Multiple Toxicity

In spite of the complexity of dealing with atmospheres containing multiple toxicants, considerable progress has been made in understanding some of the effects from studies using rodents. For example, it is fairly well agreed that carbon monoxide and hydrogen cyanide appear to be additive when expressed as fractional doses required to cause an effect (21,22). Thus, as a reasonable approximation, the fraction of an effective dose of CO can be added to that of HCN and the time at which the sum becomes unity (100%) can be used to estimate the presence of a hazardous condition. 

If more than one chemical is present in the workplace, one procedure is to assume that the effects of the toxicants are additive (unless other information to the contrary is available). The combined exposures from multiple toxicants with different TLV-TWAs is determined from the equation... 

Figures 7.7 and 7.8 show the dose-response curves generated at the species level for shoot weight and shoot length, respectively. Each dotted curve on the plot is species specific. For many species, multiple toxicity tests are available. The random...

Multiple substances may be responsible for toxicity if i) no single Phase I manipulation eliminates toxicity, but several cause a reduction, or ii) different treatments reduce or eliminate toxicity to different species. If multiple toxicants are suspected, combinations of the effective manipulations could be conducted in sequence on a single sample. If toxicity is eliminated in the combined manipulations (compared to an individual manipulation), then it is likely that multiple substances are responsible for toxicity. If the results are similar, then it is probable that all of the manipulations were successful in reducing the same substance. For example, if multiple toxicants are present and aeration and EDTA both removed some toxicity, the addition of EDTA to the post-aerated sample may suggest that metals contributed to toxicity (U.S. EPA, 1991a). 

Interpretation of test results Specific for each suspected toxicant. Interpretation is often different from the standard acceptance or rejection of a hypothesis judgement and experience of investigator will be critical to interpretation of results. The presence of multiple toxicants complicates interpretation. Focus on the toxicant that appears easiest to identify. Effects of effluent toxicants are not always additives at least one toxicant must be identified before additivity can be established. 

Analysis of results and selection of the number of streams to be treated and the treatment technology (or management option) to be used for each stream (e.g., TTE). If multiple toxicant sources have been identified, or if the toxicity tracking approach was used, the results from the process stream characterization can be analyzed to identify the streams representing the largest contributors (in terms of toxicity and chemical load) to the ETP (referred to as mass balance). The objective of the mass balance approach is to identify those streams that represent the largest contributors (in terms of toxicity and chemical load) to the final effluent or ETP (if one exists). This approach could be used if the identified toxicant is found in multiple streams, or if the substance(s) responsible for toxicity is only suspected, but has not been conclusively identified. In the latter case, the risk associated with source stream misidentification is increased. Key steps in mass balance approach include ... 

SED-TOX is an index that aggregates multiple toxicity data into an easily understandable and single value, the SED-TOX score. Although designed for the assessment of marine, estuarine and freshwater sediments, it could also easily be applied to soil samples, sludges and biosolids. This index can assist the environmental manager in the ... 

Table 5. Weight of evidence framework for integrating multiple toxicity lines of evidence.

Smith, C.J., Hansch, C., and Morton, M.J., QSAR treatment of multiple toxicities the mutagenicity and cytotoxicity of quinolines, Mutation Res., 379, 167-175, 1997. 

Lee CH (1994) A long-term leachability study of solidified wastes by the multiple toxicity characteristic leaching procedure. J Hazard Mater 38 65-74... 

Greene SL, Dargan PI, O Connor N, Jones AL, Kerins M. Multiple toxicity from 3,4-methylenedioxymethamphetamine ( ecstasy ). Am J Emerg Med 2003 21 121 1. 

LaFratta CN, Walt DR (2008) Very high density sensing arrays. Chem Rev 108 614—637 Wadkins RM, Golden JP, Pritsiolas LM et al (1998) Detection of multiple toxic against using a planar array immunoassay. Biosens Bioelectron 13 407 15... 

Hexachlorobutadiene is on the National Institute for Occupational Safety and Health list of suspected carcinogens because it has the potential to cause kidney and lung cancer. A group of 205 vineyard workers who were exposed seasonally to hexachlorobutadiene (0.8-30mgm in air over the fumigated zones) showed multiple toxic effects contributing to the development of hypotension, cardiac disease, chronic bronchitis, disturbances of nervous function, and chronic hepatitis. 

Although the toxic units and additive index are useful in determining toxicity in some cases, they have disadvantages. Their values depend on the relative proportion of chemicals in the mixture. Also, because of the logarithmic form of the concentration in log-linear transformations such as Probit and Logit, it is desirable to have a toxicity index which is logarithmic in the toxicant concentration. For these reasons, Konemann (1981) introduced a multiple toxicity index (MTI) ... 

Even the simplest model requires prior knowledge of the LCa) for each compound acting singly. The additive toxicity and multiple toxicity indices require an LC50 for the specific mixture as well as the singular compounds. Therefore, access to a large database or the ability to estimate toxicity will be extremely important. Of these two methods, the corrected sum of toxic contributions derived by Marking and Dawson appears to be the easiest to implement and to interpret. 

What is the multiple toxicity index What are the component parts of the equation used to calculate the index ... 

Fly ash from municipal waste and industrial waste incinerators contains polychlorinated dibenzo-p-dioxins (PCDDs), including tetrachlorodibenzo-/j-dioxin (TCDD) and polychlorinated dibenzofurans (PCDFs), which are lipophiles, and heavy metals, including chromium, copper, manganese, vanadium, and lead, which are hydrophilesJ29-31 These chemicals have multiple toxicities and are known to impact the human liver, immune system, respiratory system, thyroid, male reproductive function, and CNS J32 34l Several are human carcinogensJ32 35 Enhanced toxic effects are observed in the mixtures of some of theseJ21,22 36 The mixtures of toxicants present in fly ash are complex and the mechanisms for their action on the human body are largely unknown. It is known that occupational exposure to fly... 

Tobacco smoke is a complex mixture of more than 4000 different chemicals that has multiple toxic effects on the endocrine system. In... 

Huang Q, Jin X, Gaillard ET, Knight BL, Pack FD, Stoltz JH, Jayadev S, Blanchard KT. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants. Mutat Res 2004 549(l-2) 147-67. 

The SeKT battery was applied to polluted sediments from several German river systems. As control/reference sediments, tlie artificial sediment and the two natural sediments were used in all test systems. A wide variety of toxic effects were obtained. The inhibition values ranged between no effect and almost 100 %, depending on the test system and the sediment studied. Thus, an allocation of the sediment toxicity was possible for the range of sediments, based on the multiple toxic effects of the six test systems performed. 

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