Frequently Asked Questions
When is Zeuterin™ expected to be commercially available? It is now commercially available in the United States. Distribution is limited to Zeuterin™ certified licensed veterinarians. Shipping date is set to be February 17th, 2014.
What is Ark Sciences doing to promote humane treatment of animals? Ark Sciences is a social entrepreneurship venture. It is a mission-based private company founded by Joe Tosini, an ordained minister to honor his commitment to making a difference in the world. He has chosen Ark Sciences and the vast potential of its technology, as the medium to achieve one of his missions: to alleviate the suffering of animals and humans.
The executive team at Ark Sciences will not rest until we dramatically reduce the US pet euthanasia rate of 4 million annually. Our vision is Full Adoption USA by 2020. We are now training veterinarians supplying them with Zeuterin. By February 2014, it is expected to be ready for sale at a price that will allow them to sterilize up to five dogs for the price of one castration (on average), five times faster, and five times safer. We have other products on the way that will be game changing for other animals.
Why is Ark Sciences targeting non-profits? A very small number of the 20 million intact male dogs in the US belong to breeders and dog professionals. Unfortunately with surgery, we are able to neuter only 20-25% of this potential to prevent unwanted litters. There are a lot of barriers that deter dog owners from surgical neutering today--anesthesia risk, cost, access, issue with mutilation/testis removal, long term health concerns, unpredictable behavior change concerns. etc. Animal welfare organizations have the mission and the experience in organizing outreach efforts to create awareness and increase neutering rates where it matters most. Many of them are signing up to become training centers for Zeuterin technology.
While organizations are free to choose their neutering methods, substituting one million neuterings via castration with non-invasive Zinc neutering among non-profits could save over $50M of donated dollars every year. Imagine the potential windfall of $50M becoming readily available for other animal welfare programs including dog adoption, responsible breeding, pet education, etc. The Ark Sciences executive team believes this to be an effective way to launch our mission and to educate the market on the best practice approach to neutering male dogs while addressing the problem of healthy, adoptable pets being euthanized.
What is Zinc Neutering? Zinc Gluconate (What is Zinc Gluconate? ) neutralized with L-Arginine (What is L-Arginine?) is the first compound ever to be approved by the FDA as safe for sterilization. It uses Zinc Gluconate (a trace element) and Arginine (an amino acid), both of which are essential for the body. In fact, they are health supplements that millions of us use every day. Sterile water is the only other ingredient, no preservatives are added.
A specific concentration of Zinc Gluconate neutralized with Arginine creates permanent sterilization with no adverse reactions needing medical treatment nearly 99% of the time (see the question on side effects below for other minor reactions). The mechanism is targeted and precise as established in the FDA study--Zeuterin caused sterility in 99.6% of young dogs 3-10 months old, while maintaining the endocrine function of the testes.
How is it different from Chemical Castration in the past? Historically, many hazardous chemicals (e.g., Calcium Chloride in Lidocaine or 90% alcohol, Chemcast) have been used on male mammal testicles, including dogs and cats. The objective is in this case is to actually dissolve the entire testis (chemical castration), making it equivalent to castration. None of these methods has ever been approved by the FDA as safe and effective and many have known to cause serious adverse reactions. None of these methods spare the endocrine function of the testicle like Zinc Neutering does to maintain the testosterone needed for metabolic activities.
How does Zeuterin™ sterilize a male dog? After the injection, the Zeuterin™ solution diffuses in all directions from the center of the testis. The specific concentration of Zinc (a targeted spermicide) used in our formula destroys spermatozoa in all stages of maturation in the seminiferous tubules and in the epididymis. The seminiferous tubules, which were replete with spermatozoa, are now emptied and collapse.
The dog's body increases blood flow and creates inflammation to heal. Within days, scar tissue (or fibrosis) from the healing process creates blockages in the seminiferous tubules, and more importantly, in the rete testis (the part of the testis that feeds the epididymis). All sperm must finally pass through these feeder tubules, which are now effectively closed as a result of the specific location of the injection. Zinc Gluconate and Arginine are absorbed and metabolized by the body. The male dog is now safely sterilized for life. View sample histopathology slides that were used to confirm permanent sterility here.
Since Leydig cells (cells responsible for the endocrine function of the testes) survive the procedure, the endocrine function of the testes remains intact. Over time, the seminiferous tubules, rete testis, epididymis, and prostate all atrophy--reducing the size and changing the texture of testicles.
