Tag Archives: US Food and Drug Administration

Sunscreens: 2018 update

I don’t usually concern myself with SPF numbers on sunscreens as my primary focus has been on the inclusion of nanoscale metal particles (these are still considered safe). However, a recent conversation with a dental hygienist and coincidentally tripping across a June 19, 2018 posting on the blog shortly after the convo. has me reassessing my take on SPF numbers (Note: Links have been removed),

So, what’s the deal with SPF? A recent interview of Dr Steven Q Wang, M.D., chair of The Skin Cancer Foundation Photobiology Committee, finally will give us some clarity. Apparently, the SPF number, be it 15, 30, or 50, refers to the amount of UVB protection that that sunscreen provides. Rather than comparing the SPFs to each other, like we all do at the store, SPF is a reflection of the length of time it would take for the Sun’s UVB radiation to redden your skin (used exactly as directed), versus if you didn’t apply any sunscreen at all. In ideal situations (in lab settings), if you wore SPF 30, it would take 30 times longer for you to get a sunburn than if you didn’t wear any sunscreen.

What’s more, SPF 30 is not nearly half the strength of SPF 50. Rather, SPF 30 allows 3% of UVB rays to hit your skin, and SPF 50 allows about 2% of UVB rays to hit your skin. Now before you say that that is just one measly percent, it actually is much more. According to Dr Steven Q. Wang, SPF 30 allows around 1.5 times more UV radiation onto your skin than SPF 50. That’s an actual 150% difference [according to Wang’s article “… SPF 30 is allowing 50 percent more UV radiation onto your skin.”] in protection.

(author of the ‘eponymous’ blog) offers a good overview of the topic in a friendly, informative fashion albeit I found the ‘percentage’ to be a bit confusing. (S)he also provides a link to a previous posting about the ingredients in sunscreens (I do have one point of disagreement with regarding oxybenzone) as well as links to Dr. Steven Q. Wang’s May 24, 2018 Ask the Expert article about sunscreens and SPF numbers on skincancer.org. You can find the percentage under the ‘What Does the SPF Number Mean?’ subsection, in the second paragraph.

Ingredients: metallic nanoparticles and oxybenzone

The use of metallic nanoparticles  (usually zinc oxide and/or (titanium dioxide) in sunscreens was loathed by civil society groups, in particular Friends of the Earth (FOE) who campaigned relentlessly against their use in sunscreens. The nadir for FOE was in February 2012 when the Australian government published a survey showing that 13% of the respondents were not using any sunscreens due to their fear of nanoparticles. For those who don’t know, Australia has the highest rate of skin cancer in the world. (You can read about the debacle in my Feb. 9, 2012 posting.)

At the time, the only civil society group which supported the use of metallic nanoparticles in sunscreens was the Environmental Working Group (EWG).  After an examination of the research they, to their own surprise, came out in favour (grudgingly) of metallic nanoparticles. (The EWG were more concerned about the use of oxybenzone in sunscreens.)

Over time, the EWG’s perspective has been adopted by other groups to the point where sunscreens with metallic nanoparticles are commonplace in ‘natural’ or ‘organic’ sunscreens.

As for oxybenzones, in a May 23, 2018 posting about sunscreen ingredients notes this (Note: Links have been removed),

Oxybenzone – Chemical sunscreen, protects from UV damage. Oxybenzone belongs to the chemical family Benzophenone, which are persistent (difficult to get rid of), bioaccumulative (builds up in your body over time), and toxic, or PBT [or: Persistent, bioaccumulative and toxic substances (PBTs)]. They are a possible carcinogen (cancer-causing agent), endocrine disrupter; however, this is debatable. Also could cause developmental and reproductive toxicity, could cause organ system toxicity, as well as could cause irritation and potentially toxic to the environment.

It seems that the tide is turning against the use of oxybenzones (from a July 3, 2018 article by Adam Bluestein for Fast Company; Note: Links have been removed),

On July 3 [2018], Hawaii’s Governor, David Ig, will sign into law the first statewide ban on the sale of sunscreens containing chemicals that scientists say are damaging the Earth’s coral reefs. Passed by state legislators on May 1 [2018], the bill targets two chemicals, oxybenzone and octinoxate, which are found in thousands of sunscreens and other skincare products. Studies published over the past 10 years have found that these UV-filtering chemicals–called benzophenones–are highly toxic to juvenile corals and other marine life and contribute to the fatal bleaching of coral reefs (along with global warming and runoff pollutants from land). (A 2008 study by European researchers estimated that 4,000 to 6,000 tons of sunblock accumulates in coral reefs every year.) Also, though both substances are FDA-approved for use in sunscreens, the nonprofit Environmental Working Group notes numerous studies linking oxybenzone to hormone disruption and cell damage that may lead to skin cancer. In its 2018 annual sunscreen guide, the EWG found oxybenzone in two-thirds of the 650 products it reviewed.

The Hawaii ban won’t take effect until January 2021, but it’s already causing a wave of disruption that’s affecting sunscreen manufacturers, retailers, and the medical community.

For starters, several other municipalities have already or could soon join Hawaii’s effort. In May [2018], the Caribbean island of Bonaire announced a ban on chemicals sunscreens, and nonprofits such as the Sierra Club and Surfrider Foundation, along with dive industry and certain resort groups, are urging legislation to stop sunscreen pollution in California, Colorado, Florida, and the U.S. Virgin Islands. Marine nature reserves in Mexico already prohibit oxybenzone-containing sunscreens, and the U.S. National Park Service website for South Florida, Hawaii, U.S. Virgin Islands, and American Samoa recommends the use of “reef safe” sunscreens, which use natural mineral ingredients–zinc oxide or titanium oxide–to protect skin.

Makers of “eco,” “organic,” and “natural” sunscreens that already meet the new standards are seizing on the news from Hawaii to boost their visibility among the islands’ tourists–and to expand their footprint on the shelves of mainland retailers. This past spring, for example, Miami-based Raw Elements partnered with Hawaiian Airlines, Honolulu’s Waikiki Aquarium, the Aqua-Aston hotel group (Hawaii’s largest), and the Sheraton Maui Resort & Spa to get samples of its reef-safe zinc-oxide-based sunscreens to their guests. “These partnerships have had a tremendous impact raising awareness about this issue,” says founder and CEO Brian Guadagno, who notes that inquiries and sales have increased this year.

