Animals in Testing
Animals are used to test both the safety and efficacy (i.e. how well a product works) of therapeutic drugs, household products, cosmetics, chemicals and a whole host of other products. The most contentious use of animals is in the testing of cosmetics, because the suffering endured by the animals is often deemed to outweigh the value to society of developing more effective cosmetic products such as make-up or skin creams. The testing of therapeutic drugs tends to be considered more reasonable by certain people, with arguments often reasoning that efficacy and safety testing of drugs on animals in paramount to the development of new safe and effective medical and veterinary treatments. Other chemicals, such as pesticide, or household cleaners are also tested on animals for their safety before they are allowed to go out onto the market.
Thankfully, there are growing numbers of effective non-animal alternatives that can replace the use of animals in testing. However, change is slow, and many countries have regulatory requirements that stipulate that testing on animals be carried out. The first regulatory requirements to have shifted are those pertaining to cosmetics, and there have been major changes in the EU in recent years. However, for all other types of product testing, animal use is still prevalent.
In the EU the use of animals for testing of cosmetic products has been banned since 2009, the use of animals for the testing of cosmetic ingredients has been banned since March 2013. Furthermore, the EU banned the sale of any cosmetics tested on animals from March 2013 onwards (this is known as a marketing ban). However, the EU ban does have some limitations:
- The bans only apply where there is a connection with the EU (e.g. testing within the EU, or sale in the EU when the testing was carried out elsewhere
- The bans do not apply to testing to determine any risk to the environment
- The bans do not apply to worker safety tests, they are only aimed at consumer safety
Israel imposed similar cosmetic testing bans in 2007 and 2013, and similar policy change is under consideration in India and South Korea. In most other countries, the use of animals in cosmetics testing is neither expressly required nor prohibited, and therefore continues to take place at the discretion of cosmetics companies and ingredient suppliers. In Canada, the Food and Drugs Act prohibits the sale of any cosmetic containing harmful ingredients or contaminants, but does not require that animal testing be conducted to demonstrate safety.
One important exemption from the bans that are in place is any product that has ingredients that are considered a “drug” – for example, Botox is considered a medical agent, and therefore is still batch tested using animals, even though it’s primary use is as a cosmetic product.
Biomedical and Chemical Testing
Animals are used in tests to predict the toxicity, corrosivity and other safety variables, as well as the effectiveness of new products, chemicals, consumer products, medical devices and new drugs. Some of the more common product safety tests are outlined below, along with any developments in the non-animal alternatives that might replace them.
Common product safety tests:
Toxicity – LD50 test
The traditional LD50 (lethal dose 50 percent) test forced animals, often rats and mice, to ingest chemical to determine the dose that resulted in the death of 50% of the animals. In 1985, the Pharmaceutical Manufacturers’ Association came out publicly against the traditional LD50 test, and after decades of criticism and documentation of the failures of traditional LD50 tests, its use as a worldwide standard has finally ended.
Although traditional LD50 tests for acute toxicity may have been replaced with alternative methods, many of those methods still involve the lethal use of animals, even though the number of animals is reduced.
Eye irritancy – Draize test
The Draize test measures the eye irritancy of chemical and other products by dropping concentrated amounts of a test substance into an animal’s eye (often rabbits) and then assessing the eye’s reactions using a subjective numerical score to indicate the level of eye damage and injury (e.g. the degree of swelling, redness, ulcerations etc). In most instances, conscious animals are immobilized in full body restraint stocks.
Today a number of in vitro replacements are widely used in-house by industry to eliminate nearly all requirements for the classical Draize test. However, it is still used in some countries.
Skin irritation, corrosions, sensitization and absorption tests
Tests for skin irritation (level of damage caused to the skin by a substance) and corrosivity (potential of a substance to cause irreversible damage to the skin) are typically conducted on rabbits using the classic Draize skin test. The test is done by placing a chemical or chemical mixture on an area where the animal’s fur has been shaved.
