This review of current products on the market being sold to kill fleas, ticks and other insects on dogs and cats, assessment of their documented insecticidal action and incidence of harmful side-effects indicates their long-term use for prevention, widely practiced, should be avoided for animal and public health and environmental reasons. Their short-term use in emergency situations of confirmed presence of ectoparasites on companion animals may be justified with caution when all other control measures have failed. Reference is also made to the widespread use of these substances on farmed animals.
Stockholm tar was an old farm remedy for all manner of skin diseases in livestock. It is a distillate from pine wood and was popular in the last century as a hoof dressing and wound protectant. Crushed rock sulfur was often added, along with lard. Creosote, coal tar, tractor sump oil and grease were cheaper but more injurious substitutes for Stockholm tar. These latter petrochemicals were often quite effective however in treating some skin diseases and ectoparasites and became part of the agrichemical revolution after World war 11 that lead to the manufacture of the first generation of chemically engineered pesticides. Petrochemical pesticides have been manufactured and used as dips, powders, sprays, feed-additives and injections for farmed (food) animals, including laying hens and for companion animals.
The latest widely used ‘preventive’ flea and tick drugs that are given orally or are injected or put on the skin and absorbed transdermally, are said to be safer for companion animals than organochloride and other petrochemical pesticides. But they too can compromise the liver, immune and neuroendocrine systems of already immuno-compromized dogs suffering from the harmful side effects of prior drugs and vaccines, signs being more severe in some breeds than others. The increased incidence of seizures in dogs and cats I believe correlates with the increased use of fiprinil and other insecticides regularly applied to companion animals across the world. At least one dog had seizures when actually taken off fiprinil-containing Front Line flea and tick treatment, a rarely reported withdrawal effect.
The US government’s Environmental Protection Agency (EPA)announced in May 2009 that it would conduct a thorough investigation of topical anti-flea and tick products used on dogs and cats after some 44,000 reports of adverse reactions were received by the EPA in 2008. Since that time there has been little done except adding more details on packaging with regard to application and possible adverse reactions.
I have received many letters over the past two decades from readers of my nationally syndicated newspaper column Animal Doctor whose cats and dogs had adverse reactions to various flea and tick treatments. One commonly seen pet reaction is panic which, as an ethologist, I interpret as a state of terror caused by the neuro-excitatory effects of some insecticides, sometimes manifest also as transient tremors and ataxia, other times permanent damage with epileptiform seizures or death. Many are carcinogens and endocrine disruptors as well and may contribute to the increasing incidence of cancer and diseases of the thyroid and adrenal glands in dogs and cats, if not also to cognitive and behavioral problems.
I was surprised to receive my Veterinary Record professional journal from the British Veterinary Association (June 30, 2018.Vol 182 No 26).) with a 4-page glossy color advertisement wrapped around the cover page from Bayer (that now owns Monsanto) promoting Seresto, offering “up to 8 months of protection” for cats and dogs from fleas and ticks using another insecticidal concoction. The Seresto collars contain the synthetic pyrethroid flumethrin which has a similar mode of action as organochlorines to both of which felines are especially sensitive.
Pyrethroids act on the membrane of nerve cells blocking the closure of the ion gates of the sodium channel during re-polarization. This strongly disrupts the transmission of nervous impulses, causing spontaneous depolarization of the membranes or repetitive discharges. At low concentrations insects and other arthropods suffer from hyperactivity. At high concentrations they are paralyzed and die. In mammals flumethrin can cause nausea, vomiting and seizures among other harmful side effects.
The other Seresto ingredient is imidacloprid, a neonicotinoid acting as a nicotinic acetylcholine receptor (nAChR) agonist with potent insecticidal activity. Since its introduction in the early 1990s, imidacloprid has become one of the most extensively used insecticides for both crop protection and animal health applications and is implicated in the demise of the honey bee. Imidacloprid can cause seizures, thyroid gland damage, mutations, abortions and birth defects, (and is a class of widely used agricultural chemicals implicated in the catastrophic demise of honey bees, banned by the European Commission in 2013 for 2 years in Europe). There is also the concern of children and adults petting animals with these chemicals seeping over the animals’ skin, and of the animals grooming themselves and each other.
