Tomorrow's Federal Register will contain a short notice from EPA that partially corrects a decades-old Agency practice that has denied the public access to the identity of chemicals that present substantial risks.

This welcome action begins to pull back the curtain on the chemical secrecy that has been a hallmark of life for the public under the Toxic Substances Control Act (TSCA).  As I noted in a previous post, this action is one of a host of changes needed to remedy the major excesses and abuses of confidentiality under TSCA.  EPA's action makes clear that some things can be done even as we await TSCA reform.

Here's what EPA's notice outlines as the new policy and practice, to take effect immediately:

If, in submitting a "notice of substantial risk" as required under Section 8(e) of TSCA, a company claims the identity of the chemical in question to be confidential business information (CBI), EPA will:

1. review the claim at the time of submission;
2. generally deny the claim if the chemical is on the public portion of the TSCA Inventory (i.e., was not claimed CBI in that context); and
3. inform the submitter of that decision in a manner that constitutes a final EPA action and hence is not challengeable except via judicial review.

What's changing?

All three of these steps represent significant departures from the status quo:

First, EPA will actually review such claims as they come in, to determine whether they are consistent with the new policy or not.  In the past, EPA has rarely reviewed such claims ever, let alone at the time of submission, with the result being that virtually all such claims were by default allowed to persist in perpetuity.

The Federal Register notice forthrightly acknowledges this past practice: 

"Previously, EPA's general practice had been to redact chemical identity from TSCA section 8(e) postings where the identity was claimed CBI even when the chemical identity was listed on the public portion of the TSCA Chemical Substances Inventory."

Second, EPA is putting prospective claimants on notice that, when reviewing such claims, "EPA expects to find that the chemical identity clearly is not entitled to confidential treatment."  This effectively reverses prior policy and practice, under which such claims were presumed to be legitimate even without actual review of them.

Third, EPA's decisions will be communicated to the claimant via a "determination letter" that represents a final Agency action. In the past, EPA has often had to engage in a prolonged song-and-dance exchange of letters with claimants as a prelude to making a final decision – chewing up precious Agency resources and hence drastically curbing the number of EPA challenges of CBI claims.

What's the basis for the change?

EPA's new policy is based on the common-sense notion that the identity of a chemical that is already known to the public – by virtue of it being listed on the public part of the TSCA Inventory – has already been disclosed, and hence cannot be claimed CBI in a different context.

EPA also notes that, by the way, this new policy is consistent with a core part of its mission:  "To promote public understanding of the potential risks posed by chemicals in commerce."

Why this is only a first step towards what's needed

EPA's action is a great first step, but it's only that.  Unless EPA goes further, its new policy will still deny the public access to the identity of many other chemicals posing substantial risk – but whose identities have been masked as CBI and hence don't appear on the public portion of the TSCA Inventory.

(Indeed, I suspect that most of the chemicals with identities claimed CBI in Section 8(e) notices are also claimed CBI on the TSCA Inventory.  EPA did not but should provide such statistics, so that the magnitude of the change it's making – and of the larger problem – can be better gauged.)

Here's why EPA must go further:

First, public interest must trump private interest.

While TSCA provides wide latitude for companies submitting information to EPA to claim it CBI, one bright spot – in theory – is that TSCA prohibits granting CBI status to data from health and safety studies (see section 14(b)).

Why would Congress, when drafting TSCA, have gone out of its way to carve out an exemption from CBI eligibility for data from health and safety studies – effectively establishing the public's right to know such information – only to render impotent that right by denying the public the right to know to which chemical the data apply?  That makes no sense.

In its regulations, EPA itself has defined the identity of a chemical to be an integral part of a health and safety study (see here and here).

EPA's regulations also acknowledge the primacy of public over private interest.  Part 2 of Title 40 of the Code of Federal Regulations lays out EPA's regulatory provisions governing "public information," including procedures to be followed under the Freedom of Information Act (FOIA).  Look at this interesting provision found in Section 2.202(d):

"If two or more of the sections containing special rules apply to the particular information in question, and the applicable sections prescribe conflicting special rules for the treatment of the information, the rule which provides greater or wider availability to the public of the information shall govern." (emphasis added)

But as is so often the case under TSCA, what TSCA giveth with one hand it taketh away with the other.

