Critical effect chemical

National Library of Medicine, NIOSH s Registy of Toxic Effects Chemical Substances (RTECS) database, Nov. 1994 rev. the data have not been critically evaluated. 

Organ-spcctfic Defining organ-specific effects and defining chemically induced critical effects... 

For chemicals in general the identification of a potential hazard normally arises from the application of in vitro tests or from short-term toxicity studies undertaken in laboratory animals (up to a period of 90 days in the case of the rat where the test material normally should not exceed 1% of the total diet). This usually enables a critical effect to be assessed. 

Coenzymes are densely functionalized organic cofactors capable of catalyzing numerous diverse chemical reactions. Nature exploits the intrinsic chemical reactivity of these molecules to extend the chemical fimctionaUty of enzymes well beyond the reactivity of the coded amino acids. When these constituents are incorporated via covalent or non-covalent interactions into coenzyme-depen-dent enzymes, the inherent reactivity of the co enzyme is augmented and directed to effect chemical transformations with substrate and product selectivities, rates, and yields that are unachievable by either the protein or coenzyme alone. Thus, coenzymes play a critical role in the execution of a large number of essential metabolic processes. 

These two definitions reflect two sides of the same situation. In this book, the term critical effect(s) will be used for the hazard/effect considered as being the essential one(s) for the purpose of the risk characterization, e.g., for the establishment of a health-based guidance value, permissible exposure level, or Reference Dose. It should be noted that the critical effect could be a local as well as a systemic effect. It should also be recognized that the critical effect for the establishment of a tolerable exposure level is not necessarily the most severe effect of the chemical substance. For example, although a substance may cause a serious effect such as liver necrosis, the critical effect for the establishment of, e.g., an occupational exposure limit could be a less serious effect such as respiratory tract irritation, because the irritation occurs at a lower exposure level. 

The assessment factors generally apphed in the estabhshment of a tolerable intake from the NOAEL, or LOAEL, for the critical effect(s) are apphed in order to compensate for rmcertainties inherent to extrapolation of experimental animals data to a given human situation, and for rmcertainties in the toxicological database, i.e., in cases where the substance-specific knowledge required for risk assessment is not available. As a consequence of the variabihty in the extent and nature of different databases for chemical substances, the range of assessment factors apphed in the establishment of a tolerable intake has been wide (1-10,000), although a value of 100 has been used most often. An overview of different approaches in using assessment factors, historically and currently, is provided in Section 5.2. 

For threshold effects, a Tolerable Daily Intake (TDI) is calculated by dividing the NOAEL (or LOAEL) for the critical effect(s) with an overall UF. The current practice according to the D-EPA in relation to the setting of quality criteria for chemical substances in soil, drinking water, and ambient air is to divide the overall UF into three categories (D-EPA 2006) ... 

Although the overall HI is quite similar, this example Ulustrates that the contribution of each chemical is highly dependent on the AF. Moreover, the method does not reflect that the components of the mixture do not all have the same critical effect. 

The need for identifying the chemical is always a waste of time, which delays the critical effect of rinsing. 

A chemical may constitute a number of hazards of different severity. However, the primary hazard (or critical effect) will be the one used for the subsequent stages of the risk assessment process. For example, a chemical may cause reversible liver toxicity at high doses but cause tumors in the skin at lower doses. The carcinogenicity is clearly the hazard of concern. 

Risks linked with chemical processes are diverse. As already discussed, product risks include toxicity, flammability, explosion, corrosion, etc. but also include additional risks due to chemical reactivity. A process often uses conditions (temperature, pressure) that by themselves may present a risk and may lead to deviations that can generate critical effects. The plant equipment, including its control equipment, may also fail. Finally, since fine chemical processes are work-intensive, they may be subject to human error. All of these elements, that is, chemistry, energy, equipment, and operators and their interactions, constitute what we call process safety. 

Oregonator and "brusselator studied in detail by the Prigogine school were nevertheless extremely speculative schemes. A study of the behaviour of classical chemical kinetics equations assumed a high priority in order to select the structure responsible for the appearance of critical effects. The results of such a study, described in Chap. 3, can be applied to interpret critical effect experiments. 

Most of the critical effects in oxidation reactions over Pt metals were observed under isothermal conditions. Hence the complex dynamic behaviour can be directly due to the structure of the detailed catalytic reaction mechanism, specifically to the laws of physico-chemical processes in the "reaction medium-catalyst systems. The types and properties of mathematical models to describe critical effects are naturally dependent on those physico-chemical prerequisites on which these models are often based [4, 9], Let us describe the most important factors used in the literature to interpret critical effects. 

The current status of the models of fluctuational and deformational preparation of the chemical reaction barrier is discussed in the Section 3. Section 4 is dedicated to the quantitative description of H-atom transfer reactions. Section 5 describes heavy-particle transfer models for solids, conceptually linked with developing notions about the mechanism of low-temperature solid-state chemical reactions. Section 6 is dedicated to the macrokinetic peculiarities of solid-state reactions in the region of the rate constant low-temperature plateau, in particular to the emergence of non-thermal critical effects determined by the development of energetic chains. 

Thinking Critically A chemical process called crosslinking forms covalent bonds between separate polymer chains. How do you think a polymer s properties will change as the number of crosslinks increases What effect might additional crosslinking have on a thermoplastic polymer ... 

Critical effect A chemical often elicits more than one toxic effect, even in one species, or in tests of the same or different durations. The critical ef-fect(s) is the first adverse effect(s) or its known precursor(s) that occurs as dose rate increases. The critical effect(s) may change among toxicity studies of different durations, may be influenced by toxicity in other organs, and may differ depending on the availability of data on the shape of the dose-response curve. 

As risk assessment scientists continue to accumulate and develop knowledge of toxicokinetics, toxicodynamics, mechanisms of toxicity, and temporal effects of critical effects for various chemicals, evaluations become increasingly more accurate and detailed. Moreover, the science behind the use of UFs has progressed considerably. Increased understanding of... 

The development of AL values can aid the component-based approaches to risk assessment based on dose addition. AL values can be developed for the critical effect and for secondary effects. For chemicals with older AL values developed from point estimates of the POD (e.g., NOAEL values), when more recent and more thorough dose response data are available, the AL should be re-derived using more advanced (i.e., benchmark dose analysis) approaches to estimating the POD. 

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