March 2007


Melamine is a urea- and formaldehyde-based synthetic polymer used in a wide range of products: kitchen utensils and dishes, Formica, laminate flooring, whiteboards, wood-based kitchen cabinets and assemble-it-yourself furniture, fire retardants (including flame-retardant fabric), cleaning compounds (e.g., Magic Eraser), disinfectants, latex-based coatings (e.g., paint), and fertilizer. It is considered highly stable, has good heat resistance (but will melt under high heat, such as in a microwave), and is difficult to recycle.

Melamine is not widely studied in animals but is considered only minimally toxic. LD50 for oral exposure in rats is 3248 mg/kg and in mice is 3296 mg/kg. LD50 for skin exposure in rabbits is >1000 mg/kg. The lowest published lethal dose for intraperitoneal exposure in rats is 3200 mg/kg (source).

According to OSHA, potential symptoms of melamine exposure include

Irritation of eyes, skin, and mucous membranes; dermatitis; in animals: chronic inflammation of kidneys (female rats); ulceration of urinary bladder epithelium (mice), urolithiasis (rats and mice); bladder cancer (male rats).

. . .

The main constituents of the stones in the urinary bladders of rats given melamine in the diet were reported to be unchanged melamine and uric acid in a 1:1 molar ratio.

Dimelamine phosphate was reported to be a urinary product of melamine in dogs and rats, which showed a diuretic response to melamine.

According to VIN, cats would need to eat huge amounts of recalled food (on the order of 4 kg per day) before we’d see mortality rates approaching the LD50 for rats (assuming you can accurately extrapolate LD50 data for rats to other species).

Melamine is a metabolite of the insecticide cyromazine, which is used in livestock and poultry without restriction in the United States. Cyromazine breaks down into melamine. A report from the European Agency for the Evaluation of Medicinal Products notes that pharmakokinetic studies show that dealkylation of cyromazine leads to the presence of melamine in the urine of animals that have ingested cyromazine. Could cyromazine residues in beef and poultry tissue be the source of the melamine in pet food?

So, melamine might well prove not to be the toxin causing acute renal failure dogs and cats, but it could be useful as a marker for determining whether a given pet with renal failure has ingested the recalled food.

Research articles
Cremonezzi DC, Diaz MP, Valentich MA, Eynard AR, Neoplastic and preneoplastic lesions induced by melamine in rat urothelium are modulated by dietary polyunsaturated fatty acids, Food Chem Toxicol. 2004 Dec;42(12):1999–2007.

Results show that dietary PUFA [polyunsaturated fatty acids] modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO [fish oil], rich in n-3 fatty acids, showed a strong protective effect.

Neerman MF, Chen HT, Parrish AR, Simanek EE, Reduction of drug toxicity using dendrimers based on melamine, Mol Pharm. 2004 Sep–Oct;1(5):390–393. [Melamine-based dendrimers found to reduce the hepatotoxicity of cancer drugs such as methotrexate (which is almost identical to aminopterin).]

Ogasawara H, Imaida K, Ishiwata H, Toyoda K, Kawanishi T, Uneyama C, Hayashi S, Takahashi M, Hayashi Y, Urinary bladder carcinogenesis induced by melamine in F344 male rats: correlation between carcinogenicity and urolith formation, Carcinogenesis. 1995 Nov;16(11):2773–2777. [This study found that among rats fed diets containing 3 percent melamine, 90 percent developed urinary carcinomas. Note that the diets recently tested by the FDA contained far smaller amounts of melamine: 0.01–0.2 percent. Also:]

[M]elamine-induced proliferative lesions of the urinary tract of rats were directly due to the irritative stimulation of calculi, and not molecular interactions between melamine itself or its metabolites with the bladder epithelium.

Okumura M, Hasegawa R, Shirai T, Ito M, Yamada S, Fukushima S, Relationship between calculus formation and carcinogenesis in the urinary bladder of rats administered the non-genotoxic agents thymine or melamine, Carcinogenesis. 1992 Jun;13(6):1043–1045.

Heck HD, Tyl RW, The induction of bladder stones by terephthalic acid, dimethyl terephthalate, and melamine (2,4,6-triamino-s-triazine) and its relevance to risk assessment, Regul Toxicol Pharmacol. 1985 Sep;5(3):294–313.

[Melamine] induced bladder tumors in rats in chronic feeding studies. However, it is likely that these tumors were secondary to the development of calculi. . . . [Melamine is] apparently nongenotoxic, and [it does] not appear to be metabolized. Increased cell replication in the urothelium of the bladder caused by chronic physical injury was probably a major factor in the mechanism of induction of bladder tumors by bladder stones.

