Product Testing: Toxic and Tragic
Every year, millions of animals are poisoned and killed in barbaric and outdated tests that attempt to evaluate the hazards of consumer products and their ingredients. In an effort to measure toxic effects, rats, mice, guinea pigs, rabbits, and other animals are forced to swallow or inhale massive quantities of a test substance or have a chemical smeared in their eyes or on their skin. It is now evident that tests on animals often do not predict outcomes in humans, and many non-animal test methods are available and continue to be developed.
- Acute Toxicity Testing
To determine the danger of a single short-term exposure to a product or chemical, the substance is administered to animals (usually rodents) in extremely high doses via force-feeding, forced inhalation, and/or eye or skin contact. Animals in the highest-dose groups often endure severe abdominal pain, diarrhea, convulsions, seizures, paralysis, or bleeding from the nose, mouth, or genitals before they ultimately die or are killed.1
Acute toxicity testing began during the World War I era, with the now-infamous lethal dose 50 percent (LD50) test, which, even today, remains a common animal-poisoning study. In this test, groups of animals are force-fed increasing amounts of a test substance or increasing amounts are applied to their skin until half of them die. Despite its decades of use, the LD50 test and its more contemporary adaptations have never been scientifically validated to confirm that their results do indeed predict chemical effects in humans. One international study that examined the results of rat and mouse LD50 tests for 50 chemicals found that these tests predicted toxicity in humans with only 65 percent accuracy––while a series of human cell-line tests was found to predict toxicity in humans with 75 to 80 percent accuracy.2
- Eye and Skin Irritation/Corrosion Testing
The Draize eye and skin irritation and corrosion tests date back to the 1940s.3 In these tests, a substance is dripped into rabbits’ eyes or smeared onto their shaved skin. Laboratory technicians then record the damage—which can include inflamed skin, ulcers, bleeding, bloody scabs, swollen eyelids, irritated and cloudy eyes, or even blindness—at specific intervals for up to two weeks. There is no requirement to provide the animals with any pain-relieving drugs during this prolonged process.
Evidence demonstrates that animal studies have variable outcomes, are of limited reliability, and are generally poor predictors of human skin and eye reactions. The qualitative scoring of eye and skin damage in Draize tests is highly subjective. Therefore, different laboratories—and even different rounds of testing within the same laboratory—often yield different results. This variable scoring makes the Draize skin or eye test results unreliable. Additionally, the results from the Draize eye irritation and corrosion tests are often flawed because of the anatomical and physiological differences between human and rabbit eyes. Because rabbit skin is substantially more permeable than human skin, using rabbits in irritation or corrosion studies leads to flawed results. For example, a comparison of data from rabbit tests and four-hour human skin-patch tests for 65 substances found that 45 percent of classifications of chemical irritation potential based on animal tests were incorrect.4
- Skin Sensitization Testing
The guinea pig maximization test (GPMT) for skin sensitization, in which experimenters inject animals with a test substance multiple times and measure any allergic reaction, was initially described in 1969.5 This test may cause guinea pigs’ skin to become itchy, inflamed, ulcerated, or otherwise painful as a result of an allergic reaction. This reaction is further intensified by the use of adjuvants, which increase the body’s immune response.
The GPMT has been largely replaced by the murine local lymph node assay (LLNA), in which a test substance is applied to the ears of mice, who are ultimately killed so that the lymph node near the ear can be removed and the immune response of the mice measured. The number of lymphocytes isolated from the lymph node is then used as a measure of skin sensitization.6 While this test uses fewer animals and requires less time to conduct, better alternatives that forgo animals altogether have been developed and should be used in place of both of these outdated animal tests.
