Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the randomized, Phase 3 TOURMALINE-MM3 study met its primary endpoint, demonstrating single-agent oral NINLARO® (ixazomib) as a maintenance therapy resulted in a statistically significant improvement in progression-free survival (PFS) versus placebo. The trial evaluated the effect of NINLARO as a maintenance therapy in adult patients diagnosed with multiple myeloma who responded to high-dose therapy (HDT) and autologous stem cell transplant (ASCT). Takeda plans to submit data from the trial to regulatory agencies around the world. NINLARO is currently not approved as a maintenance therapy for multiple myeloma following ASCT.
“Within the maintenance setting, it is critical that we find agents that are efficacious, tolerable and convenient,” said Jesús Gomez Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “The results of the TOURMALINE-MM3 trial represent an important step toward the goal of expanding the use of NINLARO as a maintenance therapy. This is the first and only Phase 3 placebo-controlled study evaluating a proteasome inhibitor in this setting and we look forward to discussions with Health Authorities around the world.”
There were no new safety signals found in TOURMALINE-MM3. The safety profile of NINLARO in the maintenance setting is consistent with previously reported results of single-agent NINLARO use.
Full data results will be submitted for presentation at the 60th American Society of Hematology Annual Meeting in December.
Ferrofluids are colloidal suspensions of magnetic particles in a liquid carrier, which become magnetized in the presence of a magnetic field. These may be composed of iron, nickel, or cobalt, and show magnetic properties.
The particles are typically about 10 nm in diameter, and may be suspended in either oil or water. Ferrofluids are also called magnetic nanoparticles (MNPs) or magnetic beads (MBs). Ferrofluids were first introduced to the world in the 1960s by NASA Lewis Laboratories and AVCO Space Systems independently.
Image Credit: Nneirda / Shutterstock
Synthesis
Nano-sized magnetic particles (e.g. iron oxide) can be synthesized in many ways. One such reaction is by co-precipitating magnetite (Fe3O4) with ammonia (NH3) from an iron solution:
2FeCl3 + FeCl2 + 8NH3+ 4H2O → Fe3O4 + 8NH4Cl
Many MNPs used in targeted delivery systems are chemically iron oxides.
Iron oxide may be directly cytotoxic due to the formation of oxygen and nitrogen free radicals. Therefore, MNPs are mostly prepared using core-shell methodology which has several advantages:
protects the magnetic core from oxidation
prevents the formation of aggregates and agglomerates due to Van der Waals force, hydrophobic effect, and magnetic attractions
protects the surface from any chemical reactions (d) amplifies the cellular uptake rate, and
facilitates various therapeutic attachments.
The magnetic core of an iron oxide nanoparticle comprises magnetite (Fe3O4) and/or maghemite (γ‑Fe2O3), whereas the coat is made up of organic compounds such as surfactants, synthetic/natural polymers, and inorganic materials like carbon, silica, oxides, or precious metals.
Ferrofluids in Cancer Therapy
Cancer is a major killer all over the world. Over the past several decades, chemotherapy, radiotherapy, and surgery have been the main components of cancer management. Such treatments possess their own advantages and disadvantages.
Both chemotherapy and radiotherapy are nonselective in their effects, affecting healthy cells as well as cancerous ones, though radiotherapy has more localized effects. Moreover, this treatment is carried out at tissue/organ level, not at cellular level; thus, the chances of causing harm to healthy cells increase.
Treating cancer by surgical removal is another successful method, but it is impossible to carry out surgery in all cases, as some locations are inaccessible, such as the deep interior of the brain or the liver. Moreover, surgery is not an option in the presence of widespread tumor metastasis.
All such conventional treatments have limited access in one or other manner, and lack selectivity of action towards tumor cells. There is much need of a technique that targets the tumor cells specifically.
Using MNPs as drug carriers in targeted cancer therapy provides good opportunities for cancer cure, as the use of such carriers reduces the side effects pertaining to conventional treatments. Medications can be targeted to treat the desired locations inside the body with the help of the magnetic properties of ferrofluids.
Magnetic Fluid Hyperthermia (MFH) Approach
MFH uses MNPs in combination with heat. It can treat tumors which lie deep within the body areas such as the bony skull (glioblastoma) and the pelvis (prostate/cervical carcinoma). The treatment involves administration of magnetic nanoparticles into the tumor followed by exposure to an alternating current (AC) magnetic field.
The cancer cells which adhere to MNPs are exposed to the alternating magnetic field (AMF), and the temperature is set above 42–46°C. Heat alters some receptor molecules on the cancer cell surface, which enhances their recognition by natural killer cells.
