Ear To The Ground

Beneficial claims for nanoparticles may provoke EPA regulatory action

Prior posts have noted the significant potential for adverse human health impacts from nanoparticles.  Prior posts have also noted that silver nanoparticles are used in many hundreds of commercial products for which claims are made about the antimicrobial properties of the silver nanoparticles present.  Usually such claims imply disease and/or odor control "benefits" by killing or controlling microorganisms.

In a recent administrative enforcement action, EPA made manifest the extent to which it views such claims as illegal.  WalkFit, LLC, WalkFit Platinum, LLC, and Ideal Products, LLC claimed in their instruction sheets and advertising materials that the products would kill, repel or control bacteria, fungi, or "germs" due to the presence of silver nanoparticles.  EPA and the California Department of Pesticide Regulation noted that such claims are permitted only for registered pesticides, and that such products (containing silver nanoparticles) must be registered with EPA prior to sale.  [For a discussion of FIFRA and its requirements, see http://www.epa.gov/agriculture/lfra.html.]

The parties agreed to pay $210,316 in civil penalties and to correct their claims.

Given the hundreds of products containing silver nanoparticles and making similar claims, one can expect extensive enforcement actions in the future.

Information about the administrative action can be found at http://yosemite.epa.gov/opa/admpress.nsf/0/CC8BF8D3F4C6F5F385257D3200642A61.

BEFORE YOU HIT SEND, CONSIDER -- IGNORANCE IS RISK: IMPACT OF NSA MONITORING TECHNOLOGIES ON ATTORNEY-CLIENT COMMUNICATIONS (PARTS 1&2)

Knew or should have known, a standard often applied in a myriad of legal context, could soon be the one applied to attorneys who ignore the risks associated with communicating with clients using modern technologies (i.e., text messaging, emails, telephone calls, and voice-mail) without appreciating the risk. “Ignorance is Bliss,” is a dangerous proposition in the practice of law when it comes to ignoring current technologies.  What obligations require attorneys to protect their client communications, and what practical steps can be taken to meet statutory and ethical obligations related to confidentiality? Is there a real risk, or is the risk limited to action movies?

Want to read more?  For Part 1, go to:  http://www.lexisnexis.com/legalnewsroom/litigation/b/litigation-blog/archive/2013/07/23/ignorance-is-risk-impact-of-nsa-monitoring-technologies-on-attorney-client-communications-part-1.aspx

For Part 2 go to:  http://www.lexisnexis.com/legalnewsroom/litigation/b/litigation-blog/archive/2013/07/24/ignorance-is-risk-response-options-to-nsa-monitoring-of-attorney-client-communications-part-2.aspx

Are animal models a good analogy for humans? A recently published study of mice suggests that there may be problems

To set standards, animal models are frequently used.  Such use allows researchers to investigate disease and injury states in ways which would be considered unethical to inflict on humans.  For example, to determine some threshold injury or disease state, various groups of animals may be exposed to widely varying concentrations of the particular molecule being assessed.  It is assumed that because the animal commonly used is a mammal, as are we, that the biochemical and metabolic processes of the two different species have enough in common that useful data will be generated to, say, set standards of some sort (e.g., "no effects" levels, exposures that impact fertility or birth defects or cause cancer) or show the effectiveness of drugs.  But, is such data valid?  Recently published work on mice suggest there may be problems.

The study discussed in this blog grew out of a much larger effort to understand why nearly 150 clinical trials of drugs targeted at sepsis in humans failed.  Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year.  It is the leading cause of death in intensive-care units. 

These drugs were developed using mouse models and the drugs were all intended to control excessive immune responses.  Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns.  Such immune system responses may also play a role in heart disease and cancer. 

The new study indicates that mouse models do not accurately reflect the genetic and proteomic responses to acute inflammatory stress in humans.  As noted, the research grew out of a larger project to characterize human inflammatory response to serious trauma (e.g., burns, car accidents, infection). The project was aimed at studying the multitude of genetic responses that result from these acute inflammatory stimuli in humans to ascertain the key biophysiologic response to such inflammation.  As often happens in science, serendipity intervened.

