Pet Food Recall: Guidelines for Veterinarians
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Updated 12.11.07, 7:30 PT
National Pet Food Commission RecommendationsCourtesy AVMA News Bulletin, 12.11.07 The Pet Food Institute, which represents manufacturers, established the NPFC in April 2007 to review the recalls of pet food relevant to melamine contamination of ingredients from China. The independent commission included authorities on nutrition, toxicology, veterinary medicine, and quality control. In November, PFI provided the AVMA with a copy of the NPFC suggestions for improving the safety of pet food. Various recommendations target the FDA Center for Veterinary Medicine, Association of American Feed Control Officials along with state feed control agencies, PFI, pet food manufacturers in general, veterinary associations and colleges, and veterinarians in private and public practice. The NPFC offered several suggestions to the veterinary community in addition to the recommendations for an incident reporting system. The commission encouraged offering educational opportunities for veterinarians and veterinary students regarding interaction of regulators and the pet food industry, requirements for producing pet food, manufacturing processes, nutritional guarantees, and labeling regulations. Another recommendation is for the veterinary community to establish ongoing communication about pet food, ingredients, and other issues with the pet food industry, PFI, and appropriate professional and trade associations. A suggestion specifically for the American College of Veterinary Nutrition is to develop a model for recording the diet history of all animals visiting veterinarians. The first suggestion for the FDA is to complete an existing initiative to create a comprehensive Animal Feed Safety System, which would apply to pet food. The NPFC also urged the FDA to develop guidance on the criteria and time frames for companies to report adverse health effects with possible links to pet food. One of the key recommendations for AAFCO is to finish model state regulations for feed and feed ingredients. The NPFC recommendations for the pet food industry are available on the PFI Web site. UC Davis Study on Melamine & Cyanuric AcidA UC Davis research study shows that cats who were fed pet food that contained both melamine and cyanuric acid sickened within 12 hours, vomiting, losing their appetites and showing signs of kidney failure. Subsequent necropsies showed the same kind of tissue damage as pets who died earlier this year after consuming contaminated food. A necropsy on a fourth cat who was fed the two chemicals separately showed undamaged kidneys, suggesting it was the combination of the chemicals that caused the high toxicity in pets. AAVLD Survey Results ReleasedReprinted from AVMA News Bulletin, 11.13.07 The evidence is building that a combination of two adulterants in pet foods, melamine and cyanuric acid, contributed to the deaths of hundreds of cats and dogs earlier this year while manufacturers were recalling the products. The American Association of Veterinary Laboratory Diagnosticians released results of the "AAVLD survey of pet food-induced nephrotoxicity in North America, April to June 2007" and presented a preliminary case definition during the group's annual meeting from Oct. 18-24 in Reno, Nev. The AAVLD survey found 347 cases that met diagnostic criteria for "pet food-induced nephrotoxicity" from April 5-June 6. The cases involved 235 cats and 112 dogs, with 61 percent of the cats and 74 percent of the dogs having died. Dr. Wilson Rumbeiha, associate professor at the Michigan State University Diagnostic Center for Population and Animal Health, organized the AAVLD survey and presented the results. He said melamine and cyanuric acid can combine to form crystals in animal bodies, and the crystals apparently can impair renal function. According to the Food and Drug Administration, melamine and cyanuric acid were present in wheat flour from China that went into pet food in the United States. Adding melamine could throw off a test for the protein concentration of an ingredient, allowing flour to pass for a costlier high-protein ingredient such as wheat gluten. Dr. Rumbeiha said the prevailing theory for how cyanuric acid, ammelide, and ammeline adulterated pet food is that they were co-contaminants. Incomplete reactions during melamine production could lead to the formation of these co-contaminants. Four cats and one dog from the AAVLD survey formed the basis of the preliminary case definition, while a much larger sample of cases is still under review. All five animals ingested pet food that manufacturers recalled because of adulteration with melamine. Results of kidney or urine tests from each animal were positive for the presence of one or more of the four contaminants. All animals had markedly high concentrations of BUN and creatinine. Urine was isosthenuric. Casts, leukocytes, erythrocytes, and yellow-to-brown crystals with radial striations were often, but