TSCA provides an exception to the exception for health and safety data:  In disclosing such data, EPA cannot make public data that discloses either:

• "processes used in the manufacturing or processing of a chemical substance or mixture" or
• in the case of a mixture, "the portion of the mixture comprised by any of the chemical substances in the mixture."

Based presumably on this provision of TSCA, EPA regulations provide certain conditions under which a company may assert a confidentiality claim for the identity of a chemical – even when associated with a health and safety study.  It should be noted, however, that these regulations only apply to new, not existing, chemicals.  Moreover, they state that EPA will deny such a claim unless the claimant demonstrates that "the specific chemical identity is not necessary to interpret a health and safety study." See 40 CFR §720.90(c)(3).

I ask you:  How on earth could it not be essential to know the identity of a chemical in order to understand health and safety information about that chemical?

Finally, the astute reader will notice that nothing in TSCA's exception to the rule that health and safety data must be made public speaks to chemical identity.  Only the divulgence of information describing how a chemical is made or processed, or revealing how much of a given chemical is in a mixture, is excepted.

I suspect that some talented chemical industry lawyers have racked up many billable hours devising arguments as to why EPA must interpret such a limited provision so broadly as to extend it all the way to including something never mentioned at all in the provision:  chemical identity.

I would argue that such an interpretation flies in the face of:

• the express words of TSCA,
• the clear intent of Congress to provide public access to health and safety information,
• the core principles of right-to-know and the primacy of public over private interest,
• sound public policy, and
• last but not least, plain old common sense.

So I welcome EPA's action as a good first step in correcting a particularly egregious example of chemical secrecy under TSCA.  It appears that EPA sees it as a first step toward addressing this problem as well:  Its Federal Register notice describes the new policy as "part of a broader effort to increase transparency and provide more valuable information to the public."  Other recent actions announced by EPA fit this mold.  For example, its disclosure of the identities of 530 chemicals on the TSCA Inventory previously exclude as CBI; and its proposal to require disclosure of the identities of inert ingredients in pesticide formulations.

I also look forward to the next installment in EPA's effort.

Some months ago, my colleague John Balbus posted here about studies finding that when multi-walled carbon nanotubes (MWCNTs) are injected into the abdominal cavities of mice, they induce inflammation and mesothelioma-like reactions similar to those caused by asbestos.  He appropriately cautioned that – among other critical questions – these studies had not demonstrated that inhaled MWCNTs could actually move out of the lung and into the tissues where asbestos gives rise to its effects.  Well, that particular dot now appears to have been connected.

We learned about the new findings via a blog post by Liz Borkowski at The Pump Handle.  She noted a disturbing item on the NIOSH blog posted by Vince Castranova and his colleagues late last week, in which they are seeking to share more broadly results they first presented at the recently-concluded Society of Toxicology meeting in Baltimore.

The NIOSH researchers reported new data showing for the first time that MWCNTs can migrate intact from the alveoli out of the lungs of mice and into the pleura, the tissue surrounding the lungs.  And it is in the pleura (as well as the abdominal cavity) where asbestos induces its signature form of cancer, mesothelioma.

In this case, the MWCNTs were introduced into the lungs using pharyngeal aspiration, a procedure by which mice are induced to inhale a droplet of liquid in which the MWCNTs are suspended.  While this procedure is thought to mimic direct inhalation, the NIOSH researchers note this and other limitations of the study, and caution that the results are preliminary and have not yet been peer-reviewed.

They also note that it's possible that the mice used in the study are unique and may not accurately portray what would happen in people, say, workers exposed to MWCNTs.  And, as my colleague pointed out in his earlier post, whether sufficient material could or would be suspended in the air to result in inhalation exposure also remains an open question.