As Bluestein notes there are some concerns about this and other potential bans,

“Eliminating the use of sunscreen ingredients considered to be safe and effective by the FDA with a long history of use not only restricts consumer choice, but is also at odds with skin cancer prevention efforts […],” says Bayer, owner of the Coppertone brand, in a statement to Fast Company. Bayer disputes the validity of studies used to support the ban, which were published by scientists from U.S. National Oceanic & Atmospheric Administration, the nonprofit Haereticus Environmental Laboratory, Tel Aviv University, the University of Hawaii, and elsewhere. “Oxybenzone in sunscreen has not been scientifically proven to have an effect on the environment. We take this issue seriously and, along with the industry, have supported additional research to confirm that there is no effect.”

Johnson & Johnson, which markets Neutrogena sunscreens, is taking a similar stance, worrying that “the recent efforts in Hawaii to ban sunscreens that contain oxybenzone may actually adversely affect public health,” according to a company spokesperson. “Science shows that sunscreens are a key factor in preventing skin cancer, and our scientific assessment of the lab studies done to date in Hawaii show the methods were questionable and the data insufficient to draw factual conclusions about any impact on coral reefs.”

Terrified (and rightly so) about anything scaring people away from using sunblock, The American Academy of Dermatology, also opposes Hawaii’s ban. Suzanne M. Olbricht, president of the AADA, has issued a statement that the organization “is concerned that the public’s risk of developing skin cancer could increase due to potential new restrictions in Hawaii that impact access to sunscreens with ingredients necessary for broad-spectrum protection, as well as the potential stigma around sunscreen use that could develop as a result of these restrictions.”

The fact is that there are currently a large number of widely available reef-safe products on the market that provide “full spectrum” protection up to SPF50–meaning they protect against both UVB rays that cause sunburns as well as UVA radiation, which causes deeper skin damage. SPFs higher than 50 are largely a marketing gimmick, say advocates of chemical-free products: According to the Environmental Working Group, properly applied SPF 50 sunscreen blocks 98% of UVB rays; SPF 100 blocks 99%. And a sunscreen lotion’s SPF rating has little to do with its ability to shield skin from UVA rays.

I notice neither Bayer nor Johnson & Johnson nor the American Academy of Dermatology make mention of oxybenzone’s possible role as a hormone disruptor.

Given the importance that coral reefs have to the environment we all share, I’m inclined to support the oxybenzone ban based on that alone. Of course, it’s conceivable that metallic nanoparticles may also have a deleterious effect on coral reefs as their use increases. It’s to be hoped that’s not the case but if it is, then I’ll make my decisions accordingly and hope we have a viable alternative.

As for your sunscreen questions and needs, the Environment Working Group (EWG) has extensive information including a product guide on this page (scroll down to EWG’s Sunscreen Guide) and a discussion of ‘high’ SPF numbers I found useful for my decision-making.

Getting chipped

A January 23, 2018 article by John Converse Townsend for Fast Company highlights the author’s experience of ‘getting chipped’ in Wisconsin (US),

I have an RFID, or radio frequency ID, microchip implanted in my hand. Now with a wave, I can unlock doors, fire off texts, login to my computer, and even make credit card payments.

There are others like me: The majority of employees at the Wisconsin tech company Three Square Market (or 32M) have RFID implants, too. Last summer, with the help of Andy “Gonzo” Whitehead, a local body piercer with 17 years of experience, the company hosted a “chipping party” for employees who’d volunteered to test the technology in the workplace.

“We first presented the concept of being chipped to the employees, thinking we might get a few people interested,” CEO [Chief Executive Officer] Todd Westby, who has implants in both hands, told me. “Literally out of the box, we had 40 people out of close to 90 that were here that said, within 10 minutes, ‘I would like to be chipped.’”

Westby’s left hand can get him into the office, make phone calls, and stores his living will and drivers license information, while the chip in his right hand is using for testing new applications. (The CEO’s entire family is chipped, too.) Other employees said they have bitcoin wallets and photos stored on their devices.

The legendary Gonzo Whitehead was waiting for me when I arrived at Three Square Market HQ, located in quiet River Falls, 40 minutes east of Minneapolis. The minutes leading up to the big moment were a bit nervy, after seeing the size of the needle (it’s huge), but the experience was easier than I could have imagined. The RFID chip is the size of a grain of basmati rice, but the pain wasn’t so bad–comparable to a bee sting, and maybe less so. I experienced a bit of bruising afterward (no bleeding), and today the last remaining mark of trauma is a tiny, fading scar between my thumb and index finger. Unless you were looking for it, the chip resting under my skin is invisible.

Truth is, the applications for RFID implants are pretty cool. But right now, they’re also limited. Without a near-field communication (NFC) writer/reader, which powers on a “passive” RFID chip to write and read information to the device’s memory, an implant isn’t of much use. But that’s mostly a hardware issue. As NFC technology becomes available, which is increasingly everywhere thanks to Samsung Pay and Apple Pay and new contactless “tap-and-go” credit cards, the possibilities become limitless. [emphasis mine]

Health and privacy?

Townsend does cover a few possible downsides to the ‘limitless possibilities’ offered by RFID’s combined with NFC technology,

From a health perspective, the RFID implants are biologically safe–not so different from birth control implants [emphasis mine]. [US Food and Drug Administration] FDA-sanctioned for use in humans since 2004, the chips neither trigger metal detectors nor disrupt [magnetic resonance imaging] MRIs, and their glass casings hold up to pressure testing, whether that’s being dropped from a rooftop or being run over by a pickup truck.

The privacy side of things is a bit more complicated, but the undeniable reality is that privacy isn’t as prized as we’d like to think [emphasis mine]. It’s already a regular concession to convenience.

“Your information’s for sale every day,” McMullen [Patrick McMullen, president, Three Square Market] says. “Thirty-four billion avenues exist for your information to travel down every single day, whether you’re checking Facebook, checking out at the supermarket, driving your car . . . your information’s everywhere.

Townsend may not be fully up-to-date on the subject of birth control implants. I think ‘safeish’ might be a better description in light of this news of almost two years ago (from a March 1, 2016 news item on CBS [Columbia Broadcasting Service] News [online]), Note: Links have been removed,

[US] Federal health regulators plan to warn consumers more strongly about Essure, a contraceptive implant that has drawn thousands of complaints from women reporting chronic pain, bleeding and other health problems.

