Toxicity quantitative measure

The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

Hazard, risk, failure, and reliability are interrelated concepts concerned witli uncertain events and tlierefore amenable to quantitative measurement via probability. "Hazard" is defined as a potentially dangerous event. For example, tlie release of toxic fumes, a power outage, or pump failure. Actualization of the potential danger represented by a hazard results in undesirable consequences associated with risk. 

The quantitative measurement of toxicity level is expressed by parameters like NOEL (no observed effect level), NOAEL (no observed adverse effect level), and ADI (acceptable daily intake). The NOEL values are divided by 100 to obtain ADI values. The 100 safety factor derives from 10 x 10, where the 10s represent the animal-to-human conversion rate and the human variability factor. Currently, the most useful index of safety is the ADI, expressed as milligrams of test substance per kilogram of body weight (ppm), with the recommendation not to eat more than the ADI per day. The FDA, EU, and WHO agree on the ADI principle. 

Anderson NL et al. Effects of toxic agents at the protein level quantitative measurement of 213 mouse liver proteins following xenobiotic treatment. 

A second approach to the problem of toxic potency measurement has been to expose laboratory animals, usually rodents, to the smoke from the combustion of small samples of a burning material. Measurement of their response to the smoke leads to one of several biological endpoints, such as the LC50 (the concentration of smoke lethal to 50% of the test animals). In this approach, the animals respond to all the toxicants that are present in the smoke. It presumes that rodent mortality can be related to human mortality or, more simplistically, that the relative toxicity of the smokes will be similar in humans and rodents. However, since the relative contributions of the individual toxic chemicals in the smoke are not determined, a quantitative relationship between man and rodent is impossible using this approach. 

The detection of a test gas using mass spectrometers is far and away the most sensitive leak detection method and the one most widely used in industry. The MS leak detectors developed for this purpose make possible quantitative measurement of leak rates in a range extending aaoss many powers of ten (see Section 5.2) whereby the lower limit = 10 mbar l/s, thus making it possible to demonstrate the inherent gas permeability of solids where helium is used as the test gas. It is actually possible in principle to detect all gases using mass spectrometry. Of all the available options, the use of helium as a tracer gas has proved to be especially practical. The detection of helium using the mass spectrometer is absolutely ( ) unequivocal. Helium is chemically inert, non-explosive, non-toxic, is present in normal air in a concentration of only 5 ppm and is quite economical. Two types of mass spectrometer are used in commercially available MSLD s ... 

They did not report the minimum lethal dose or any other quantitative measure of toxicity, but nobody reading their paper would have missed the fact that the compounds are violently poisonous. During World War II, research on the fluorophosphonates was carried on for military purposes, and Adrian and his coworkers in Britain noted the similarity between the physiological action of the fluorophosphonates and that of reversible inhibitors of choline esterase (Adrian et al., 1947). This led to a number of scientific investigations of the action of nerve gases on various esterases. 

Multi-element trace analysis is an important prerequisite for the quality assurance of foodstuffs with respect to the characterization of non-essential, toxic and essential (nutrient) elements as pollutions or as mineral elements relevant to health. Contamination with heavy metals such as Cd, Pb or Hg has become a serious problem with increasing environmental (artificial) contamination e.g., due to industrial pollution. The increasing use of inorganic mass spectrometric techniques (especially of ICP-MS) in the analysis of foodstuffs for multi-element analysis of trace elements or the detection of selected elements and species at a low concentration level has resulted from advances in very sensitive and quantitative measurements of metals, metalloids and several non-metals, including their speciation. 

Ehrlich provided a quantitative measure to accompany the concept that a therapeutic dose must be evaluated relative to a toxic dose. Although Ehrlich s chemotherapeutic index has been displaced by more precise measures of effectiveness and toxicity, the spirit of Equation 1.1 remains a central idea of modern drug discovery. Ehrlich s work in the field of medicine, especially in the area of autoimmune disorders, resulted in his sharing of the Nobel Prize in Medicine in 1908. 

To be complete, toxicity hazard assessment should consider the specific effects caused by wastewaters to a receiving stream. As applied thus far, the pT-method only provides a quantitative measurement of wastewater toxicity. 

In Phase II further effluent treatments are conducted to identify the specific substance(s) responsible for toxicity. Toxicity tests are combined with chemical analysis to obtain a quantitative measurement of the suspected toxicants. The objectives in Phase III are to confirm that the substances responsible for toxicity have been correctly identified, and ensure that all of the toxicity has been accounted for. A weight-of-evidence approach is used to confirm that the substances responsible for toxicity have been identified. In both Phase II and III there are many possible approaches to identifying and confirming the substance(s) responsible for toxicity. 

In the field of toxic substances which pollute our environment, special importance must be attached to the heavy metal lead, which, until the late eighties arose primarily from automobile exhaust [EWERS and SCHLIPKOTER, 1984], For quantitative measurement of the impact of this lead, it is essential to establish the correlation between the lead content of the plants and soils, the traffic density, and the distance from the road. 

Metabonomics (the quantitative measurement of time-related responses to stimuli within the body)17,18 may prove to be of some use to assess the potential of a material to elicit an irritant response following topical application. The concept being that certain stimuli change the metabolite profile in intermediate biochemical pathways. Analysis of body fluids such as urine, saliva, plasma, biopsy material, etc. produces a fingerprint of biochemical changes characteristic of the nature or site of a toxic (or other) effect. 

In addition to using PMs, predictions of toxic hazard can also be made by using structure-activity relationships (SARs). A quantitative structure-activity relationship (QSAR) can be defined as any mathematical model for predicting biological activity from the structure or physicochemical properties of a chemical. In this chapter, the premodifer quantitative is used in accordance with the recommendation of Livingstone (1995) to indicate that a quantitative measure of chemical structure is used. In contrast, a SAR is simply a (qualitative) association between a specific molecular (sub)structure and biological activity. 

Toxicity is measured by the concentration in mg liter-1 of a compound that causes the death of a certain percentage (usually 50 or 100%) of the test population of a chosen organism (e.g., silvery minnows) in a chosen time (e.g., 96 hours). For organic inhibitors, the higher the concentration needed to achieve a lethal dose of 50%, the less toxic the inhibitor. In Table 12.3 the actual lethal concentration (LC50) (at 96 hr) is compared with that calculated by means of a quantitative structure-activity relation (QSAR). The basic calculation is that of the distribution coefficient of the inhibition of the primary alcohol octanol. 

---