What age should the dog be for the procedure? Zeuterin™ is currently US FDA approved for dogs 3-10 months old.
When does the dog become sterile? The sterilization procedure effectively shuts down sperm production within 1 to 3 days. However, sperm in the vas deferens and possibly the epididymis can reside for up to 30 days. Hence, a sexually mature zinc neutered dog must be kept away from female dogs in heat for up to 60 days post injection. Note that neutering via vasectomy and castration can leave sperm in the vas deferens remnants for up to 21 days.
Is Zeuterin™ safe? Yes, the FDA clinical trial for Zinc Gluconate established its safety and the FDA approval assures us all that Zeuterin™ is safe and effective.
The FDA Approval Study, several follow-up studies, and field trials all have established that Zinc Neutering can safely sterilize a dog and reduce its testosterone levels by about half using this non-invasive and virtually painless injection.
Are there any preservatives in your formulation? No. Zeuterin does not contain any preservatives. Simply discard any unused product 10 hours after first needle insertion into the vial to avoid complications due to possible product contamination.
What are the side effects? While adverse reactions requiring medical treatment occurred in 1.1% of the dogs, there were minor reactions observed in 6.3% of dogs during the FDA study. Local reactions included testicular swelling (normal reaction to the injection), pain (dogs may resist sitting or may sit with both hind legs open), biting and licking at the scrotum, swelling of the prepuce and irritation, dermatitis, ulceration, infection, dryness or bruising of the scrotum. Systemic reactions included an increase in the white blood cell count, vomiting, anorexia (loss of appetite), lethargy (tiredness or abnormal attitude), and diarrhea.
Most reactions were seen within the first 7 days after the injection. Over 93% of dogs did not show any signs of post procedure pain. When pain was detected, it was most commonly seen in the first 2 days. No pain management medications were used in the study. Vomiting was most commonly seen on the day of the injection (within 1 minute and 4 hours after the injection). It is recommended to withhold food for 12 hours prior to injection to help prevent vomiting, which occurred in 4% of dogs. Your dog's testicles may remain slightly enlarged but non-painful for a few months after the injection. Proper injection technique and owner observation post-injection is critical to avoid any potential undesirable side effects.
Are there any studies on long-term side effects? Yes, 40 dogs were studied for over two years (fourteen in human years) and a few of the dogs were informally checked to be fine after 5 years. Since 1999, when the initial clinical studies were performed, there have not been any reports of long-term side effects related to the procedure.
Does this sterilization procedure increase or decrease the risk for testicular or prostate cancer? Long-term observations have shown no increase in risk for testicular cancer. However, no studies have been performed to evaluate if Zeuterin™ decreases the risk of testicular cancer. For prostate cancer, see A population study of neutering status as a risk factor for canine prostate cancer that concludes that surgically castrated dogs are at double the risk to get prostate cancer. To the extent such increased risks are related to testosterone elimination caused by castration, higher risk of such cancers is not expected after zinc neutering.
What happens physically to the testicles? During the procedure, a single injection of Zeuterin™ is administered directly into each testicle. Following the procedure, over time, the testicles generally shrink and change texture due to fibrosis. Long term changes in testicle size may be asymmetrical.
Will the dog look intact after the procedure? Yes. Cosmetic testicular implants like Neuticles should not be needed or used.
How can an injection into the testicles be "virtually painless"? Pain is either somatic or visceral. Any needle inserted through the skin will cause somatic pain for an instant. However, the needle used for this procedure is a very fine 30 guage Botox needle that people over forty may even find hard to see, minimizing that pain.
What is unusual and not generally known about the physiology of the testes is that the severe testicular pain experienced is visceral and triggered by rapid pressure deforming the testicular capsule. Ark-certified vets are specifically trained to deliver the injection very slowly to avoid triggering the testicular pressure receptors. Indeed, 97.5% of dogs (76% not even sedated) in the FDA study did not show any signs of pain during the procedure.
How does zinc neutering affect testosterone levels? Studies have shown that testosterone production decreases 41-52% in treated dogs. The reduction is permanent.
How is testosterone lowered by Zeuterin™? The dosage and concentration is designed to ensure Leydig Cells in the interstitial space of the testes survive the procedure. Stimulated by Luteinizing Hormone (LH) produced in the pituitary gland, the Leydig Cells continue to support testosterone-related metabolic activity and growth. In the absence of spermatogenesis, Sertoli cells stop communicating the need for testosterone to mature sperm cells. The pituitary gland detects this lowered demand and lowers the LH levels. Since LH levels determine how much testosterone is produced by the Leydig cells, overall testosterone levels are reduced by 41-52% for all dogs permanently.