The Food and Drug Administration announced Monday it would add a boxed warning — its most serious type — to alert doctors and patients to problems reported with the nickel-titanium implant.

But the FDA stopped short of removing the device from the market, a step favored by many women who have petitioned the agency in the last year. Instead, the agency is requiring manufacturer Bayer to conduct studies of the device to further assess its risks in different groups of women.

The FDA is requiring Bayer to conduct a study of 2,000 patients comparing problems like unplanned pregnancy and pelvic pain between patients getting Essure and those receiving traditional “tube tying” surgery. Agency officials said they have reviewed more than 600 reports of women becoming pregnant after receiving Essure. Women are supposed to get a test after three months to make sure Essure is working appropriately, but the agency noted some women do not follow-up for the test.

FDA officials acknowledged the proposed study would take years to complete, but said Bayer would be expected to submit interim results by mid-2017.

According to a Sept. 25, 2017 article by Kerri O’Brien for WRIC.com, Bayer had suspended sales of their device in all countries except the US,

Bayer, the manufacturer of Essure, has announced it’s halting sales of Essure in all countries outside of the U.S. In a statement, Bayer told 8News it’s due to a lack of interest in the product outside of the U.S.

“Bayer made a commercial decision this Spring to discontinue the distribution of Essure® outside of the U.S. where there is not as much patient interest in permanent birth control,” the statement read.

The move also comes after the European Union suspended sales of the device. The suspension was prompted by the National Standards Authority of Ireland declining to renew Essure’s CE marketing. “CE,” according to the European Commission website signifies products sold in the EEA that has been assessed to meet “high safety, health, and environmental protection requirements.”

These excerpts are about the Essure birth control implant. Perhaps others are safer? That noted, it does seem that Townsend was a bit dismissive of safety concerns.

As for privacy, he does investigate further to discover this,

As technology evolves and becomes more sophisticated, the methods to break it also evolve and get more sophisticated, says D.C.-based privacy expert Michelle De Mooy. Even so, McMullen believes that our personal information is safer in our hand than in our wallets. He  says the smartphone you touch 2,500 times a day does 100 times more reporting of data than does an RFID implant, plus the chip can save you from pickpockets and avoid credit card skimmers altogether.

Well, the first sentence suggests some caution. As for De Mooy, there’s this from her profile page on the Center for Democracy and Technology website (Note: A link has been removed),

Michelle De Mooy is Director of the Privacy & Data Project at the Center for Democracy & Technology. She advocates for data privacy rights and protections in legislation and regulation, works closely with industry and other stakeholders to investigate good data practices and controls, as well as identifying and researching emerging technology that impacts personal privacy. She leads CDT’s health privacy work, chairing the Health Privacy Working Group and focusing on the intersection between individual privacy, health information and technology. Michelle’s current research is focused on ethical and privacy-aware internal research and development in wearables, the application of data analytics to health information found on non-traditional platforms, like social media, and the growing market for genetic data. She has testified before Congress on health policy, spoken about native advertising at the Federal Trade Commission, and written about employee wellness programs for US News & World Report’s “Policy Dose” blog. Michelle is a frequent media contributor, appearing in the New York Times, the Guardian, the Wall Street Journal, Vice, and the Los Angeles Times, as well as on The Today Show, Voice of America, and Government Matters TV programs.

Ethics anyone?

Townsend does raise some ethical issues (Note: A link has been removed),

… Word from CEO Todd Westby is that parents in Wisconsin have been asking whether (and when) they can have their children implanted with GPS-enabled devices (which, incidentally, is the subject of the “Arkangel” episode in the new season of Black Mirror [US television programme]). But that, of course, raises ethical questions: What if a kid refused to be chipped? What if they never knew?

Final comments on implanted RFID chips and bodyhacking

It doesn’t seem that implantable chips have changed much since I first wrote about them in a May 27, 2010 posting titled: Researcher infects self with virus.  In that instance, Dr Mark Gasson, a researcher at the University of Reading. introduced a virus into a computer chip implanted in his body.

Of course since 2010, there are additional implantable items such as computer chips and more making their way into our bodies and it doesn’t seem to be much public discussion (other than in popular culture) about the implications.

Presumably, there are policy makers tracking these developments. I have to wonder if the technology gurus will continue to tout these technologies as already here or having made such inroads that we (the public) are presented with a fait accompli with the policy makers following behind.

New iron oxide nanoparticle as an MRI (magnetic resonance imaging) contrast agent

This high-resolution transmission electron micrograph of particles made by the research team shows the particles’ highly uniform size and shape. These are iron oxide particles just 3 nanometers across, coated with a zwitterion layer. Their small size means they can easily be cleared through the kidneys after injection. Courtesy of the researchers

A Feb. 14, 2017 news item on ScienceDaily announces a new MRI (magnetic resonance imaging) contrast agent,

A new, specially coated iron oxide nanoparticle developed by a team at MIT [Massachusetts Institute of Technology] and elsewhere could provide an alternative to conventional gadolinium-based contrast agents used for magnetic resonance imaging (MRI) procedures. In rare cases, the currently used gadolinium agents have been found to produce adverse effects in patients with impaired kidney function.

A Feb. 14, 2017 MIT news release (also on EurekAlert), which originated the news item, provides more technical detail,

 

The advent of MRI technology, which is used to observe details of specific organs or blood vessels, has been an enormous boon to medical diagnostics over the last few decades. About a third of the 60 million MRI procedures done annually worldwide use contrast-enhancing agents, mostly containing the element gadolinium. While these contrast agents have mostly proven safe over many years of use, some rare but significant side effects have shown up in a very small subset of patients. There may soon be a safer substitute thanks to this new research.

In place of gadolinium-based contrast agents, the researchers have found that they can produce similar MRI contrast with tiny nanoparticles of iron oxide that have been treated with a zwitterion coating. (Zwitterions are molecules that have areas of both positive and negative electrical charges, which cancel out to make them neutral overall.) The findings are being published this week in the Proceedings of the National Academy of Sciences, in a paper by Moungi Bawendi, the Lester Wolfe Professor of Chemistry at MIT; He Wei, an MIT postdoc; Oliver Bruns, an MIT research scientist; Michael Kaul at the University Medical Center Hamburg-Eppendorf in Germany; and 15 others.