Skin corrosivity and irritation can be easily measured using in vitro systems based on human cell and tissue cultures, such as EPISKIN and EpiDerm, which have both been approved as complete replacement for animal tests by the European Centre for the Validation of Alternative Methods (ECVAM). However, their US counterpart, the Interagency Coordinating Committee of the Validation of Alternative Methods (ICCVAM) still requires that they be used with animal tests.
Mutagenicity and carcinogenicity
Mutagenicity and carcinogenicity tests examine potential genetic effect from pharmaceuticals, industrial chemicals and consumer products, classifying the chemicals for cell mutations and carcinogens. Rats and ice are commonly used in these studies.
It is now widely accepted by regulatory officials and toxicologists that screening for mutagenic potential, along with cell and DNA damage can be done via in vitro methods such as the AMES test, the In Vitro Cell Line Mutation Test or the In Vitro Chromosomal Aberration Test.
Toxicokinetics and absorption, distribution, metabolism and excretion (ADME)
To determine how a toxic substance will affect the body, a series of tests on the drug’s absorption, distribution, metabolism and excretion (ADME) are carried out. These studies often involve rats and mice, who are given the substance through means of intravenous injection, inhalation, topical applications to the skin or force feeding. However, ADME can be identified and modeled using computer and in vitro approaches. In vitro methods are especially useful for studies in the biological activity and mechanisms of toxic response of chemicals. Due to interspecies differences in metabolic enzymes, human-based models are vital for accurate predictions.
Some chemicals and drugs are essentially nontoxic but become hazardous once ingested and metabolized by the body. This is one area of toxicology for which animal models are widely acknowledged by toxicologists to be inappropriate because of the enormous species differences in metabolic parameters. Instead of using animals, information fro in vitro systems utilizing human cell lines, genetically engineered human cells, and subcellular components, as well as several computer-based systems are being utilized to detect metabolism-mediated toxicity.
This test is deigned to identify potential bacterial contamination of injectable products, implants, medical devices, dialysis machines, cellular therapies, recombinant proteins and IV products. For over seventy years rabbits have been used in pyrogen testing and injected with test materials to check for reactions to contamination. However, there are alternatives to animal-based pyrogen testing (such as the Limulus amoebocyte lysate (LAL) test), some of which are already validated for use in the European Union.
Phototoxicity is the potential for drugs and chemicals to become toxic when human recipients are exposed to sunlight. There is now an in vitro replacement to identify phototoxic potential, and EpiDerm has also been proven to be an alternative to animal-based phototoxicity studies.
Embryotoxicity examines the toxic effects of a substance on the development of an embryo. In these studies, pregnant animals are killed just prior to delivery and the fetuses are examined for any sign on toxic effects by the test substance. Using rodents for such studies in particularly inappropriate due to the major physiological, biochemical, and structural difference between human and rodent placentas.
There are currently more than a dozen in vitro methods representing various aspects of the reproductive process. The Embryonic Stem Cell Test (EST) has been validated by the European Centre for the Validation of Alterative Methods (ECVAM) and accepted by the European Union for the identification of embryotoxicants.
This represents a class of chemical believed to have particularly toxic effects on human and wildlife reproductive systems. An in vitro test method, LUMI-CELL has been recommended for use as an initial screen to identify substances that might act as endocrine disruptors.
Used to determine the negative effects of chemical entering the environment, these tests measure acute toxicity using fish in a 96 hour LC50 (Lethal Concentration 50%) test, and for chronic toxicity over a period of up to 200 days to monitor growth, spawning, hatching and mortality. There are alternatives used to predict toxic effects to aquatic organisms (e.g. computational systems).
Toxicogenomics (and its sister disciplines of proteomics and metabonomics) integrates the interactions between human genes and toxic substances, proteins and metabolic activities, respectively. The ultimate goal of toxicogenomics is a single or series of DNA chips that would provide almost immediate toxicity profiles of all test substances. A single chip could replace the information derived from 20,000 individual experiments.