Nonetheless, these new findings strongly suggest that, like asbestos, MWCNTs behave as stable fibers capable of penetrating and migrating through the lung.  And together with the earlier studies showing that introducing MWCNTs into the tissues surrounding the lung induces mesothelioma-like reactions, it's fair to say the alert level on MWCNTs just went up significantly.

In some nanotechnology circles, it is almost a mantra that, once released to the environment, nanoparticles will inevitably aggregate or agglomerate into larger masses and thereby lose their nanoscale-related properties and, by implication at least, any associated risks.

But can we count on nanoparticles released to the environment to self-regulate their own risk so conveniently?

For example, the National Nanotechnology Initiative prominently features on its website an article it commissioned, titled "Understanding Risk Assessment of Engineered Nanomaterials:  How can we know what is a risk and what is not?"  In a section designed to lead readers to question published studies that suggest nanomaterials might pose risks, the article says: "In solution or in air, it's quite difficult to keep nanomaterials separate, as they tend to clump in larger aggregates or agglomerates."  This is a point the author of this rather short article felt compelled to repeat twice more.

An FAQ issued by Germany's Federal Institute for Risk Assessment states that "nanoparticles tend to aggregate into larger unions which are generally larger than 100 nm. The toxic effects of nanoparticles linked to their small size and higher reactivity are then no longer relevant."

And a recent post on the blog of the nanotechnology practice group at Porter and Wright asserts that nanoparticles "have been shown to have fewer potential adverse health effects when they occur in cluster form (aggregates and/or agglomerates).  In the 'good news' department, scientists studying aerosol dispersion of nanoparticles have found they tend to cling together when dispersed into the environment." 

I won't even begin to try to lay out here how much more complex and unpredictable than this nanoparticle aggregation and environmental fate and transport are in the real-world.  Instead, let me just cite two excellent papers that do so:  see Maynard and Weisner et al.

But I do want to briefly discuss and cite some recent studies supporting three reasons why we can't count on nanoparticles released to the environment to self-regulate their own risk so conveniently: 

1.  Some nanomaterials can be stabilized as nanoscale particles in solution under environmental conditions.  A number of studies have found that carbon-based nanomaterials – despite their inherently very low water solubility – can be "solubilized," that is, can enter and remain in stable suspensions upon interaction with water or with other common, naturally occurring substances.  The latest study, authored by Salonen et al. and published in the journal Small, finds that C₇₀ fullerenes can form "stable, homogeneous suspensions" in water through interaction with ubiquitous phenolic acids that are present in and released from virtually all plant matter.  It appears that individual C₇₀ fullerenes first become coated with the phenolic acid, and then form small, loose clusters with diameters on the order of a few nanometers.  This study merited a "spotlight" on the Nanowerk website.

Earlier work has found similar behavior:  Fortner et al. identified the formation of stable suspensions of "nanocrystals" of C₆₀ fullerenes in water – nanoscale (25-500 nm diameter) aggregates they call "nano-C₆₀" that have entirely shed the extreme hydrophobicity of the individual fullerenes.  Hyung et al. found that multi-walled carbon nanotubes could be stabilized as individual particles through interaction with natural organic matter found in river waters; the natural material actually worked better than commonly used surfactants selected to serve that same solubilizing function.

2.  For performance reasons, nanoparticles are being actively engineered not to clump.  For most nanomaterial applications, optimal performance depends on minimizing any disordered clumping or even maximizing dispersal, so that the properties of individual nanoparticles or highly ordered nanostructures can fully exert themselves.  For this reason, researchers are working overtime to coat, cap, chemically modify or otherwise force nanoparticles not to aggregate or agglomerate.  See, for example, Yang et al.'s use of special capping agents to prevent aggregation of platinum nanoparticles, and Nadagouda and Varma's similar work with silver and palladium nanoparticles.  Similar efforts have been mounted to chemically modify ceramic nanoparticles to ensure dispersal.

So even to the extent that native or current forms of nanoparticles do readily clump or retain their hydrophobicity, any assumption that engineered nanomaterials entering commerce and the environment will inevitably do so is wholly unwarranted.