Contrast agents, injected into the patient during an MRI procedure and designed to be quickly cleared from the body by the kidneys afterwards, are needed to make fine details of organ structures, blood vessels, and other specific tissues clearly visible in the images. Some agents produce dark areas in the resulting image, while others produce light areas. The primary agents for producing light areas contain gadolinium.

Iron oxide particles have been largely used as negative (dark) contrast agents, but radiologists vastly prefer positive (light) contrast agents such as gadolinium-based agents, as negative contrast can sometimes be difficult to distinguish from certain imaging artifacts and internal bleeding. But while the gadolinium-based agents have become the standard, evidence shows that in some very rare cases they can lead to an untreatable condition called nephrogenic systemic fibrosis, which can be fatal. In addition, evidence now shows that the gadolinium can build up in the brain, and although no effects of this buildup have yet been demonstrated, the FDA is investigating it for potential harm.

“Over the last decade, more and more side effects have come to light” from the gadolinium agents, Bruns says, so that led the research team to search for alternatives. “None of these issues exist for iron oxide,” at least none that have yet been detected, he says.

The key new finding by this team was to combine two existing techniques: making very tiny particles of iron oxide, and attaching certain molecules (called surface ligands) to the outsides of these particles to optimize their characteristics. The iron oxide inorganic core is small enough to produce a pronounced positive contrast in MRI, and the zwitterionic surface ligand, which was recently developed by Wei and coworkers in the Bawendi research group, makes the iron oxide particles water-soluble, compact, and biocompatible.

The combination of a very tiny iron oxide core and an ultrathin ligand shell leads to a total hydrodynamic diameter of 4.7 nanometers, below the 5.5-nanometer renal clearance threshold. This means that the coated iron oxide should quickly clear through the kidneys and not accumulate. This renal clearance property is an important feature where the particles perform comparably to gadolinium-based contrast agents.

Now that initial tests have demonstrated the particles’ effectiveness as contrast agents, Wei and Bruns say the next step will be to do further toxicology testing to show the particles’ safety, and to continue to improve the characteristics of the material. “It’s not perfect. We have more work to do,” Bruns says. But because iron oxide has been used for so long and in so many ways, even as an iron supplement, any negative effects could likely be treated by well-established protocols, the researchers say. If all goes well, the team is considering setting up a startup company to bring the material to production.

For some patients who are currently excluded from getting MRIs because of potential side effects of gadolinium, the new agents “could allow those patients to be eligible again” for the procedure, Bruns says. And, if it does turn out that the accumulation of gadolinium in the brain has negative effects, an overall phase-out of gadolinium for such uses could be needed. “If that turned out to be the case, this could potentially be a complete replacement,” he says.

Ralph Weissleder, a physician at Massachusetts General Hospital who was not involved in this work, says, “The work is of high interest, given the limitations of gadolinium-based contrast agents, which typically have short vascular half-lives and may be contraindicated in renally compromised patients.”

The research team included researchers in MIT’s chemistry, biological engineering, nuclear science and engineering, brain and cognitive sciences, and materials science and engineering departments and its program in Health Sciences and Technology; and at the University Medical Center Hamburg-Eppendorf; Brown University; and the Massachusetts General Hospital. It was supported by the MIT-Harvard NIH Center for Cancer Nanotechnology, the Army Research Office through MIT’s Institute for Soldier Nanotechnologies, the NIH-funded Laser Biomedical Research Center, the MIT Deshpande Center, and the European Union Seventh Framework Program.

Here’s a link to and a citation for the paper,

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents by He Wei, Oliver T. Bruns, Michael G. Kaul, Eric C. Hansen, Mariya Barch, Agata Wiśniowsk, Ou Chen, Yue Chen, Nan Li, Satoshi Okada, Jose M. Cordero, Markus Heine, Christian T. Farrar, Daniel M. Montana, Gerhard Adam, Harald Ittrich, Alan Jasanoff, Peter Nielsen, and Moungi G. Bawendi. PNAS February 13, 2017 doi: 10.1073/pnas.1620145114 Published online before print February 13, 2017

This paper is behind a paywall.

AquAdvantage salmon (genetically modified) approved for consumption in Canada

This is an update of the AquAdvantage salmon story covered in my Dec. 4, 2015 post (scroll down about 40% of the way). At the time, the US Food and Drug Administration (FDA) had just given approval for consumption of the fish. There was speculation there would be a long hard fight over approval in Canada. This does not seem to have been the case, according to a May 10, 2016 news item announcing Health Canada’s on phys.org,

Canada’s health ministry on Thursday [May 19, 2016] approved a type of genetically modified salmon as safe to eat, making it the first transgenic animal destined for Canadian dinner tables.

This comes six months after US authorities gave the green light to sell the fish in American grocery stores.

The decisions by Health Canada and the US Food and Drug Administration follow two decades of controversy over the fish, which is an Atlantic salmon injected with genes from Pacific Chinook salmon and a fish known as the ocean pout to make it grow faster.

The resulting fish, called AquAdvantage Salmon, is made by AquaBounty Technologies in Massachusetts, and can reach adult size in 16 to 18 months instead of 30 months for normal Atlantic salmon.

A May 19, 2016 BIOTECanada news release on businesswire provides more detail about one of the salmon’s Canadian connections,

Canadian technology emanating from Memorial University developed the AquAdvantage salmon by introducing a growth hormone gene from Chinook salmon into the genome of Atlantic salmon. This results in a salmon which grows faster and reaches market size quicker and AquAdvantage salmon is identical to other farmed salmon. The AquAdvantage salmon also received US FDA approval in November 2015. With the growing world population, AquaBounty is one of many biotechnology companies offering safe and sustainable means to enhance the security and supply of food in the world. AquaBounty has improved the productivity of aquaculture through its use of biotechnology and modern breeding technics that have led to the development of AquAdvantage salmon.

“Importantly, today’s approval is a result of a four year science-based regulatory approval process which involved four federal government departments including Agriculture and AgriFood, Canada Food Inspection Agency, Environment and Climate Change, Fisheries and Oceans and Health which demonstrates the rigour and scope of science based regulatory approvals in Canada. Coupled with the report from the [US] National Academy of Sciences today’s [May 19, 2016] approval clearly demonstrates that genetic engineering of food is not only necessary but also extremely safe,” concluded Casey [Andrew Casey, President and CEO BIOTECanada].