Superparamagnetic iron oxide nanoparticles (SPIONs) show great promise in biomedical applications as they are small enough to be used at cellular level, and display magnetic behavior only in the presence of a magnetic field.
In 2005, the first Phase 1 clinical study was conducted in patients with recurrent prostatic tumor which concluded that magnetic hyperthermia is a feasible as well as well-tolerated treatment modality.
Another study, two years later, was conducted using magnetic hyperthermia in combination with radiotherapy in 14 brain cancer patients, demonstrating that the therapy was well‑tolerated in all patients, though with minimal or no clinical benefit.
The treatment operates at cellular level rather than at the tissue or organ level, so it is able to target cancer cells selectively compared to the conventional approaches used in the treatment of tumors. In a recent study, it has been seen that a proteasome inhibitor used along with MFH can be used to treat larger tumors unlike other conventional methods.
MFH is projected to be a major breakthrough in cancer treatment, and promises to be a viable therapy for treating human tumors.
Other Applications
Other areas in which MNPs may prove to be useful include lung cancer which is notoriously difficult to treat because of the lack of adequate drug concentrations at the sites of disease. One in vitro study has used aerosols containing superparamagnetic nanoparticles of iron oxide delivered to the lung to reach effective dosage levels in the affected areas of the lung without adverse effects.
Another proposed delivery method uses magnetic targeted carriers using ferromagnetic particles below micron size, to deliver relaxant drugs during the administration of local anesthesia as well as in targeted cancer therapy.
Another area which is exploring the feasibility of MNPs is gene therapy to introduce genes into targeted cells without having to use viral and retroviral vectors, which are especially noted to be associated with adverse effects.
Achieve Life Sciences Inc ACHV 11.08% shares are skyrocketing as the clinical-stage biotech moves one step closer to filing a New Drug Application for its smoking cessation pipeline candidate cytisine.
The stock was rallying 33.15 percent to $4.82 Wednesday morning.
What Happened
After a meeting with the FDA regarding both clinical and non-clinical development plans for cytisine, Achieve Life Sciences said the Phase 3 clinical program as well as a future NDA filing are further defined.
In late June, the company reported positive results for cytisine based on a series of drug metabolism, drug-to-drug interaction and transponder studies.
Why It’s Important
Cytisine is a plant-based alkaloid which binds to the nicotinic acetylcholine receptor. It has been approved and marketed in central and eastern Europe for over 15 years and has helped over 20 million people tackle nicotine addiction, according to Achieve.
What’s Next
The company said it will conduct a Phase 2b optimization trial in about 250 smokers in the U.S., with various dosing schedules to determine efficacy, safety and compliance profiles. The primary endpoint is a reduction in cigarettes consumed during treatment.
Achieve Life Sciences said it will initiate the Phase 2b trial in Q4’18, with top-line results expected in Q2’19. The results will help define the Phase 3 study, which is planned to be initiated in 2019.
In the name of science, Andrew Huberman has gone diving 40 feet underwater with great white sharks. He’s gone mountain climbing without ropes or harnesses, traversing some sections where one slip would have sent him plummeting 650 feet.
Now, the Stanford neuroscientist is embarking on a different kind of daring quest, testing an intriguing but unproven hypothesis: that virtual reality could be used to preserve or even restore vision for patients with glaucoma.
Academics and companies all over the world are betting on virtual reality to help patients with conditions like anxiety, depression, PTSD, and ADHD. Huberman believes in the potential of the technology for vision issues, too, but he speaks about it less like an evangelist than someone who’s discovered a useful tool. He’s also harnessing it in pioneering ways.
In the case of his glaucoma clinical trial, Huberman is asking patients to gaze at flashing white dots in the hopes that they can trigger the firing of neurons that connect the eye to the brain and coax them to regenerate.
He’s also using virtual reality to study the physiology of anxiety and fear. He has recruited volunteers to watch virtual reality footage of scenarios they may never encounter in real life: Being attacked by a dog. Climbing more than 250 feet up a tree. And swimming with sharks.
Huberman, 42, traveled to many of the shoots, putting himself in personal danger to collect the footage of the sharks. An intense and earnest man, he said he’s not interested in the extreme for its own sake, but rather “for how it can inform the typical person — and mostly how it can be used to relieve suffering.”
