The ongoing controversy surrounding cosmetic testing on animals in the United States stems from concern over animal abuse, especially from organizations like PETA (People for the Ethical Treatment of Animals). Over the last 20 years, animal-based methods such as the Draize test (for eye and skin irritability) have come under fire for “several aspects …: the subjectivity of the method; the overestimation of human responses; and the method’s cruelty” (Vinardell & Mitjans, 2008); the LLNA test (for human sensitization potency) has been criticised for “ethical implications, and it is also time consuming and expensive” (Johansson, Lindstedt, Albrekt, & Borrebaeck, 2011). As technology advances, various alternatives to animal testing are being created and implemented effectively to combat the inefficiency of these tests. The alternatives are not only morally-conscious but appealing as a more cost-effective approach to cosmetic testing. While there are certain aspects of animal testing that might make it a more reliable testing method (like their biology in relation to humans), there are still animal activists and scientists who believe alternatives like in vitro testing and in silico testing provide a more ethical and economically-beneficial solution. It is in a cosmetic company’s best interest to consider all aspects of its reputation, including pleasing the consumer when it comes to ethical concerns over its practices in order to improve their overall appeal, and many alternatives to animal testing have been produced to achieve that. In vitro testing involves procedures such as testing human organs on a chip and has been successfully validated as an alternative for in vivo (animal) toxicity testing because many scientists believe this provides the closest representation to a human’s biology when testing cosmetic products. This is supported by research conducted by Judith Swain, executive director of the Singapore Institute for Clinical Sciences, who found that a little-appreciated advantage is that the chips are more consistent than whole mice. According to Swain, “People may say it’s halfway between in vitro models and animal models, but it goes past that. It endeavours to create the smallest functional unit so that you can control things and you’re not confounded by variability” (Baker, 2011). Although researchers have many ways to study proteins and cultured cells, experimenting on animal tissue requires whole animals or fresh body parts. Such experiments are costly and often unreliable, and can raise ethical issues when it comes to skin irritation of a live animal. Organs on chips are still very much a work in progress, but advances in maintaining cells and producing nanomaterials mean that they could eventually enhance or replace these animal experiments. All in vitro tests are based on human biology, so they are believed to be more accurate for predicting sensitization in humans than the traditional animal-based tests (Johansson, Lindstedt, Albrekt, & Borrebaeck, 2011). However, the main obstacle is still the “difficulty of accurately mimicking the complex physiological systems of whole living organisms”—an obstacle that will be hard to overcome (Festing & Wilkinson 2007). Nevertheless, these are factors that animal activists are willing to overlook because animal use does not guarantee a complete correlation to human biology either. Each human organ represents a new challenge, but as technology advances, creating more complex cultures is getting easier, says Shuichi Takayama, a bioengineer at the University of Michigan, Ann Arbor, who has constructed chips that represent bone, liver and lung. The cell types needed for these chips are becoming more accessible, as are the growth factors and proteins needed to keep the organ cells healthy (Baker, 2011). The simplicity of most cell-based in vitro assays have the potential to completely replace or decrease the use of tests involving experimental animals, it is just necessary that cosmetic companies make the first step to stimulate this transition. The growing popularity of organs on chips as the best alternative to animal testing can be attributed to its innovativeness and ethical factors contradicting the use of animals in cosmetic testing. Another alternative to animal use is in silico testing, which can be a more appealing solution because of its cost-effectiveness and efficiency in characterizing and predicting toxic outcomes in humans and the environment. TIMES software, a commercial mechanically-based in silico model, has been explored to develop structure-activity relationships for skin sensitizers. It has been recently assessed in an external validation study that showed good consistency (83%) between experimental and estimated values for 40 new chemicals (Natsch, Emter, & Ellis, 2009). Additional improvements are still required; developments offer promising tools to support the analysis of skin sensitization potential, an important factor in determining the safety of a product. Some researchers argue, replacing the current animal tests cannot be accomplished with a single in vitro test, but that rather the integration of outcomes from different in vitro and in silico assays will be needed for a more accurate prediction of the skin sensitization potential of different chemicals (Natsch, Emter, & Ellis, 2009). The combination of both methods would therefore increase their reliability as compared to traditional animal experimentation. In silico approaches are also a more practicable and relatively inexpensive alternative to laborious and time-consuming animal testing as of the last decade for a wide range of species (Tang et al, 2008). It is important to note in silico toxicology differs from traditional toxicology in many ways, but perhaps the most important is that of scale. Raunio, a professor employed in Health Sciences at the University of Eastern Finland, indicates that the scale in the amount of chemicals that are analyzed, degrees of biological organization examined, extent of endpoints and pathways studied, and range of exposure conditions are all considered simultaneously when using in silico tests like TIMES software (2011). The National Research Council, a collective scientific community of engineers and health professionals, envisions a future in which all routine toxicity testing would be conducted in human cells in vitro by evaluating cellular responses in a battery of toxicity pathway assays using high-throughput tests. Obviously, challenges exist in ensuring that the suite of assays provides “sufficient coverage of toxicity pathways so as to capture the broad range of possible pathway perturbations” (Raunio, 2011). The identification and characterization of these pathways is not the sole responsibility of the toxicology community; most research into these pathways comes from, and will continue to arise from, modern cell biology, during which in silico testing can prove to be very useful. As the ethics of animal testing comes into question, in vitro testing and in silico testing both provide reliable, ethical, and more affordable alternatives to animal testing, although there is no single agreed upon alternative for animal use. Some argue that one form of testing (organs on a chip) is more effective than the other (TIMES software), while others argue that the use of both methods can provide even more effective results. Of course, it is expected that the development and implementation of both in silico and in vitro methods will have to face scientific and regulatory barriers because of the restricted amount of information on biological processes, especially when it comes to more complicated safety tests. Regardless, if companies were willing to make the switch to either method, they would recieve the support of animal activists and supporters and would see long term benefits in terms of its expenses in the future due to the average lower cost of in vitro and in silico tests. The ultimate goal of alternative testing is to eliminate the use of animals altogether, whether it be through the use of one alternative or multiple in conjunction, and there is still room for improvement in the case of newer procedures.