There’s another connection, the salmon hatcheries are based in Prince Edward Island.

While BIOTECanada’s Andrew Casey is crowing about this approval, it should be noted that there was a losing court battle with British Columbia’s Living Oceans Society and Nova Scotia’s Ecology Action Centre both challenging the federal government’s approval. They may have lost *the* battle but, as the cliché goes, ‘the war is not over yet’. There’s an Issue about the lack of labeling and there’s always the  possibility that retailers and/or consumers may decide to boycott the fish.

As for BIOTECanada, there’s this description from the news release,

BIOTECanada is the national industry association with more than 230 members reflecting the diverse nature of Canada’s health, industrial and agricultural biotechnology sectors. In addition to providing significant health benefits for Canadians, the biotechnology industry has quickly become an essential part of the transformation of many traditional cornerstones of the Canadian economy including manufacturing, automotive, energy, aerospace and forestry industries. Biotechnology in all of its applications from health, agriculture and industrial is offering solutions for the collective population.

You can find the BIOTECanada website here.

Personally, I’m a bit ambivalent about it all. I understand the necessity for changing our food production processes but I do think more attention should be paid to consumers’ concerns and that organizations such as BIOTECanada could do a better job of communicating.

*’the’ added on Aug. 4, 2016.

Opioid addiction and nanotechnology in Pennsylvania, US

Combating a drug addiction ‘crisis’ with a nanotechnology-enabled solution is the main topic although the technology is being implemented for another problem first according to this May 4, 2016 article by John Luciew for pennlive.com (Note: Links have been removed),

Treating pain is a constant in medicine. It’s part of the human condition, known as the “fifth vital sign” among physicians. Effectively treating pain will continue to play a central role in medicine, despite the societal shock waves brought on by the rapid rise in opioid addiction across America.

The fallout from our nation’s opioid addiction crisis is roiling the medical and pharmaceutical industries, where regulatory action is rapidly reining in opioid painkiller prescriptions with new guidelines and stricter controls.

By harnessing nanotechnology and small-particles physics, Iroko Pharmaceuticals is developing a new class of low-dose prescription painkillers. Company executives say their line of nonsteroidal anti-inflammatory drugs could be the opioid alternative that the medical community has been looking for amid America’s addiction crisis.

The pharmaceutical company is Pennsylvania-based (US) and it isn’t tackling the ‘opioid addiction crisis’ yet. First, there’s this,

Its new line of prescription painkillers are predicated upon a highly patented process of pulverizing drug molecules so they are up to 100 times smaller, which markedly increases their pain-killing effectiveness at dramatically lower doses.

Right now, Iroko is focusing this nanotechnology on creating a full line of low-dose prescription painkillers based upon the class of drugs known as nonsteroidal anti-inflammatories, or NSAIDs. There are six NSAID molecules, the most common being Ibuprofen. Iroko is planning nanotechnology technology versions for all six NSAID molecules, three of which have already received approval from the Food and Drug Administration.

Luciew has done some homework on the technology,

“We solved a chemistry problem by using physics,” explained Iroko Chairman Osagie Imasogie, who founded the company [Iroko Pharmaceuticals] in 2007.

Yet, the company that actually solved the physics problem was iCeutica, founded in Australia and now based in King of Prussia, Pa.

iCeutica owns the patented SoluMatrix fine particle process that pulverizes drug molecules into nano-sized particles, enabling low doses of a drug to be better absorbed by the body, thus providing faster and far more effective pain relief.

Of course, the practice of crushing and grinding drug powders is as old as the pharmacist’s mortar and pestle. But there’s never been a way of pulverizing a drug molecule into nano particles that was scalable for industrial production — not until iCeutica created its SoluMatrix process, that is.

iCeutica provides a description of the technology on its SoluMatrix webpage,

iCeutica’s proprietary SoluMatrix™ Fine Particle Technology fuels new product development and solves problems of bioavailability, variability, side effects and delivery of marketed or development-stage pharmaceuticals.

The SoluMatrix technology is a scaleable and cost-effective manufacturing process that can produce submicron-sized drug particles that are 10 to 200 times smaller than conventional drug particles. The particles generated using this technology, which both grinds the drug particles into a superfine powder and protects those submicron particles from subsequent agglomeration (or clumping together into big particles), comprise a single unit operation and can be manufactured into tablets, capsules and other dosage forms without further processing.

The SoluMatrix technology improves the performance of pharmaceuticals by dramatically changing how the drug dissolves and is absorbed. By making submicron-sized particles of a drug, it is possible to:

Unfortunately there aren’t more details. I’m somewhat puzzled  by the submicron measurement why not state the size using the term nanometre?

Getting back  to Iroko, Imasogie, impressed with the SoluMatrix technology, has made a major investment in iCeutica and is chair of iCeutica’s board. His homebase company, Iroko holds exclusive global rights to SoluMatrix.

Luciew’s article describes the current situation in the NSAID market,

Iroko officials acknowledge that NSAID painkillers carry their own health risks, including the potential for stomach ulcers, kidney problems and cardio-vascular ailments, up to and including stroke and heart attack. The fears associated with NSAIDs peaked a decade ago with the Vioxx case, a popular prescription NSAID that was eventually taken off the market due to associated cardiac and other risks.

The latest FDA guidelines for NSAID use calls for the lowest effective dose, which precisely describes the nanotechnology-driven low-dose NSAID drugs Iroko is rolling out. What is more, due to the ongoing opioid crisis, both the FDA and the Centers for Disease Control are heavily emphasizing non-opioid alternatives for pain relief, further opening to door for Iroko’s pain products.

That said about the issues with NSAIDs, Luciew outlines Iroko’s current offerings and explains what makes this technology so attractive,

According to Imasogie, Iroko’s line of low-dose, nanotechnology NSAIDs fits both sets of regulatory safety criteria. The new drugs are the lowest effective dose for NSAIDs, and are a viable pain-killing alternative to opioids, especially when it comes to treating osteoarthritis and other moderate pain.

“No one is going to give an NSAID if you have cancer,” Imasogie says. “But for chronic low back pain, yes.”