When reviewers rejected one of the group's papers because it failed to show that events in humans were reproduced in mice, the researchers began to question the relevance of mouse models.  So they decided to compare their data about human responses to that from corresponding murine (rodent) model systems.  The researchers compared changes in the expression of thousands of genes, the time course of those changes (using software designed to normalize the different time frames in which responses occur in mice and humans), and the regulation of major signaling pathways involved.

In humans, the genetic response was highly consistent even though patients were subjected to different inflammatory stimuli and different subsequent treatments, suggesting that the drugs targeting these molecular mechanisms could work for multiple inflammatory diseases. The common patterns seen in humans were not reproduced in mouse models, and the responses among the various mouse models varied widely.  The researchers also compared existing gene expression data from human patients and corresponding mouse models for several acute inflammatory diseases, including sepsis and acute respiratory distress syndrome, as well as response to injury.  Again, mouse models poorly mimicked the response among humans, which were highly consistent.  What was seen was that different conditions in mice — burns, trauma, sepsis — did not engender the same response.  Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. 

Learned commentary on the study were highly varied.  Some noted that the "commonality" alleged in various mouse models of humans was set too low, that there needs to be a higher degree to which a model reproduces human disease in terms of molecular mechanisms, rather than just phenotype (the observable physical or biochemical characteristics of an organism).  Critics noted that the research focused on one strain of mice, and that until data was in on other strains, it was too early to draw sweeping conclusions.  Other critics noted that the paper was correct insofar as the behavior of white blood cells goes, but that it was improper to draw any sweeping conclusions about other bodily organs (e.g., lungs, liver, heart, brain).

What does this mean, then, if anything, for litigators?  Now that Daubert has come to California, one has to think in terms of genes, RNA, molecular pathways etc.  It is not enough to allow an expert to waive his/her hands and say X causes Y without asking --- why is that?  Explain to me exactly how disease Z comes about in terms of genes being utilized or blocked, molecules conveying messages, modifications happening to normal pathways. 

The study can be found at http://www.pnas.org/content/110/9/3507.   

An alternative strategy for addressing colony collapse disorder amongst honey bees

Prior posts have noted the many and varied theories regarding the cause of colony collapse disorder amongst honey bees.  (See also http://en.wikipedia.org/wiki/Colony_collapse_disorder.)  This problems poses a risk to a huge number of agricultural products.  See http://en.wikipedia.org/wiki/List_of_crop_plants_pollinated_by_bees. 

I have found that as a general rule complex problems usually have complex, multi-factorial causes, which is why there is still so much debate over causation.  However, there is an alternative strategy for pollination of crops, the use of wild and diverse insects.

50 researchers studied the activity of wild pollinators and managed colonies of bees on 41 different crops in 19 countries worldwide.  They found that pollination by wild insects (e.g., wild bees, beetles, flies, and butterflies) resulted in a higher proportion of flowers forming seeds and fruits.  Wild insects cause twice as much fruit to start to grow as equivalent visits by managed honey bees.  This suggests that farmers may obtain better yields by restoring and/or conserving natural areas within fields to encourage wild pollinators rather than relying on honey bees.  Such a strategy reminds of one of the practices of Integrated Pest Management ("IPM"), which similarly encouraged the conservation of natural areas so that predators would be available to attack insects causing crop damage; it also reduces the need for pesticides.

The authors of the report note that it is the great variety of shapes of wild insects mingling with flowers that spreads pollen more efficiently.  Wild insects also switch more among plants and varieties, thus cross-pollinating.

Emphasizing the same theme, a separate study by European researchers showed that wild bees in general have a larger role in plant pollination than domesticated honey bees.

The study can be found at:  http://www.sciencemag.org/content/339/6127/1608.short.