“When the curtain goes down for me, I don’t want to look back on my career and say: ‘Oh, we did all this nice work in mice,’” Huberman told STAT in a recent interview in his lab at Stanford. “I decided about six years ago that, unless I made a deliberate attempt to create a tool to cure blindness, a deliberate attempt to alleviate pathologic anxiety, it wasn’t going to happen the way it could happen.”
“I hope I don’t die trying, but if I do, I do,” Huberman said. “A bad thing about being dead is that the research might halt.” Optics equipment used to take high-resolution images of the retinas of glaucoma patients in Huberman’s clinical trial.LAURA MORTON FOR STAT
In his quest to relieve suffering, Huberman picked a formidable target in glaucoma, a disease in which the neurons that relay information from the eye to the brain suffer damage, resulting in a loss of vision. Many patients take prescription eye drops to slow or prevent their vision loss, but there’s no proven way to reverse damage already done.
Huberman’s new clinical trial grew out of an experiment in visually impaired mice. In that study — detailed in a 2016 paper published in Nature Neuroscience — he and his team used gene therapy (to activate a signaling pathway involved in stimulating growth) and visual stimulation (in the form of moving black and white bars that the mice were forced to look at) to try to coax the neurons connecting a mouse’s eye to its brain to regenerate. Fewer than 5 percent of the neurons, called retinal ganglion cells, grew back. But that was enough to help the mice see better, measured by whether they ran away from perceived threats.
The visual improvement was greatest when Huberman and his team used both gene therapy and visual stimulation. Their clinical trial is not testing the former component of the mouse experiment, but rather a more sophisticated version of the moving stripes.
The trial has so far enrolled two glaucoma patients, a 17-year-old woman and a 76-year-old man. A third patient is expected to join soon, with still more being screened. The goal is to eventually enroll 200 glaucoma patients who have lost some vision but are not completely blind. (Huberman has no hope that the experimental treatment will work in people who can’t see at all.)
When patients sign up, Huberman’s team measures their vision and maps the damage to their retinal ganglion cells. “If you have a hole in your neural retina that gives you a blank spot just X number of degrees, or this position off, the center of your visual field, we want to know that,” Huberman said. That information allows the programmers on his team to customize the visual reality experience for each patient, placing flashing white spots in specific locations in their field of vision.
To keep things interesting, the virtual reality experience involves more than white dots. When patients put on special headsets, they’re transported into an art gallery with empty frames on the walls. They can move their eyes or their head to explore the gallery, but the point of it all is the visual stimulation: those flashing white dots, which dance across the screen for periods of one to three minutes at different sizes and speeds.
When patients complete the task, they get rewarded with a great work of art that appears in one of the empty frames. Among them: Vincent van Gogh’s iconic landscape “The Starry Night” and Rene Magritte’s surrealist portrait of “The Son of Man,” clad in a suit with a green apple obscuring his face.
Delivering this visual stimulation using virtual reality solves a stubborn problem in the field. Researchers have long tried to regenerate patients’ neurons by having them stare at some kind of stimuli on computers or TV screens. But it hasn’t worked. One theory why: Patients’ eyes tend to wander, and when that happens there’s no way to precisely target the visual stimulation to the damaged regions of patients’ eyes. With virtual reality, “you control their entire world and you know exactly where their eyes are,” Huberman said.
Patients get sent home with a virtual reality headset and are instructed to use it five days a week for 30 minutes at a time, while sitting down. Huberman and his team haven’t decided how long they’ll ask the patients to keep doing the visual exercise, but for now they’re bringing them in every six weeks to track changes in their vision.
“When the curtain goes down for me, I don’t want to look back on my career and say: ‘Oh, we did all this nice work in mice.’ ”
ANDREW HUBERMAN, STANFORD
Three independent vision specialists consulted by STAT said that while Huberman’s approach is innovative, there are plenty of reasons why it might not work.
Dr. Anne Coleman, a glaucoma specialist at UCLA School of Medicine said that the experimental treatment doesn’t pose a safety risk, but she hopes that patients considering the trial will keep in mind that it’s still early and unproven so that it does not bring them “false hope.”
For now, the trial lacks a control group of patients who would not get the visual stimulation, an element generally considered the gold standard in medical research. (Huberman said he’s considering adding a control group later on but wants to see more data first.) The trial is also open both to patients who take medication to relieve high pressure in their eyes and those who do not, which could potentially confound the results. (Huberman said he expects nearly everyone in the trial in the trial to be on eye drops, since they’re the standard treatment.)
