Toxicity tests are carried out to determine the toxicity level a chemical has to live organisms. To measure the toxicity level of a chemical, these tests evaluate the biological response and, or the physiological damage that a living model has when it is exposed to different concentrations of the compound. With these data, it is possible to assess how safe an exposure to a certain substance is for the environment or if it is safe in its use in humans. For this purpose different model systems are used, such as cells or organoids, called in vitro models; animal models; or even computational models, maned in silico.
The testing process consists of several steps starting with the simplest models and scaling progressively to more complex ones including invertebrates and vertebrates animals, mammals, and, finally, humans. Thus, if a compound presents high toxicity, it is not necessary to proceed with tests in higher organism models because its harmful effect is clear enough. In a search for a more ethical and efficient viewpoint of toxicity testing, some years ago, the conscience about reducing animal testing became an important concern, resulting in the development of several alternative models, including zebrafish larvae, a little tropical fish, or computer-based models (in silico models).
Zebrafish is a cost-effective and highly valuable vertebrate model presenting several advantages including their small size, low growth and maintenance costs, fast development, high genetic homology with humans (70-75%), and the possibility of performing high-throughput screening with them, like in vitro. But, more importantly, this model has lower ethical issues as presents a fast organogenesis (5 days) enabling multiple test types in the embryonic stage of the animal, decreasing the use of adult fish or superior animals. Concerning computational models, their cost-effectiveness, testing capacity, and no ethical issues make these models very best alternative; nevertheless, they have a long way according to their reliability since biological systems are too complex even for modern computers.
Importantly, the results of a toxicity test can be used to decide whether a drug or product meets the safety requirements of the government-set regulations.
There are various types of toxicity and each has a different approach to testing as it is explained below.
This toxicity refers to how dangerous a chemical is and its effect on an organism such as a human, cell or plant. Chemical toxicity tests measure the harmful effects of a substance, the severity of the effects it produces, and in which doses appear.
One of the main and most severe chemical toxicity effect checked are the cytotoxicity and genotoxicity, meaning, the capacity of generating toxicity in the cell and mutations in the DNA respectively. Mutations are DNA sequence alterations that produce mistakes in the body’s proteins. Both can be measure in vitro in cells, and for the mutagenicity, also bacteria are commonly used, such as The Ames Test in the case of genotoxicity.
There are two forms of chemical toxicity, acute and chronic. Acute is the measurement of the reaction when the subject is exposed to high doses of a chemical in a short period. Chronic toxicity occurs when the subject is repeatedly exposed to smaller doses of a chemical, often over several months or years, such as chemicals present in the water or the environment.
This is the toxic effect produced by the toxins that living organisms create, for example, the venoms produced by animals, or the toxins present in plants and mushrooms. Biological toxicity comes from harmful bacteria, viruses, animals, and fungi. This form of toxin can be digested, breathed in, or absorbed through the skin.
As we have seen for the chemicals, these compounds have to be tested using live organisms to assess their effect on human health. The testing models can be live animals or a suitable alternative model such as the zebrafish.
These assays evaluate the amount of the harmful substance that it would cause an adverse reaction and the type of damage that cause to the organism.
This refers to substances that have a toxic effect on the organism due to their physical nature, meaning, they do not interfere directly with any biological process, and their harmful effect is associated with their tiny size, their corrosive nature, or their prevention of the proper biologic function. Representative examples of these types of substances are those that produce small particles including asbestos, coal dust, or silicon dioxide; asphyxiant gases that displace the oxygen; or radiation that can be extremely harmful in large doses.
Physical toxicity can have both a fatal effect or serious tissue damage leading to long-term health conditions. The deleterious effect of radiation is a good example of long-term damage, where the genotoxic effect of the radiation produces also accumulative DNA damage.
Many of these types of compounds cause environmental hazards and damage such as dirty water, metals in soil, and carbon monoxide in the air we breathe. These toxins can also get into the food chain if they are eaten by animals or absorbed by plants.
As with other toxicants, toxicity testing of these type of substances has to be assessed in animal models or alternative models such as zebrafish or others.
Some of the toxic effects of these compounds are associated to reach a certain concentration and, therefore, toxicity assays are necessary to decide if a product presents a hazard to human health and whether it can be approved for use.
In sum, it is important to understand the different forms of toxicity and their effect on human health and the environment to take the appropriate prevention measures and to establish their proper use and maximum amounts. Also, it is important in order to develop drugs that can counteract their effects and protect the public safety. With this research, it is possible to understand the consequences of the use of the chemicals and toxins, how they can affect the ecosystem and human lives, and how those that are essential can be used in the safest manner.
Sources
https://www.wikidoc.org/index.php/Toxicity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127354/
https://www.news-medical.net/life-sciences/What-is-Genotoxicity-Testing.aspx