not always, in the urine sediment. Histologically, the most common finding was characteristic yellow-brown crystals in the renal distal tubules and collecting ducts—with or without microscopically visible tubular necrosis, degeneration, or sloughed epithelium. Also at the AAVLD meeting, Dr. Birgit Puschner of the California Animal Health and Food Safety Laboratory presented results from a pilot study on the effects of adding melamine and cyanuric acid experimentally to the diet of several cats. The study found that neither melamine nor cyanuric acid alone had an observable effect on renal function, but the combination caused acute renal failure. Dr. Steve Ensley of the Iowa State University Veterinary Diagnostic Laboratory summarized preliminary results from a similar study in pigs, which also suggested that the combination of melamine and cyanuric acid is a more potent nephrotoxin than either is individually. Dr. Barbara Powers, AAVLD president and director of the Colorado State University Veterinary Diagnostic Laboratory, said the adulteration of pet food demonstrated a broader need for veterinarians to create a system for evaluating any toxins that may contaminate the food supply in the future. The AAVLD formed a work group that wrote a white paper in May proposing to expand the focus of the National Animal Health Laboratory Network beyond infectious disease to include toxins. Dr. Stephen Hooser, assistant director of the Purdue University Animal Disease Diagnostic Laboratory, chaired the work group. He said the white paper proposed additional federal funding for existing NAHLN veterinary toxicology laboratories. Funding would go toward equipment, personnel, and information technology. Analysis of Oregon Case Data by Dr. DeBessTo our knowledge, only tests of three deceased animals in Oregon were conducted after laboratory testing for melamine was developed. Of the three tests, two were confirmed as positive and one negative, as related to the contaminated pet food. There may have been other tests that were conducted, but, if so, they were not reported to Dr. DeBess; thus, they are not included in these results. Overall, Dr. DeBess received 127 reports of ill animals during the food recall period. Of this number, 62% were cats and 46% were female. Of those affected the mean BUN value was of 124 mg/dl, mean creatinine value was of 7.5 mg/dl and the mean phosphorous value was of 13.1 mg/dl. The mean age of those affected was 8.6 years. Unfortunately, 38.6% (49 – 20 dogs, 29 cats) of them died of renal failure. No specific breeds had a higher frequency of renal dysfunction. Geographically, 23% of the cases were reported from Lane County (Eugene and Springfield area), 19% were from Multnomah County and 13% from Washington County. The remainder of the reported cases were scattered throughout Oregon. Animals that died had a mean BUN of 161 mg/dl, a mean creatinine of 10.4 mg/dl and a mean phosphorous of 16 mg/dl. When separated by species, dogs that died had a mean BUN of 145 mg/dl, a mean creatinine of 7.4 mg/dl and a mean phosphorous of 16.1 mg/dl. In general, affected dogs – at 6.7 years of age – were younger than the average age of the deceased cats. Cats that died had a mean BUN of 172mg/dl, a mean creatinine of 12.4 and a mean phosphorous of 15.8 mg/dl. The mean age of cats was 11 years. In those cases that survived, cats had a mean BUN of 113, and dogs of 80 mg/dl. Mean creatinine in cats that survived was of 6.8, and 3.9 in dogs. The levels of phosphorous were 11.3 in cats, and 9.9 in dogs that survived. The take home message is that creatinine levels were the most significant indicator of survival (p<0.05). Melamine & Cyanuric Acid Reaction Forms Same Crystals Seen in Sick PetsTests conducted on contaminated pet food and necropsies from affected animals have resulted in a new theory to explain how animals are being adversely affected by contaminated pet foods. A chemical reaction between melamine and cyanuric acid is suspected of forming crystals and blocking kidney function. The investigation into contaminated pet food has focused on melamine contamination of ingredients imported from China, such as wheat gluten, rice protein concentrate and corn gluten (imported into South Africa). It is now believed that cyanuric acid, as well as melamine, has been found in urine samples from animals that died. Analysis of the crystals in the kidneys of affected animals have revealed that they are approximately 70 percent cyanuric acid and 30 percent melamine, and are extremely insoluble. Furthermore, tests mixing melamine and cyanuric acid in samples of cat urine resulted in almost immediate formation of crystals that were identical to crystals found in the kidneys of affected animals. Two other melamine-related substances—ammelide and ammeline—may also play roles and are under investigation. Study: Melamine crystalluria in sheepThe toxic effects of melamine given directly or in the feed to merino wethers were studied. A single dose of 100 g increased urea in blood