Bayer is now marketing a plethora of insecticidal products world-wide. The products within the “Bayer Pest Solution Center” are organized into three categories: Prevent, Treat, Control. The prevention section comprises three Bayer lines – K9 Advantix® II, Seresto® and Advantage® II - while the treatment and control sections feature Bayer’s new products. Bayer is also supporting pet specialty retailers with training modules and toolkits for employees to enable them to help their customers. These new products containing similar ingredients include - Advantage® Treatment Spray for dogs, Advantage® Treatment Spray for cats, Advantage® Treatment Shampoo for dogs, and Advantage® Treatment Shampoo for cats and an array of Advantage™ Household Spot & Crevice Spray, Advantage™ Carpet & Upholstery Spot Spray, and Advantage™ Household Fogger to kill indicated pests in the home, and Advantage™ Yard & Premise Spray that kills pests in the yard and around the house.
It should be noted that there is no guarantee of animals not developing allergic reactions to flea and other insect bites, or from contracting an insect-born disease, the company stating: “Advantix® provides repellent (anti-feeding) activity against ticks, sand flies and mosquitoes, thus preventing the repelled parasites from taking a blood meal and thus reducing the risk of disease transmission (e.g. Lyme borreliosis, babesiosis, anaplasmosis, ehrlichiosis, rickettsiosis, leishmaniosis). However, there may be an attachment of single ticks or bites by single sand flies or mosquitoes. For this reason, a transmission of infectious diseases by these parasites cannot be completely excluded if conditions are unfavourable….. Following topical application in dogs, the solution rapidly distributes over the body surface of the animal. Both active substances remain detectable on the skin and hair of the treated animal for 4 weeks…. Acute dermal studies in the rat and target animal, overdose and serum kinetic studies have established that systemic absorption of both active substances after application on intact skin is low, transient and not relevant for the clinical efficacy”. Why no long-term studies?
Elanco’s broad spectrum parasiticide Trifexis® (spinosad + milbemycin oxime) is the monthly, beef-flavored tablet marketed to kill fleas and prevents flea infestations, prevents heartworm disease, and treats and controls adult hookworm, roundworm and whipworm infections in dogs. The company states that “Trifexis is safe for use in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater. (Comfortis is Elanco’s product for cats consisting only of spinosad). Treatment with fewer than three monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention. Prior to administration of Trifexis, dogs should be tested for existing heartworm infection. Use with caution in breeding females. The safe use of Trifexis in breeding males has not been evaluated. Use with caution in dogs with pre-existing epilepsy. The most common adverse reactions reported are vomiting, depression/lethargy, itching, decreased appetite, and diarrhea”.
In one study rats given 0.05% spinosad for 2 years had vacuolation and/or inflammation involving the thyroid, lymphoid tissue, and lung. The spinosyns and spinosoids have a novel mode of action, primarily targeting binding sites on the nicotinic acetylcholine receptors ( nAChRs) of the insect nervous system that are distinct from those at which other insecticides have their activity. Spinosoid binding leads to disruption of acetylcholine neurotransmission. Spinosad also has secondary effects as a γ-amino-butyric acid (GABA) neurotransmitter agonist. It kills insects by hyperexcitation of the insect nervous system.
Milbemycin oxime is produced by Streptomyces hygroscopicusaureolacrimosus. It opens glutamate sensitive chloride channels in neurons and myocytes of invertebrates, leading to hyperpolarization of these cells and blocking of signal transfer. Milbemycin oxime is active against a broad spectrum of nematodes. Its miticide spectrum includes Sarcoptes and Demodex. The drug is FDA-approved for prevention of heartworm in dogs and cats, although it is less potent against heartworms than ivermectin. The substance is often combined with other parasiticides to achieve a broader spectrum of action. Such products include: Milbemax and Interceptor Plus (with praziquantel). Sentinel Flavor Tabs (with lufenuron), Trifexis (with spinosad) ,and NexGard Spectra (with afoxolaner).
(These entries from the Internet illustrate the wide range of biocidal properties of these chemical compounds).