3.  Even agglomerated or clumped nanoparticles can be toxic.  The assumption that aggregated nanoparticles lose all of their nanoscale properties or become benign is also unwarranted.  Maynard and Kuempel have amply demonstrated that even large aggregates on individual nanoparticles typically retain many of their nanostructural features and properties.  But what about toxicity?

Fortner et al. found that their fullerene nanocrystals exhibited antimicrobial activity, suppressing bacterial growth and respiration.  In addition to confirming nano-C₆₀'s antibacterial activity, a recent paper by Lyon and Alvarez cited a number of studies demonstrating that the formation of these nanoscale aggregates in water yields a material with high toxicity to aquatic invertebrates, fish and the cells of higher organisms.  The aggregates have also been shown to enter and accumulate in those cells and to adhere to lipids.

Finally, Salonen et al. showed that their phenolic acid-coated C₇₀ clusters could readily translocate across the membranes of human cells in culture and enter the membrane surrounding the cell nucleus.  Moreover, they induced the contraction and ultimate death of those cells – ironically, apparently by aggregating into micro-sized particles through interaction with the cell membranes.

Once again, we find that nanomaterials' actual behavior confounds conventional wisdom and, when approaching their toxicology, forces us to question or abandon our assumptions and biases.

Section 8(e) of the Toxic Substances Control Act (TSCA) requires any company that manufactures, imports, processes or distributes chemicals in the U.S. to notify EPA within 30 days if it obtains new information that "reasonably supports the conclusion that such substance or mixture presents a substantial risk of injury to health or the environment."  Are there Section 8(e) notices for nanomaterials?

EPA posts "sanitized" versions of Section 8(e) notices on its website, stripped of any information deemed confidential by the submitter – which, as allowed under TSCA, frequently includes the identity of the substance, the submitter or both.

So how many of these "substantial risk" notices have been received for nanomaterials?

EPA provides no ability to search for such documents on its Section 8(e) notice website, so we had to do examine each of EPA's month-by-month listings.  These postings extend from September 2008 back to January 2004 – excluding, for some strange reason, the second half of 2004.  (A note that has been on the site for a long time now optimistically states:  "Attention: The 2000-2004 submissions will be posted on this page in the near future.")

Our search found eight Section 8(e) notices that were identified as pertaining to nanomaterials (though there may be others that claimed the nanomaterial identity confidential).  Here they are:

In my next post, I'll look more closely at the Section 8(e) notices EPA has received for carbon nanotubes.

The manufacture of carbon nanotubes (CNTs) is a very complicated business.  Different production processes leave behind different kinds of metal catalysts, which yield differences in physical and chemical – as well as toxicological – properties of the CNTs. 

Removal of metals can alter the surface and other properties.  These properties affect both the performance and the potential toxicity or other biological activity of the CNTs.

While a given material's intended use often dictates the means of manufacturing and subsequent processing, the challenge is to integrate safety considerations up front rather than as an afterthought to be considered only at the end of the design process.  But to do so, we need to develop a much better understanding of how properties and structural features correlate with safety risks. 

A pair of interesting papers just published in the journal Chemical Research in Toxicology examines the relationship between these physicochemical properties and potential hazard. 

In these papers, a group of European researchers created and characterized five kinds of CNTs, and then explored the question of what features are the most important in determining hazard:  residual metals, the presence of oxygenated functional groups, or surface defects.  As measures of hazard, the authors examined the ability of each CNT to scavenge free radicals (a protective function since free radicals can damage cell membranes), cause lung inflammation in rats, and damage DNA.  The results are intriguing:

• The presence of oxygenated functional groups on the surface of the CNTs appears to be most closely associated with genotoxicity. 
• Lung inflammation increased with the number of surface defects or oxy groups, and also with increasing metal concentration. 
• Somewhat counter-intuitively, CNTs that lacked both residual metals and surface defects were the only ones not effective as scavengers of free radicals.  Introduction of surface defects into these CNTs enhanced their ability to scavenge free radicals, supporting the hypothesis that such scavenging is associated with surface defects. 

