Update on CDC Report on trace perchlorate in baby formula

The AP recently made reference to a CDC study reporting that traces of perchlorate found in powdered baby formula could exceed what's considered a safe dose for adults if mixed with water also contaminated with perchlorate. The article acknowledged that the government requires that baby formula contain iodine, which counteracts the effects of not only perchlorate, but also nitrate and thiocyanate. All three ions inhibit the uptake of iodine by the thyroid by the same mode of toxicity.

Overall, the thyroid is susceptible to four major stressors, including iodine deficiency. The following points put these stressors in perspective, especially with regard to environmental remediation. 

1. Iodine deficiency has a much stronger effect on lowering the total iodide uptake by the thyroid in humans than can be compensated for by reducing environmental exposure to perchlorate, nitrate, and/or thiocyanate.
2. Reducing human exposure to perchlorate, nitrate and thiocyanate can not compensate for mild or moderate iodine deficiency in humans.
3. Lowering nitrate exposure in drinking water is a more effective approach to increasing maternal total iodide uptake than lowering the perchlorate Drinking Water Equivalent Level (DWEL) below the EPA Reference Dose level of 24.5 parts per billion.

In summary, there is a legitimate concern relating to exposure of infants and fetuses to nitrate and perchlorate because of their effect on developmental thyroid function.Such concerns can be addressed by ensuring adequate iodine intake, and exercising care in choosing how to meet dietary needs, including avoiding consumption of vegetables and fruit suspected or known to be hydrated with water containing one or more of the thyroid stressors mentioned above.

A full GFS Update on this topic can be found at www.gfschemicals.com.

For a broader perspective on issues such as these, the reader can Google "seattle perchlorate symposium" for numerous hits, or try the following link:

http://www.kleinfelder.com/perchlorate.2008.seattle/.

Vanishing Zeptogram ?

The gap between analytical measurement capabilities and the realm of toxicological effects keeps widening. The March 27, 2006 issue of C&E News (www.cen-online.org) reports (p. 38) on a nanoelectromechanical system device capable of "weighing" masses in the zeptogram range (ten to the -21st power). The device's sensing elements are diminuitive beams of silicon carbide clamped on each end to other SiC bases, which then integrate with the rest of the device's electronics. The beams are 150 nm wide and 2,300 nm long, and are set to vibrate at multi-megahertz frequencies. This flexing frequency can be slowed by small plumes of gas in such a way as to detect masses below 10 zg,  corresponding, for example, to individual peptides several tens of amino acids long.  This ultra-sensitivity may be useful in detecting chemical and biological warfare agents.

Microdosing and the Vanishing Zero

The July 2005 issue of Drug Discovery News featured an interesting editorial (p. 8) by Randall Willis on the topic of microdosing in the "nether region between preclinical and clinical testing - Phase 0."  To some who have been alerted to the WSJ article of July 25, 2005 (posted here elsewhere), the regimen involved here may appear to intersect the conditions being used to study the effects on human health of ultra trace agents in the environment, namely parts per billion or smaller.  Microdosing simply involves the administration of sub-pharmacological or sub-therapeutic doses - micrograms - of a drug candidate to humans.  At least one study seems to indicate that microdose data are largely predictive of therapeutic dose response.            

Mainstream chemists interested in the nuances of chemical analysis would appreciate the fact that these protocols are only possible because of the technical advances in instrument detection limits that allow "almost single molecule detection."  Greater complexity comes from a realization that "sub-dosing" involves microgram quantities of chemical agents, similar to many environmental exposure levels (ppb).  Compare that to therapeutic dosages of an agent like perchlorate (historically used in treatment of Graves' disease) that has been administered at dosages of hundreds of milligrams per day, thousands of times higher than environmental exposure levels.  Small wonder that uncertainty drives many an environmental debate.

More on the topic:  www.drugdiscoverynews.com.

Minute Dose Health Risk Issues

The July 25, 2005 edition of the Wall Street Journal featured a front page article by Peter Waldman on the issue of the effects of minute doses of chemical agents on hormonal processes that impact human health. The evaluation of effects of substituents in amounts as low as parts per trillion "challenges an axiom of toxicology stated by the Swiss chemist Paracelsus nearly 500 years ago:  The dose makes the poison." 

There are many complicating factors. Some chemical agents seem to require the presence of a secondary agent in order to manifest biological effects. Accurate analytical measurement of part per trillion levels of analytes presents significant challenges. And the possibility or likelihood of natural occurrence of some agents (such as perchlorate) commonly regarded as "industrial chemicals" further complicates the "risk vs. benefit" debate. 

For more information go to  www.wsj.com.

IC/MS Perchlorate Analysis

Analysis of perchlorate at low ppb levels has been complicated by the possible occurrence of both false positives and false negatives due to matrix effects and co-eluting substances detected by non-specific conductivity detection.  The July 2005 issue of American Laboratory News  (Vol. 37, No. 15) features an article (pp. 16-20) that describes how an isocratic IC system and a single quadrupole 1100 MSD can determine perchlorate at sub-part per billion levels.  It should be noted that this detection limit likely intrudes on the levels at which perchlorate may be found as a naturally occurring substituent of groundwater in many areas.  The publication web site is www.americanlaboratory.com.   

NIST Method Extends Sensitivity Threshold

From a January 2005 press release, physicists at the National Institute of Standards and Technology have developed a laser-based methodology that can identify a single atom or molecule hidden among ten trillion others. Initially envisioned as a portable “optical nose” for atmospheric monitoring, this technology may soon find its way from the lab into the real world. The technique is believed to be more than 1,000 times more sensitive than conventional methods.

Mass Spec Sensitivity to 480 Molecules Reported

For some time, the sensitivity of Mass Spectrometry has been represented by a lower detection limit in the region of tens of thousands of molecules. Now, a recent report of a soft ionization method developed by Gary Siuzdak and co-workers at Scripps Research Institute allows the extension of detection capability to a limit of 500 molecules or less. A series of dilution experiments involving a peptide (des-Arg⁹-bradykinin) commonly used as a sensitivity standard demonstrated a lower detection limit of 800x10^-24 moles. The technique appears to allow extraction of minute amounts of analyte from complex matrices containing salts and other contaminants that can compromise Mass Spec analysis [Anal. Chem., 76, 4484 (2004)].