Three of Iroko’s six low-dose NSAID offerings have already received FDA approval and are on the market:

  • Zorvolex (diclofenac), approved in October 2013 for the management of mild to moderate acute pain in adults and in August 2014 for the management of osteoarthritis pain.
  • Tivorbex, approved in February 2014 for treatment of mild to moderate acute pain in adults.
  • Vivlodex, approved in October 2015 as another option for treatment of osteoarthritis pain. Three more of Iroko’s low-dose NSAIDs are awaiting approval.

These nano drugs are effective at doses of 35 to 40 milligrams to as low as 10 milligrams, the company says. That’s compared to other NSAID doses that start at 200 milligrams. As a result, Iroko’s low-dose NSAID drugs are being marketed as providing a prescription alternative to opioids at the precise moment everyone from the White House to the white-coat-clad family physician is searching for one.

If you the have time and interest, I encourage you to read Luciew’s article in its entirety. He covers more market issues and includes an enbedded video in his piece.

One last note about Iroko Pharmaceuticals, the company is named after a tree found on the African continent and executives of the company have hinted they are experimenting with SoluMatrix to make low-dose opioids available in the future.

While I have my doubts about the opioid addiction ‘crisis’, I do believe that lower, more effective doses of painkillers, regardless of their drug class, can only benefit patients.

Cornell University researchers breach blood-brain barrier

There are other teams working on ways to breach the blood-brain barrier (my March 26, 2015 post highlights work from a team at the University of Montréal) but this team from  Cornell is working with a drug that has already been approved by the US Food and Drug Administration (FDA) according to an April 8, 2016 news item on ScienceDaily,

Cornell researchers have discovered a way to penetrate the blood brain barrier (BBB) that may soon permit delivery of drugs directly into the brain to treat disorders such as Alzheimer’s disease and chemotherapy-resistant cancers.

The BBB is a layer of endothelial cells that selectively allow entry of molecules needed for brain function, such as amino acids, oxygen, glucose and water, while keeping others out.

Cornell researchers report that an FDA-approved drug called Lexiscan activates receptors — called adenosine receptors — that are expressed on these BBB cells.

An April 4, 2016 Cornell University news release by Krishna Ramanujan, which originated the news item, expands on the theme,

“We can open the BBB for a brief window of time, long enough to deliver therapies to the brain, but not too long so as to harm the brain. We hope in the future, this will be used to treat many types of neurological disorders,” said Margaret Bynoe, associate professor in the Department of Microbiology and Immunology in Cornell’s College of Veterinary Medicine. …

The researchers were able to deliver chemotherapy drugs into the brains of mice, as well as large molecules, like an antibody that binds to Alzheimer’s disease plaques, according to the paper.

To test whether this drug delivery system has application to the human BBB, the lab engineered a BBB model using human primary brain endothelial cells. They observed that Lexiscan opened the engineered BBB in a manner similar to its actions in mice.

Bynoe and Kim discovered that a protein called P-glycoprotein is highly expressed on brain endothelial cells and blocks the entry of most drugs delivered to the brain. Lexiscan acts on one of the adenosine receptors expressed on BBB endothelial cells specifically activating them. They showed that Lexiscan down-regulates P-glycoprotein expression and function on the BBB endothelial cells. It acts like a switch that can be turned on and off in a time dependent manner, which provides a measure of safety for the patient.

“We demonstrated that down-modulation of P-glycoprotein function coincides exquisitely with chemotherapeutic drug accumulation” in the brains of mice and across an engineered BBB using human endothelial cells, Bynoe said. “The amount of chemotherapeutic drugs that accumulated in the brain was significant.”

In addition to P-glycoprotein’s role in inhibiting foreign substances from penetrating the BBB, the protein is also expressed by many different types of cancers and makes these cancers resistant to chemotherapy.

“This finding has significant implications beyond modulation of the BBB,” Bynoe said. “It suggests that in the future, we may be able to modulate adenosine receptors to regulate P-glycoprotein in the treatment of cancer cells resistant to chemotherapy.”

Because Lexiscan is an FDA-approved drug, ”the potential for a breakthrough in drug delivery systems for diseases such as Alzheimer’s disease, Parkinson’s disease, autism, brain tumors and chemotherapy-resistant cancers is not far off,” Bynoe said.

Another advantage is that these molecules (adenosine receptors  and P-glycoprotein are naturally expressed in mammals. “We don’t have to knock out a gene or insert one for a therapy to work,” Bynoe said.

The study was funded by the National Institutes of Health and the Kwanjung Educational Foundation.

Here’s a link to and a citation for the paper,

A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier by Do-Geun Kim and Margaret S. Bynoe. J Clin Invest. doi:10.1172/JCI76207 First published April 4, 2016

Copyright © 2016, The American Society for Clinical Investigation.

This paper appears to be open access.

$1.4B for US National Nanotechnology Initiative (NNI) in 2017 budget

According to an April 1, 2016 news item on Nanowerk, the US National Nanotechnology (NNI) has released its 2017 budget supplement,

The President’s Budget for Fiscal Year 2017 provides $1.4 billion for the National Nanotechnology Initiative (NNI), affirming the important role that nanotechnology continues to play in the Administration’s innovation agenda. NNI
Cumulatively totaling nearly $24 billion since the inception of the NNI in 2001, the President’s 2017 Budget supports nanoscale science, engineering, and technology R&D at 11 agencies.

Another 9 agencies have nanotechnology-related mission interests or regulatory responsibilities.

An April 1, 2016 NNI news release, which originated the news item, affirms the Obama administration’s commitment to the NNI and notes the supplement serves as an annual report amongst other functions,

Throughout its two terms, the Obama Administration has maintained strong fiscal support for the NNI and has implemented new programs and activities to engage the broader nanotechnology community to support the NNI’s vision that the ability to understand and control matter at the nanoscale will lead to new innovations that will improve our quality of life and benefit society.

This Budget Supplement documents progress of these participating agencies in addressing the goals and objectives of the NNI. It also serves as the Annual Report for the NNI called for under the provisions of the 21st Century Nanotechnology Research and Development Act of 2003 (Public Law 108-153, 15 USC §7501). The report also addresses the requirement for Department of Defense reporting on its nanotechnology investments, per 10 USC §2358.

For additional details and to view the full document, visit www.nano.gov/2017BudgetSupplement.

