Toxicity indices

RI TSCA UCL UF WIPP WIPPLWA risk index Toxic Substances Control Act upper confidence limit uncertainty factor Waste Isolation Pilot Plant Waste Isolation Pilot Plant Land Withdrawal Act... 

To standardize the multivariate bioassay-derived data and facilitate their integration in the index, toxicity data are first converted into Toxic Units (TU), which are dimensionless ratios originally defined as the actual concentration of a particular toxic substance, divided by the incipient lethal concentration for that substance (Sprague and Ramsay, 1965). A similar term can be used to define the toxicity potential of a sediment sample, whereby ... 

Bombardier, M. and Bermingham, N. (1999) The SED-TOX index Toxicity-directed management tool to assess and rank sediments based on their hazard - Concept and application, Environmental Toxicology and Chemistry 18, 685-698. 

Because digitoxin has a very low therapeutic index, toxicity occurs rather routinely and can be fatal patients must be monitored closely. Moderate overdoses can be picked up by GI or CNS complaints however, more serious toxicity on cardiac rhythm is more difficult to distinguish from the effects of heart disease. Digitalis antibody fragments are available for serious toxicity, i.e., when cardiac arrest is imminent. The fragments bind the drug and are excreted by the kidneys. 

Z Therapeutic index = toxic dose/effective dose... 

Monitoring plasma aminoglycoside levels is important because these drugs have a low therapeutic index toxicity occurs when plasma levels are only three to four times higher than their minimal inhibitory concentrations. Decreases in renal function may elevate the plasma levels of aminoglycosides to toxic levels within a few hours. The answer is IE). 

Poor therapeutic index (toxic at therapeutic dose). Fever/chills, nephrotoxicity (reduce risk by hydrating patient), nausea, headache, thrombophlebitis (add heparin to reduce risk), anemia, hepatotoxicity, cardiotoxicity. 

Eigenmann [26] presents data on oxygen index, toxicity index and smoke density of polymers, which contain different flame-retardants. Other flame-retardant polymers can also be used. 

AIChE. DOW S Index toxicity. American Institute of Chemical EngineersNewYork. 1994... 

If the material in two process alternatives is both flammable and highly toxic, then they can be compared on both bases separately. If the assessments of the relative flammability and toxicity are in conflict, then we can only resort to a safety index. 

Workers in the metals treatment industry are exposed to fumes, dusts, and mists containing metals and metal compounds, as well as to various chemicals from sources such as grinding wheels and lubricants. Exposure can be by inhalation, ingestion, or skin contact. Historically, metal toxicology was concerned with overt effects such as abdominal coHc from lead toxicity. Because of the occupational health and safety standards of the 1990s such effects are rare. Subtie, chronic, or long-term effects of metals treatment exposure are under study. An index to safety precautions for various metal treatment processes is available (6). As additional information is gained, standards are adjusted. 

Fig. 1. Blood—drug concentration curve used to determine bioavailabiLitv and bioequivalence. C is the maximum dmg concentration in the blood and corresponds to some The AUC (shaded) represents the total amount of orally adininistered dmg the time from points A to B represents dmg onset, from points B to D, the duration MEC = minimum effective concentration MTC = minimum toxic concentration and TI = therapeutic index.

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

In several cases, such as shellfish areas and aquatic reserves, the usual water quaUty parameters do not apply because they are nonspecific as to detrimental effects on aquatic life. Eor example, COD is an overall measure of organic content, but it does not differentiate between toxic and nontoxic organics. In these cases, a species diversity index has been employed as related to either free-floating or benthic organisms. The index indicates the overall condition to the aquatic environment. It is related to the number of species in the sample. The higher the species diversity index, the more productive the aquatic system. The species diversity index is computed by the equation K- = (S — 1)/logjg I, where S is the number of species and /the total number of individual organisms counted. 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

As computing capabiUty has improved, the need for automated methods of determining connectivity indexes, as well as group compositions and other stmctural parameters, for existing databases of chemical species has increased in importance. New naming techniques, such as SMILES, have been proposed which can be easily translated to these indexes and parameters by computer algorithms. Discussions of the more recent work in this area are available (281,282). SMILES has been used to input Contaminant stmctures into an expert system for aquatic toxicity prediction by generating LSER parameter values (243,258). 

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