SUMMARY OF CONCERNS

On a molecular level:

• Does intrathyroidal sulfite play a role in the autoimmunity to myeloperoxidase and thyroid apoptosis associated with propylthiouracil (PTU)? Can perchlorate inhibit the thyroidal molybdenum co-factor enzyme sulfite oxidase sufficiently to also produce intrathyroidal sulfite and induce some of the same immunological effects as PTU? What about direct affects by perchlorate and thiocyanate on mitochondrial ATPase stimulated by sulfite or other anions? How does the perchlorate-induced skin contact sensitivity reported by Burleson compare with lymph node activity triggered by the propylthiouracil metabolite propyluracil-2-sulfonate or BAY K8644? Does perchlorate, albumin and citrate (a mixture used to separate liver cells) interfer with synthesis of molybdenum co-factor enzymes?
• Why is the calculated half-life of radiolabeled perchlorate 32 hours in skin when it is only 7 hours in the blood serum and thyroid? Can perchlorate react with iron or other metals in the skin when exposed to ultraviolet light? Does perchlorate target mesothelium like bromate? (Although perchlorate clearly isn't as reactive as bromate). Does perchlorate adhere to or utilize favorable lattice energies produced by hyaluronic acid, alter intracellular calcium levels (like BAY K8644), or inhibit sulfation of CD44 and/or chondroitin (like chlorate) so that it interfers with the proper function of the CD44 cell adhesion/merlin tumor suppressor/ezrin growth factor system, particularly in regards to the mediation of transforming growth factor beta?
• Can perchlorate act synergistically with vanadium (in pervanadate form) as the latter enhances blood serum betaglycan and ezrin expression in the CD44/Merlin/Ezrin system? Can it act synergistically with vanadium (in vanadate form) as the latter inhibits anion-stimulated mitochondrial ATP-ase? Why does vanadium appear to make thyroid peroxidase more efficient in rats? Could vanadium replace iron in the active site of thyroid peroxidase (in the same manner tungsten can replace molybdenum in molybdenum cofactor enzymes) and complex/react with perchlorate?
  
• Does perchlorate form complexes with phosphoric acid in the lacunae of osteoclasts resorpting bone mineral? Could this potential effect, or malfunction of CD44/Merlin/Ezrin, be contributing to the unusual incidence of osteosarcoma (primary bone cancer) found at the perchlorate processing center at Hill Air Force Base outside Ogden UT and the potash mining town of Allan SK?
  

On a clinical level: 

• How variable is urinary excretion of perchlorate? Does renal retention of thiocyanate establish that pendrin is the sole renal iodide transporter? Do diabetics with incipient untreated nephropathy who retain iodide in the bloodstream also retain perchlorate? How effectively does acidosis diminish renal pendrin function and promote perchlorate accumulation in the bloodstream? Could the malaria-adaptive Southeast Asian ovalcytosis mutation of the AE1 gene lead to greater renal retention of perchlorate and contribute to the high thyroid cancer rate amongst Filipina immigrants to the US? Is this also what happened to the "Texas Businessman" with congenital distal renal tubular acidosis who came down with thyroid cancer after living next to Rancho Cordova's 300 ppb perchlorate well?
• Is there linkage between autoimmunity to thyroid peroxidase or myeloperoxidase and exposure to perchlorate?
• Does perchlorate disrupt calcitonin levels secondary to it's BAY K8644-like ability to reverse the polarity of L-type calcium channels?
• At what point does perchlorate raise prolactin levels (in a manner similar to BAY K8644) by obstructing the sodium iodide symporter in the choroid plexus and raising intracerebral thiocyanate and nitrate? Does this rise in prolactin activate type III iodothyronine 5-deiodinase and impair the effectiveness of thyroid hormone?
  

