Identifying toxicity

In identifying toxicity, its class is followed by a number designating flammability. The identifying numbers are... 

Identification of Toxic Species. In trying to identify toxic species suitable for further studies, careful consideration should be given to zoology and, where applicable, clinical toxicology. Zoological knowledge allows the identification of the species which use toxins for purposes of offence and/or defense. For example, observations of carnivorous fish showed that many appear able to identify toxic species and avoid... 

Screening Techniques for Detecting Toxicity. Simple toxicity screening techniques are necessary to identify toxic species and to monitor the efficacy of isolation and purification procedures used to purify toxins. Atterwill and Steele 108) have recently comprehensively reviewed in vitro methods for toxicology and so much of the following is in the nature of a general overview. 

From this it can be decided whether it makes sense to identify toxicity risk using LD values determined for a means of penetration different from inhalation, skin or orally. If it does make sense, it will be possible to estimate risk although regulations did not provide any criteria. Note that on top of the space of variables mentioned above it is possible to have in this space bodies , which can be of help in interpreting axes. 

Immunotoxicity testing in rodents exposed to industrial and/or environmental chemicals, has been recognized as an important toxicological concern for over 25 years. Early immunotoxicity testing relied primarily on the mouse, due to the plethora of immune structure and function research performed by immunologists to better understand the human immune system. As such, the mouse has been the most employed rodent for immunotoxicity testing. Immune system function assays employed in screening for immunotoxicity were developed in adult mice. These same immune function assays have served to help identify toxicant induced immunosuppression in the rat. 

Shafer KH, Cooke M, DeRoos F, et al. 1981. WCOT capillary column GC/FT-IR and GC/MS for identifying toxic organic pollutants. Appl Spectroscopy 35 469-472. 

The gold standard for human studies is called the randomized, controlled clinical trial. Such trials are close to experimental animal studies, but for obvious ethical reasons, they cannot be conducted to identify toxicity. They are, instead, designed to determine whether certain pharmaceutical or nutritional regimens, for example, reduce the risks of disease. They may provide information about adverse side effects, but they are not designed for studying toxicity. 

Epidemiology studies are, of course, useful only after human exposure has occurred. For certain classes of toxic agents, carcinogens being the most notable, exposure may have to take place for several decades before the effect, if it exists, is observable - some adverse effects, such as cancers, require many years to develop. The obvious point is that epidemiology studies cannot be used to identify toxic properties prior to the introduction of a chemical into commerce. This is one reason toxicologists were invented ... 

The strength and quality of the scientific evidence regarding chemical toxicity, dose-response characteristics, and human exposures varies enormously among chemical products and pollutants. Some of the reasons for these differences were described in the chapters concerned with identifying toxicity. The problems encountered in the... 

Suppose there are several animal studies available for a chemical, including some which have involved long-term exposures, and some relating to possible reproductive and developmental effects. Assume data for both mice and rats are available, and that there are well-defined NOAELs for each of the identified toxicity endpoints. The lowest NOAEL from all those available derives from a chronic study, and is 10 mg/(kg day). Given such a data base, and the defaults listed above, a Dy for this chemical applicable to the general population, would be derived as follows... 

There are occasional outbursts of skepticism about the value of the risk assessment approach. Some argue its full use is overly burdensome, that the only real need is to identify toxic chemicals and then eliminate them or reduce their presence. Perhaps this approach is appropriate for a few chemicals that exhibit extremely high toxicity or that are excessively persistent and bioaccumulate in an environment, and for which there are reasonably good substitutes available. But as a general approach, it ignores the elementary principle that all chemicals will... 

Wong, D.C.L. van Compemolle, R. Nowlin, J.G. O Neal, D.L. Johnson, G.M. Use of supercritical fluid extraction and fast ion bombardment mass spectrometry to identify toxic chemicals from a refinery effluent adsorbed onto granular activated carbon. Chemosphere 1996, 32, 621. 

These 16 chapters, which discuss many of the present state-of-the-art techniques for monitoring toxic substances in the environment, bring together numerous different approaches for identifying toxic substances. The papers are not meant to represent a comprehensive review of each particular area of monitoring but rather to describe recently developed methodology with several examples of applications. 

Determination of amitriptyline plasma concentrations is not routinely recommended but maybe useful in identifying toxicity, drug interactions, or noncompliance (adjustments in dosage should be made according to clinical response not... 

Burgess, R.M. (2000). Characterising and identifying toxicants in marine waters a review of marine Toxicity Identification Evaluations (TIEs). International Journal of Environment and Pollution, 13, pp. 2—33. 

Mechanistic toxicology examines the biochemical processes by which identified toxicants have an impact on the organism. 

Recommendation 3b. The Army should identify toxic agent reaction products likely to be present at potentially harmful levels in liquid-phase process streams, liquid wastes, and solid wastes, including waste streams generated during closure activities. 

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 ... 

The selected case study (Section 7) demonstrates the hazard potential of river sediments. In numerous investigations, pT-values were generated for sediments and dredged material of the rivers Rhine (with its tributaries Moselle and Saar), Ems, Weser, Elbe, Oder and their estuaries, as well as the North and Baltic Seas. Several pT-values were also generated for sediments in the Sepetiba Bay (Federal State of Rio de Janeiro, Brazil) to identify toxic areas. Again, the pT-method was used as an ecotoxicological discriminator to map out sediment quality in polluted zones (Soares and de Freitas, 2000). 

Samples to be screened for further chemical monitoring tests and/or tests for identifying toxic substances... 

Detecting and identifying toxic compounds in environmental samples (compounds with unknown structures and properties) require the use of time-consuming, costly methods to isolate them from the matrix, then the application of complex techniques to separate the compounds present in an extract, and finally the determination of their structure (identification). Applying such a procedure to all samples collected from a selected area is very expensive. Samples therefore need to be selected, for example, with the aid of the results of ecotoxicological tests samples with the determined toxicity may contain toxic compounds. 

The sponsor should consider evaluating forced degradation products in animal studies to determine if they present a toxicity issue, and, if so, an appropriate limit to ensure safety. Failure to identify toxic degradation products early in the development program can be costly mistake if the drug has to be abandoned later because of potential toxicity concerns. 

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