Time critical target

The efficient and immediate response to time critical targets (targets that move) has become increasingly important for an effective defense strategy. 

Legierse KCHM, Verhaar HJM, Vaes WHJ, De Bruijn JHM, Hermens JLM. 1999. Analysis of the time-dependent acute aquatic toxicity of organophosphorus pesticides the critical target occupation model. Environ Sci Technol 33 917-925. 

Today, selected targets of interest are transferred to the HTS aiming at discovering a hit , and subsequently a lead structure within one to two months. After that time, the target concerned is replaced by a new one. Thus, rapid characterization and structure elucidation of the active principles of interest from natural sources are critical with reference to competition with synthetic libraries of pure and structurally defined compounds. Elaboration of LC-MS and LC-NMR techniques to accelerate structure elucidation of bioactive principles from natural sources is currently underway. Combination of these techniques with databases comprising a maximum of known natural compounds will probably contribute substantially to more interest in natural products for application in drug discovery. 

Studies in animals confirm that the upper respiratory tract is a critical target for airborne formaldehyde. Studies of monkeys, rats, and mice exposed to concentrations in the range of 0.3-40 ppm for acute to chronic periods of time demonstrate that formaldehyde nonneoplastic effects are restricted to lesions (squamous metaplasia and hyperplasia) in the epithelium of the upper respiratory tract (Chang et al. 

The development of a VMP requires several decisions. If the facility is new, due consideration is given to determine, on time, the target dates for routine production to ensure completion of validation for facility approval otherwise manufacturing at risk is the alternative choice. The deadline determination provides ample opportunity to perform validation of utilities, critical equipment installation, and qualification prior to construction work. In addition, it provides a sufficient time frame to identify the critical processes and steps involved. The parameters critical for each step shall be established. The critical equipment required shall be determined. Critical processes, steps involved, parameters, and equipment are identified. For existing facilities, establish the criteria for revalidation based on known vulnerabilities and engineering projects in progress. 

A mathematical model of long-term toxicokinetics in humans has been developed [14,15]. Subsequently, a more detailed description of Cd toxicokinetics was formulated considering additional events that modify the behavior of Cd in humans [16,17]. The kidney and particularly the cortex, is considered the critical target tissue for Cd and its accumulation is of decisive importance for risk assessment. In long-term exposures (life-long) either a simple one-compartment model or a more multi-compartment model predicts that 1/3 to 1/2 of the total body burden accumulates in the kidney and that the concentration of Cd in the kidney cortex is 1.25 times higher than the average concentration in the whole kidney [8]. 

As a increases, a critical value " i-.iiiis reached each time the th layer of target atoms moves out of the shadow cone allowing for large-angle backscattering (BS) or small-/i collisions as shown in figure Bl.23.3. If the BS intensity 1, is monitored as a fimction of a, steep rises [36] witli well defined maxima are observed when the... 

CAAA Impact on Nonutility Power Producers. The SO2 and NO regulations being implemented as part of the CAAA of 1990 primarily target electric utiHty power plants. However, under Phase II of the CAAA, nonutiHty power producers will be requited to acquire emissions allowances for any SO2 being emitted from new faciHties. Although industrial emitters of SO2 and NO are not directly affected, the EPA did undertake a study to estimate what contribution industrial producers have on annual estimated SO2 production in the United States (10). The report found that annual industrial SO2 emissions would remain below the predeterrnined critical limit of 5.6 x 10 tons/yr until at least 2015 (10). Thus, the agency recommended no new controls for industrial SO2 emissions at this time. 

---