On an epidemiological level:

• Is there a significant difference in neonatal thyroid hormone levels before and after a perchlorate-contaminated well is shut down?
• Is the increase in congenital hypothyroidism (thyroid birth defects) in California influenced by perchlorate water contamination? In particular, was the dramatic increase in thyroid birth defects amongst Chinese, South Asians, Middle Easterners, Filipinos, and Hawaiian-Californians since 1990 due to moving into perchlorate-contaminated neighborhoods along the Ronald Reagan, Pomona, and Riverside Freeways in Southern California, or was the cause low-carotene, low-soy diets?
• Is the increase and persistence of interferon gamma and myeloperoxidase-linked opportunistic infections like coccidiodomycosis and tuberculosis in Central Arizona due entirely to the increase in new residents and dust from construction created by the introduction of Colorado River water in 1986, or is the perchlorate in that new water a factor as well?
• Are there any specific "indicator" cancer clusters, e.g. chloromas from myeloperoxidase abnormalities, or mesotheliomas and meningiomas from merlin tumor suppressor abnormalities similar to what is found in follicular variant papillary thyroid cancer, that link perchlorate with above-average mortality rates for thyroid, brain, breast and/or connective tissue cancer?
• Could the post-Cold War decline in both radioiodide fallout from nuclear testing and use of perchlorate slurry explosives in mining be a factor in the simultaneous decline of peritoneal mesothelioma relative to pleural mesothelioma?

Suspect areas would be major perchlorate-processing towns like Ogden UT, Waco TX, Cumberland MD, and Niagara Falls NY, or rural areas such as Summers County WV, Vermillion County IN, and Sutter County CA (male brain cancer), or Deming NM and Sanborn NY (female breast cancer), that are immediately downstream or adjacent to perchlorate processing areas. Of particular interest is the presumed natural perchlorate langbeinite potash region in far southeast New Mexico. See maps and data for these cancers at the National Cancer Institute's Atlas of Cancer Mortality: http://www3.cancer.gov/atlasplus/type.html.

The reader should keep in mind that radioiodide from nuclear weapons testing may be a confounding factor. See http://rex.nci.nih.gov/massmedia/exesumfig1.html for an estimated distribution of fallout from the Nevada Nuclear test site prior to 1964.

In my view the Atlas of Cancer Mortality maps at the State Economic Area scale that best approximate probable environmental perchlorate exposure are Female Brain Cancer Mortality 1950-69, Male Connective Tissue Cancer Mortality 1970-1994, and Female Thyroid Cancer Mortality 1970-1994. On the county scale within the suspect State Economic Areas, Female Brain Cancer Mortality 1950-1969 and Male All Cancer Mortality 1970-1994 may provide better spatial resolution. A detailed state-by-state list of perchlorate sites follows

For example, the age-adjusted 1970-1994 male mortality from connective tissue cancer is higher than average in the traditional Blacklands cotton growing region north and south of Waco in central Texas, and the West Texas cotton region around Lubbock. Within those cotton growing regions the 1970-1994 age-adjusted female mortality from thyroid cancer is also above average in the urban areas of Waco and Amarillo/Lubbock, the latter two (along with many other towns in the region) sharing the same water supply of Lake Meredith on the Canadian River. Waco and Amarillo are in turn adjacent to known perchlorate sites at the PANTEX nuclear weapons facility and the McGregor Naval Weapons station. Since World War II the McGregor facility has also doubled as a fertilzer production facility for Texas A & M that potentially is a source of historical agricultural perchlorate contamination throughout the Blacklands cotton belt. Within the cotton growing region to the west of Lubbock, Hockley County has a slightly higher male cancer mortality rate than neighboring counties with similar economies.

Using this spatial context coupled with correspondence from a woman in the Hockley County area with follicular variant papillary thyroid cancer, in August 2000 I sampled water from the Ogallala aquifer in Hockley and Cochrane Counties and found low (4-5 ppb) levels of perchlorate. Subsequent investigation by Texas authorities revealed ~30 ppb perchlorate in the water supply of Levelland, the county seat for Hockley County. The perchlorate was not in any municipal well, but was found exclusively in the municipal water tower. Levelland, like Amarillo and Lubbock, receives water from Lake Meredith.