Severe injury potential case studies

There are tens of thousands of substances that are harmful, as mentioned in Section 12.1.5. With widespread environmental exposures comes the risk that many of these will influence the same mechanism for injury to humans or other organisms as may have been the case for the previously mentioned tadpole example. Even though effects of exposures to multiple substances are systematically used to advance studies on the effects of pharmaceuticals on humans (Lehar et al. 2008), the complexities have prevented broader generalisations about deleterious effects on health and the environment. There are, however, some examples of potential rules of thumb. For instance, it has been shown (Silva et al. 2002) that the response of several substances may be best described by adding their amounts weighted by their toxicity equivalency factors. 

Very few studies have examined the role of cytokines and chemokines in acetaminophen toxicity in the clinical setting. Interleukin 8 (the human homologue of MIP-2) was shown to be increased in patients with acetaminophen toxicity and to correspond with markers of hepatic injury (James et al. 2001). Further investigation in this area may help to identify potential early determinants of severe cases of acetaminophen toxicity. 

The initial hazard identification of pancreatic toxicity in a prechnical study is always concerning because of the potentially serious human health risks, which may include fulminant, hfe-threatening cases of DIAP or a lifelong iUness, such as CP, type 1 diabetes, or pancreatic neoplasia. Because both the exocrine and the endocrine pancreas have enormous reserve capacities and there are limited sensitive and specific biomarkers to detect pancreatic injury in both animals and humans, there is always the concern that subclinical DIAP may initially go undetected in humans. Further, AP may progress until a threshold of severity is evident in minimally or asymptomatic healthy human volunteers exposed to drug candidates with unknown risks and/or in previously healthy patients that receive standard-of-care agents with marked... 

---