from 28 to 315 mg per 100 ml for a period of 11 days. There was complete loss of appetite and excretion of urine ceased on the tenth day. When the sheep was examined post mortem on the eleventh day the tubules of the kidney were packed with crystals. Nephrosis and erosive abomasitis were seen also. Daily doses of 50 and 25 g killed the sheep after 7 and 9 days, respectively. In those sheep the blood urea was high just before death and post mortem crystals in the kidney tubules, nephrosis, haemorrhagic cystitis and acute typhlitis were seen. The dose of 50 g also caused ulcers in the abomasum. With 10 g daily one sheep did not die but 2 did so after 16 and 31 days. The 2 sheep which died lost appetite and stopped urinating 3 days before death and urea and creatinine in blood then increased sharply. There were crystals in the kidneys and severe oedema of the lungs. In another experiment volume of urine was reduced by offering water freely for 1 h on alternate days. Melamine was mixed with maizemeal and offered to 3 sheep to supply 7 g per sheep per day. All sheep survived for 6 weeks and there was no excessively high value for urea in blood. When daily intake of water was restricted to 600 ml much of the maizemeal containing melamine was refused but the sheep showed no ill effect. The production of white crystals on cooling, the appearance of a white deposit on the addition of picric acid and absorbancy of acidified crystals at 235 m micro indicated the presence of melamine in the urine of treated sheep. Melamine had no effect on pH of contents or motility of rumen and there was no sign of damage to liver. Source: Clark, R. 1966. Melamine crystalluria in sheep. Journal South African Veterinary Medical Assoc., 1966, Vol. 37, pp. 349-351. CAB Record Number: 19671407708 ACVIM Treatment GuidelinesCourtesy of the American College of Veterinary Internal Medicine Acute renal failure remains the primary problem being treated in response to consumption of the recalled food. Clinical presentation varies. Some of these pets are quite azotemic and ill whereas others may present only with polyuria and polydipsia, dilute urine and blood work which shows mild azotemia or no significant changes. Some pets that have consumed recalled food remain asymptomatic but in fact have significant changes on their blood work and/or urinalysis. Therefore, the best recommendation for pet owners remains to consult with a veterinarian if a pet has eaten the recalled food in all cases, but particularly if the pet is showing any illness including anorexia, lethargy, vomiting, diarrhea, polyuria, or polydipsia. Recommendations still include doing a general blood test (CBC, biochemistry panel) and urinalysis. Crystalluria is being found in many of these cases and veterinarians should request a urine review for crystal morphology from their diagnostic laboratory. These crystals have been described as round and yellow with radiant striations and appear similar to uric acid or urate crystals. Veterinarians should contact their diagnostic veterinary laboratory if they have further questions. Fluid therapy and symptomatic treatment tailored to the individual pet, the existing protocols of treating pets affected by the recalled food, are still the best courses of action. Many pets are responding well to treatment. Recheck blood work in 3 - 4 weeks may be advisable when minor disease is present. ASPCA Treatment RecommendationsExcerpted from an ASPCA press release Recent media reports that laboratory experiments on the interaction of melamine and cyanuric acid in cat urine showed the formation of crystals are not surprising to ASPCA experts, and offer a glimmer of hope to veterinarians who have been worrying about how to save sick animals who have ingested the contaminated food. “The fact that we have started to learn how the presence of melamine may be impacting these animals, gives us a small glimmer of hope—that at least we know we are on the right track when it comes to treating the animals affected,” said Dr.. Steven Hansen, a board-certified toxicologist and senior vice president with the ASPCA, who manages the ASPCA’s Animal Poison Control Center (APCC). "These findings really start putting everything else we have seen into perspective.” In a study that was done several years ago on dogs and rats, the presence of melamine in their systems was found to only lead to the development of crystals in urine, but there were no further adverse effects—and nothing that showed a direct link between the chemical mechanism of melamine and the renal failure recently seen in the affected animals. “Now that we see that crystals are formed when melamine and cyanuric acid are combined in cat urine, it may be that the cause of renal failure is somehow related to the obstruction caused by these crystals,” continued Dr. Hansen. This also explains why animals whose symptoms were detected early enough, and who were rushed to their veterinarians and put on aggressive fluid therapy—as the ASPCA has been recommending—survived; since