weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. In some cases shifts away from animal studies have been mandated by law or regulation; the European Union (EU) prohibited use of animal testing for cosmetics in 2013. Dose response complexities Most chemicals display a classic dose response curve – at a low dose (below a threshold), no effect is observed. Some show a phenomenon known as sufficient challenge – a small exposure produces animals that "grow more rapidly, have better general appearance and coat quality, have fewer tumors, and live longer than the control animals". A few chemicals have no well-defined safe level of exposure. These are treated with special care. Some chemicals are subject to bioaccumulation as they are stored in rather than being excreted from the body; these also receive special consideration. Several measures are commonly used to describe toxic dosages according to the degree of effect on an organism or a population, and some are specifically defined by various laws or organizational usage. These include: LD50 = Median lethal dose, a dose that will kill 50% of an exposed population NOEL = No-Observed-Effect-Level, the highest dose known to show no effect NOAEL = No-Observed-Adverse-Effect-Level, the highest dose known to show no adverse effects PEL = Permissible Exposure Limit, the highest concentration permitted under US OSHA regulations STEL = Short-Term Exposure Limit, the highest concentration permitted for short periods of time, in general 15–30 minutes TWA = Time-Weighted Average, the average amount of an agent's concentration over a specified period of time, usually 8 hours TTC = The Threshold of Toxicological Concern concept has been applied to low-level contaminants, such as the constituents of tobacco smoke Types Medical toxicology is the discipline that requires physician status (MD or DO degree plus specialty education and experience). Clinical toxicology is the discipline that can be practiced not only by physicians but also other health professionals with a master's degree in clinical toxicology: physician extenders (physician assistants, nurse practitioners), nurses, pharmacists, and allied health professionals. Forensic toxicology is the discipline that makes use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal