or auxiliary chemicals in the spray tank. Chemical or physical incompatibility of herbicide mixtures has been reviewed elsewhere and is outside the scope of this chapter. 

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E. D. Wed, "Additivity, Synergism and Antagonism in Flame Retardancy - Recent Developments," paper presented at 3rdMnnualBCC Conference on... 

Schinazi RF (1991) Combined therapeutic modalities for viral infections - rationale and clinical potential. In Chou TC, Rideout DC (eds) Synergism and antagonism in chemotherapy. Academic, Orlando, FL, pp 110-181... 

Magos, L. and M. Webb. 1979. Synergism and antagonism in the toxicology of mercury. Pages 581-599 in J.O. Nriagu (ed.). The Biogeochemistry of Mercury in the Environment. Elsevier/North-Holland Biomedical Press, NY. 

In many cases, adequate information about the underlying mechanisms of combined actions is not available. This led Berenbaum (1985, 1989) to propose three classes of combined action zero interaction, synergism, and antagonism. 

Environmental/Health/Safety Constraints Combination effects include both synergism and antagonism. These constraints combine the following activities ... 

Weil, E.D. "Addilisitv. Synergism and Antagonism in Home Retardaney — Recent Developments." paper presented ai Jni Annual RCC Conference on Recent Advances m Flame Retardaney of Pidymerie Materials. Stamford, Conn., May 19-21, 1992. 

Additives interact in a variety of ways, both in the bulk oil and on surfaces. Knowing the nature of additive interactions and their impacts on performance can help in oil formulations and improve lubricated systems. Additive interactions in the bulk phase have been particularly useful in understanding synergism and antagonism between different classes of additives. Many of these interactions affect processes on surfaces. 

As an addition compound was reported to be formed193 between thorium salicylate and an undissociated salicylic acid molecule, addition of neutral donors to salicylic acid or other carboxylic acids may give regions of synergism and antagonism with tetravalent ions also, as with U(VI). No study however has been reported on this. 

In the extraction of Np(IV), from nitiric acid, by carboxylic acid-TLA mixtures, both synergism and antagonism were observed60, as in the case of U(VI). 

Koster R. Synergism and antagonism between physostigmine and diisopropyl fluorophosphate in cats. /. Pharmacol. Exp. Then, 1946, 88, 39-46. 

Thus, synergisms and antagonisms are defined in quantitative terms, in relation to a specific additivity expectation. The additive effects of a combination of chemicals that can be calculated by using CA or IA serve as a point of reference for identifying a synergism or antagonism. 

Interaction Chemicals influence each other by physical, chemical, or biological means before or after reaching the molecular site of toxic action. Toxicological interactions are responses that deviate from those expected under some definition of additivity (e.g., following the concepts of IA or CA). The most commonly used terms for interaction are synergism and antagonism. ... 

Figure 9.13 Synergism and antagonism of insecticides by piperonyl butoxide.

Table 9.14 Synergism and antagonism of some phosphorothioates by sesamex against houseflies...

Toxicity, Synergism, and Antagonism in Anaerobic Waste Treatment Processes... 

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