Our pharmacokinetics department offers the clients a broad spectrum of high quality of services in the areas of in vitro ADME, in vivo pharmacokinetics and bioanalysis services, ranging from small molecules to large molecules, such as protein and antibody. The animal species involved in our services are non-human primate, canine, mice, rat, rabbit and hamster. Meanwhile, non-human primate experimental platform and isotope platform for protein/antibody are certified by the Shanghai Government. Email:marketing@medicilon.com.cn Web:www.medicilon.com
A scientific workshop was held in 2006 to discuss the use of in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) data in chemical bioaccumulation assessments for fish. Computer-based (in silico) modeling tools are widely used to estimate chemical bioaccumulation. These in silico methods have inherent limitations that result in inaccurate estimates for many compounds. Based on a review of the science, workshop participants concluded that two factors, absorption and metabolism, represent the greatest sources of uncertainty in current bioaccumulation models. Both factors can be investigated experimentally using in vitro adme test systems. A variety of abiotic and biotic systems have been used to predict chemical accumulation by invertebrates, and dietary absorption of drugs and xenobiotics by mammals. Research is needed to determine whether these or similar methods can be used to better predict chemical absorption across the gills and gut of fish. Scientists studying mammals have developed a stepwise approach to extrapolate in vitro hepatic metabolism data to the whole animal. A series of demonstration projects was proposed to investigate the utility of these in vitro–in vivo extrapolation procedures in bioaccumulation assessments for fish and delineate the applicability domain of different in vitro test systems. Anticipating research progress on these topics, participants developed a “decision tree” to show how in vitro information for individual compounds could be used in a tiered approach to improve bioaccumulation assessments for fish and inform the possible need for whole-animal testing. The accumulation of xenobiotics in fish and other aquatic biota is an issue of long-standing concern to industry, government regulators, the academic community, and the general public. Extensive research has been conducted to understand the chemical and biological processes that promote bioaccumulation, and detailed information is available for a small number of compounds, several of which are now banned from production and use. Increasingly, however, there is a need to perform less intensive assessments for a much larger number of compounds. Regulatory programs in Europe and North America are being revised to support the 2004 enactment of the United Nations Stockholm Convention (also known as the Persistent Organic Pollutants (POPs) Protocol), which governs the assessment, use, trade, release, and replacement of all persistent (P), bioaccumulative (B), and inherently toxic substances (iT), or PBiTs (UNEP 2006). For example, the Canadian Environmental Protection Act (CEPA) required the Ministers of Environment and Health to categorize the hazard of approximately 23,000 chemicals on a Domestic Substances List (CDSL) and, as necessary, conduct screening level assessments to determine whether they are “. . . toxic or capable of becoming toxic to the environment or human health” (Government of Canada 1999; the word “toxic” is defined in Part 5, Section 64 of the Act). Legislation in Europe (Registration, Evaluation, and Authorization of Chemicals program; REACH) could result in similar reviews of tens of thousands of compounds (Rogers 2003). In most cases, these reviews are conducted in the absence of measured bioaccumulation data. Moreover, because of ethical concerns, many government agencies and animal welfare organizations are advocating large reductions in vertebrate testing, including testing with fish. These considerations suggest a need for alternative methods to assess the potential for chemicals to accumulate in fish. One method that is receiving considerable attention involves the use of in vitro test systems, alone or in combination with mathematical models. This report describes the results of a workshop held March 3–4, 2006, in San Diego, California, USA. Workshop participants were asked to review the state-of-thescience regarding the incorporation of in vitro ADME(Absorption, Distribution, Metabolism, and Excretion) information into bioaccumulation assessments for fish, and identify research needed to expand the utility and applications of this approach. An important outcome of this workshop was a proposal to conduct research on hepatic biotransformation in fish, with the goal of relating in vitro metabolic rate, in vivo metabolic rate, and measured levels of accumulation for a set of strategically selected compounds. Participants also discussed how in vitro data could be used in a tiered approach for bioaccumulation assessments. Based on this discussion, a “decision tree” was proposed to identify information required at each tier in the assessment process and provide guidance on the need for whole animal testing. The scope of the workshop was limited to consideration of in vitro methods that could be used to predict chemical accumulation in fish under standardized laboratory conditions. Participants recognized that a large number of factors may complicate efforts to predict accumulation in a natural setting, including the distribution of chemicals among environmental compartments, food web structure and function, and seasonal movements of animals. The extrapolation of bioaccumulation predictions from the lab to the field, and among different environmental settings, was identified as an important topic for future scientific workshops.