I don’t seem to have posted about the 2016 NNI budget allotment but 2017’s $1.4B represents a drop of $100M since 2015’s $1.5 allotment.

The 2017 NNI budget supplement describes the NNI’s main focus,

Over the past year, the NNI participating agencies, the White House Office of Science and Technology Policy (OSTP), and the National Nanotechnology Coordination Office (NNCO) have been charting the future directions of the NNI, including putting greater focus on promoting commercialization and increasing education and outreach efforts to the broader nanotechnology community. As part of this effort, and in keeping with recommendations from the 2014 review of the NNI by the President’s Council of Advisors for Science and Technology, the NNI has been working to establish Nanotechnology-Inspired Grand Challenges, ambitious but achievable goals that will harness nanotechnology to solve National or global problems and that have the potential to capture the public’s imagination. Based upon inputs from NNI agencies and the broader community, the first Nanotechnology-Inspired Grand Challenge (for future computing) was announced by OSTP on October 20, 2015, calling for a collaborative effort to “create a new type of computer that can proactively interpret and learn from data, solve unfamiliar problems using what it has learned, and operate with the energy efficiency of the human brain.” This Grand Challenge has generated broad interest within the nanotechnology community—not only NNI agencies, but also industry, technical societies, and private foundations—and planning is underway to address how the agencies and the community will work together to achieve this goal. Topics for additional Nanotechnology-Inspired Grand Challenges are under review.

Interestingly, it also offers an explanation of the images on its cover (Note: Links have been removed),

US_NNI_2017_budget_cover

About the cover

Each year’s National Nanotechnology Initiative Supplement to the President’s Budget features cover images illustrating recent developments in nanotechnology stemming from NNI activities that have the potential to make major contributions to National priorities. The text below explains the significance of each of the featured images on this year’s cover.

US_NNI_2017_front_cover_CloseUp

Front cover featured images (above): Images illustrating three novel nanomedicine applications. Center: microneedle array for glucose-responsive insulin delivery imaged using fluorescence microscopy. This “smart insulin patch” is based on painless microneedles loaded with hypoxia-sensitive vesicles ~100 nm in diameter that release insulin in response to high glucose levels. Dr. Zhen Gu and colleagues at the University of North Carolina (UNC) at Chapel Hill and North Carolina State University have demonstrated that this patch effectively regulates the blood glucose of type 1 diabetic mice with faster response than current pH-sensitive formulations. The inset image on the lower right shows the structure of the nanovesicles; each microneedle contains more than 100 million of these vesicles. The research was supported by the American Diabetes Association, the State of North Carolina, the National Institutes of Health (NIH), and the National Science Foundation (NSF). Left: colorized rendering of a candidate universal flu vaccine nanoparticle. The vaccine molecule, developed at the NIH Vaccine Research Center, displays only the conserved part of the viral spike and stimulates the production of antibodies to fight against the ever-changing flu virus. The vaccine is engineered from a ~13 nm ferritin core (blue) combined with a 7 nm influenza antigen (green). Image credit: NIH National Institute of Allergy and Infectious Diseases (NIAID). Right: colorized scanning electron micrograph of Ebola virus particles on an infected VERO E6 cell. Blue represents individual Ebola virus particles. The image was produced by John Bernbaum and Jiro Wada at NIAID. When the Ebola outbreak struck in 2014, the Food and Drug Administration authorized emergency use of lateral flow immunoassays for Ebola detection that use gold nanoparticles for visual interpretation of the tests.

US_NNI_2017_back_cover._CloseUp

Back cover featured images (above): Images illustrating examples of NNI educational outreach activities. Center: Comic from the NSF/NNI competition Generation Nano: Small Science Superheroes. Illustration by Amina Khan, NSF. Left of Center: Polymer Nanocone Array (biomimetic of antimicrobial insect surface) by Kyle Nowlin, UNC-Greensboro, winner from the first cycle of the NNI’s student image contest, EnvisioNano. Right of Center: Gelatin Nanoparticles in Brain (nasal delivery of stroke medication to the brain) by Elizabeth Sawicki, University of Illinois at Urbana-Champaign, winner from the second cycle of EnvisioNano. Outside right: still photo from the video Chlorination-less (water treatment method using reusable nanodiamond powder) by Abelardo Colon and Jennifer Gill, University of Puerto Rico at Rio Piedras, the winning video from the NNI’s Student Video Contest. Outside left: Society of Emerging NanoTechnologies (SENT) student group at the University of Central Florida, one of the initial nodes in the developing U.S. Nano and Emerging Technologies Student Network; photo by Alexis Vilaboy.

A couple of lawyers talk wrote about managing nanotechnology risks

Because they are lawyers, I was intrigued by a Nov. 4, 2015 article on managing nanotechnology risks by Michael Lisak and James Mizgala of Sidley Austin LLP for Industry Week. I was also intrigued by the language (Note: A link has been removed),

The inclusion of nanotechnologies within manufacturing processes and products has increased exponentially over the past decade. Fortune recently noted that nanotechnology touches almost all Fortune 500 companies and that the industry’s $20 billion worldwide size is expected to double over the next decade. [emphasis mine]

Yet, potential safety issues have been raised and regulatory uncertainties persist. As such, proactive manufacturers seeking to protect their employees, consumers, the environment and their businesses – while continuing to develop, manufacture and market their products – may face difficult choices in how to best navigate this challenging and fluid landscape, while avoiding potential “nanotort,”  [emphasis mine] whistleblower, consumer fraud and regulatory enforcement lawsuits. Doing so requires forward-thinking advice based upon detailed analyses of each manufacturer’s products and conduct in the context of rapidly evolving scientific, regulatory and legal developments.

I wonder how many terms lawyers are going to coin in addition to “nanotort”?

The lawyers focus largely on two types of nanoparticles, carbon nanotubes, with a special emphasis on multi-walled carbon nantubes (MWCNT) and nano titanium dioxide,

Despite this scientific uncertainty, international organizations, such as the International Agency for Research on Cancer [a World Health Organization agency], have already concluded that nano titanium dioxide in its powder form and multi-walled carbon nanotube-7 (“MWCNT-7”) [emphasis mine] are “possibly carcinogenic to humans.” As such, California’s Department of Public Health lists titanium dioxide and MWCNT-7 as “ingredients known or suspected to cause cancer, birth defects, or other reproductive toxicity as determined by the authoritative scientific bodies.”  Considering that processed (i.e., non-powdered) titanium dioxide is found in products like toothpaste, shampoo, chewing gum and candies, it is not surprising that some have focused upon such statements.