Does this procedure have any effect on behavior? As with surgical castration, Zeuterin™ may or may not eliminate male behavior such as roaming, marking, aggression, or mounting in dogs. Formal statistical evidence comparing neutering via zinc versus castration is not there.
Some studies, not yet peer-reviewed, suggest a correlation between several undesirable behaviors in dogs that have been neutered via castration (See Behavioral and Physical Effects of Spaying and Neutering Domestic Dogs (Canis familiaris) by Parvene Farhoody in May, 2010). To the extent such undesirable behaviors seen in surgically castrated dogs are caused by the complete elimination of testosterone, Zinc Neutering would be unlikely to cause them.
Any known benefits/risks for senior dogs? Benefits: Avoid anesthesia/surgical procedure and maintain hormone function. Risks: No known additional risks
Are there any case studies on your products? Yes. Here is a compilation of some reports that have been published (NEUTERSOL: A CLINICAL PERSPECTIVE, James R. Weedon, DVM, MPH, DACVPM, Spay-Neuter Assistance Program, Inc., Houston, TX)
Why do adverse reactions (beyond side effects) occur in 1.1% of treated dogs? There are some misconceptions about this procedure being "dangerous" and that Zinc Gluconate and Arginine create some acid-like deadly combination. The truth is that this combination has the same pH as water (i.e. 7), will not irritate normal skin, and 98.9% of dogs did not need any medical attention after the procedure during the FDA study.
The adverse reactions have several causes:
Some of these issues can cause an itch or irritation in the testicle or scrotum causing the dog to lick and bite as there is no E-collar in place after sterilization. If the dog is not monitored to prevent the licking and biting, serious irritation, infections, and/or ulcers can result. Most of these conditions can be treated with topical ointments. In some instances, scrotal ablation or castration may become necessary.
In free roaming or poorly maintained dogs (depending on the shelter), scrotal dermatitis is more common, and after care may not be possible; rate of adverse reactions and severity is documented to be higher in these populations. In such instances, dogs that are not surgery candidates may well be rejected for zinc neutering as well. In disease-prone areas, proper disinfection and follow-up protocols must be meticulously followed.
As new organizations embark on zinc neutering, they should expect to treat one scrotal ulceration for every 100 dogs sterilized via scrotal ablation and possible castration. Most scrotal irritations observed during the first 3 days heal on their own unless the dog starts to lick and/or bite the area and creates an infection.
Experience shows that there may be a learning curve for vets in handling these adverse reactions effectively. A hot line will be established for support and record keeping. Over time these rates should reduce to 1-2 dog needing any medical attention for every 200, which is the rate observed in controlled studies in the US environment (rates observed in rural Mexico were much higher due to the condition of the dogs). Such costs should be factored in to determine overall savings for the non-profit organization.
How do I minimize adverse reactions? To minimize the occurrence of adverse reactions, such as scrotal irritation, inflammation or infection, it is critical that you closely monitor your dog's activity post-injection and that you take all precautions necessary to prevent injury to the testicles and to prevent your dog from licking or biting the scrotal area. Restrict your dog's exercise to leash walking; not allow your dog to run, jump, or engage in play activity; not allow your dog to lay on hard or wet surfaces; not allow your dog to lick or bite the scrotal area.
When to choose non-surgical zinc neutering over castration?
For dog breeds more susceptible to complications from anesthesia (e.g., brachycephalic breeds like Pugs, Pekingese, Bulldog, etc.) or for dogs compromised in any way and at higher risk of anesthesia death Zinc Neutering may well be the only humane option. (See The risk of death: the Confidential Enquiry into Perioperative Small Animal Fatalities in which one hundred and seventeen centres participated in the study between June 2002 and June 2004. During that time, 98,036 dogs, 79,178 cats and 8,209 rabbits were anesthetized or sedated and 163, 189 and 114 anesthetic-related deaths were identified respectively, resulting in risks of death of 0.17% in dogs, 0.24% in cats and 1.39% in rabbits).