this treatment may help to prevent additional crystals from forming, and aid in flushing out the existing crystals from the animals’ urinary tracts, thus relieving the obstruction and reversing the effects of renal failure. “Patience is the key,” said Dr. Murray, who has successfully treated several animals thus-affected with aggressive fluid therapy at BMAH. “We now understand that we have to bathe these crystals in fluid for as long as possible. With other causes of kidney failure, if there is no improvement in the animal’s condition after a day or two, the prognosis is usually not encouraging. “In this case, however, when treating animals who have been sickened by eating the contaminated foods, longer-term intravenous fluids may be required —so we would strongly recommend that all veterinarians treating such cases be patient and continue administering fluids longer than they might otherwise, because they can really be life-saving.” Submitting Samples for TestingOregon State University's Veterinary Diagnostic Lab is available to assist practitioners in submitting samples for testing through the California Animal Health and Food Safety Laboratory. Oregon samples are charged the out-of-state fee of $200. According to Dr. Jerry Heidel, VDL director, Michigan State's lab will be offering similar testing soon. The VDL has an agreement with Michigan State to run the test at the in-state price for Michigan residents ($100 per sample). The test must go through the VDL to receive that rate. Kidney, urine, or food can be tested. Practitioners can contact the VDL at (541) 737-3261 for assistance. Practitioners are encouraged to submit a full complement of tissues for pathology and analytic chemistry analyses. Although the kidney is the main organ of interest, it is the bare minimum. It is important to note that samples from the kidneys should not be preserved in formalin, as the crystals seem to dissolve over time in formalin. Instead, they should be preserved in 100 percent ethanol or snap-frozen in OCT medium and sent to a diagnostic laboratory on dry ice. Similarly, a full complement of fresh tissues from dead animals, or urine and serum samples from live animals, should be collected and frozen for future analytic chemistry analyses. Any recalled product that is brought to a veterinary clinic should be collected and frozen. Thorough notes on these cases should be kept in patient medical records. It is important that veterinarians adhere to the record-keeping requirements of Oregon's veterinary practice act, including those for record retention. As mentioned previously, the California Animal Health and Food Safety Laboratory is offering testing services, detailed below (as of 4.17.07):
AAVLD Releases Proposed Testing ProtocolCourtesy of the American Veterinary Medical Association On April 17, the American Association of Veterinary Laboratory Diagnosticians issued the following proposed protocol for testing dead animals with nephrotoxicosis possibly associated with adulterated pet food If possible, serum and urine should be taken antemortem for a chemical analysis and urinalysis, including sediment examination. Typical crystals should be birefringent with polarized light. Information regarding the pet food involved—such as brand, lot number, and UPC—should be recorded. Samples of all food should be held by the client, the attending veterinarian, or the diagnostic laboratory. A standard necropsy should be performed, using the judgment of the pathologist/veterinarian in charge, with particular attention paid to the urinary system. Photographs of pertinent lesions are recommended. Samples of all important organs should be preserved in fixative. Lung, heart, liver, spleen, kidney, urinary bladder, adrenal gland, pancreas, thyroid/parathyroid, ileum, and brain are suggested, but others may be needed, depending on the lesions observed. Sections should be no thicker than 4 mm and fixed at fixative:tissue ratio of 10:1. In addition, samples of kidney, liver, fat, and urine should be taken, frozen, and held for future testing when a specific toxicologic assay is developed (as much tissue as is practical should be frozen and saved). If possible, sections of kidney should also be preserved in 100 percent (absolute) ethanol and/or snap-frozen in OCT medium to preserve crystals that might be washed away by prolonged formalin fixation. All fixed tissues should be processed and embedded in paraffin within one to two days of fixation to best preserve crystal integrity. Routine H&E stains appear adequate to demonstrate crystals and renal tubular lesions, though Gomori's silver stain or polarized light may be used to highlight the crystals. Crystals can be viewed with or without staining on frozen or fixed sections. Testing for other possible causes or contributing diseases should also be pursued, as a substantial proportion of the cases appear to be multifactorial. Examples include parvoviral enteritis, chronic tubulointerstitial disease, lymphosarcoma, or ethylene glycol