It's more complicated than I can describe here and it's likely that multiple features contribute to most or all of the observed effects.  But these papers begin the difficult task of teasing out which are the most important properties in determining hazard potential. 

The findings inch us closer to the day when designers of nanomaterials can incorporate specific properties that meet the dual goals of performance and low toxicity. 

The insurance industry is out in front on nanotechnology yet again.  As the giant reinsurer Swiss Re did way back in May 2004 with its groundbreaking report Nanotechnology: Small matter, many unknowns, it is once again the insurance industry sounding an early alarm about nanomaterials.  In this case, it's the Continental Western Insurance Group (CWG), which has just announced that it will exclude coverage for "the, as of yet, unknown and unknowable risks created by the products and processes that involve nanotubes."

Starting November 15, CWG says it will attach a Nanotubes and Nanotechnology Exclusion to all of the policies it issues for business auto, business owners, garage, motor carrier, commercial general liability and commercial liability umbrella coverage.

The Group issues policies through four individual companies:  Continental Western Insurance Company, Union Insurance Company, Firemen's Insurance Company of Washington D.C. and Acadia Insurance Company.

Why the company is acting now

CWG's statement notes: "Reports have raised concerns regarding health risks from workers that may be inhaling carbon nanotubes during the manufacture of certain products. The carbon nanotubes resemble asbestos fibers in appearance, raising the concern that they may cause illness similar to that linked to asbestos. Further analysis is needed to determine long term affects."

The Group goes on to say "it would not be prudent for us to knowingly provide coverage for risks that are, as of yet, unknown and unquantifiable. We are all too aware of what happened to companies involved with asbestos-related exposures in the past, and see this as a very similar issue."

This is one more striking illustration of how the lack of good data on nanomaterials' risk has big business implications.

If this is the start of a trend, maybe our and others' efforts to get more federal funding devoted to nanomaterial safety research will get an unexpected boost.

John Balbus, M.D., M.P.H., is Chief Health Scientist.

A new paper by Shaw et al., published in May in the Proceedings of the National Academy of Sciences, “suggests a generalizable and scalable method for the systematic characterization and comparison of novel nanomaterials” using high throughput in vitro tests.  Does this mean that the National Academy of Sciences’ vision for toxicity testing in the 21st century – proposed for conventional chemicals – is already here for nanomaterials?  Not quite. 

The National Academy of Sciences (NAS), the Environmental Protection Agency, industry, environmental NGOs, and animal rights groups all look to high throughput in vitro testing to reduce animal testing while increasing the efficiency and lowering the cost of assessing chemicals and other materials for safety concerns.  But, as the NAS report acknowledges, achieving this shared vision will require a tremendous input of new research (and monetary resources) in order to refine and validate the next generation of toxicological test methods.  I discussed this in a previous blog post.

The Shaw et al. study makes a meaningful advance in the path towards in vitro screening.  The investigators used a variety of assays, cell types, and doses to test 50 different nanoparticles, thereby developing a multidimensional data profile for each.  They then applied statistical clustering techniques to examine whether differences in the structures of the nanoparticles, subtle or otherwise, changed their toxicity profiles.  For three nanoparticles that showed interesting differences in their profiles, the authors conducted short-term in vivo assays to seek to validate what they had seen in vitro.

The authors were able to demonstrate that using four different assays and a range of doses and cell types provided a robust set of data with which to categorize and distinguish the different nanoparticles.  The authors did not try to use the assays to predict specific health effects, but rather to create a classification system for previously untested nanoparticles and then use comparisons with nanoparticles that had already been thoroughly assessed by in vivo tests to make inferences about potential toxicity. 

The three nanoparticles chosen for in vivo validation in this study are all intended for use as medical diagnostic agents, and hence have been widely tested in animals.  The study demonstrated that the nanoparticle that appeared to have the highest toxicity of the three in the in vitro assays also caused the greatest response in vivo.