Melnick RL, Boorman GA, Haseman JK, Montali RJ, Huff J, Urolithiasis and bladder carcinogenicity of melamine in rodents, Toxicol Appl Pharmacol. 1984 Feb;72(2):292–303. [This multi-variable study examined the effects of melamine on mice and rats fed a melamine-laced diet (in concentrations ranging from 750 to 18,000 ppm) for either 13 or 103 weeks “to determine its toxicologic profile, including carcinogenic potential.” Most of the study’s findings relate to urinary bladded stones (generally increased among groups fed melamine, and more so among males than females) and carcinomas (increased incidence among male rats fed higher amounts of melamine; not found among male or female mice), although among female rats, “chronic inflammation of the kidney was observed at an increased incidence (relative to controls) in both the low (4500 ppm) and high (9000 ppm) dose groups.”]

Mast RW, Jeffcoat AR, Sadler BM, Kraska RC, Friedman MA, Metabolism, disposition and excretion of [14C]melamine in male Fischer 344 rats, Food Chem Toxicol. 1983 Dec;21(6):807–810. [This study found that in (male) rats melamine is not metabolized, “distrubtes in body water,” concentrates in the kidneys and urinary bladder at slightly higher levels than elsewhere in the body, and is cleared by the kidneys at a rate of 2.5 ml/min.]

National Toxicology Program, NTP Carcinogenesis Bioassay of Melamine (CAS No. 108-78-1) in F344/N Rats and B6C3F1 Mice (Feed Study), Natl Toxicol Program Tech Rep Ser. 1983 Mar;245:1–171. [Full report here.]

Questions

  • Given the wide variety of materials that contain melamine (including many dog bowls and cat bowls, as well as disinfectants used in the food manufacturing inustry), is it possible that exposure is commonplace? Could the finding in pet food and cats that ate recalled food be incidental?
  • Some veterinarians have been skeptical of the finding that aminopterin was repsonsible for the deaths and illness from the recalled food because of the lack of hepatic symptoms. Is it possible that the presence of melamine had a protectant effect on the liver and thus reduced the number of hepatic symptoms seen?
  • How long before we know whether the melamine in the recalled food is causing urinary bladder cancer among pets that ate it?
  • Why have the FDA and other labs not been able to confirm the New York State lab’s finding of aminopterin (excepting a Canadian lab that reports finding aminopterin in amounts too low to cause damage)?
  • Why is the FDA no longer focusing on aminopterin? Given the lack of evidence that melamine is nephrotoxic in cats and dogs, is the FDA looking for yet more contaminants?

Melamine resources
Wikipedia
MSDS
OSHA Chemical Sampling Information
National Toxicology Program report
PAN Pesticides Database
“What the FDA Isn’t Telling Us about Melamine”

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The news reports today are all over the board. These four stories appeared within three hours of one another:

What are we to conclude? The food is safe? Caution is still needed? The illness is mysterious and something to worry about? The problem is fear itself, and we are overreacting? Catmanager has no idea. But I’m sort of glad for the confusion; it reminds us that in a crisis events aren’t orderly, we don’t have immediate answers to questions, and we need both to remain skeptical and to keep an open mind. I’ve seen a lot of skepticism but somewhat less open-mindedness.

The discovery of melamine in the recalled food (and in the urine and kidneys of some affected cats) is unlikely to be the end of the story. So keep asking questions and keep demanding that governments and corporations share information. But don’t jump to conclusions. Remember that no one at this point has a panoramic view of the situation.

The Iowa State University College of Veterinary Medicine has been granted full accreditation. The school had been on limited accreditation status for the past few years.

Scientific American offers a special report on the pet food recall (PetConnection blogged about it earlier). While mostly a summary of the recall peppered with stories of pets that have been affected, what interested catmanager was the details about the process used to identify aminopterin as the toxin in the food:

[The Cornell lab] received samples of both food products and animal remains from Menu Foods a day or two before the recall. Using liquid chromatography-mass spectrometry (a process that separates complex mixtures and analyzes ingredients by measuring a weight-to-charge ratio), researchers compared the constituent chemicals in the food to standards for common molds, heavy metals and ethylene glycol (or antifreeze, which Goldstein says is the number one cause of kidney failure). All test results were negative.

