Test substance, characteristics

Four types of exposure conditions are employed in both acute and chronic tests and in both freshwater and saltwater media static, static-renewal (semi-static), recirculation, and flow-through. The choice for which test type to use usually depends on test substance characteristics, test duration, test species, and regulatoiy requirements. 

For studies involving test substance application to soil, there may be a requirement for more soil information than for studies where applications are made to foliage of established crops. The study protocol should describe any specific requirements relative to soil type selection and how to confirm the soil characteristics for the study. Most studies simply require that the soil be identified by its name (e.g., Keystone silt loam) and composition (e.g., percent sand, silt, and clay). This information can typically be acquired from farm records, a soil survey of the local area, or a typical soil analysis by a local soil analysis laboratory. In some instances, a GLP compliant soil analysis must be completed. The study protocol must clearly define what is needed and how it is to be obtained. Unless specified in the protocol, non-GLP sources are adequate to identify the soil and its characteristics. The source of the soil information should be identified in the field trial record. 

Chemical characteristics and environmental conditions will influence the design of fleld studies to assess distributions of occurrence and exposure." Important chemical characteristics of the test substance include water solubility. Aloe, vapor pressure, degradation rate and potentially labile functional groups. These characteristics also need to be known for toxicologically important fiansformation products. One shortcoming in many fleld studies is a failure to address adequately exposure to toxic transformation products. 

Tracer materials are defined as any product included in the test substance that can be recovered analytically for determining the drift from the application. This may be the active ingredient in an actual tank mix, or it may be a material added to the tank mix for subsequent detection. The selection of an appropriate tracer for assessing deposition rates in the field is critical to the success of a field study. Tracer materials such as low-level active ingredient products, colored dyes, fluorescent dyes, metallic salts, rare earth elements and radioactive isotopes have been used with varying degrees of success in the field. An appropriate tracer should have the following characteristics ... 

Effects elicited in vitro and in vivo by the particular test substance in question differ in their characteristics. 

In any type of ocular bum and later on rinsing therapy, we have found that the speed of the penetration was roughly correlated to the concentration of the corrosive and the type of corrosive. This question is still scientifically open but estimations of penetration of sodium hydroxide are from about 5-8 pm/s depth propagation into the tissues, derived from measurements of Rihawi et al. on rabbit corneas [43]. Theoretical work on penetration characteristics of different chemicals have been published by Pospisil and Holzhuetter [44]. They have proved that, in first order estimation, the chemical properties like molecular size and shape, partition coefficients, and the type of interaction with the intrinsic membrane parameters determine the penetration characteristics. In very good estimations, they have shown that, for a various set of test substances, the penetration is almost exactly predicted by their modelization. 

Current . ..Whether a test substance has any potential utility or to determine physical or chemical characteristics of a test substance. 

Study" means ary experiment in which a test substance is studied in a test system under laboratory conditions or in the environment to determine or help predict its metabolism, product performance (efficacy as required by 40 CFR 158.160), environmental and chemical fate, persistence and residue, or other characteristics in humans, other living organisms, or media. 

These assays are generally performed by applying a test substance to well characterized cell systems (e.g. bacterial or mammalian cell cultures) and evaluating changes in the growth and characteristics of the cells. This may involve assessing the speed with which colonies form and the size of the colonies as well as... 

The standardized guidelines have been compiled to cover test methods in animal studies and in vitro studies on absorption, distribution, metabolism cind excretion in the Notification No. 496 of the PAB in 1998. The guidelines can be applicable for the drugs to be submitted after October 1999. The following principles should be considered in order to select the most appropriate methods bcised on the characteristics of test substance. It is required that the exposure data related to toxicological studies be obtained before the first human study and other pharmacokinetic data before the completion of Phcise I study in principle in accordance with the guidelines on nonclinical safety studies for conducting clinical trials (Notification No. 1019 of the PAB, 1998). 

Experimental conditions of the in vitro and in vivo experiments differed and may have led to different effects than expected. These conditions include factors such as temperature or age, sex, and strain of animal Effects elicited in vitro and in vivo by the particular test substance in question differ in their characteristics Tests used to measure responses may differ greatly for in vitro and in vivo studies, and the types of data obtained may not be comparable... 

In order to more easily design and ultimately interpret the results of a validation study, it is important to define two factors that define the reliability of an alternative method before the study starts. These factors are reproducibility and predictive capability of the alternative method. It is of critical importance that these performance factors are clearly stated before a validation study starts. When these performance characteristics are defined beforehand, they provide critical information needed to design the study so that it includes the appropriate number of laboratories, an acceptable set of test substances, and the appropriate range of toxicity. They also provide benchmarks that can be used to set the criteria that an alternative method must meet in order to be considered reliable. If the data obtained from the study meet or exceed these predefined performance criteria, then it confirms that the alternative method performs as described by its developers. If the method fails to perform at a level equivalent to the criteria set at the start of the study, then its performance cannot be confirmed. 

The other dominant technology is the polymerase chain reaction (PCR) system, which is a means of amplifying (i.e., rapidly growing) small quantities of bacterial DNA to reach critical mass for analysis. Since characteristic segments of DNA are a form of fingerprint for a microbe, this system is used to expand the quantity of a test substance to a level at which it can be assayed by DNA-sensing technology. 

The interpretation of the term maybe present in terms of the statistical confidence in the screening test result depends on the performance characteristics of the assay and the verification of reliable performance by a body of actual test application data. Nonetheless, the confirmation that the test substance actually is present in the sample requires independent determination. For method development purposes, screening tests should be considered a part of an analytical system for a given substance, where the complete system consists of a separate confirmatory technique to verify the initial screening result. 

Sampling Begins approximately 2 weeks after the microcosms are constructed and continues for 2 or 3 months after the last treatment with test material frequency depends upon the characteristics of test substance and on treatment regime... 

A typical battery of tests for a drug substance at this stage of development is shown in Table 1. At this stage, it is likely that individual impurities will not have been identified and that final detailed characterization of the structure will be tentative. Drug substance characteristics such as crystal state and polymorphism will not be well understood, and stability data will be limited. 

When using an internal standard, you should add an internal standard to the sample at the first stage in the extraction procedure, so that any loss or degradation of test substance during purification is accompanied by an equivalent change in the internal standard, as long as the extraction characteristics of the internal standard and the test substance are very similar. 

Van Dooren and Muller investigated in great detail by factorial designs the effects of apparatus, test substance, reference material, atmosphere (152), as well as heating rate and particle size (153,159,160) on results in quantitative DSC. The former set of experimental factors are called baseline-related characteristics if the curve is described using these parameters, large standard deviations should be taken into account. A baseline equation, based on heat balance considerations, is... 

The retardation time At = t — to (where to is the transit time of the carrier gas) is characteristic of the adsorbing power of the solid. If we compare two catalysts 1 and 2 with the retention times h and <2 and assume the conditions (1) that the concentration of the test substance is so small that no appreciable blocking of the adsorbing surface occurs (operation on the linear portion of the adsorption isotherm), (2) that only the adsorbing ability of the active centers and not their number is different, and (3) that the retention is due only to adsorption, then the heats of desorption Xj — X2 = AX are related to A[Pg.659]

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