While the Shaw et al. study has considerable strengths, a couple of critical limitations highlight the large gap that still needs to be bridged if in vitro screening is to be effective in protecting human and ecosystem health from risks arising from the wide array of nanomaterial applications under development.

First, all of the 50 nanomaterials tested were designed for intravenous injection as medical diagnostic agents.  Because of this, the nanoparticles were water-soluble, making them easier to use in in vitro systems.  Most nanoparticles intended for non-medical purposes are poorly soluble and therefore difficult to apply and dose accurately in the liquid medium found in cellular assays.  And while in vitro assays using cells grown and exposed to a nanoparticle in liquid media reasonably simulate an injection exposure pathway, making inferences about health effects from exposure via other routes of exposure that are more relevant to non-medical uses – inhalation, dermal contact and even ingestion – is more difficult.

Second, both the nanomaterials and the endpoints assessed were of limited relevance to evaluating the kinds of effects that could arise from consumer, environmental, or occupational exposures to nanoparticles.  Most were variants of iron oxides, which are not commonly found nanomaterials in consumer products.  In addition, the investigators were most concerned with acute reactions to the injected materials, and therefore used acute assays and cell types relevant to intravenous injection:  vascular cells, monocytes (a type of white blood cell), and hepatocytes. 

The supporting in vivo test was also a short-term assay designed to look for changes in monocyte counts.  This test is most relevant to identifying immediate systemic inflammation, but would be very unlikely to detect perturbational changes that occur over longer time periods and could lead to chronic effects such cancer, neurodevelopmental toxicity, endocrine disruption, etc.  The latter types of effects are of greater concern for occupational, consumer, and environmental exposures. 

The authors note that this approach is most valuable as an initial screen in the relatively rigorous evaluation process required by the Food and Drug Administration (FDA) for approval of pharmaceuticals.  They point to the ability to identify the most promising nanomaterials by comparing their profiles to those of materials that have already gained FDA approval – and therefore were already extensively tested.  Of course, any nanomaterials selected through this screening process would then themselves be put through an extensive set of safety tests. 

This is a very different application of high throughput screening than, for example, would be needed to help evaluate a novel material for which a Premanufacturing Notice is submitted under the Toxic Substances Control Act, where there is no backup of rigorous safety testing to assure protection.  Such an approach may have value, however, in screening alternative nanoparticles as companies develop new products.

So while this study is a step in the right direction, there is still a lot more good science needed if high throughput in vitro screening tests are to become a reliable means to assess the safety of occupational, consumer, and environmental exposures to nanomaterials.

The proliferation of nanoscale materials in consumer products is impressive:  nano titanium dioxide and zinc oxide in sunscreen, buckyballs in face creams, and nanosilver in socks are but a few examples of what is currently available for purchase.  But they make me wonder:  what happens when the nanomaterials in or released from these products are washed down the drain?  

A recent study published in Environmental Science & Technology (ES & T) demonstrates that nanoscale silver, added to socks to reduce the growth of odor-causing bacteria, readily washes out into wash water.  Testing of the wash water demonstrates that some of the silver is present in nanoparticle form, although dissolved silver ions are also present.  And of course, at the end of the day, nanoparticles present in personal care products, such as nanoscale zinc oxide and titanium dioxide in sunscreen and carbon fullerenes in face creams, will also be washed down the drain in the sink, shower, or tub. 

For most communities, the wastewater treatment plant is the next downstream recipient of these down-the-drain nanoparticles.  The impact that wastewater treatment has on nanomaterials, or conversely, the impact that nanomaterials have on wastewater treatment, is largely unknown. 

According to Cynthia Finley, Ph.D., Director for Regulatory Affairs at the National Association of Clean Water Agencies, “Our first concern is that nanoparticles could interfere with the wastewater treatment process and undermine our ability to meet our obligations under the Clean Water Act.”

