Animal & Veterinary
Riding the Wave--Kudos Roll in for Dr. Reimschuessel
By Dr. Carmela Stamper, Contributing Writer/Editor, Communications
In November 2009, the Board of Publications for the journal, Toxicological Sciences, honored Dr. Renate Reimschuessel and her co-authors with the “Best Paper in Toxicological Sciences” award. Their winning paper is entitled “Identification and Characterization of Contaminants in Pet Food Leading to an Outbreak of Renal Toxicity in Cats and Dogs.”1
A collaborative effort by Dr. Reimschuessel, an FDA scientist at CVM’s Office of Research, and scientists at Procter and Gamble (P&G), the paper describes the research conducted during the height of the 2007 pet food recall because of melamine contamination. The journal’s award committee recognized the paper as an outstanding example of how different scientific techniques were used together to find the cause of toxicity. The committee also thought the paper was important because it gave a clear picture of how toxicologists solved the contaminated pet food mystery. The award was presented to Dr. Reimschuessel and her co-authors at the 49th annual meeting of the Society of Toxicology in March 2010 in Salt Lake City, Utah.
The award-winning paper describes the steps taken by the authors to establish the link between contaminated wheat gluten and kidney failure (renal toxicity) in pets. The contaminated wheat gluten was used to make canned pet food in a manufacturing facility in China and led to kidney failure in U.S. dogs and cats after the pets ate food made at the facility.
The first step was to identify the contaminants in the wheat gluten. Scientists at FDA’s Forensic Chemistry Center, P&G, and Cornell University independently discovered that melamine was a main contaminant. Later, scientists at the Forensic Chemistry Center and P&G found that cyanuric acid was another main contaminant. Several other contaminants were also present in smaller amounts.
The next step involved figuring out if the contaminants were directly toxic to dogs and cats. After determining that the individual contaminants were not directly toxic, P&G scientists began testing various combinations for toxicity in rats.
While the P&G scientists were testing the toxicity of the pet food contaminants in rats, Dr. Reimschuessel was busy reviewing case reports of sick pets submitted to CVM by veterinarians. She obtained frozen, unpreserved kidney samples from a cat that died of kidney failure after eating the suspect canned pet food. Other veterinary pathologists had looked at kidney samples from other pets that died of kidney failure after eating the suspect food, but those samples had been preserved in formalin. (Formalin is a chemical typically used to preserve biopsy samples.) When looking at the cat’s kidney under the microscope, Dr. Reimschuessel saw many more crystals in the unpreserved samples than what the other pathologists reported seeing in the preserved ones. Using this observation, she tested the crystals and found they dissolved in formalin.
On April 13, 2007, Dr. George Daston at P&G and Dr. Reimschuessel shared their findings. In P&G’s study looking at the toxicity of the contaminants in the pet food, crystals were not found in the rat kidneys. However, the kidney samples had been preserved in formalin. Based on Dr. Reimschuessel’s finding that formalin dissolves the crystals, the P&G scientists started another rat study in which they froze kidney samples rather than preserve them in formalin.
In this second study, the P&G scientists found that certain combinations of the pet food contaminants caused kidney failure in rats, similar to the type of kidney failure seen in the sick dogs and cats. Dr. Reimschuessel and her co-authors then looked at samples of the rats’ kidneys under the microscope and found crystals inside the renal tubules (the tiny tubes that concentrate urine). The rat kidney crystals looked the same as the crystals in the cat kidney examined by Dr. Reimschuessel, and the crystals seen in cat and dog kidneys by other veterinary pathologists.
Dr. Reimschuessel and her colleagues pieced together that the crystals acted like physical plugs, blocking the renal tubules and damaging the kidneys, causing them to fail. To analyze the chemical make-up of the crystals, the scientists collected information on the infrared spectra from several kidney crystals. (Infrared spectra are light wavelengths found just outside the red end of the visible light spectrum.) They compared the spectra from the rat and cat kidney crystals to the spectra from the crystals found in the contaminated wheat gluten and from reference crystals made of known compounds. The scientists found that the spectra from the rat and cat kidney crystals matched the spectra from the wheat gluten crystals. The findings were confirmed by the Forensic Chemistry Center. The spectra from all three types of crystals (rat, cat, and wheat gluten) matched the spectrum from a reference crystal made of melamine and cyanuric acid. By discovering that the chemical make-up of the kidney crystals was identical to the two main contaminants found in the wheat gluten, Dr. Reimschuessel and her colleagues linked the contaminated pet food to the kidney failure in pets.
The paper lays out the impressive detective work by government and industry scientists. To echo the sentiments of the journal’s award committee, toxicologists, like Dr. Reimschuessel and her co-authors, “create a safer and healthier world”2 by studying the effects that toxic compounds have on people, animals, and the environment.
1Dobson, LMR, Motlagh S, Quijano M, Cambron RT, et al. “Identification and Characterization of Contaminants in Pet Food Leading to an Outbreak of Renal Toxicity in Cats and Dogs.” Toxicological Sciences. 2008, 106: 251-262.