Animal models human risk

Other major early contributions of biochemical engineering have been in the development of the artificial kidney and physiologically based pharmacokinetic models. The artificial kidney has been literally a lifesaver. Pharmacokinetic models divide the body of an animal or human into various compartments that act as bioreactors. These mathematical models have been used very successfully in developing therapeutic strategies for the optimal delivery of chemotherapeutic drugs and in assessing risk from exposure to toxins. 

Immunotoxicology data most often available for use in risk assessment is derived from experimental animal studies. Although animal models provide an opportunity to establish more reliable exposure estimates and conduct more informative tests than human studies, the level of accuracy that can be achieved using such data in extrapolating to humans is often a matter of debate. In immunotoxicology testing, a set of tests usually referred to... 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

During the last 10 years it has been attempted to develop in vitro methods as alternative methods in the study of effects where animal models have previously been necessary. Such effects include skin and eye irritation and specific organ damage. Validation programs have been launched, and some of the above-mentioned methods have been sufficiently validated for use in regulatory risk assessment of chemical substances and may now for certain purposes be used as stand-alone evidence. Results from nonvahdated methods can in some cases be used as supportive evidence to human and animal data. 

Island would likely become a national wildlife refuge. The cleanup standards, which EPA would establish for each end use scenario, differ in terms of receptors and exposures to inhabitants, which should be defined in an appropriate risk assessment. Receptors are plants, biota, animals, and humans that are exposed to a contaminant of concern. The risk assessment should assess the risks to both human health and ecological receptors, because they may require different end states. PMCD assigned the U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) to prepare the Conceptual Site Model (CSM) for JACADS closure and to perform the risk assessment. 

Many experimental obs vations, some of which have predicted human cancer data, have been possible because of organ-specific animal models for chemical carcinogenesis. These models, being similar to thdr human counterparts, strengthen the association of environmental exposures with cancer development, and aid in the extrapolation of carcinogenesis data from animal species to humans. They also provide a valuable resource for studies of pathogenesis, risk-modifying factors, and cancer prevention. 

Sexual function and fertility reflect a wide variety of functions that are necessary for reproduction and may be affected by exposure to environmental factors. Any disturbance in the integrity of the reproductive system may affect these functions. Patterns of reported infertility vary around the world, but approximately 10% of all couples experience infertility at some time during their reproductive years. Human studies on altered sexual function/fertility provide the most direct means of assessing risk, but data are often unavailable. For many environmental chemicals, it is still necessary to rely on information derived from experimental animal models and laboratory studies. 

Fertility assessment in test animals has limited sensitivity as a measure of reproductive injury, because, unlike humans, males of most test species produce sperm in excess of the minimum requirements for fertility. In addition, test animals can undergo multiple matings (Amann, 1981 Working, 1988 Chapin Heindel, 1993). In some strains of rats and mice, production of sperm can be reduced by 90% or more without compromising fertility (Aafjes et al., 1980 Meistrich, 1982 Working, 1988) in human males, less severe reduction in sperm production can cause reduced fertility. Thus, measurement of change in sperm count or fertility in laboratory rodents may be insufficient to assess reproductive health risk in humans. Other animal models may be more suitable for assessing fertility (Chapin et al., 1998). However, it should not be assumed that a reduction in sperm count (i.e., <90%) will have no effect on fertility in rodents (Wine et al., 1997). 

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