The trial also comes with another important caveat: What works in mice rarely works in people. While the mouse study is interesting, “translating that in humans who have to physically go out and interact with the world, I think, is a whole other level,” said Lotfi Merabet, a clinician-scientist at Massachusetts Eye and Ear who specializes in vision rehabilitation.
Huberman speaks candidly about potential weaknesses in his hypothesis: While the neurons could regenerate all the way up to the brain in tiny mice, the much greater distance in humans could prove too far to traverse. And the neurons involved in vision may not have the same capacity to regenerate in adult patients as they do during development.
There’s also the matter of money.
The Glaucoma Research Foundation is providing initial seed funding for Huberman’s trial, but that won’t be enough. Huberman is scrambling to raise money from other foundations, private donors, and government grants.
Thomas Brunner, president and CEO of the Glaucoma Research Foundation, said he’s pleased to see the experimental treatment moving from mice to humans at a quicker pace than usual for patients who are desperate to stop the ravages of glaucoma.
“The idea of testing early and then refining is much more appealing to me than people who are a little more afraid to take a risk,” Brunner said. Huberman, he said, is “a risk-taker, which is something I admire.” Huberman (right) and videographer Morne Hardenberg gather virtual reality footage of great white sharks off the coast of Guadalupe Island in 2017.COURTESY MICHAEL MULLER
Huberman has a Ph.D. in neuroscience from the University of California, Davis, and an associate professorship at Stanford, where he moved his lab in 2016 after five years at the University of California, San Diego.
He also has a taste for the extreme.
In his free time and on his own dime, Huberman has soaked in an ice bath for 10 minutes. He’s training right now for an ocean swim tens of miles long. He’s also training for an ocean dive — without scuba gear — in which he plans to hold his breath. (The depth has yet to be determined, but he said a good goal would be 70 feet underwater.)
“I realize I’m a little unusual in the kinds of eclectic things that I do for fun,” Huberman conceded.
Huberman grew up doing martial arts, so he’s comfortable in scenarios where there’s a physical threat, he said. And, no, he does not think you should try any of this at home or elsewhere without training and supervision from professionals.
He’s driven by a sense of adventure, sure, but he also does it because he’s interested in understanding fear — and wants to find teachable interventions to help people overcome it. For example, he tried out a nasal breathing technique when he went climbing without protective equipment in the Pyrenees mountain range in Spain; he navigated through sections where, as he put it, “basically one slip and you’re dead.”
Huberman said he has always been curious about why some people find a situation tolerable or pleasurable — while others find it terrifying.
He’s not so interested in people who are naturally comfortable in extreme or stressful scenarios. His real interest, he said, is in someone like himself — “the person who’s not comfortable doing it but learns how to be. That’s information you can transfer.”
Huberman’s fascination with the extreme has informed his virtual reality research.
Plenty of researchers use the technology in clinical experiments. But what sets Huberman apart is the lengths he’s gone to gather his virtual reality footage.
For his study on anxiety using virtual reality to evoke fear, he initially thought about pulling from existing libraries of scary stock footage. But they weren’t right for his purposes: The clips were too short; he needed something at least 10 minutes long. And they usually opened right away with a frightening experience, instead of opening with a calming scene from everyday life — necessary for his team to collect baseline measurements.
So Huberman decided to collect his own virtual reality footage, using special 360-degree cameras.
To evoke the claustrophobia of being trapped in an elevator, he and his team captured footage in what he fondly refers to as the “dungeon-like” elevator in his lab building at Stanford. They recruited other occupants of the building to serve as extras, and the building’s maintenance team helped them halt the elevator abruptly.
To elicit a fear of heights, they asked a professional tree-trimmer to wear a camera on his body while climbing more than 250 feet up a tree in the region east of the San Francisco Bay.
And to simulate the frightening experience of being attacked by a dog, they went to nearby Redwood City, Calif., to solicit the help of a professional dog trainer and his 120-pound pitbull. With the camera running, the trainer gave the dog a cue to attack his arm and then cried out as if in pain. (In fact, the trainer was wearing a special dog-bite-resistant sleeve to protect himself from injury.)
Gathering all this footage has proved to be remarkably cheap, Huberman said. The lab’s many collaborators have helped them at little to no cost or allowed them to piggyback onto other trips, all in the name of research. (Other costs of the fear study, such as the virtual reality headsets, are being paid for using internal funds, Huberman said.)
