Public receptor

Worst-case scenario. When considering the stationary source s worst-case scenario, there are selection factors to be considered. In addition to the largest inventories of a substance, the following conditions must also be considered smaller quantities handled at higher process temperatures and pressures, and proximity to the boundary of the stationary source. Sources must analyze and report additional worst-case scenarios for a hazard class if the worst-case scenario from another covered process affects a different set of public receptors than the original worst-case scenario. It is interesting to note that worst-case release data indicate that the distances and thus the populations that could be threatened are greater for toxic substances than for flammable substances. 

The EPA requires, in addition, periodic audits by the implementing agency, such as the state or local air permitting agency. The frequency of such audits would be based on (1) accident history, (2) quantities of regulated substances, (3) proximity to public receptors, and (4) hazards identified in the Risk Management Program [2(220)]. 

The offsite consequence analysis requires that the facility determine (1) the worst-case consequence distance, where all of the chemical is released under an F atmospheric stability condition and a wind speed of 1.5 m/s (meters per second) and (2) alternative release scenarios. This is done for each chemical. The worst-case and alternative release scenarios require that the toxic plume from the hypothetical spill be modeled to a toxic endpoint (in mg/m ) and the downwind distance to that endpoint be determined. The facility must also identify offsite receptors within the circle defined by the worst case and alternative release scenarios. Offsite receptors include public receptors (list population within circle, identify schools, commercial or industrial areas, etc.) and environmental receptors (wUdUfe sanctuaries, preserves, national forests, state parks, etc.). The facility does not need to consider the consequence of a toxic plume on the offsite receptors, only identify them. 

After the inherent hazards are reduced, layers of protection are frequently used to protect the receptors of the hazard—the public, the environment, workers, other processes, or the process itself (Figure 1.1). In the strictest sense, one could argue that the definition of inherently safer applies only to elimination or reduction of the hazard. In the broad sense, the strength of a layer of protection can be improved by features that are permanent and inseparable from that layer. Thus, layers of protection can be classified into three categories, listed in decreasing order of reliability passive, active, and procedural. A passive layer of protection can be described as inherently safer than an active... 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

Figure 17.8 Comparison of the antagonist potencies of some neuroleptics on different NT receptors. Data are shown for haloperidol (HAL), chlorpromazine (CPZ), clozapine (CLOZ) and risperidone (RISP) acting on dopamine Dj and D2, 5-HT2 (S2), alpha (0(2) adrenoceptors and cholinergic muscarinic receptors (M). The height of each column shows an average of the dissociation constants obtained from a number of publications (see Seeman 1990). The values, which can vary some fiftyfold, are expressed as the negative logarithms (i.e. 9 = 10 M,lnM) so that the higher the column, the more potent the compound. The order of potency of the four compounds at each receptor is shown alongside...

Deakin, JFW, Graeff, FG and Guimaraes, FS (1992) 5-HT receptor subtypes and the modulation of aversion. In Central Serotonin Receptors and Psychotropic Drugs (Eds Marsden, CA and Heal, DJ), Blackwell Scientific Publications, Oxford, pp. 147-174. 

Martonosi, A. (1975) In Biomembranes - Lipids, Proteins and Receptors, Proc. of a NATO Advanced Study Institute (Burton. R.M. and Packer, L., Eds.), pp. 369-.390, Bi-Science Publications Div., Webster Groves, Missouri. 

The best studied of the endocarmabinoids are anandamide (A -arachidonyl-ethanolamine, AEA)(1) and 2-arachidonylglycerol (2-AG)(2). Anandamide was first identified from porcine brain extracts by Devane and co-workers in 1992 [13], while 2-AG was first reported in 1995 to have been isolated from canine gut [14] and rat brain [15]. More recently, noladin ether (2-arachidonyl-glyceryl ether, 2-AGE)(3) [16], virodhamine (D-arachidonyl-ethanolamine)(4) [17] and A-arachidonyl-dopamine (NADA)(5) [18] were proposed as endogenous ligands for the cannabinoid receptors. In a subsequent publication, the authors failed to detect noladin ether in mammalian brains and questioned the relevance of this compound as an endocarmabinoid [19]. Anandamide, noladin ether and NADA have functional selectivity for CBi receptors, virodhamine is CB2 selective and 2-AG is essentially non-selective. 

Noladin ether (3) was recently isolated from porcine brain [16] and found to bind to the CBi receptor (/fj = 21.2 nM), to bind weakly to the CB2 receptor K, > 3 /iM) and it causes typical cannabinoid-like effects such as sedation, hypothermia, intestinal immobility and mild antinociception in mice [16]. This endocannabinoid had previously been synthesised independently by both Mechoulam and co-workers [176] and Sugiura et al. [173]. SAR studies of this endocannabinoid are lacking in the literature, however, a recent publication highlighted the importance of the tetra-unsaturated C20 chain... 

A series of 29 3-alkyl 5-arylimidazolidinones, or hydantoins, active at the CBi receptor has been published by Kanyonyo et al. [344] with a subsequent publication describing the relationship between the experimentally derived lipophilicity and proposed modes of binding for non-polar and polar hydantoins derivatives [345] (Table 6.49). 

Phencyclidine (1 -[1-phenylcyclohexyl]pi peridine HC1 PCP) and its active derivatives produce unique behavioral effects in animals and psychotomimetic effects in humans. Drugs of this class have been demonstrated to bind saturably, reversibly, and with high affinity to specific binding sites in brain (Hampton et al. 1982 Quirion et al. 1981 Sircar and Zukin 1983 Vincent et al. 1979 Zukin and Zukin 1979). These sites have been shown to exhibit a characteristic heterogeneous regional distribution pattern (Quirion et al. 1981 Sircar et al., submitted for publication Zukin and Zukin 1979) distinct from that of any other receptor type. 

Sircar R. Nichtenhauser, R. Ieni, J.R. and Zukin, S-R Characterization and autoradiographic visualization of 3H-(+)SKF-10,047 binding in rat and mouse brain Further evidence for sigma opioid/phencyclidine receptors commonality. Submitted for publication. 

ZuKin, S.R. Tempel, A. Gardner, E.L. and Zukin, R.S. Interaction of 3H(-)SKF-10,047 with brain sigma opioid receptors Characterization and autoradiographic visualization. Submitted for publication. 

Contreras, P.C. Quirion, R. O Donohue, T.L. Autoradiographic distribution of phencyclidine receptors in the rat brain using (3H)TCP. Submitted for publication. 

FDA, Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Life-Threatening Serotonin Syndrome , FDA Public Health Advisory (2006) http //www.fda.gov/Cder/Drug/advisory/ S SRI S S200607.htm... 

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