- Carcinogenicity Testing
The rodent carcinogenicity bioassay is a test in which rats or mice are forced to ingest or inhale a test substance or the test substance is injected into or spread on their skin. The substances are administered to the animals for up to two years before they are killed so that researchers can look for signs of cancer, such as abnormal cells or tumor formation. A 2002 review of existing data suggests a high degree of both false positives and false negatives when using rodents to predict carcinogenicity in humans.7
- Reproductive and Developmental Toxicity Testing
Reproductive and developmental toxicity tests attempt to assess the effect a substance has on the reproductive ability of an animal and on the development of offspring. During these tests, experimenters administer a test substance to rats several weeks prior to mating through gestation, and both the fertility of the adults and the growth, survival, and development of the offspring are examined. In two-generation studies, the first-generation offspring from developmental toxicity studies are mated to observe the effects that a substance has on the fertility and toxicity of the second-generation offspring. The two-generation test increases the number of animals used in these tests and subjects them to potentially harmful substances for extended periods of time.8
Product Testing Requirements
No U.S. law requires that cosmetics and household products be tested on animals. The U.S. Food and Drug Administration (FDA) advises cosmetics manufacturers “to employ whatever testing is appropriate and effective for substantiating the safety of their products” and notes that the Federal Food, Drug, and Cosmetic Act “does not specifically require the use of animals in testing cosmetics for safety.”9 Likewise, the Consumer Product Safety Commission (CPSC) does not require that household products be tested on animals. The CPSC’s animal testing policy, as published in the Federal Register, states, “Neither the Federal Hazardous Substances Act [FHSA] nor the Commission’s regulations requires animal testing. The FHSA and its implementing regulations only require that a product be labeled to reflect the hazards associated with that product.”10
While some countries, such as China, require specific animal tests for these products, the European Union, Israel, and India have banned the sale of any cosmetics or cosmetics ingredients that have been tested on animals.11–13 Animal testing for cosmetics or household products has not yet been banned in the U.S., and companies will continue to test on animals as long as some countries, such as China, require it and other countries, such as the U.S., allow it.
In the U.S., the Environmental Protection Agency (EPA) regulates industrial chemicals and products that are labeled as pesticides, such as lawn fertilizers, weedkillers, and “antimicrobials.”14 By law, every pesticide must undergo dozens of separate painful and deadly animal tests, including testing on dogs, before being marketed .15 The FDA has similar testing requirements for drugs as well as chemicals that are used as additives or preservatives in processed foods.16, 17
Non-Animal Test Methods
Today, hundreds of cosmetics and household-product companies have rejected animal tests and are taking advantage of non-animal testing methods, including cell and tissue cultures, reconstructed skin grown from human cells, and computerized “structure-activity relationship” models that allow extrapolation of existing data to predict the activity of a chemical. The Organisation for Economic Co-operation and Development (OECD) publishes internationally agreed-upon test guidelines that can be used by government, industry, or independent laboratories. Pushed by PETA, these test guidelines include novel alternatives to outdated animal test methods and allow for the replacement of previously required animal tests.
- Acute Toxicity Testing
Replacements and refinements for acute toxicity tests on animals are being developed. The 3T3 neutral red uptake cytotoxicity test can be used to determine if a chemical can be labeled nontoxic.18 Additional non-animal methods will be required to eliminate the use of animals in acute toxicity testing altogether. In September 2015, the PETA International Science Consortium cosponsored an acute systemic toxicity workshop with the goal of developing a strategy to replace in vivo acute systemic toxicity testing.