The study, which is not a formal clinical trial, so far has recruited 85 volunteers, with the goal of eventually signing up 250 people, some of whom have diagnosed anxiety. The most effective recruitment method has not been the placement of traditional fliers tacked to a telephone pole, but rather the lab’s Instagram page. One of Huberman’s flyers recruiting volunteers for a study using virtual reality to evoke fear.LAURA MORTON FOR STATWhen most volunteers watch the footage — all while having their heart rate, sweating, breathing, pupil size, and body posture measured — they will most likely have no idea of all that went into capturing it.
In the case of the shark footage, Huberman teamed up with an A-list photographer named Michael Muller, who has a passion for photographing sharks in the wild. Their team has twice boarded a research vessel for a 22-hour voyage out into the Pacific Ocean to spend a few days out on the crystal-clear water off the coast of Guadalupe Island.
Visiting tourists or researchers often go underwater in protective metal cages to observe the hundreds of great white sharks that congregate in the area. But Huberman said he managed to get permits from the Mexican government so that he and his team could exit the cage and swim with the sharks for his research project.
The experience was “incredibly calming,” said Huberman, who underwent training on how to stay safe.
Huberman speaks fondly about the sharks. But he also calls them “really diabolic little guys,” too, before quickly correcting himself: At about 3,000 pounds and 15 feet long, they’re “not so little guys.”
Huberman said that, if he returns to Guadalupe Island, he wants to run a field study measuring his collaborators’ respiration, pupil size, and heart rate while they swim among the sharks.
And although he hasn’t yet figured out how to do it, he said he wants to collect perhaps his most extreme virtual reality footage yet: a simulation of the experience of being eaten by a shark.
https://bit.ly/2tNAlQN
Nevada’s plan to execute a convicted murderer with a never-before-used combination of drugs is on hold for at least 60 days.
The state was planning to use three drugs — midazolam (a sedative), fentanyl (the high-potency opioid) and cisatracurium (a paralytic) — to execute Scott Dozier on Wednesday night.
Clark County District Judge Elizabeth Gonzalez ruled in favor of the company that makes midazolam, which sued the state, saying Nevada had illegitimately acquired the product for the execution. It wants the state to return its stock of the drug to the company. Gonzalez granted a temporary restraining order.
“If the state is permitted to use the midazolam manufactured by plaintiff, plaintiff has shown a reasonable probability it will suffer irreparable damages,” Gonzalez said in her Las Vegas court.
The drug maker, Alvogen, and the state are scheduled to return to court September 10 for another hearing in the case.
The execution would have been the first time that fentanyl, one of the central drugs in the US opioid epidemic, has been used in a capital punishment case in the United States, said Robert Dunham, executive director of the Death Penalty Information Center. It would likely have been a first for cisatracurium to be used as well, he said.
Dozier, 47, is not making legal challenges to halt his execution. “Life in prison isn’t a life,” he told the Las Vegas Review-Journal. “This isn’t living, man. It’s just surviving.”
“If people say they’re going to kill me, get to it,” he told the newspaper.
This undated Nevada Department of Corrections photo shows death row inmate Scott Raymond Dozier.
His attorney, Thomas Ericsson, told CNN that his client wants to be executed.
Although Dozier is not trying to stop his execution, there is opposition to the drug cocktail the state plans to use in carrying out the death sentence.
“Nevada should not use prisoners as guinea pigs in experimental executions, even if they ask to die,” tweeted the ACLU of Nevada.
ACLU of Nevada
@ACLUNV
Join the Nevada Coalition Against the Death Penalty for a rally and vigil at 7 p.m. Wednesday at the Governor’s Mansion! Nevada should not use prisoners as guinea pigs in experimental executions, even if they ask to die.
Dozier was convicted of first-degree murder in the death of Jeremiah Miller, who was killed and dismembered in 2002. The victim’s torso was found in a suitcase dumped in a trash bin in Las Vegas, according to the Nevada Department of Corrections. Dozier was also convicted of second-degree murder in the death of another victim found buried in the Arizona desert.
The Wednesday execution would be Nevada’s first in 12 years, after Daryl Mack was executed in 2006, and the first to take place in a new execution facility at Ely State Prison. Lethal injection is the only method of capital punishment that Nevada uses.
Subsidiaries of Ligand Pharmaceutical Inc. (LGND) and Johnson & Johnson have entered into a research-and-development agreement focused on a “transgenic chicken platform” aimed at generating and discovering antibodies for humans, according to a securities filing.
Ligand’s company Crystal Bioscience Inc., and Janssen Research & Development LLC, which is part of the Janssen Pharmaceutical Cos. of Johnson & Johnson, agreed to work together on Ligand’s development of the platform, the filing said.
