Chemical mixtures additive effects

If workers are exposed simultaneously or successively to more than one chemical agent, the risk shall be assessed on the basis of the risk presented by all such chemical agents in combination. Usually, additive effects are assumed for the mixture of chemical agents, so the cumulative exposure is calculated as follows ... 

Other quaternary ammonium germicides, ben-zethonium chloride and benzalkonium bromide, have been used in several ophthalmic solutions. While these have the advantage of not being a chemical mixture, they do not possess the bactericidal effectiveness of benzalkonium chloride and are subject to the same incompatibility limitations. In addition, the maximum concentration for benzethonium chloride is 0.01%. Several new products that form gels in the eye, like Timolol Gel Forming Solution and Timoptic-XE, employ another quaternary preservative, BDAB, in the formulation. 

In some applications, it is necessary to inject nutrients or other chemicals into the aquifer to effect a more efficient restoration. Most of the time, additives are injected into separate wells. These additives may include surfactants, nutrients, pH adjustment chemicals, or additional carbon sources. Some success has been achieved with injected heated air to improve volatility of the chemicals. Where a small quantity of methane (as a primary substrate) is required, it can be added with the injection air. The lower explosive limit (LEL) of methane in air is 5% thus, extreme care must be used to control the mixture and the methane content of the vapor that reaches the surface. 

Several other nmr procedures have been used for the determination of fractionation factors. These have advantages in some systems. Instead of determining the effect of the concentration of an exchanging site on the averaged chemical shift, the effect on the averaged relaxation rate of water protons can be used in a very similar way (Silverman, 1981 Kassebaum and Silverman, 1989), For example, addition of the enzyme Co(ii)-carbonic anhydrase to an aqueous solution increases the observed value of XjT because the proton-relaxation rate is the average of that for the bulk solvent (cfl. 0.3 s ) and that for water bound to the cobalt ca. 6x 10 s ). The average is different in an H2O/D2O mixture if the bulk solvent and the Cobound solvent have different deuterium contents, and it has been used to determine a value for the fractionation factor of Co-bound water molecules in the enzyme. 

When epidemiological studies form the basis for the risk assessment of a single chemical or even complex mixtures, such as various combustion emissions, it may be stated that in those cases the effects of combined action of chemicals have been incorporated. Examples can, for instance, be found in the updated WHO Air Quality guidelines (WHO 2000). Thus, the guideline value for, e.g., ozone was derived from epidemiological studies of persons exposed to ozone as part of the total mixture of chemicals in polluted ambient air. In addition, the risk estimate for exposure to polycyclic aromatic hydrocarbons was derived from studies on coke-oven workers heavily exposed to benzo[fl]pyrene as a component of a mixture of PAH and possibly many other chemicals at the workplace. Therefore, in some instances the derivation of a tolerable intake for a single compound can be based on studies where the compound was part of a complex chemical mixture. 

For the purposes of estimating the potential toxicity of the chemical mixture, it is assumed the toxicity of the individual component compounds is additive. Data from the Registry of Toxic Effects of Chemical Substances (RTECS) and from the Hazardous Substances Data Bank will be accepted, as well as peer-reviewed primary data. 

There are other such scenarios that can be proposed. Evidence exists for both additive and synergistic actions. There is nothing magical about mixtures. The effects of mixtures can be explained in terms of the actions of the individual chemicals, all of which obey the usual physicochemical laws.3°... 

In several wood-preserving facilities, other wood preservatives such as creosote and chromate-copper—arsenate (CCA) have been used in addition to PCP (e.g., Lamar Glaser, 1994 Mueller et al., 1991a Mahaffey et al., 1991). Environmental contamination by chemical mixtures is likely in these sites. When PCP has been dissolved in an organic carrier such as oil, soil is also contaminated with the solvent (Trudell et al., 1994 Lamar Dietrich, 1990). Chlorinated dimeric impurities in technical CP formulations are also found in contaminated soil. Design of successful bioremediation must address the effects of other chemicals on CP biodegradation. 

Additive effect Effect of a mixture of chemicals whereby the summation of the known effects of individual chemicals is essentially additive. For example, if individual aqueous solutions of chemical A and chemical B each yield an IC50 = 50% v/v (or 2 toxic units) for a particular biotest, their combined toxicity will correspond to an IC50 = 25% v/v (or 4 toxic units). See also Additivity. Volume 2(1,10). 

Environmental exposures are present through the human lifetime. However, they may vary considerably over time at the same location, for example, because of the local or global changes in emission and environmental pollution levels. Environmental exposures of humans consist of exposures outdoors and indoors as well as at workplaces these environments may significantly differ. The exposure media include air, water, and soil and dust. Historically, research on human exposures to chemicals and associated health effects has been conducted mostly on single chemicals. In addition, several studies have dealt with complex mixtures, such as diesel fuel and gasoline, by-products from coal combustion, and tobacco smoke. A common problem of complex mixtures is that the composition may vary from one exposure to another and, as a result, the associated toxicity may vary. For a better understanding... 

In summary, deviations from expected additive effects are well documented and can be assessed in terms of synergism or antagonism. In some cases, the mechanisms underlying such deviations are well understood. A typical case of interaction occurs when 1 substance induces toxifying (or detoxifying) steps effective for another mixture component, which in turn alters profoundly the efficacy of the second chemical. 

In some cases, the effects of complex environmental mixtures could be accounted for in terms of concentration-additive effects of a few chemicals. In sediments of the German river Spittelwasser, which were contaminated by chemical industries in its vicinity, around 10 chemicals of a cocktail of several hundred compounds were found to explain the toxicity of the complex mixture to different aquatic organisms (Brack et al. 1999). The complex mixture of chemicals contained in motorway runoff proved toxic to a crustacean species (Gammarus pulex). Boxall and Maltby (1997) identified 3 polycyclic aromatic hydrocarbons (PAHs) as the cause of this toxicity. Subsequent laboratory experiments with reconstituted mixtures revealed that the toxicity of motorway runoff could indeed be traced to the combined concentration-additive effects of the 3 PAHs. Svenson et al. (2000) identified 4 fatty acids and 2 monoterpenes to be responsible for the inhibitory effects on the nitrification activity of the bacteria Nitrobacter in wastewater from a plant for drying wood-derived fuel. The toxicity of the synthetic mixture composed of 6 dominant toxicants agreed well with the toxicity of the original sample. 

A classification of whole products would minimize the risk of not discovering possible additive and synergistic effect of chemical mixtures. A labelling of the risk of the whole product would be less confusing and increase the clarity of the risk communication to consumers. 

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