Test group

Protons are equivalent to one another and have the same chemical shift when they are m equivalent environments Often it is an easy matter to decide simply by mspec tion when protons are equivalent or not In more difficult cases mentally replacing a proton m a molecule by a test group can help We 11 illustrate the procedure for a sim pie case—the protons of propane To see if they have the same chemical shift replace one of the methyl protons at C 1 by chlorine then do the same thing for a proton at C 3 Both replacements give the same molecule 1 chloropropane Therefore the methyl protons at C 1 are equivalent to those at C 3... 

If the two structures produced by mental replacement of two different hydrogens in a molecule by a test group are the same the hydrogens are chemically equivalent Thus... 

When enantiomers are generated by replacing first one proton and then another by a test group the pair of protons are enantwtopic (Section 7 9) The methylene protons at C 2 of 1 propanol for example are enantiotopic... 

The concept of heterotopic atoms, groups, and faces can be extended from enantiotopic to diastereotopic types. If each of two nominally equivalent ligands in a molecule is replaced by a test group and the molecules that are generated are diaster-eomeric, then the ligands are diastereotopic. Similarly, if reaction at one face of a trigonal atom generates a molecule diastereomeric with that produced at the alternate face, the faces are diastereotopic. 

Replacing one of these protons by chlorine as a test group gives (/ )-2-chloro-l-propanol replacing the other gives (.S)-2-chloro-l-propanol. Enantiotopic protons have the sane chemical shift, regardless of the field strength of the NMR spectrometer. 

Enantiotopic (Section 7.9) Describing two atoms or groups in a molecule whose environments are nonsuperimposable mirror images of each other. The two protons shown in bold in CH3CH2CI, for example, are enantiotopic. Replacement of first one, then the other, by some arbitrary test group yields compounds that are enantiomers of each other. 

Despite these intense efforts to test different chemical modifications, there is so far little success in developing potent and safe antivirals. For hepatitis C virus (HCV), McHutchison et al. reported in vivo side effects of a 20-nucleotide PS-modified ohgonucleotide (ISIS-14803) (McHutchison et al. 2006). In a test group of 28 patients, only 3 patients responded to the treatment by a reduction in the HCV viral load. The researchers concluded that further studies are needed to evaluate this novel agent and its side effects. Previously, ISIS Pharmaceuticals reported a 3.8 log reduction in plasma virus in patients with chronic HCV infection, using ISIS-14803 (www.isispharm.com). 

In tire tests, therefore, a stiffer tire construction reduces the wear. The stiffer construction not only includes the carcass and belt (i.e., height to width ratio), but also the tread pattern and the stiffness of the tread compound. Therefore, a correct road test requires two identical vehicles, each equipped with a test group of four identical tires. If this is not possible at least one axle has to have identical tires. If this is not the case an average slip will balance the acting force on the axle. This will be larger for the stiffer tire than is required if both tires had the same stiffness and smaller for the softer tire. Hence, the result is falsified to the advantage of the softer tire. The same argument holds for multi-section tires. 

In rats, daily administration of 5 or 10 mg/kg doses of endosulfan by gavage in corn oil during gestational days (Gd) 6-14 or 6-19 produced a dose-related increase in maternal deaths in these test groups (FMC 1980a Gupta et al. 1978). 

No acute-duration oral MRL was derived for endosulfan because no suitable end point was available among the reliable acute-duration studies. The lowest LOAEL, 1.8 mg/kg/day, was for a serious end point, convulsions in pregnant rabbits, appearing 10 days after the start of daily gavage dosing in the EMC (1981) study. Because animals from both the control and the test groups developed ascites, and six rabbits were added without concurrent controls, the reliability of these results is questionable. 

The acceptable limits for toxic exposure depend on whether the exposure is brief or prolonged. Lethal concentration for airborne materials and lethal dose for non-airbome materials are measured by tests on animals. The limits for brief exposure to toxic materials that are airborne are usually measured by the concentration of toxicant that is lethal to 50% of the test group over a given... 

Jacobson et al. (1955) assessed the lethality of 1,2-dimethylhydrazine and 1,1-dimethylhydrazine in rats following a 4-h exposure. Lethality was assessed over a 14-d post-exposure variability in the response. For 1,1-dimethylhydrazine, an LC50 of 252 ppm was calculated, and an LC2o of 210 ppm (515 mg/m3) was estimated from the exposure-response graphs in the report. The exposure-response curve was steep (slope = 8.65 SE = 2.8), suggesting very little variability among the test groups. 

Screening for gestational diabetes mellitus utilizes the oral glucose challenge test. Groups at high risk are African Americans, Native Americans, Asian Americans, Latino Americans, and Pacific Islanders. 

During cardiac sensitization tests, groups of two purebred male beagle dogs were exposed to concentrations at 0, 2,600, 5,200, 10,000, or 21,600 ppm (Mullin 1977) or concentrations of 9,000, 12,000, 13,000, 14,000, 15,000, 18,000, 19,000, or 20,000 ppm for 5 min (Hardy et al. 1989a). The vapor was administered to each restrained animal via a face mask. Prior to administration of intravenous epinephrine challenge, no evidence for cardiotoxicity was observed at these concentrations. (See Section 3.4 for discussion of cardiac sensitization tests.)... 

Duplicates of each test group and quadruplicates of solvent or negative controls should be set up. The sensitivity of the assay is improved with larger numbers scored in the negative controls (Richardson et al., 1989). 

TABLE 7.2. Numbers of Animals for Chronic and Subchronic Study per Test Group... 

TEST GROUP (15) A. 0.1 ML Substance ID Closed Patch-48H B. 0.1 ml FCA ID Application of C. 0.1 ml Substance Substance + FCA ID Closed Patch-24H Substance Vehicle Closed Patch-24H Vehicle 0... 

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