June 20, 2008
Validation of Animal Tests
Although some animal tests in use today were created nearly 80 years ago, most have never been formally validated (i.e., assessed in multiple laboratories to see if they reliably give the correct answers). However, there is a great deal of scientific evidence that some of the most common animal tests may be poor predictors of human effects. For example:
Eye and skin irritation tests:
- Among 281 cases of accidental human eye exposure to 14 household products, investigators with the US Food and Drug Administration determined that rabbit test results correctly predicted human responses less than half the time. 
- Animal tests failed to correctly predict human skin reactions for nearly half of 65 consumer products examined. 
- Excessively high variability in test results and interpretation between labs. A comparison of test results across 24 labs documented variability up to 100%. 
Acute toxicity tests (often conducted using oral, inhalation and skin routes):
- Animal tests seriously underestimate human risk, as documented human sensitivity to some chemicals is as much as 2,000-times greater than in animals. 
- Only 65 percent agreement between rat and mouse test results for the same 50 chemicals. 
- “The information obtained from conventional acute toxicity studies is of little or no value in the pharmaceutical development process.” 
Birth defect tests (often conducted in both rats and rabbits):
- Tests in both rats and rabbits failed to detect the developmentally toxic effects of PCBs, ACE-inhibiting drugs, and other substances, and rabbits gave false negative results for toluene, tetracycline, diethylstilboestrol (DES), and other drugs. 
- Less than 74 precent agreement between rat, mouse and rabbit test results for the same chemicals. 
- Testing in a second animal species increases the already high rate of false positive results. 
Cancer tests (usually conducted in both rats and mice):
- Failed to detect the hazards of asbestos, benzene, bromodichloromethane, cigarette smoke, dichlorovos, lindane, DDT, selenium sulfide, and many other substances, delaying consumer warnings and worker protection measures by decades in some cases. 
- Only 50-70 percent agreement between rat and mouse test results for the same chemicals. 
- Less than 60 percent agreement in the interpretation test results between labs for the same chemicals. 
- Many biological mechanisms leading to cancer in rodents are irrelevant to humans (e.g., buildup of alpha 2u-globulin in the kidneys of male rats, peroxisome proliferation in rodent livers, calcium phosphate-containing urinary buildup in rats). 
- Rodents possess cancer-prone organs for which there are no human equivalents (e.g., forestomach, Harderian gland, Zymbal’s gland). 
- Animals are sometimes administered 100-times or more the equivalent human intake of a chemical (e.g., to consume the level of the pesticide Alar that was fed to rats and mice in one study would require eating 28,000 pounds of apples daily for 10 years). 
- Commonly used strains of rats and mice are highly prone to spontaneous tumor development—even “control” animals who are not administered a test chemical—which confounds the interpretation of test results. 
As a direct consequence of the shortcomings cited above, pharmaceutical regulators have reported that fully 92% of drugs that pass preclinical (animal) testing fail clinical trials because animal studies so often “fail to predict the specific safety problem that ultimately halts development.” 
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