, also known as safety testing
, is conducted by pharmaceutical companies testing drugs, or by contract animal testing facilities such as Huntingdon Life Sciences
and Inveresk Research International on behalf of a wide variety of customers, including the manufacturers of household and personal goods such as shampoos and domestic cleaning products.
Around one million animals are used every year in Europe in toxicology tests. In the UK, one-fifth of animal experimentats are toxicology tests.
The tests are conducted without anesthesia, since drugs can change test results. The tests examine finished products such as pesticides, medications, food additives such as artificial sweeteners, packing materials, and air freshener, or their chemical ingredients. The substances are applied to the skin or eyes; injected intravenously, intramuscularly, or subcutaneously; inhaled either by placing a mask over the animals and restraining them, or by placing them in an inhalation chamber; or administered orally, through a tube into the stomach, or placing them in the animals' food. Doses may be given once, repeated regularly for many months, or for the lifespan of the animal.
Types of test
Examples of toxicology tests include the LD50
test (Lethal Dose 50%), which involves administering a chemical to an animal population to determine what dose will kill 50 percent of the test subjects. The oral LD50 test has been banned in parts of Europe, and the U.S. Environmental Protection Agency (EPA) has announced that it no longer supports it. The test was phased out of the Organisation for Economic Co-operation and Development
's guidelines in December 2002, though the inhaled and skin-application LD50 tests remain in the guideline. The UK banned the oral LD50 in 1999, but the inhaled and skin-application tests are still used, and the oral LD50 is still used by the Ministry of Defence
Following the principles of reduction and refinement, the LD50 test is being replaced by methods such as the fixed dose procedure
, that use fewer animals and aim to cause less suffering. Nonetheless, the oral LD50 is still widely used. Nature
writes that, as of 2005, "the LD50 acute toxicity test ... still accounts for one-third of all animal [toxicity] tests worldwide."
The Draize test
involves applying 0.5mL or 0.5g of a substance to an animal's eye or skin for four hours; the test subjects are usually albino rabbits who are conscious and held immobilized in stocks. The animals are observed for up to 14 days for signs of erythema and edema on the skin, and redness, swelling, discharge, ulceration, hemorrhaging, cloudiness, or blindness in the eye. The animals are killed after the test. Despite two decades of research into alternatives to this test, no non-animal alternatives have yet been successful, although the low-volume eye test
is being investigated as an alternative that may reduce, but not eliminate, animal suffering.
The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are performed, lasting less than a month (acute), one to three months (subchronic), and more than three months (chronic) to test general toxicity (damage to organs), eye and skin irritancy, mutagenicity, carcinogenicity, teratogenicity, and reproductive problems. The cost of the full complement of tests is several million dollars per substance and it may take three or four years to complete. Most toxicity tests involve testing ingredients rather than finished products. However, according to BUAV, manufacturers regard these tests as crude and believe they overestimate the toxic effects of the substances. They therefore repeat the tests using their finished products in order to obtain a less toxic label. (pdf)
Other tests include the:
- 90-day repeat-dose test, administered by mouth, inhalation, or skin to 30-80 rats, rabbits, or guinea pigs;
- 90-day-repeat-dose test by mouth in non-rodents, in which dogs are used;
- teratogenicity test, which tests for the effects of a substance on a fetus, and involves at least 80 mice, rats, hamsters, or rabbits;
- chronic toxicity test, which involves at least 160 rats, who are given daily doses of the substance for most of their lifespan;
- carcinogenicity test, another lifetime study testing for cancer in 400-500 rodents;
- one- and two-generation reproduction toxicity test, which involves more than 100 rats or mice;
- test for embryonic genetic damage, which involves 10-60 rats, hamsters, mice and their offspring;
- toxicokinetic study, which involves eight to ten animals to study the absorption, metabolism, distribution, and excretion of a substance. (pdf)
Predictiveness and utility
Questions have been raised about the predictiveness and overall utility of toxicology testing.
writes that most animal tests either over- or underestimate risk, or do not reflect toxicity in humans particularly well. This variability stems from trying to use the effects of high doses of chemicals in small numbers of a laboratory animal to predict the effects of low doses in large numbers of humans. Although relationships do exist, opinion is divided on how to use data on one species to make exact predictions about the level of risk in another species.
Embryotoxicity tests are one example; these involve feeding chemicals to pregnant animals, then determining the effects both on the embryos and on the offspring of two subsequent generations. Horst Spielmann, a toxicologist at the Federal Institute for Risk Assessment in Berlin, told Nature: "Animal embryotoxicity tests are not reliably predictive for humans. When we find that cortisone is embryotoxic in all species tested except human, what are we supposed to make of them?"
Addressing the criticism that toxicology testing is inaccurate, Professor Robert L. Brent wrote in Pediatrics that: "There is no question that [these] studies are helpful in raising concerns about the reproductive effects of drugs and chemicals, but negative animal studies do not guarantee that these agents are free from reproductive effects..