“Our second concern is that the nanomaterials will make it through the wastewater treatment process and be discharged into receiving waters.  Although currently there is no requirement for us to treat nanomaterials, we take our responsibilities seriously, and are mindful of the potential impacts of unregulated chemicals.  Right now we don’t know how to treat nanomaterials in wastewater, so research will be very important in determining the appropriate response of wastewater treatment agencies.”

Depending on their characteristics, nanoparticles could wind up in the sludge (the solid materials removed from wastewater in the course of its treatment) or could be discharged with the treated wastewater.  The disposition of nanoparticles following wastewater treatment will determine their subsequent fate and transport pathways; if nanoparticles primarily find their way into sewage sludge, then impact studies will need to focus on potential releases following land application and incineration, the main means by which we manage such sludge.  If, however, nanoparticles primarily flow out in the discharge water, impact studies must consider their potential effects on aquatic organisms and ecosystems.

Another new paper published in ES & T describes a computer model that seeks to predict the movement of three types of nanoparticles – nano silver, nano titanium dioxide, and carbon nanotubes – throughout the materials’ life cycles.  If validated for nanomaterials, models such as these can be useful, because they help us predict where nanoparticles may go, and hence where we might want to search for possible adverse impacts. 

Of course, given how little data are actually available, modeling studies like these are constructed on a mountain of assumptions, or even best guesses.  In this study, the authors assume that 60% of nano titanium dioxide produced is used in cosmetics and sunscreens, and that 95% of this material winds up in wastewater treatment plants.  In contrast, the authors assume that carbon nanotubes are more likely to be used as additives to solid materials, such as plastics or other composites, and therefore they are more likely to be disposed of with solid waste.  Because the uses of nano silver are currently much more diverse, the authors assume some would end up in wastewaters, some would be released to air and some would be disposed of as solid waste.

As more real data are acquired, models need to be adjusted and or updated.  For example, the model I just described assumes that dissolved silver, rather than silver nanoparticles, will be the dominant form of silver released into wastewaters.  Based on the results of the sock study, however, we now have good reason to expect that silver still in the form of nanoparticles will be released into wastewaters – something any good model would need to account for.   

All this is to say that we are a long way from understanding the environmental fate and transport of down-the-drain nanomaterials.  The development of models, as imperfect as they may be, can still help to guide research by allowing us to make predictions that we can then empirically test.  Through such bootstrapping, we can hopefully move toward developing better guidance and standards that wastewater treatment system operators will need to protect the environment and public health.  

But better models and more research don’t ensure safety.  Our concerns regarding down-the-drain nanomaterial releases are yet another reason we urge that nanomaterials not be used in dispersive applications until their potential effects to human health and the environment are fully understood and mitigated.

Update:  Jen Jackson of the East Bay Municipal Utilities District wasn't able to get back to me with her thoughts until after I published this post.  Here's what she says:

“There is growing concern among wastewater agencies about the proliferation of products containing nanomaterials, such as nanosilver and nanocopper.  Nanomaterials may behave differently than larger molecules when they reach wastewater treatment plants.  We don’t know whether some nanomaterials may impair the wastewater treatment process, or sail through treatment plants into local waterways.  Unfortunately, research on the impact of nanoparticles to the wastewater treatment process has not kept pace with the number of uses and applications of nanomaterials."

John Balbus, M.D., M.P.H., is Chief Health Scientist.

A new study published today in Nature Nanotechnology finds that multi-walled carbon nanotubes (MWCNTs) cause inflammatory changes in mice that closely resemble those caused by asbestos.  This is the second study in a few months to make this finding.  (I posted on the first, Takagi et al., a few weeks ago.)  So is the case closed on multi-walled carbon nanotubes?  Or is too early to draw conclusions?

These two studies used different approaches to compare the effects of MWCNTs and asbestos.  Although both directly injected the nanotubes into the peritoneal cavities of mice (the peritoneum is the lining of the abdominal organs and walls, and is the part of the body – along with the pleura lining the lungs – where asbestos causes mesotheliomas to arise), the new study used a 60-fold lower dose and measured only inflammatory changes, not the actual development of mesotheliomas.  Takagi et al., on the other hand, used special mice that were genetically highly susceptible to cancer formation, and observed the mice until they developed tumors. 

