Toxicity expression

The interplay between the chemical and biological properties of the threat agent, on the one hand, and the specific attack scenario, on the other, can influence the lethality of the attack. Table 2-2 shows the relative respiratory toxicities (expressed as the lethal concentration of toxin at which 50 percent of test animals are killed, or LCT50, in milligrams per minute per cubic meter) of a variety of toxic gases compared with chlorine gas, which was used as a chemical weapon in World War I. According to Table 2-2, the nerve agent sarin (GB) has a respiratory toxicity approximately 100 times that of chlorine, while sulfur mustard (HD) is about 7 times more toxic. However, the lethality of an attack... 

The nature of an effect includes the adversity of the toxicity expressed as the level of and the basis for NOAEL and LOAEL values (Section 4.2.2), and the severity of the specific endpoint or key event (Section 4.2.3), for example judging skin irritation less severe than teratogenicity. An additional assessment factor for severe and/or irreversible effects has been proposed by various groups. This section gives an overview of such proposals and evaluations. Then, the key issues are summarized and our recommendations are presented. 

Table 7 Example application of process in Box B to evaluate the risk of dioxins in Dutch sediments. No observed effect (NOEC) concentrations for chronic toxicity of dioxins in vertebrates (immune, reproductive and developmental toxicity) expressed as internal concentration (ng TEQ/g Iw). The sediment to fish bioconcentration factor is set at 4 (ng TEQ/g Organic Carbon to ng/g lipid weight in fish) based on Traas et al. (2001). Based on a species-specific biomagnification factor (BMP) from fish to animal (ng TEQ/g Iw) the internal NOEC is extrapolated to a NOEC in sediment. These data are used to construct the SSDs in Figures 5 and 6.

Diuron Cellumen Mitochondrial membrane potential (72 h) Mitochondrial toxicity Expression 99.90 7.58... 

Where n is the number of bioassays exhibiting calculable (geno)toxic response, N is the total number of bioassays carried out, Ti is (geno)toxicity expressed in TU of each test before or after samples have been submitted to a biodegradation procedure and Q is the effluent flow. PEEP values reflect an index varying from 0 ad infinitum in theory, but which in practice does not exceed 10 for effluents. 

Matsumura F. 1994. How important is the protein phosphorylation pathway in the toxic expression of dioxin-type chemicals Biochem Pharmacol 48 215-224. 

Apart from this classic approach, it would be possible to improve the properties of known CWs, e.g. microencapsulation so that less stable or highly volatile substances can be used. Nanotechnology offers new possibilities, as described recently by Price and Peterson (2008). The other option is to improve penetration using known enhancers like dimethyl sulfoxide (DMSO). While the percutaneous toxicity (expressed as LD50 in rats) of one of the toxic organophosphates - O-isopropyl 5-2-diisopropylaminoethyl methyl phosphnothiolate - is 59.1 P-g/kg, in mixture with DMSO this value is decreased to 10.1 pg/kg (Bajgar, 1989). 

Ethyl benzene is only moderately aquatically toxic expressing LC50 values in the range of 40-100mgl for bluegill, fathead minnow, and grass shrimp. 

Fig. 2. Toxicity assay. (A) Toxicity of test compounds and uninfected cells stained with crystal violet. The densitometry of these wells allows quantitation of stain uptake, and thus of compound toxicity, expressed as a percentage of the density of the no drug control. (B) Toxicity of compounds D, E, and F. Compound E is not significantly toxic at any concentration tested. Compound D has a TC50 of 46 pM compound F has a TC50 of 30 pM (interpolated values).

Therefore volume of culture counted (1 x 1 x 0.1 mm) = 0.1 mm3 = 0.1 pL Therefore number of cells/mL = count x 104 For detecting selective toxicity, express the count as % dead cells. 

Figure 10. Relationship between vapour pressure and the relative percutaneous toxicity (expressed as the ratio of the percutaneous LD50 to the intravenous LD50) of four nerve agents (VX, GF, GD and GB indicated by solid circles). A notable exception to this relationship is GA (indicated with a solid triangle) which may undergo dermal metabolism prior to systemic absorption...

Genetic conditions, including cystinosis, cystinuria, and tyro-sinemia, and deficiencies of vitamins C and E or selenium increase the risk for mercury poisoning (Calabrese 1978 Goetz 1985). Vitamin E and selenium reduce the toxic expression but not the accumulation of mercury (Goetz 1985). 

FIGURE 7.6 Simulated vole population depression with decreasing toxicity (expressed as NOEL) for a vinclozolin-like pesticide. Halving the NOEL led to a linear decrease in population impact. 

In particular, three-dimensional tissue constructs with human cells have opened a new avenue for tissue engineering for pharmaceutical and pathophysiological applications (8). These technologies have a great potential to estimate the dynamic pharmacological effects of drug candidates, metastasis processes of cancer cells, and toxicity expression of nanomaterials. 

Chapter 12 presents a critical discussion of Pb neurotoxicity in human populations. This is broadly held to be the most significant toxic expression of Pb exposures in sensitive human populations, notably developmental neurotoxicity in utero and in the early postnatal developmental window in infants, toddlers, and even older children. Two factors defining effect... 

Lead toxicokinetics serves two critical roles in the delineation of lead toxicity. First, it provides the kinetic imderpinnings for expressions of lead intoxication in humans and other species. The rate of Pb entry into, and deposition within, tissues and cellular organelles is a prerequisite for toxic expressions with differing Pb exposiures. 

PbP is the pathway by which Pb that is absorbed from receiving compartments or is resorbed from bone stores is transferred to target tissues or is excreted. Compared to the history of PbB as a widely accepted biomarker of Pb exposure, consensus acceptance of PbP as a potentially useful biomarker is relatively recent (NAS/NRC, 1993 U.S. EPA, 1986). There are two reasons for this. First, analytical methodological problems for measuring PbP on a routine basis are daunting. Second, while PbP is qualitatively assumed to be the more direct biomarker of dose in dose—toxic response relationships than PbB, quantitative expressions of these relationships are largely lacking. That is, what level of PbP is linked to what toxic expression(s) in dose—toxic response relationships ... 

Do ALA-D variants affect the degree of toxic expression of lead in exposed subjects, particularly by raising or lowering the PbB threshold in... 

Substances and preparations are generally classified according to the product s toxicity, expressed as LD q or LCjq. S)rmbols are used to indicate danger, accompanied by R phrases describing the danger and S phrases advising precautions. 

Chronic toxicity more t5 ically refers to adverse health effects which result fi om repeated and/or prolonged exposures. The specific toxicity expressed will be determined by the characteristics of exposure (route, duration, frequency, magnitude), the mechanism(s) of toxic action, and the shape of the dose-response curve. When the adverse health effect results from absorption of the hazardous agent and subsequent distribution to a target organ, the term systemic toxicity is often used. Metabolism may or may not be involved in systemic toxicity. 

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