Sep 11, 2007

Animal Chip Implants Linked to Cancer


Even though this is only a preliminary study not definitive, I find this both concerning and disappointing. Concerning because cancer has been such an oppressive enemy for so long, disappointing in that yet again a government official is playing both sides. To top it off, I have heard many cities in the US are now making micro-chipping MANDATORY for pets. And previous to that, many people just jumped on board because of how useful it would be if their animal companions got lost or stolen.

I wonder (and worry) if eventually they will not find a similar problem in the melatonin chips that are wildly popular with ferret folk?

This weekend the Associated Press broke a story suggesting a link between VeriChip's implantable chip technology in animals and the formation of cancerous tumors. The story has been picked up widely, from the mainstream media to tech blogs to pet publications. Following is what the RFID industry needs to know.

From 1996 to 2006, a handful of studies reported incidences of tumors in lab mice and rats that had been implanted with chips. Specifically, malignant tumors (sarcomas) developed near and around the chips, in some cases completely enveloping them. A 1998 study in the US found the incidence of cancer to be higher than 10 percent in a group of 177 tested mice. A 1997 German study revealed a cancer incidence of one percent in a group of over four thousand, with the researchers noting that the tumors "are clearly due to the implanted microchips." And just last year a study in France saw 4.1 percent of 1,260 chipped mice develop cancer.

The significance of these findings is not just the potential danger to chipped pets, but the fact that the technology in question is essentially the same as that used in the VeriChip product for humans.

Note, however, that the findings are preliminary and do not definitively condemn the technology as a cause of cancer in animals or in humans. One study said as much, cautioning, "Blind leaps from the detection of tumors to the prediction of human health risk should be avoided." Ohio State University veterinarian oncologist Dr. Cheryl London commented, "It's much easier to cause cancer in mice than it is in people. So it may be that what you're seeing in mice represents an exaggerated phenomenon of what may occur in people." Perhaps most significant of all is the fact that millions of pets have been chipped over the last fifteen years, and no widespread problem has surfaced. (Although after the attention this story will bring, new cases might well be uncovered.)

Still, the studies warrant further investigation, according to a number of cancer researchers whom the AP asked to review and interpret the research. Dr. Robert Benezra, head of the Cancer Biology Genetics Program at the Memorial Sloan-Kettering Cancer Center in New York, told the AP, "There's no way in the world, having read this information, that I would have one of those chips implanted in my skin, or in one of my family members." Others were less dramatic. National Cancer Institute veterinary oncologist Dr. Chand Khanna acknowledged that the studies "suggest some reason to be concerned about tumor formations" and advocated further investigation. Forensic pathologist Dr. Oded Foreman of the Jackson Laboratory in Maine said that there "might be a little hint that something real is happening here."

One curious wrinkle to the story is how the studies have gone relatively unnoticed, even by VeriChip itself...

Read The Full Story Here

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Sep 2, 2007

2007 Week 36: Erythritol toxicity


Sugar diseases are a problem for ferrets - particularly insulinoma - and we are always looking for safe sweeteners to help the medicine go down easier. (Frankly, I got tired of pink Pepto Bismol baths pretty quickly.)

Erythritol is under consideration as it is widely available in Japan. But as it is a sugar alcohol like xylitol, it raises some questions of toxicity.

Here are some papers from PubMed regarding its effects after testing on dogs, rats, mice, and rabbits.

"Chronic (1-year) oral toxicity study of erythritol in dogs."
Highlights from the abstract:
-> There were no clinically relevant changes in hematological or clinicochemical parameters attributable to treatment.
-> ...however, the available data did not indicate treatment-related effects on the urinary excretion of electrolytes (K+, Na+, Mg2+, and Pi) or enzymes (gamma-glutamyltranspeptidase, N-acetyl glucosaminidase, and lactate dehydrogenase
-> Quantitation of erythritol in the urine demonstrated that 50 to 80% of the ingested dose was absorbed and excreted in the urine.
-> It was concluded that daily erythritol consumption of up to 3.5 g/kg body wt was well tolerated by dogs.

