Toxicological testing requirement

TABLE 14.2. Toxicological Testing Requirements under EC Seventh Amendment (Directive 92/32/EC-Notiflcation of New Substances)... 

TABLE VI. TOXICOLOGICAL TEST REQUIRED WHEN RESIDUE LEVELS EXCEED 3PPM,THE DRUG IS A SUSPECT CARCINOGEN, OR THE DRUG IS EXPECTED TO BIOACCUMULATE... 

Conditions migration data (ppm) Toxicological tests required by the SCF Usual decision of the SCF... 

In countries like the United States, the development of a pesticide from initial discovery in the laboratory to marketing takes at least eight years. The costs of development have substantially increased in 1964 the cost was 2.9 million, but by 1987 it had risen to 50 million due to increasingly stringent environmental and toxicological tests required by the EPA. 

TABLE 11.12 Examples of Toxicological Tests Required for the Registrstlon of a... 

Kirkland, D. 1. (1993). Genetic toxicology testing requirements Official and unofficial views from Europe. Environ Mol Mutagen 21, 8-14 discussion 46-57. 

Shelby, M. D., and Sofuni, T. (1991). Toxicology testing requirements and the U.S.-Japan collaborative study on in vitro tests for chromosomal aberrations. Environ Health Perspect 94, 255-259. 

For toxicological tests requiring nonrodents, researchers choose species in which the organ systems of interest closely resemble those of humans. While the number of animals required also varies with each drug according to statistical principles (516a), table 6-1 shows the usual number for each type of toxicological test. 

The clinical studies proposed determine the duration of toxicology testing required, whether reproductive toxicology is required, and whether special toxicity tests due to the drug s route of administration are required. Prior to human exposure, in vitro tests for the evaluation of mutations and chromosomal damage are generally required. 

The analytical team is responsible for the analytical definition and method development to characterize the product candidate to meet toxicological testing requirements. 

Keywords Food packaging Food contact materials Food contact substances Migration Non-intentionally added substance Chemical risk assessment Toxicological testing requirements... 

Table 11.2 Toxicological testing requirements for food contact substances authorization in the European Union (EU), adapted from (Muncke 2009)... 

Focusing on validation process of in vitro methods, it is possible to underline some differences between tools for research and ones for toxicological testing. A research model is validated when there are some specific evidences confirming that the information from the model is able to correctly describe the process in the intact animal. Tools for toxicity testing are often used to evaluate safety hypothesis so they can be used without requiring in vivo confirmation. They are validated using a subset of well-known materials and, once validated, systems will be applied to new unknown materials or mixtures in order to evaluate their toxicity and compare their potential with other chemicals. 

Toxicology/Testing - toxicology/testing advisors to management and for testing requirements... 

The area of occupational toxicology has received a great deal of attention in the chemical industry. Historically, the chemical industry has focused on the occupational environment and developed many of our current toxicological methods to address health and safety concerns. However, since the mid-1970s the chemical industry has increasingly become subject to testing requirements relevant to the protection of the environment and the public at large, as mandated by Environmental... 

The development of a toxicological testing program for occupational health hazard evaluation requires consideration of (1) the compounds to be tested, (2) the stage of drug development at which testing occurs, (3) the specific tests to be conducted, and (4) the means for funding. 

Besides, the list also includes the Toxic Substances Control Act in the USA (1976). the Canadian Environmental Protection Act (1994 ), the Chemical Substances Control Law in Japan (1973), and the Australian Chemicals Act (1989). These regulations, which also affect pigments, demand that all new products be registered. Various toxicological test results have to be presented, depending on the country. The discussed legal requirements are supplemented by many other more or less specific environmental acts, not only in the countries thus mentioned, but also in practically all other industrialized nations. 

The major FDA concern came to be better comprehension of diethylene glycol s toxicology. The imminent trial in court required this. In a more basic sense, the crisis made FDA scientists aware of inadequacies in the state of the discipline. In constant contact with their peers at the AMA and at the University of Chicago and Johns Hopkins, a team of FDA scientists launched a project that "developed the first valid process for determining the comparative toxicity of compounds, a statistically based and legally defensible process that opened the door to modern toxicological testing methods" (77). 

Direct isolation of sufficient quantities of each metabolite for structural characterization, assay validation and pharmacological or toxicological testing from in vivo studies using biological specimens is, therefore, often impossible, particularly from dmgs with a low therapeutic index. Furthermore, many metabolites have structural modifications which are difficult to replicate by traditional chemical methods. A number of synthetic steps may be required to prepare such metabolites from the API, or, in the worst case, a completely new synthetic route may need to be developed. 

REACH is an extraordinarily ambitious program. There are discussions underway regarding proposals to limit the numbers of chemicals to be subjected to these requirements. The potential for toxicological testing on a massive scale raises questions about the availability of facilities to carry out such tests, and runs counter to the objective of reducing the numbers of animals used for such purposes. The need to accomplish REACH objectives without the overuse of laboratory animals has promoted discussion and research regarding the use of alternative methods to collect the necessary data tools such as in vitro tests and quantitative structure-activity relationships (QSARs) are being promoted, and this has led to substantial research efforts to test their predictive validity. Time will tell where all of this activity leads us. 

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