Cornell’s initial tests were inconclusive, so the university sent samples to the NYDASM [New York State Department of Agriculture & Markets] food safety lab, which has an expanded set of contaminants to compare with the food. This lab detected aminopterin after switching to a UV-light detector to help them visualize the poison; it was initially difficult to pinpoint because of the food’s gummy consistency, which makes it hard to load into their machines and then to isolate out components.

Cornell is now trying to replicate the results of the state lab.

Charges were dropped today against the former head of the Nebraska VMA, who had been accused of injecting vodka into race horses.

The spring issue of Equine News, a newsletter from the Washington State University College of Veteirnary Medicine is now available. The current issue includes stories on laminitis, the current outbreak of equine herpes virus, and postpartum care for mares.

The FDA slapped Iams on the wrist for using chromium tripicolinate in some of its Eukanuba prescription diets.

The FDA also announced a public meeting on their Animal Feed Safety System to be held in May.

During the past several years, FDA has been considering changes to the Agency’s Animal Feed Safety System (AFSS), which is a program aimed at protecting human and animal health by ensuring that animal feed is safe. As part of this effort, FDA is developing a model for ranking the relative risks to human and animal health from contaminants in animal feed.

In light of the current pet food recall, catmanager thinks the tone of this meeting might be a bit different from the public meeting held last September.

Coming in June to the CW, a new TV drama about a veterinarian who moves his family to South Africa.

If you live in Virginia, Happy Rabies Awareness Week (catmanager is sorry to say he wasn’t aware—but then I don’t live in Virginia).

The PetsitUSA blog reports on a lab now offering aminopterin testing (although the press release from which they quote makes it sound like the lab isn’t quite set up to run the test). They also mention that Iowa State’s lab has offered to test food and pets. Catmanager spoke with a veterinarian at this lab earlier this week. I found out that Iowa is still getting set up to test for aminopterin but does plan to offer that service. They hope to be set up soon. The veterinarian I spoke with thought the test would cost under $100, but he cautioned that pricing hadn’t been set and would depend on precisely which materials are needed to run the test.

Compassion Fatigue Intervention offers advice to veterinarians on helping clients cope with the recall-related deaths of their patients.

You may be seeing what is called “complicated grief.” This type of grief occurs when the circumstances of a pet’s death make grieving more difficult than usual (as is the case with accidental death)

The therapist behind this blog offers sensible advice. Her final point: don’t forget to take care of yourself too. Veterinary professionals aren’t immune to feelings of shock, sadness, and anger over the death and illness that tainted food has caused.

(Pet Connection has also created a page of pet-loss resources.)

One of the posters at the Vet Tech blog reports on some truly novel pet foods. Canned beaver, anyone?

This guy really, really doesn’t like alternative/holistic medicine. He tells the story of his veterinarian girlfriend’s firing after questioning her bosses about the necessity of treating pets with applied kinesiology and acupuncture.

She was told something to the effect of “I do it if the patient asks. At the very worst, it’s not like it’ll hurt.”

My wife spoke with an AP reporter yesterday about the food recall. One question the reporter asked was whether the state veterinarians had asked local veterinarians to send in data on pets affected by the recall. Oregon’s state veterinarian has been collecting data in his state and released numbers earlier this week.

The reporter’s question got catmanager wondering about how the state veterinarians and state veterinary medical associations had responded to the pet food recall.

What I discovered was disappointing and might go a long way toward explaining why it’s been so hard to get official numbers: almost none of the states seem to want to collect the information (or if they do, they’re making it darned difficult to find out how and to whom to report data). I know Gina and the crew at Pet Connection have proposed a national, centralized system to which veterinarians could submit morbidity and mortality data during crises like the current one. This is a wonderful, long-overdue idea, and I urge pet owners to press the idea on their congressmen and -women. I also urge them to agitate at the state level. I see no reason why the states cannot develop their own reporting structures (perhaps in conjunction with the federal government). Doing so will allow local information to be disseminated more quickly (rather than waiting for the federal government to disaggregate data from around the country, states could release their own data) and will give states the information needed to more effectively manage crises like the present one. If you’re concerned about how the pet food recall has been handled, don’t forget to work for change at the local level as well as the national.

