Tungsten alloy and cancer in rats: Kalinich responds.

We would like to address Schell's comments about our article published in EHP (Kalinich et al. 2005). Schell expresses concern about certain statements we made in our article about embedded tungsten alloy fragments, especially our reference to the undisputed Centers for Disease Control and Prevention (CDC) finding that there is an increased incidence of childhood leukemia in areas where there are high levels of environmental tungsten (CDC 2003; Sheppard and Witten 2004). Schell contends that our results showing the carcinogenic potential of embedded tungsten alloy fragments have no bearing on the situation in Fallon, Nevada, and believes that our mentioning them "is both inappropriate and misleading." We respectfully disagree.

In our article (Kalinich et al. 2005) we report an unexpected response in rats to tungsten alloys that could not have been predicted by looking at tungsten toxicity alone. We suggested that our results support the advisability for further consideration of tungsten compounds or synergistic effects of tungsten with other environmental factors in cases such as Fallon. We cited several reports in support of such a view. Miller et al. (2001, 2002) indicated that the presence of tungsten in an in vitro model system increased the toxicity of both nickel and cobalt in a synergistic manner. Wei et al. (1985, 1987) reported that tungsten exhibited a promoting effect on N-nitroso-N-methylurea-induced mammary carcinogenesis in rats. Other investigators have also suggested the cause for the Fallon cancer cluster might be an as yet uninvestigated factor or the result of simultaneous or sequential exposure to one or more agents (Daughton 2005).

At this time it is not clear whether these similar findings from diverse research are an unrelated coincidence or whether they suggest a toxicologic property of tungsten not yet understood. What is clear, however, is the need for further research in this area, not only a toxicologic assessment of tungsten alone but also potential synergistic interactions with known toxic agents. The currently proposed National Toxicology Program study of tungsten is an important first step in resolving these issues.

The author declares he has no competing financial interests.

REFERENCES

CDC. 2003. Cross-Sectional Exposure Assessment of Environmental Contaminants in Churchill County, Nevada. Final Report. Atlanta, GA:Centers for Disease Control and Prevention. Available: http://www.cdc.gov/nceh/clusters/ Fallon/study.htm [accessed 2 November 2005].

Daughton CG. 2005. Overlooked in Fallon? [Letter]. Environ Health Perspect 113:A224-A225.

Kalinich JF, Emond CA, Dalton TK, Mog SR, Coleman GD, Kordell JE, et al. 2005. Embedded weapons-grade tungsten alloy shrapnel rapidly induces metastatic high-grade rhabdomyosarcomas in F344 rats. Environ Health Perspect 113:729-734.

Miller AC, Mog S, McKinney L, Luo L, Allen J, Xu J, et al. 2001. Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy-metal tungsten-alloy metals: induction of genotoxic effects. Carcinogenesis 22:115-125.

Miller AC, Xu J, Prasanna PGS, Page N. 2002. Potential late health effects of the heavy metals, depleted uranium and tungsten, used in armor piercing munitions: comparison of neoplastic transformation and genetoxicity using the known carcinogen nickel. Mil Med 107:129-122.

Sheppard PR, Witten ML. 2004. Heavy metal content in airborne dust of childhood leukemia cluster areas: even small towns have air pollutants [Abstract]. Eos Trans American Geophysical Union 85: Fall meeting suppl., abstract A11A0025. Available: http://www.agu.org/cgi-bin/SFgate/ SFgate?&listenv=table&multiple=l&range=l&directget= 1&application=fm04&database=%2Fdata%2Fepubs %2Fwais%2Findexes%2Ffm04%2Ffm04&maxhits= 200&=%22A11A-0025%22 [accessed 4 November 2005].

Wei HJ, Luo XM, Yang SP. 1985. Effects of molybdenum and tungsten on mammary carcinogenesis in SD rats. J Natl Cancer Inst 74:469-473.

Wei HJ, Luo XM, Yang SP. 1987. Effect of molybdenum and tungsten on mammary carcinogenesis in Sprague-Dawley (SD) rats [in Chinese]. Zhonghua Zhong Liu Za Zhi 9:204-207.

John F. Kalinich

Armed Forces Radiobiology 

Research Institute

Bethesda, Maryland

E-mail: [e-mail]