The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Abstract for TestSmart--A Humane and Efficient Approach to Screening Information Data Sets (SIDS) Data

Urinary Biomarkers as Humane Endpoints for Toxicity Screening

Raymond Poon
Bureau of Chemical Hazards, Health Canada

Because of the noninvasive and nonstressful nature of specimen collection, urinalysis is one of the most humane means of conducting toxicity screening in animals. The number of animals used can be reduced because each animal acts as its own control (and recovery), and the ease of specimen collection enables meaningful time course measurements from a few animals. Relevant urinalysis procedures can be incorporated into a toxicity test protocol without affecting other test results or requiring additional animals. Many of the urinary tests detect early, biochemical or subclinical changes. Incorporation of these sensitive toxicity endpoints enables the use of lower dose ranges, and hence reduces the possibility of animals suffering due to high dose effects.

One of the advantages of urinalysis is the wide selection of tests. The traditional urinalysis such as examination of cellular casts and formed elements, measurement of proteinuria, hematuria, glucose, ketone bodies and osmolality are well-established as screening tests or diagnostic adjuncts. Elevated levels of specific urinary proteins and enzymes are widely used as sensitive biomarkers of kidney dysfunctions. In toxicological research, urinary caffeine metabolites, glucaric acid, ascorbic acids and 7-β hydroxycortisol are regarded as biochemical indicators of hepatic response to hepatotoxins. Alterations in the urinary porphyrin profile and sigma-aminolevulinic acid level are considered early indicators of toxic effects of some heavy metals. Biomarkers are now being developed to detect oxidative stress, and adverse effects on bone, lungs, and the circulatory system.

Newer urinary tests are predominantly enzymatic, chromatographic or immunologic procedures that can be automated for high throughput screening purposes. The objective and quantitative results are amenable to statistical treatment, quality control and standardization.

At present, urinalysis is under-utilized in chemical toxicity screening. Efforts should be made to promote the routine use of validated urinary tests, and to support continued research into new urinary biomarkers. It is recommended that urinalysis should be considered an integral part of screening tests and incorporated into relevant toxicity test guidelines.