Antagonism between toxicants

Sunda, W. G. and Huntsman, S. A. (1996). Antagonisms between cadmium and zinc toxicity and manganese limitation in a coastal diatom, Limnol. Oceanogr., 41, 373-387. 

Patynowski et al. (2002) showed that yeasts produce an unidentified inhibitory factor (maybe a toxic metabolite) that could be responsible for the inhibition of bacterial growth. These results could explain the antagonism between yeasts and malolactic bacteria, since yeasts are known to produce compounds during alcoholic fermentation such as ethanol, SO2, medium-chain fatty acids and antibacterial proteins/peptides (Weeks et al. 1969 De Oliva et al. 2004 Comitini et al. 2005 Osborne and Edwards 2007). The nature and quantity of peptides and other molecules released by yeasts are different depending on winemaking techniques and the yeast strain. 

Mutual antagonism between both cations in a cation pair was not observed in many cases. Mutual antagonism is a situation where each cation of a cation pair can antagonize the toxicity produced by the other. For example, in the ammonium—sodium system antagonism was observed with ammonium as the toxic cation while synergism was observed when sodium served as the toxic cation. 

Arsenic. In general, arsenic antagonizes selenium toxicity (Levander 1977). This effect extends to selenium in sodium selenite and selenate, seleniferous wheat, selenocystine, and selenomethionine (Levander 1977). However, a very pronounced synergistic toxicity exists between arsenic and two... 

Because there is rarely actual data on the mixture of concern, an additivity approach (adding all the toxic effects of the individual components) is sometimes used. This approach involves a number of assumptions and has certain limitations due to the lack of consideration for potential synergism or antagonism between individual chemical compounds. Further research is needed on human health effects from chemical mixtures to more accurately predict the risks involved in these common environmental situations. 

Sulfur has an antagonistic effect on several essential trace elements. Excessive amounts of sulfur can induce a secondary deficiency of copper (mainly in animals), cobalt and selenium. Ho vever, not only the sulfur amino acid cysteine but also sulfate eliminates the adverse effects of copper-, cobalt-or selenium-based toxicities (Baker and Czarnecki-Maulden 1987). Sulfate increases the urinary loss of selenate, but not of selenite this explains the assumption that there is a direct antagonism between sulfate and selenate (Schrauzer 1998). 

Chemical analyses revealed no specific components as the cause of observed toxicity. Antagonism between sea salt and toxic chemicals is hypothesized to cause differential toxicity at varying salinities, as opposed to differential solubility of the toxicants. Extrapolation of laboratory results indicates that proposed tire reefs should not pose a serious threat to water quality in Chesapeake... 

Allows for (1) interactions between contaminants in complex sediment mixtures (additivity, antagonism, synergism) (2) actions of unmeasured toxic chemicals (3) actions of other stressors (physical, biological). 

Whereas small molecules employ p450 activation/inhibition profiles to elucidate metabolic interactions/antagonisms, there is no comparable tool to model the potential interactions of multiple biologies or between biologies and cytotoxics. To assess potential interactions between a protein therapeutic and cytotoxic chemotherapy SOC, one approach is to conduct a single-dose PK interaction study to assess the impact of the protein therapeutic on the PK of the SOC cytotoxics in a pharmacologically relevant species (Table 25.2 [7,8]). The objective of these studies is to determine whether the protein therapeutic has an effect on the PK, particularly the peak concentration (Cmax) and/or time of peak concentration (Tmax) that might result in potentiation of the toxicity of the cytotoxic, or reduced efficacy associated with decreased exposure. 

The outcome of the interaction between chemicals in a mixture may be a toxic effect that is greater or smaller than expected from the toxicity of the single compounds. When a chemical is not toxic by itself, but causes another chemical to be more toxic, this is called potentiation. When a mixture is more toxic than expected from the toxicity of its individual compounds, this is termed synergism. Antagonism is used to indicate that a mixture is less toxic than expected from the toxicities of the individual components. In all cases, the interpretation of the mixture effects depends on the choice of the reference model. For that reason, it is important to discuss here in more detail the most commonly used reference concepts of CA and IA. 

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