But all is not perfect for wild pollinators.  Two recent studies have found that the number of American bumblebees is decreasing rapidly in the Midwest.  Comparing an 1890 survey with current populations demonstrated that half of the wild bee species present in 1890 are present today (54 out of 109).  Particularly hard hit is the American bubblebee.  There are 4,000 species of wild bees in America, and 49 of them are bubblebees.  After 447 hours of searching, researchers only found one American bubblebee, a queen.  The American bubblebee was the most dominant bubblebee in the Midwest, but it has disappeared from much of its range.  It is still strongly present in Texas and the West, however. 

The studies can be found at:  http://www.sciencemag.org/content/339/6127/1611 and http://www.pnas.org/content/108/2/662.short.

It is likely that the decline of insect and bee populations is the result of combination of pesticides (which weaken immune systems), disease, and parasites.  There is no simple solution on the horizon, but it may be that what protects honey bees will also protect wild insect populations that contribute so much to crop pollination. 

 

 

U.S. Supreme Court notes that compliance orders are reviewable before action has to be taken

Until a couple of weeks ago, the lower Federal courts generally held that an entity subject to a compliance order had to implement the actions required before being in a position to challenge the order and perhaps seek reimbursement for unnecessary expenditures.  Not so anymore.

The EPA issued a compliance order which accused the landowners of depositing fill materials on a residential lot they owned, stated that the owners engaged in the discharge of pollutants into a navigable waterway without a permit, in violation of § 301 of the Clean Water Act, 33 U.S.C. Section 1311, and directed the owners to restore the site in accordance with an EPA-created restoration work plan.  The EPA denied the owners' request for a hearing, and the owners sued the EPA, claiming that the EPA acted arbitrarily and capriciously in violation of 5 U.S.C. Section 706(2)(A), and violated their right to due process of law, when it issued the compliance order.  Like most environmental laws, the penalty for not implementing the compliance order is very large under the CWA (may not "exceed [$37,500] per day for each violation."  21 U.S.C. Section 1319(d)).

The landowners sought declarative and injunctive relief, but the District Court dismissed the claims for want of subject-matter jurisdiction.  The Ninth Circuit affirmed, concluding that the Clean Water Act precluded pre-enforcement judicial review of compliance orders and that such preclusion did not violate due process.  On appeal, the U.S. Supreme Court unanimously disagreed.

The Court, at 2012 U.S. LEXIS 2320, found that the APA provides for judicial review of "final agency action for which there is no other adequate remedy in a court."  5 U.S.C. Section 704.  The compliance order here has all the hallmarks of APA finality.  Through it, the EPA determined rights or obligations, and required the landowners to restore their property according to an agency-approved plan and to give the EPA access. The Court also found that legal consequences flow from the order, which, according to the Government's litigating position, exposes the landowners to double penalties in future enforcement proceedings. The order also severely limits their ability to obtain a permit for their fill from the Army Corps of Engineers per 33 U.S.C. Section 1344 and 33 C.F.R. Section 326.3(e)(1)(iv). 

Further, the order's issuance marks the consummation of the agency's decisionmaking process for the EPA's findings in the compliance order were not subject to further agency review.  The landowners also had "no other adequate remedy in a court," as required by 5 U.S.C. Section 704.  A civil action brought by the EPA under 33 U.S.C. Section 1319 ordinarily provides judicial review in such cases, but the landowners could not initiate that process.  Each day they failed to implement the order, additional potential liability accrued.  The Court also found that applying to the Corps of Engineers for a permit and then filing suit under the APA if that permit is denied also does not provide an adequate remedy for the EPA's action.

Overturning case law that the lower courts have followed for years, the Court found that the CWA is not a statute that "preclude[s] judicial review" under the APA.  Instead, the APA was seen as creating a presumption favoring judicial review of administrative action.

 

EPA lacks authority to regulate nanomaterials, states EPA IG, even if regulations are soon issued under FIFRA and TSCA

Prior posts have noted the wide use of nanomaterials in consumer goods, and the threat to human health that particles of such size may pose.