Under the deal, Ligand will be able to earn milestone payments contingent on various deliverables and will be able to sell the platform to others in the market.
Toxicologists today unveiled a digital chemical safety screening tool that could greatly reduce the need for six common animal tests. Those tests account for nearly 60% of the estimated 3 million to 4 million animals used annually in risk testing worldwide.
The computerized tool—built on a massive database of molecular structures and existing safety data—appears to match, and sometimes improve on, the results of animal tests for properties such as skin sensitization and eye irritation, the researchers report in today’s issue of Toxicological Sciences. But it also has limitations; for instance, the method can’t reliably evaluate a chemical’s risk of causing cancer. And it’s not clear how open regulatory agencies will be to adopting a nonanimal approach.
Still, “We’re really excited about the potential of this model,” says toxicologist Nicole Kleinstreuer, deputy director of a center that evaluates alternatives to animal testing at the National Institute of Environmental Health Sciences (NIEHS) in Durham, North Carolina. Kleinstreuer, who was not involved in the work, adds that using “big data … to build predictive models is an extremely promising avenue for reducing and replacing animal testing.”
Most developed nations require new chemicals that enter commerce to undergo at least some safety testing. But the long-standing practice of exposing rabbits, rats, and other animals to chemicals to evaluate risks is facing growing public objections and cost concerns, helping spur a hunt for alternatives. In the United States, the Environmental Protection Agency (EPA) has been backing research into new ways of evaluating chemicals through programs such as its Toxicity Forecaster (ToxCast) effort. And in 2016, Congress passed an updated chemical safety law—the Toxic Substances Control Act (TSCA)—that orders federal regulators to take steps to reduce the number of animals that companies use to test compounds for safety.
One approach is to use what is already known about the safety of existing compounds to predict the risks posed by new chemicals with similar molecular structures. Two years ago, a team led by Thomas Hartung of the Johns Hopkins University Bloomberg School of Public Health in Baltimore, Maryland, took a step toward that goal by assembling test data on 9800 chemicals regulated by the European Chemicals Agency (ECHA) in Helsinki. They then showed that chemicals with similar structures can have similar health effects, such as being an irritant
In today’s paper, Hartung’s team goes bigger. First, the researchers expanded their database to 10 million chemical structures by adding information from the public database PubChem and the U.S. National Toxicology Program. Next, they compared the structures and toxicological properties of every possible pair of compounds in their database—a total of 50 trillion comparisons—creating a vast similarity map that groups compounds by structure and effect. Finally, they tested the model: They asked it to predict a randomly chosen chemical’s toxicological profile by linking it to similar “neighbors” on the map and compared the results to six actual animal tests of the compound.
On average, the computational tool reproduced the animal test results 87% of the time. That’s better than animal tests themselves can do, Hartung says: In reviewing the literature, his group found that repeated animal tests replicated past results just 81% of the time, on average. “This is an important finding,” Hartung says, because regulators often expect alternative methods to animal testing to be reproducible at the 95% threshold—a standard even the animal tests aren’t meeting.
“Our data shows that we can replace six common tests—which account for 57% of the world’s animal toxicology testing—with computer-based prediction and get more reliable results,” Hartung says. And it could help eliminate duplication of effort, he adds. The team found, for instance, that 69 chemicals were each tested at least 45 separate times using the so-called Draize rabbit test—a method that involves placing a chemical in the rabbit’s eye and has drawn extensive public opposition.
The screening method has weaknesses. Although it can predict simple effects such as irritation, more complex endpoints such as cancer are out of its reach, says Mike Rasenberg, who heads ECHA’s Computational Assessment & Dissemination unit. “This won’t be the end of animal testing,” he predicts, “but it’s a useful concept for looking at simple toxicity.”
The question now is how regulators will view the method. Rasenberg thinks European regulators will accept it for simple endpoints because it meets validating criteria for so-called quantitative structure-activity relationship models.
In the United States, the NIEHS center is working on validating the method. And once that validation is complete, EPA “will be able to review the evaluation results to determine how and if they can be used to inform chemicals evaluated under TSCA,” officials said in a statement. “If evaluation is favorable, these types of models could be used in conjunction with other tools such as ToxCast to inform screening-level hazard determinations or rank/prioritize large numbers of substances.”
Hartung says he hopes the screening method will also be of interest to countries that are gearing up for implementing new chemical laws, such as Turkey and South Korea.
In the meantime, the researchers have teamed up with Underwriters Laboratories headquartered in Northbrook, Illinois, to make the tool available to companies that might want to screen products before submitting them for regulatory review.