"Four-week oral toxicity study with erythritol in rats."
Highlights from the abstract:
->Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study.
->Small statistically significant changes in certain hematological, clinical chemistry, and urine parameters were noted in the high-dose group but were judged not to be biologically important.
->Based on these results, it was concluded that the feeding of erythritol at a dietary level of 10% did not result in toxicologically significant effects.

"Subchronic oral toxicity studies with erythritol in mice and rats."
Highlights from the abstract:
->There were no treatment-related mortalities in either mice or rats.
->Hematological and clinicochemical examinations of blood and plasma did not reveal any treatment-related effects.
->Urine output increased with increasing erythritol dose.
->Increased relative and absolute kidney weights were observed in both sexes of mice in the 20% erythritol group, in male mice of the 5 and 10% groups, and in rats of the 10 and 20% erythritol groups.
->In rats, the creatinine-normalized urinary excretion of GGT, NAG, and some electrolytes (Na+, K+, and Ca2+) was increased in some erythritol groups but a clear dose-response relationship was evident only for calcium.
->In particular, the morphological integrity of the kidneys was not adversely affected by the treatment in either species. The increases in urinary excretion of protein, GGT, NAG, and electrolytes were considered to result from extensive osmotic diuresis and a potential overload of the renal excretory system at the high dose levels employed.

"Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data."
Highlights from the abstract:
->The majority of the safety studies conducted were feeding studies in which erythritol was mixed into the diet at concentrations as high as 20%
->The metabolic studies in animals have shown that erythritol is almost completely absorbed, not metabolized systemically and is excreted unchanged in the urine.
->The safety studies have demonstrated that erythritol is well tolerated and elicits no toxicological effects.
->Erythritol administered orally to humans was rapidly absorbed from the gastrointestinal tract and quantitatively excreted in the urine without undergoing metabolic change.

"Chronic toxicity and carcinogenicity study of erythritol in rats."
Highlights from the abstract:
->All treatments were well tolerated without diarrhea or other side effects.
->Hematological and clinicochemical examinations did not reveal noticeable changes which could be attributed to treatment.
->urine samples collected during five 48-hr periods ... showed that about 60% of ingested erythritol was excreted unchanged. The urine volumes increased with increasing dietary erythritol levels.
->Except for more frequent pelvic nephrocalcinosis (precipitation of calcium phosphate in the renal tubules, with resultant renal insufficiency.)in female rats of all erythritol dose groups, the histopathological examinations did not reveal any nonneoplastic, preneoplastic, or neoplastic changes that could be attributed
->In the absence of morphological alterations in the kidneys or other signs of nephrotoxicity, the increased excretions of NAG, GGT, LMP, and TP are regarded as innocuous, functional sequelae of the renal elimination of erythritol.
->Except for nephrocalcinosis, which is commonly seen in polyol-fed rats, no other treatment-related, morphological changes were observed in the kidneys. Evidence for a tumor-inducing or tumor-promoting effect of erythritol was not seen.

"Embryotoxicity and teratogenicity study with erythritol in rats."
Highlights from the abstract:
->The treatment was generally well tolerated and no mortality occurred in any group.
->Examination of the fetuses for external, visceral, and skeletal alterations did not reveal any fetotoxic, embryotoxic, or teratogenic effects.
->In conclusion, no adverse effects were observed at erythritol doses of up to about 6.6 g/kg body wt/day, i.e., the highest dose tested.

"Teratology study of erythritol in rabbits."
Highlights from the abstract:
->Maternal effects (auricular edema, and bradypragia) were observed in the high-dose group.
->No deaths or significant abnormalities occurred in animals given 1.0 or 2.24 g/kg
->No effect was observed in the reproductive performance of the dams or in fetal development from ingestion at any of the treatment levels.

"Erythritol: a review of biological and toxicological studies."
Highlights from the abstract:

One thing often mentioned in the studies is that there were noticable changes (enlargements, weight increases) to the 'cecum'. As ferrets do not have one, I did not list it with the other highlights.

If you read the abstracts with dosing details you will also notice that testing was done a rather high levels. I would think from these that it is _possible_ to safely use erythritol in healthy ferrets especially in the under 1gm/kg range that I am considering. However, there are certain drugs that cause increases or decreases in K or other electrolyte uptake. That is something to consider before using erythritol as a sweetener for medicine .

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