- Eye and Skin Irritation/Corrosion Testing
The OECD lists several test methods that can be used as replacements for the archaic and inaccurate Draize rabbit eye test. The fluorescein leakage (FL) test method uses a fluorescent dye to measure a chemical’s ability to break through a solid layer of cells, thereby mimicking the damage that the chemical would cause to the eye.19 Other in vitro methods, such as EpiOcularTM, which uses human-derived keratinocytes, and the short time exposure (STE) test, which uses a rabbit corneal cell line, can also be used to replace the Draize eye test. 20,21
Recombinant human epidermis (RHE) models, which are human cell–derived skin equivalents, have been validated and accepted in Canada, the European Union, and virtually all other member countries of the OECD as total replacements for animal-based skin irritation or corrosion studies. Corrositex® can be used to assess skin corrosion, and RHE tests (EpiSkin™, EpiDerm™, and SkinEthic™) can be used to measure both skin irritation and corrosion.22–24 PETA was directly involved in funding the final validation of EpiDermTM, which led to a significant reduction in the number of animals required for skin irritation testing globally. A clinical skin patch test conducted on human volunteers has also been shown to produce reliable skin irritation data that are “inherently superior to that given by a surrogate model, such as the rabbit.”25
- Skin Sensitization Testing
In place of the outdated GPMT and LLNA, which require substantial animal use, the OECD has published test guidelines for two tests conducted in test tubes or in cultured cells. The direct peptide reactivity assay (DPRA) tests whether some of the events required for an allergic reaction occur in response to a test substance, allowing chemicals to be tested in a tube rather than on the skin of guinea pigs or mice.26 Another non-animal test, KeratinoSensTM, allows a test substance to be added to a layer of cells that reacts a certain way if the chemical would cause an adverse reaction on human skin.27
- Carcinogenicity Testing
Some of the early steps in the development of cancer are well known and are consistent among different types of cancers and across various cell types and organs. In vitro tests that examine these known steps in tumor formation have been developed to assess the risk of a substance’s potential carcinogenicity. For example, the cell transformation assay measures both the tumor-initiating activity and the tumor-promoting activity of a substance and serves as a reliable indicator of carcinogenicity without the use of animals.28
- Reproductive and Developmental Toxicity Testing
Because of the broad range of outcomes measured in reproductive and developmental toxicity tests, a single test that covers all adverse outcomes has not been developed. However, progress is being made in advancing in vitro methods that can be used to examine specific steps in the development of reproductive or developmental toxicity. For example, the embryonic stem cell test assesses the differentiation of embryonic stem cells to predict embryotoxicity, and the micromass test evaluates developmental toxicity using changes in cell differentiation and growth.29, 30 When animal tests are conducted, the extended one-generation reproductive toxicity test can be used in place of the two-generation test to decrease the number of animals used as well as the length of time that animals are exposed to potential toxins.31
The Way Forward
In 2007, the National Academy of Sciences’ National Research Council released the EPA-commissioned report Toxicity Testing in the 21st Century: A Vision and a Strategy, calling for a collaborative effort across the scientific community to rely less on animal tests and more on human-relevant non-animal tests.
PETA works with regulatory agencies to promote the development and acceptance of non-animal testing methods. In 2001, PETA persuaded the U.S. Congress to require the EPA to allocate $4 million to non-animal research, development, and method validation. The EPA and other governmental agencies have since dedicated millions more to non-animal methods. For example, the EPA and the National Institutes of Health have tested more than 10,000 compounds in high-throughput screening assays in the ToxCast™ program and at the National Center for Advancing Translational Sciences Chemical Genomics Center. As part of the Tox21 program, the agencies have also identified human genes that can be used to evaluate human responses to chemical exposure.
PETA also funds the development of non-animal test methods and other alternatives to replace animal use. To date, PETA has provided more than $2 million in funding ($4 million including in-kind donations of time and materials from participating laboratories and manufacturers) for promising non-animal test methods and other alternatives to animal use.
To help consumers identify products that are cruelty-free, PETA’s Beauty Without Bunnies program compiles information on the testing policies of companies and publishes a list of companies that have signed our statement of assurance to confirm that they do not conduct or commission animal tests for their products, ingredients, or formulations. Shoppers can support this project by purchasing products that comply with PETA’s “cruelty-free company” standard, boycotting those that do not comply, and asking local stores to carry cruelty-free items.
Consult PETA’s database of companies that don’t test on animals and request a free copy of PETA’s global Cruelty-Free Shopping Guide to find cruelty-free brands of all kinds of products.
1Organisation for Economic Co-operation and Development, “Guidance Document on the Recognition, Assessment, and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation,” OECD Environmental Health and Safety Publications, Series on Testing and Assessment 19 (2000).
2B. Ekwall, “Overview of the Final MEIC Results: II. The In Vitro–In Vivo Evaluation, Including the Selection of a Practical Battery of Cell Tests for Prediction of Acute Lethal Blood Concentrations in Humans,” Toxicology in Vitro 13 (1999): 665–673.
3M.K. Robinson et al., “Non-Animal Testing Strategies for Assessment of the Skin Corrosion and Skin Irritation Potential of Ingredients and Finished Products,” Food and Chemical Toxicology 40 (2002): 573–592.
4M.J. Bartek et al., “Skin Permeability In Vivo: Comparison in Rat, Rabbit, Pig, and Man,” Journal of Investigative Dermatology 58 (1972): 114–123.
