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September 10, 2007

RFID-associated tumors in mice: abstracts for four studies

Below are four abstracts related to tumors in mice and rats (one study was negative for tumors) associated with microchip implantation. The full citations and abstracts are listed in the extended post.

The first is a study from 1997, which was studying parental preceptual x-ray and chemical carcinogen exposure on around 4300 mice. Tumor nodules encasing the chip were seen in 36 mice. "Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected."

The next is a study from 1999, looking at a short-term method for chemical carcinogenicy . "Microscopic examination of all implant sites revealed that 18 of 177 animals had a subcutaneous histologically malignant sarcoma."

"An unusual preneoplastic mesenchymal change characterized by the term 'mesenchymal dysplasia' was present in most groups and was considered to be a prodromal change to sarcoma development."

The third from 1990, looked at the tissue stability and reaction to microchip implants in 140 mice. No tumors were found.  "Neoplastic changes were not observed in the tissue around the glass-sealed devices with polypropylene cap for up to 24 months."

A fourth, from two separate chronic toxicity/oncogenicity studies. "The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases."

"All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma."

Exp Toxicol Pathol. 1997 Aug;49(3-4):197-200.

Subcutaneous soft tissue tumours at the site of implanted microchips in mice.

Tillmann T, Kamino K, Dasenbrock C, Ernst H, Kohler M, Morawietz G, Campo E, Cardesa A, Tomatis L, Mohr U.

Institute of Experimental Pathology, Hannover Medical School, Germany.

An experiment using 4279 CBA/J mice of two generations was carried out to investigate the influence of parental preconceptual exposure to X-ray radiation or to chemical carcinogens. Microchips were implanted subcutaneously in the dorsolateral back for unique identification of each animal. The animals were kept for lifespan under standard laboratory conditions. In 36 mice a circumscribed neoplasm occurred in the area of the implanted microchip. Females were significantly more frequently affected than male mice. An influence of age or different treatment on the s.c. tumour incidence in two mice generations could not be observed. Macroscopically, firm, pale white nodules up to 25 mm in diameter with the microchip in its center were found. Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected.


Toxicol Pathol. 1999 Sep-Oct;27(5):519-27.

Transponder-induced sarcoma in the heterozygous p53+/- mouse.

Blanchard KT, Barthel C, French JE, Holden HE, Moretz R, Pack FD, Tennant RW, Stoll RE.

Department of Toxicology and Safety Assessment, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877, USA. kblancha@rdg.boehringer-ingelheim.com

Heterozygous p53+/- transgenic mice are being studied for utility as a short-term alternative model to the 2-yr rodent carcinogenicity bioassay. During a 26-wk study to assess the potential carcinogenicity of oxymetholone using p-cresidine as a positive control, glass/polypropylene microchips (radio transponder identification devices) were subcutaneously implanted into male and female p53+/- mice. During week 15, the first palpable mass was clinically observed at an implant site. This rapidly growing mass virtually quadrupled in size by week 25. Microscopic examination of all implant sites revealed that 18 of 177 animals had a subcutaneous histologically malignant sarcoma. The neoplasms were characterized as undifferentiated sarcomas unrelated to drug treatment, as indicated by the relatively even distribution among dose groups, including controls. An unusual preneoplastic mesenchymal change characterized by the term "mesenchymal dysplasia" was present in most groups and was considered to be a prodromal change to sarcoma development. The tumors were observed to arise from dysplastic mesenchymal tissue that developed within the tissue capsule surrounding the transponder. The preneoplastic changes, including mesenchymal dysplasia, appeared to arise at the transponder's plastic anchoring barb and then progressed as a neoplasm to eventually surround the entire microchip. Capsule membrane endothelialization, inflammation, mesenchymal basophilia and dysplasia, and sarcoma were considered unequivocal preneoplastic/neoplastic responses to the transponder and were not related to treatment with either oxymetholone or p-cresidine.

Toxicol Pathol. 1990;18(3):412-6.

Tissue reaction to an implantable identification device in mice.

Rao GN, Edmondson J.

Division of Toxicology Research and Testing, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

Long-term toxicity and carcinogenicity studies require positive identification of animals. Due to the unreliability of traditional methods, it was necessary to investigate more dependable identification methods that can be read directly or by electronic means. A two-year study to determine the stability of and tissue reaction to a microchip glass-sealed device implanted in subcutaneous tissue of mice was conducted. Seventy B6C3F1 mice of each sex were anesthetized and implanted with the microchip. The devices were read by an electronic detector and palpated at periodic intervals. Ten mice of each sex were necropsied at 3 months and at 15 months with the remaining animals necropsied at 24 months. Of the 140 devices implanted, 3 were lost and 4 failed during the 24-month study. Devices were palpable and appeared to be fixed at one location with no obvious swelling due to inflammation or palpable masses around the implants for 24 months. At the 3, 15, and 24 month necropsies, implants were encapsulated by connective tissue. Light microscopic evaluation indicated that the capsule around the implants was thin and composed of fibrocytes and mature collagen fibers, with minimal to mild inflammation and occasional granulomatous reaction. Neoplastic changes were not observed in the tissue around the glass-sealed devices with polypropylene cap for up to 24 months.

Exp Toxicol Pathol. 2001 Feb;52(6):483-91.

Tumors in long-term rat studies associated with microchip animal identification devices.
Elcock LE, Stuart BP, Wahle BS, Hoss HE, Crabb K, Millard DM, Mueller RE, Hastings TF, Lake SG.

Bayer Corporation, Toxicology Department, Stilwell, Kansas 66085, USA. laura.elcock.b@bayer.com

Tumors surrounding implanted microchip animal identification devices were noted in two separate chronic toxicity/oncogenicity studies using F344 rats. The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases. No sex-related trends were noted. All tumors occurred during the second year of the studies, were located in the subcutaneous dorsal thoracic area (the site of microchip implantation) and contained embedded microchip devices. All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma. The following diagnostic techniques were employed: light microscopy, scanning electron microscopy, and immunohistochemistry. The mechanism of carcinogenicity appeared to be that of foreign-body induced tumorigenesis.

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