toxicosis. Questions or comments may be directed to Dr. Dalen W. Agnew, Diagnostic Center for Population and Animal Health, Michigan State University, 4125 Beaumont Road, Lansing, MI 48910-8104. Phone: (517) 432-5806; agnewd@dcpah.msu.edu. Report Cases: AAVLD SurveyCourtesy of the American Veterinary Medical Association The AAVLD Veterinary Analytical Toxicology Committee is seeking data on cases that meet certain criteria. Through the a Web-based survey that was launched April 6, the AAVLD will gather scientific data from diagnostic laboratories and—directly and indirectly— from veterinarians on cases of possible pet food-induced nephrotoxicosis. The organization is asking AAVLD laboratories, along with other laboratories and private practitioners who wish to participate, to report incidents in the United States and Canada using this survey tool. The survey is accessible to AAVLD laboratories on the members-only area of the Web site, www.aavld.org. Nonmembers can enter case data via the public area by clicking on News and then on AAVLD Pet Food Toxicity Survey. Cases should meet two of the following four criteria:
Drs. Wilson Rumbeiha and Dalen Agnew at the Michigan State University Diagnostic Center for Population and Animal Health are coordinating the survey. Dr. Brent Hoff of the Animal Health Laboratory at the University of Guelph is a collaborator. In a post-survey follow-up, pathologists will review cases in which association with adulterated pet food is questionable, including those meeting the least number of criteria. Dr. Barbara Powers, AAVLD president and director of the Colorado State University Veterinary Diagnostic Laboratory, said that the survey goal is to distinguish true cases of nephropathy unique to this recall, hopefully resulting in a set of criteria defining a true case. Other survey objectives are to characterize the spectrum of lesions; the temporal and geographic distributions of the suspected intoxications; the species, breeds, and ages of affected animals; and when possible, the brands, lot numbers, and UPC numbers of pet food involved in the toxic exposure, and results of chemical analyses. The data will be made available to the FDA for its investigations and will form the basis for a retrospective study to be presented at the AAVLD meeting in October. Report Suspect Cases to the Oregon Public Health VeterinarianDr. DeBess has asked that veterinarians who are treating, or have treated, patients who have consumed the recalled food to report suspected cases to him via e-mail at: emilio.e.debess@state.or.us. You do not have to have tested the food or performed a necropsy to make a report. Please provide Dr. DeBess with the following information:
Dr. DeBess is applying the following general definitions to these cases:
The OVMA is working with Dr. DeBess to coordinate this reporting effort and to share this information with the media. We will post updated numbers and any new information on this recall as soon as it comes to our attention. Report Cases to the FDA The FDA has provided the following case definition for field
investigation/cases: veterinary-documented renal failure, necropsy
results if animal died, food consumed within one week of death Royal Canin US Recalls Prescription & Retail Dry Dog and Cat Food
Royal Canin has voluntarily recalled the following dry pet food products that contain rice protein concentrate due to the presence of a melamine derivative: Royal Canin Sensible Choice ® (available in pet specialty stores nationwide) Dry Dog Food
Royal Canin Veterinary Diet ™ (available only in veterinary clinics) Dry Dog Food
Dry Cat Food
Hill's Pet Nutrition Recalls Prescription Diet m/d Feline Dry FoodHill's Pet Nutrition, Inc. is voluntarily recalling its Prescription Diet m/d Feline dry food. During a two-month period in early 2007, wheat gluten for this product was provided by a company that also supplied wheat gluten to Menu Foods. FDA tests of wheat gluten samples from this period show the presence of a small amount of melamine. This is the only product Hill's currently sells in the United States that contains wheat gluten from any supplier. No other Hill's Prescription Diet® or Science Diet® products are affected by this voluntary recall. Hill's Science Diet Savory Cuts Feline canned cat foods, manufactured by Menu Foods, were previously withdrawn from the market as a precaution. The voluntary recall of Hill's Prescription Diet m/d Feline dry food involves discontinuation of all retail sales and product retrieval from sellers. This recall does not include Prescription Diet m/d Feline canned food which contains no wheat gluten. Consumers should stop using this product and return it for a refund. Following is a list of Prescription Diet m/d Feline dry products included in this recall:
Sources include: AP, American Veterinary Medical Association, AAVLD, ACVIM, FDA, Hill's Pet Nutrition, Oregon State Public Health Veterinarian, Pet Connection, ASPCA, USA Today, Royal Canin This page will be updated as events warrant. |