In the hands of an experienced practitioner, a non-invasive zinc neutering injection is faster, gentler, safer, and cheaper than castration. Zeuterin™ will sterilize the dog and eliminate testosterone needed to support spermatogenesis, while preserving testosterone needed for other metabolic functions, a roughly 41-52% permanent reduction. While retaining some testosterone has beneficial effects, this procedure may not reduce the risks of diseases associated with male hormones, such as testicular (tumor rates are 7% but rate of metastatic testicular cancer is less than 1% overall) or perianal tumors (uncommon, as only 2% of all skin tumors are peri-anal but rate of metastasis is over 50%) in dogs.
Studies show that for many dog breeds and individual dogs with genetic predispositions, surgical castration may compromise long-term health (See Long-Term Health Risks and Benefits Associated with Spay / Neuter in Dogs Laura J. Sanborn, M.S., May 14, 2007) If such long-term risks related to surgical castration are due to near elimination of testosterone in the body, they are unlikely to manifest after zinc neutering.
It is widely accepted that neutering suppresses mating behaviors to varying degrees and also that there are no guarantees. However, there is emerging evidence that surgical castration may negatively impact dog behavior that is not mating related (e.g., fear, anxiety, trainability, etc.). To the extent such undesirable behaviors are the result of testosterone elimination, zinc neutering is unlikely to manifest them.
Is Zeuterin™ more expensive than surgical castration?
What is the connection between Neutersol™ and Esterilsol™?
Esterilsol is Ark Sciences' product for international markets. Esterilsol™ is now registered in 4 countries and pending approval in key markets around the world. It is approved for all dogs over 3 months of age in Mexico. Over the last four years, Ark Sciences has utilized Esterilsol™ extensively in Mexico in dogs three months and older to assess its efficacy as well as refining and improving the injection technique to minimize reactions.
In early 2011, Ark Sciences having acquired full rights to the intellectual property for Neutersol, started to set up a US manufacturing site.. This manufacturing facility is expected to start supplying commercial product by February 2014. Initial focus will be on non-profit animal shelters and high volume spay/neuter clinics at a game-changing low price.
Why did you not win the Found Animals Michelson Prize of $25M for your technology?
Why did you develop a product only for males?
How do I get my dog sterilized with Zeuterin™?
Is there any way to verify that the procedure has been done correctly? Efficacy rate at the FDA trial was documented at 99.6% (about the same as a perfectly taken pill) so the dog is considered neutered after the procedure and a sterilization certificate is provided. If desired, sterilization of the dog can be verified by viewing the dog semen under a microscope after 30 days.
How do you identify a treated dog? Leading microchip companies are capable of keeping neutering status in their databases. Tattooed serial numbers can also be used if a microchip is not practical. This will prevent the dog from being castrated if rescued at a later date.
During the "training period", we will use an optional "Z" tattoo next to the inner thigh area. It will be formed using a tattoo pen. Since this would be the most invasive part of the whole sterilization procedure, we will have to analyze the results to see if this method will survive as a standard practice. Veterinarians familiar with the sterilization procedure will also be able to tell if a dog has been sterilized after a few months by palpating the testicles--the testicles become smaller and firmer as scar tissue forms over time.
Many dog owners are understandably concerned about onlookers and "dog run" friends giving them the evil eye--assuming their anatomically correct male dog is intact. To address this concern, we are finishing up final designs on collar add-ons and fun T-shirts for dogs neutered via zinc rather than castration to flaunt their special status.
Can veterinarians sign sterilization certificates for treated dogs? Yes. Sample certificates are available on request.
I’m a vet. How do I learn to use your product?
Do you have to be a licensed veterinarian to neuter using your product? More than that, it must be administered by a veterinarian or a vet tech under the supervision of a licensed veterinarian. Further, each vet or vet tech must be fully trained by Ark Sciences prior to administering Zeuterin™.
Why do you have such a strict training and data collection protocol? Is the procedure prone to errors? No. Once the vet is trained, errors are uncommon. Adverse reaction rates in the FDA study and in field trials are substantially lower than castration even without a tight training protocol. It became clear from our FDA study and other field experiences that even the low 1.1% adverse reaction rate (ones that required medical treatment) could be reduced if the injection technique is well understood and followed. Improvements from 90% to 99% are much easier than going beyond 99%--hence our intense focus on the procedure and data collection to get real-time feedback. Our goal is to create a near perfect track record of our procedure as each and every dog is important to us.
"It’s very easy on the puppy: no anesthesia, no stitches, no post-injection swelling or complications, no complaints."
MVZ, José Jesús Villalobos Gómez
Del Valle, Mexico
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