An example of the risk posed by nanomaterials is sunscreen. Dermal penetration of some nanomaterials into the skin can potentially pose a hazard to human health. [Prior posts have noted
that particles in this size range can breach the blood-brain "barrier."] Also, by washing sunscreen off by showering, users of materials containing nanomaterials may be unknowingly releasing nanomaterials into the water supply. Furthermore, because of titanium dioxide contaminants within the product, improper disposal of sunscreen presents a risk of harm greater than previously hypothecated. The titanium dioxide in an "empty" sunscreen bottle that is disposed in a landfill may
eventually end up leaching into waterways and being ingested by humans.

Unfortunately, a report from the EPA Office of Inspector General (EPA IG) has concluded that the EPA lacks the data or ability to manage the challenges associated with nanomaterials. According to the report, the problem begins with the lack of data from manufacturers of nanomaterials and continues with EPA's lack of formal processes to handle information and lack of communication strategy to manage all nano-related data. The result of these organizational deficiencies, the report says, is that the agency "will not be able to assure that it is effectively managing nanomaterial risks" until these internal processes are improved.

Regarding the lack of data, most companies are unwilling to voluntarily provide information. As much as 90% of industry data is labeled as confidential and therefore was not accessible to EPA. According to the EPA IG's report, only 29 companies disclosed data about their use of 123 different nanomaterials. EPA also set up a program that encouraged companies to further provide information about research, development, and use of nanomaterials. However, only four companies participated.

In prior reports the EPA IG has noted that EPA has an action plan that is moving forward. The major question, of course, is will it be effective.

The EPA IG report can be found at
http://www.epa.gov/oig/reports/2012/20121229-12-P-0162.pdf

One component of the EPA action plan that is moving forward involves proposed mandatory reporting rules for nanomaterials under the FIFRA. Additionally, EPA is developing regulations under TSCA. The TSCA regulations would include four areas: premanufacture notification, a significant new use rule, an information gathering rule, and a test rule. However, as noted above, the EPA IG has questioned if EPA has sufficient information or processes to effectively manage the human health and environmental risks of nanomaterials. A primary shortcoming is the lack of environmental and human health exposure and toxicological data. The four main problems are the lack of a formal process for coordinating and disseminating mandated information; the lack of an overall message to external stakeholders about policy changes and risks; regulating nanomaterials as chemicals will be limited by the limitations of existing statutes; and, a lack of information about risks and a reliance on industry-submitted data.

The TSCA regulatory program for nanomaterials can be found at http://epa.gov/oppt/nano/.

Information on the over 1,000+ manufacturer identified products using nanomaterials can be found at http://www.nanotechproject.org/inventories/consumer/.

Colony collapse disorder, has the answer finally been found? Possibly

Prior posts have discussed the various research done and theories put forth related to colony collapse disorder (see http://en.wikipedia.org/wiki/Colony_collapse_disorder for an overview). The range of potential causes includes pesticides, global warming, disease, and habitat destruction.

The problem has been getting worse since 2006. Once again, researchers believe they may have an answer. It is intriguing, and may even be correct. As often happens with answers to scientific questions, it is multifactoral.

Researchers knew that the pesticide imidacloprid (see http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~bZTZKk:1 and http://en.wikipedia.org/wiki/Imidacloprid) adversely affected a honeybee's ability to learn; imidaclopid is a systemic neonicotinoid insecticide. They wondered if the insecticide had other adverse effects. In particular, because colonies that go on to collapse appear to have a greater and more varied load of parasites and pathogens than other honeybee colonies, they wondered if there was an impact on the bee's immune system (see, for example, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847501/ and http://www.apimondia.com/apiacta/articles/2003/glinski_1.pdf).