There’s a lot of poison in the world, for example, apples contain seeds which have arsenic in them and, for another, peanuts can be carcinogenic and they can also kill you, as they are poison to people who are allergic to them.

On the occasion of Dunkin’ Donuts removing nano titanium dioxide as an ingredient in the powdered sugar used to coat donuts, I wrote a March 13, 2015 posting, where I quote extensively from Dr. Andrew Maynard’s (then director of the University of Michigan Risk Science Center now director of the Risk Innovation Lab at Arizona State University) 2020 science blog posting about nano titanium dioxide and Dunkin’ Donuts,

He describes some of the research on nano titanium dioxide (Note: Links have been removed),

… In 2004 the European Food Safety Agency carried out a comprehensive safety review of the material. After considering the available evidence on the same materials that are currently being used in products like Dunkin’ Donuts, the review panel concluded that there no evidence for safety concerns.

Most research on titanium dioxide nanoparticles has been carried out on ones that are inhaled, not ones we eat. Yet nanoparticles in the gut are a very different proposition to those that are breathed in.

Studies into the impacts of ingested nanoparticles are still in their infancy, and more research is definitely needed. Early indications are that the gastrointestinal tract is pretty good at handling small quantities of these fine particles. This stands to reason given the naturally occurring nanoparticles we inadvertently eat every day, from charred foods and soil residue on veggies and salad, to more esoteric products such as clay-baked potatoes. There’s even evidence that nanoparticles occur naturally inside the gastrointestinal tract.

You can find Andrew’s entire discussion in his March 12, 2015 post on the 2020 Science blog. Andrew had written earlier in a July 12, 2014 posting about something he terms ‘nano donut math’ as reported by As You Sow, the activist group that made a Dunkin’ Donuts shareholder proposal which resulted in the company’s decision to stop using nano titanium dioxide in the powdered sugar found on their donuts. In any event, Andrew made this point,

In other words, if a Dunkin’ Donut Powdered Cake Donut contained 8.9 mg of TiO2 particles smaller than 10 nm, it would have to have been doused with over 1 million tons of sugar coating! (Note update at the end of this piece)

Clearly something’s wrong here – either Dunkin’ Donuts are not using food grade TiO2 but a nanopowder with particle so small they would be no use whatsoever in the sugar coating (as well as being incredibly expensive, and not FDA approved).  Or there’s something rather wrong with the analysis!

If it’s the latter – and it’s hard to imagine any other plausible reason for the data – it looks like As You Sow ended up using rather dubious figures to back up their stakeholder resolution.  I’d certainly be interested in more information on the procedures Analytical Sciences used and the checks and balances they had in place, especially as there are a number of things that can mess up a particle analysis like this.

Update July 14: My bad, I made a slight error in the size distribution calculation first time round.  This has been corrected in the article above.  Originally, I cited the estimated Mass Median Diameter (MMD) of the TiO2 particles as 167 nm, and the Geometric Standard Deviation (GSD) as 1.6.  Correcting an error in the Excel spreadsheet used to calculate the distribution (these things happen!) led to a revised estimate of MMD = 168 nm and a GSD of 1.44.  These may look like subtle differences, but when calculating the estimated particle mass below 10 nm, they make a massive difference.  With the revised figures, you’d expect less than one trillionth of  a percent of the mass of the TiO2 powder to be below 10 nm!! (the original estimate was a tenth of a millionth of a percent).  In other words – pretty much nothing!  The full analysis can be found here.

Update November 16 2014.  Based on this post, As You Sow checked the data from Analytical Sciences LLC and revised the report accordingly.  This is noted above.

It would seem that if there are concerns over nano titanium dioxide in food, the biggest would not be the amounts ingested by consumers but inhalation by workers should they breathe in large quantities when they are handling the material.

As for the MWCNTs, they have long raised alarms but most especially the long MWCNTs and for people handling them during the course of their work day. Any MWCNTs found in sports equipment and other consumer products are bound in the material and don’t pose any danger of being inhaled into the lungs, unless they should be released from their bound state (e.g. fire might release them).

After some searching for MWCNT-7, I found something which seems also to be known as Mitsui MWCNT-7 or Mitsui 7-MWCNT (here’s one of my sources). As best I understand it, Mitsui is a company that produces an MWCNT which they have coined an MWCNT-7 and which has been used in nanotoxicity testing. As best I can tell, MWCNT is MWCNT-7.

The lawyers (Lisak and Mizgala) note things have changed for manufacturers since the early days and they make some suggestions,

One thing is certain – gone are the days when “sophisticated” manufacturers incorporating nanotechnologies within their products can reasonably expect to shield themselves by pointing to scientific and regulatory uncertainties, especially given the amount of money they are spending on research and development, as well as sales and marketing efforts.

Accordingly, manufacturers should consider undertaking meaningful risk management analyses specific to their applicable products. …

First, manufacturers should fully understand the life-cycle of nanomaterials within their organization. For some, nanomaterials may be an explicit focus of innovation and production, making it easier to pinpoint where nanotechnology fits into their processes and products. For others, nanomaterials may exist either higher-up or in the back-end of their products’ supply chain. …

Second, manufacturers should understand and stay current with the scientific state-of-the-art as well as regulatory requirements and developments potentially applicable to their employees, consumers and the environment. An important consideration related to efforts to understand the state-of-the-art is whether or not manufacturers should themselves expend resources to advance “the science” in seeking to help find answers to some of the aforementioned uncertainties. …

The lawyers go on to suggest that manufacturers should consider proactively researching nanotoxicity so as to better defend themselves against any future legal suits.

Encouraging companies to proactive with toxicity issues is in line with what seems to be an international (Europe & US) regulatory movement putting more onus on producers and manufacturers to take responsibility for safety testing. (This was communicated to me in a conversation I had with an official at the European Union Joint Research Centre where he mentioned REACH regulations and the new emphasis in response to my mention of similar FDA (US Food and Drug Administration) regulations. (We were at the 2014 9th World Congress on Alternatives to Animal Testing in Prague, Czech republic.)

For anyone interested in the International Agency for Research on Cancer you can find it here.