Before jumping into the results of my canvassing, some caveats:

  • Catmanager is not a member of any of the state veterinary medical associations. So I was unable to access the members-only sections of their Web sites. Sites that had no publicly available information about the recall might still have information that is only available to the members.
  • Also, although I have not heard reports of this happening, it is possible that some (or even all) state VMAs have contacted their members via e-mail, fax, or phone to alert them about the recall.
  • In most states the state veterinarian is a position within the department of agriculture. Not all states have Web pages specifically for the office of state veterinarian. I’ve done my best to identify the appropriate Web sites for all the state veterinarians, but I might have missed some and thus missed information about the recall on their Web site.
  • Furthermore, in many cases the state veterinarian’s primary responsibility is for food animals. Because of this, some might have deemed the pet food recall to be outside their purview and thus have made a conscious decision not to post information about it.

With caveats out of the way, onward to the data! As of 27 March,

  • 24 state VMAs plus the Puerto Rico VMA provided (publicly accessible) information about the recall on their Web sites.
  • Of these, 16 included only links to other sites (typically the AVMA, Menu Foods, and the FDA); and 8 included at least some original content, such as a summary of the recall or a press release generated by the VMA.
  • In catmanager’s opinion, the Georgia and Oregon VMAs have done the best job of providing information to the public.
  • 15 of the 50 state veterinarian Web sites (including Web sites of departments that comprise state veterinarians’s offices) provide publicly available information about the recall.
  • 1 (Connecticut) addresses the need for the state veterinarian to work closely with the state VMA during the crisis
  • Only 3 (4 if you count Connecticut) discuss what the state is doing to respond to the crisis (in each case: spot checking retailers to make sure they’ve pulled the recalled pet food; in the case of Georgia: also conducting lab testing of the recalled food)
  • 1 state (Vermont) asks veterinarians to report deaths and illnesses that they suspect are related to recalled food. (We know that Oregon has been collecting this data, but I couldn’t find on the Oregon state Web site where they invite veterinarians to submit data.

The data
The table that follows lists all fifty states, the District of Columbia, and Puerto Rico. From the left, the columns indicate state; whether I found publicly available information about the recall on the state VMA’s Web site; any comments I wanted to make about the state VMA’s Web site; whether I found information about the recall on the state veterinarian’s Web site (or the department or agency to which the state veterinarian’s office belongs); and any comments I wanted to make about the state vet’s Web site. To check out the state VMA Web sites, go here. To check out the state veterinarian Web sites, go here.

State VMA mentions recall Notes State vet mentions recall Notes
Ala. no   no  
Ak. ? no Web site no  
Ariz. yes links to information elsewhere no  
Ark. no   no  
Cal. yes links to information elsewhere, plus a client information sheet created by the CVMA and a fact sheet for veterinarians supplied by Iams no  
Col. yes links to information elsewhere no  
Conn. yes links to AVMA advice to pet owners yes press release urging pet owners to check their pets’ food and the Dept of Ag to work closely w/CVMA to ensure the public is getting “accurate information” about the recall
Del. no   no  
D.C. no   ?  
Fl. yes press release and links to information elsewhere no  
Geo. yes information for pet owners on main page; FAQ for pet owners; information for member veterinarians (not publicly accessible); one of the better responses yes a couple of hard-to-find press releases: one notes the state lab will be testing samples and inspectors will be checking that retailers comply with the recall
Hi. no   no  
Idaho no   no  
Ill. no yes Update, 3/28: Now recommends AVMA main page for info. no  
Ind. yes links to information elsewhere no  
Iowa yes information for pet owners (from AVMA); information for member veterinarians (not publicly accessible) no  
Kan. yes information from AVMA no  
Ken. yes links to AVMA no  
La. yes three press releases in .doc format yes press release on main Dept. of Ag and Forestry site
Maine no   no  
Md. yes mostly information for pet owners (from AVMA) no  
Mass. yes links to information elsewhere yes link to PDF
Mich. yes several documents in .doc format; links to information elsewhere no  
Minn. yes “Information about Dog Food Recall” (which links to the original FDA press release) no  
Miss. unknown no Web site no  
Mo. yes links to AVMA no  
Mt. no   no  
Neb. yes brief description on Web site; links to information elsewhere no  
Nev. no   no  
N.H. no   no  
N.J. yes links to FAQ in .doc format (same as La.) yes reprints FDA’s original news release
N.M. no   no  
N.Y. no no publicly available information; possibly information available for members only yes press release announcing discovery of toxin (seems to be the only mention)
N.C. no   yes on main Dept. of Ag page
N.D. no   no  
Ohio no   yes on main Dept. of Ag page (link to Menu Foods)
Okla. yes links to information elsewhere no  
Ore. yes plenty of information, most on the site; one of the best yes link to FDA’s original press release
Penn. no yes Update, 3/28: Now has page dedicated to recall information, including alerts sent to PVMA members and links to information elsewhere. One of the better state VMA responses. yes press release and links to information elsewhere
P.R. yes links to Menu Foods ? no Web site
R.I. yes links to AVMA press releases; site mentions only the Iams and Eukanuba recall yes press release (notes officials will be spot checking retail outlets for compliance with recall); links to FDA, Menu
S.C. yes links to information elsewhere (link to VIN actually goes to the Veterinary News Network) no  
S.D. no   no  
Tenn. no   no  
Texas yes links to AVMA and Menu Foods no  
Utah no   no  
Vt. no   yes press releases on main Agency of Ag page; one asks vets to report deaths and notes inspectors have been checking retailers for compliance with the recall
Va. no   no  
Wash. yes press release; links to information elsewhere yes overview (written for pet owners) and links to information elsewhere
W.V. no   yes press release on main Dept of Ag page
Wisc. no information might be available in members-only section yes info on main Dept. of Ag page with more info here, including links and advice for pet owners, vets, and retailers [This is the most informative state vet site I found.]
Wy. no   no  