To gain insight they set up an experiment using 30 hives. The bees were feed a protein food (rather than pollen, which is fed to developing larvae) that was spiked with imidacloprid. For ten of the hives the concentration of insecticide was 10 ppb; for another ten, 20 ppb. Previous experiments have demonstrated that neither dose perceptibly harms the honeybee. An additional 10 hives were given unspiked protein food, providing the necessary experimental control. When young bees emerged, they were collected and feed spores of the fungal parasite Nosema (see http://en.wikipedia.org/wiki/Nosema_apis). 12 days later the bees were killed and assessed for their infestation.

Both groups of bees that were feed the spiked protein food harbored an average of 700,000 parasite spores per bee; bees from the "control" colony, less than 200,000. Though the insecticide was at levels thought to be harmless, it was impacting the bee's immune system and causing a more significant infestation to manifest.

Whether this is the actual cause of colony collapse disorder remains to be seen. As they say, only time will tell. However, the thesis is plausible.

The study is noted at http://www.chemeurope.com/en/publications/333610/pesticide-exposure-in-honey-bees-results-in-increased-levels-of-the-gut-pathogen-nosema.html.

Statistics, a weak link in environmental, medical, & toxicological studies?

Statistics are used throughout science both by those proposing a conclusion and those opposed to said conclusion.

Statistics form the basis for a wide variety of claims made about environmental, medical, and toxicological matters.  I would even go so far as to note that they are often utilized by charlatans to give the illusion of analysis and certainty, when no such conclusions are justified.

An interesting assessment and discussion of the problem one often encounters with statistics used in various studies can be found at http://www.sciencenews.org/view/feature/id/57091/title/Odds_Are,_Its_Wrong.  I commend it to your review.  A skeptical attitude toward any expert needs to be an attorney's SOP, especially in this age of Daubert.  (See http://en.wikipedia.org/wiki/Daubert_standard for an overview of Daubert.)

Coriander oil is found to kill E. Coli, Salmonella, & MRSA

Prior posts have noted the adverse environmental effects that are being seen with some bactericides.  Prior posts have also noted the wide variety of substances that can act as selection factors affecting the evolution of various organisms.

Researchers now report that oil extracted from coriander seeds can kill a wide variety of pathogenic bacteria.  The researchers found that coriander oil was able to damage the membrane of bacterial cells, which ultimately lead to the bacterium’s demise.

Although it is always desirable to see reports that products assumed to be "natural" have useful properties and thus the potential to replace substances often viewed as toxic or potentially harmful, it is important to bear in mind that just like various chemicals noted in prior posts, coriander oil will act as a selection factor and that ultimately resistant organisms will emerge.

The study can be found at http://jmm.sgmjournals.org/content/early/2011/08/23/jmm.0.034157-0. 

New study supports association between exposure to persistent organic pollutants and Type II diabetes

Prior research has indicated that persistent organic pollutants (e.g., organochlorine pesticides; PCB's) may interfere with the body's ability to regulate blood sugar; some persistent organic pollutants have also been associated with obesity, itself a major risk factor for diabetes.  Although many persistent organic pollutants have been banned, they (well) persist and are present in many humans.

Researchers measured blood levels of several persistent organic pollutants in about 2,000 older adults.  Just over 15 percent had Type II diabetes; the risk was higher, the researchers found, among people with the highest levels of organochlorine pesticides.  Those with levels in the top 10% were about twice as likely to have diabetes as their counterparts in the bottom 10%.  But, the link appeared to be limited to people who were overweight or obese.  As such, the researchers suggest that the being overweight or obese and the presence of persistent organic pollutants could be synergistic vis-a-vis Type II diabetes.

The researchers accounted for participants' age, sex, waist size, and blood pressure levels. However, they had no information on, among other things, diet and exercise habits, which might explain away the association.  In support of their viewpoint, the researchers point out that persistent organic pollutants have been shown to be endocrine disruptors, which may support a causal relationship.

The report can be found at http://care.diabetesjournals.org/content/early/2011/07/26/dc10-2303.abstract.