5B. Magnusson and A.M. Kligman, “The Identification of Contact Allergens by Animal Assay. The Guinea Pig Maximisation Test,” Journal of Investigative Dermatology 52 (1969): 268–276.
6G.F. Gerberick et al., “Local Lymph Node Assay (LLNA) for Detection of Sensitization Capacity of Chemicals,” Methods 41 (2007): 54–60.
7K. Ennever and L.B. Lave, “Implications of the Lack of Accuracy of the Lifetime Rodent Bioassay for Predicting Human Carcinogenicity,” Regulatory Toxicology and Pharmacology 38 (2003): 52–57.
8AltTox, “Toxicity Endpoints and Tests: Reproductive and Developmental Toxicity,” 21 May 2014 .
9U.S. Food and Drug Administration, “Animal Testing & Cosmetics,” 5 April 2006, Office of Cosmetics and Colors Factsheet, U.S. Department of Health and Human Services .
10U.S. Consumer Product Safety Commission, “Codification of Animal Testing Policy,” 10 December 2012 .
11J. Kanter, “E.U. Bans Cosmetics With Animal-Tested Ingredients,” The New York Times, 11 March 2013.
12G. Fisher, “Import Ban on Animal-Tested Products Goes Into Effect,” The Times of Israel, 1 January 2013.
13A. Dhar, “India Bans Testing of Cosmetics on Animals,” The Hindu, 29 June 2013.
14U.S. Environmental Protection Agency, “About Pesticides,” 9 May 2012 .
15U.S. Environmental Protection Agency, “Protecting the Public From Pesticide Residues in Food,” Pesticides: Topical & Chemical Fact Sheets, 9 May 2012 .
16G. Lawton, “The Quest for Valid Alternatives: Minimizing Animal Testing,” Chemistry & Industry, 19 (1997).
17National Library of Medicine, “Toxicology Tutor I: Basic Principles,” 21 April 2005, National Institutes of Health .
18European Union Reference Laboratory for Alternative to Animal Testing, “EURL ECVAM Recommendation on the 3T3 NRU Assay for Supporting the Identification of Substances Not Requiring Classification for Acute Oral Toxicity,” 1 February 2016 .
19Organisation for Economic Co-operation and Development, “Test No. 460: Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 2 October 2012 .
20Organisation for Economic Co-operation and Development, “Test No. 492: Reconstructed Human Cornea-Like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section , 28 July 2015 .
21Organisation for Economic Co-operation and Development, “Test No. 491: Short Time Exposure In Vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 28 July 2015 .
22Organisation for Economic Co-operation and Development, “Test No. 435: In Vitro Membrane Barrier Test Method for Skin Corrosion,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, 17 August 2006 .
23Organisation for Economic Co-operation and Development, “Test No. 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (Rhe) Test Method,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 26 September 2014 .
24Organisation for Economic Co-operation and Development, “Test No. 439: In Vitro Skin Irritation – Reconstructed Human Epidermis Test Method,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 26 July 2013 .
25M.K. Robinson et al., “Validity and Ethics of the Human 4-h Patch Test as an Alternative Method to Assess Acute Skin Irritation Potential,” Contact Dermatitis 45 (2001): 1–12.
26Organisation for Economic Co-operation and Development, “Test No. 442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA),” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 5 February 2015 .
27Organisation for Economic Co-operation and Development, “Test No. 442D: In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 5 February 2015 .
28European Union Reference Laboratory for Alternative to Animal Testing, “EURL ECVAM Recommendation on the Cell Transformation Assay Based on the Bhas 42 Cell Line,” 1 February 2016 .
29A.E. Seiler and H. Spielmann, “The Validated Embryonic Stem Cell Test to Predict Embryotoxicity In Vitro,” Nature Protocols 6 (2011): 961–978.
30H. Spielmann et al., “Validation of the Rat Limb Bud Micromass Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests,” Alternatives to Laboratory Animals 32 (2004): 245–274.
31Organisation for Economic Co-operation and Development. “Test No. 443: Extended One-Generation Reproductive Toxicity Study,” OECD Environmental Health and Safety Publications, OECD Guidelines for the Testing of Chemicals, Section 4, 2 October 2012.