Despite these differences, these studies together make a strong case that multi-walled carbon nanotubes cause inflammation and cancers in a similar fashion to asbestos, at least if they have been deposited directly within the peritoneum. 

But the studies only tell a part of the story.  In order to have a better handle on the risks from inhaling MWCNTs, studies need to be done to determine whether there could be substantial concentrations in the air that workers (or other exposed persons) breathe.  Then we need to find out whether inhaled MWCNTs will make their way from the airspaces of the lungs, through the lung tissue, to the lung and abdominal cavity linings – something asbestos does with relative ease. 

If these first two steps in causing disease are demonstrated, it is likely that MWCNTs will persist and continue to cause inflammation as long as asbestos does, but this needs further investigation as well.  So the case isn’t closed, but the evidence is stacking up.

Until these questions are answered, companies using MWCNTs should carefully characterize their materials and refrain from exposing workers to nanotubes longer than 5 microns with fibrous shapes.  And researchers developing applications for MWCNTs should look to develop forms that don’t have those size and shape characteristics.  These studies don’t show that other forms are harmless, but it can’t hurt to sidestep the trouble you can see.

John Balbus, M.D., M.P.H., is Chief Health Scientist.

We and many others have made analogies between nanoparticles and asbestos.  The purpose of the analogy has generally been to emphasize the long latency that can occur between exposure to toxic materials and the development and subsequent recognition of disease arising from that exposure.  And, of course, the enormous legal and financial burden of failing to adequately consider risks before allowing widespread exposure.  But a new study suggests that the analogy may be even stronger than we thought:  It may extend to the capacity to cause mesothelioma, the rare form of cancer associated with exposure to asbestos.

In a recent study published in the Journal of Toxicological Sciences, researchers at Japan’s National Institute of Health Sciences injected commercial multi-walled carbon nanotubes (MWCNTs) into the peritoneal cavities of mice that were bred to be especially susceptible to mesothelioma.  (The peritoneal cavity is the space between the abdominal organs and abdominal wall that is lined with mesothelial cells, which can give rise to mesotheliomas).

They compared the mice’s response to injected MWCNTs to the response to crocidolite asbestos (the form of asbestos most strongly associated with mesothelioma), and also to fullerenes.  They found that the potency of MWCNTs in causing mesotheliomas in these mice was at least as high as the asbestos.  In contrast, fullerenes did not cause any mesotheliomas.

The physicochemical characteristics of MWCNTs are similar in many ways to asbestos.  Both are rigid, rod-like shapes with a high length to width (aspect) ratio and lengths that can extend to 5 microns or longer. Both are biopersistent and contain iron.  Given that all of these characteristics collectively contribute to the carcinogenicity of asbestos, this study suggests these same characteristics may cause MWCNTs to be carcinogenic as well.

This study doesn’t prove that inhaling MWCNTs causes mesothelioma; it would first have to be shown that inhaled MWCNTs can make their way through the lung to contact mesothelial cells, and then persist there long enough to initiate carcinogenesis in less susceptible animals.  Asbestos does this, of course, and there’s no obvious reason why MWCNTs should behave differently.  More pieces of the puzzle need to be filled to demonstrate the actual degree of risk, but this is clearly a large red flag.

Because MWCNTs, unlike asbestos, are deliberately engineered, it’s possible that characteristics like iron content and fiber length may be controlled to render the tubes less or even non-carcinogenic.  But with the wide variations noted for single-walled carbon nanotubes (see our earlier post), manufacturers of MWCNTs would have to demonstrate the ability to manufacture product consistently to specifications, and users of MWCNTs would need to be wary of variations from producer to producer.  In the meantime, researchers developing and using MWCNTs, especially for applications that could yield long-term exposures, such as incorporation into hip prostheses, need to proceed with extreme caution and carefully assess the potential for carcinogenicity from their devices.