A Colorado bill that would have allowed nonveterinarians to offer animal massage, dentistry, breeding, and other services without the direct supervision of a licensed veterinarian (but with the written consent of an animal’s owner) was voted down in committee.

A cure for rabies? A Wisconsin pediatrician appeals to the veterinary community to help perfect the “Milwaukee Protocol.” Dr. Rodney Willoughby, who in 2004 successfully (!) treated a 15-year-old girl infected with rabies is exploring the role of biopterin (yes, another pterin; unlike aminopterin, this one seems to be beneficial) and hopes veterinarians will join him. If you’re a veterinarian (or veterinary college) with intensive care units and you’d like to host animals with full onset rabies, I think Dr. Willoughby would appreciate hearing from you. His full appeal to veterinarians and much more information about his research will be published in the April edition of Scientific American.

A Seoul veterinarian claims to have cloned a wolf.

Thais veterinarians hope pornography will encourage pandas in a Thai zoo to mate. (This is a legitimate, AP story published in the New York Times. Really.)

The Times also runs a story on the recent legislative attempts to ban horse slaughter.

Recall-related stories
Recall-related data collected on VIN make it into a snippet of an article in the Chicago Tribune.

The L.A. Times offers a longer story on the data being collected online. The article mentions VIN and Pet Connection and notes that VIN will be sending a survey out to members to collect “more complete information.” If you’re on VIN, watch for this!

Watch Early Show veterinarian Dr. Debbye Turner offer advice to pet owners (of course it’s about the pet food recall).

Listen to a New York veterinarian discuss pet foods (including home-cooked foods) with a reporter from the Lockport (NY) Union-Sun and Journal.

Canadians (and a surprising number of U.S. citizens) opine about whether pet food should be regulated in Canada.

Journal issues newly available online:

  • Comparative Immunology, Microbiology and Infectious Diseases, Vol. 30, Issue 3 (May 2007)
  • Journal of Applied Microbiology, Vol. 102, Issue 4 (April 2007)
  • Journal of Feline Medicine and Surgery, Vol. 9, Issue 2 (April 2007) [Note: catmanager will provide a journal summary of this issue at a later time.]
  • Preventive Veterinary Medicine, Vol. 80, Issue 1 (15 June 2007)
  • Theriogenology, Vol. 67, Issue 6 (1 April 2007)
  • Veterinary Parasitology, Vol. 145, Issues 1–3 (10 April 2007)

The latest issue of the Journal of Small Animal Practice (Vol. 48, Issue 4, April 2007) is now available online. Of note in this issue:

  • A comparison (188–192; abstract) of radiographic, ultrasonographic, and computed tomography evaluations of the middle ear finds that “A combination of radiography and ultrasound can provide a more accurate assessment of the bulla than either of them alone.” The authors caution, however, that because the results are dependent on the skill of the ultrasonographer, this might not be a useful diagnostic modality for all practitioners. In lieu of a combination approach, radiographs are the superior diagnostic tool.
  • A retrospective study (194–200; abstract) evaluates the use of circular external fixators in dogs.
  • A study (202–208; abstract) concludes that aldosterone is a dead end for the study of feline hypertension.
  • A retrospective study (211–217; abstract) investigates the epidemiology (including breed distribution, age of onset, severity of symptoms) of canine keratoconjunctivitis sicca.

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