The British government authority that approves drugs for veterinary use in the U.K. has advised that Merck’s Bravecto chewable tablets of all sizes must have a label warning: “Use with caution in dogs with pre-existing epilepsy.” (The Veterinary Record, Sept. 2017, p.340). The warning from the manufacturer posted in the U.S. does not yet include this and reads: “The most frequently reported adverse reactions include vomiting or diarrhea. Other side effects that may be seen include decreased appetite, lethargy, increased thirst, and flatulance.(sic). Consult your veterinarian if you notice any of the above side effects. Bravecto is for use only in dogs”. Another entry states: “The most common adverse reactions recorded in clinical trials were vomiting, decreased appetite, diarrhea, lethargy, polydipsia, and flatulence. Bravecto has not been shown to be effective for 12-weeks’ duration in puppies less than 6 months of age. Bravecto is not effective against lone star ticks beyond 8 weeks of dosing”.
According to Parasitepedia.net “ Fluralaner (the active ingredient of Bravecto) and other isoxazolines are non-competitive GABA (gamma-aminobutyric acid) receptor antagonists that bind to chloride channels in nerve and muscle cells, which blocks the transmission of neuronal signals. Affected parasites are paralyzed and die. This mechanism exists not only in insects but also in mammals and other vertebrates. However, the binding affinity of fluralaner to GABA receptors of invertebrates is much higher than to GABA receptors in vertebrates. For this reason it is significantly less toxic to mammals than to insects and other pests.”
“Less toxic” is quite different from not toxic. Long-term toxicity has not been evaluated, especially chronic neurological and carcinogenic effects. Simparica from Zoetis, which is an insecticide from this same isooxazoline group, is noted by the company “for use only in dogs, 6 months of age and older ( italics mine). Simparica may cause abnormal neurologic signs such as tremors, decreased conscious proprioception, ataxia, decreased or absent menace, and/or seizures. Simparica has not been evaluated in dogs that are pregnant, breeding or lactating. Simparica has been safely used in dogs treated with commonly prescribed vaccines, parasiticides and other medications. The most frequently reported adverse reactions were vomiting and diarrhea.—Prescribe a tasty chewable for dogs that’s been demonstrated to deliver persistent protection for 35 days—.”
Hartz’s flea and tick products for dogs and cats, marketed widely in drug and grocery stores, are available in sprays, shampoos, collars, and topical spot-on applications. Ingredients variously include: Tetrachlorovinphos,( a highly toxic organophosphate in the EPA’s category of probable carcinogens); S-Methoprene, ( an insect growth and metamorphosis disruptor); Etofenprox, ( a pyrethroid ether), Piperonyl Butoxide (PBO), ( an enhancer or synergist of various pesticides especially pyrethrins); n-octyl bicycloheptene dicarboximide (MGK 264), ( another synergist); and Pyriproxyfen (NylarPyriproxyfen), ( may have effects on the blood and liver leading to anemia, impaired functions and tissue lesions and was reported to have some estrogenic activity in human ovarian carcinoma cells. It is a potent insect growth and metamorphosis disruptor), and Phenothrin (also called sumithrin and d-phenothrin, a synthetic pyrethroid).
Since Seresto flea and tick collars were introduced in 2012, the EPA has received incident reports of at least 1,698 related pet deaths. Overall, through June 2020, the agency has received more than 75,000 incident reports related to the collars, including nearly 1,000 involving human harm.
From 1992 to 2008, the EPA received about 4,600 incident reports regarding pet collars containing tetrachlorvinphos, including 363 deaths. The Natural Resources Defense Council. (NRDC) filed a petition against the agency more than a decade ago over its approval of this pesticide that is linked to cancer and brain development issues in children.In April 2020, a federal appeals court called the EPA’s refusal to respond to NRDC’s requests “nothing short of egregious” and told agency officials to make a decision on whether to ban the pesticide within 90 days. The EPA decided not to ban tetrachlorvinphos which continues to be sold under the brand name Hartz Ultra Guard, Hartz InControl and Longlife. NRDC has challenged that decision and that lawsuit is currently pending.
Repeated human exposure to selamectin from handling and petting dogs treated with this drug on their skin can pose potential health risks, especially to veterinarians, veterinary technologists, dog trainers/handlers, and pet owners according to the research report Human exposure to selamectin from dogs treated with revolution: methodological consideration for selamectin isolation. Gupta RC and associates, Toxicol Mech Methods. 2005;15(4):317-21.
This industry advocates year-round use for life for companion animals. Long-term effects on food animals are a non-issue since most live very short lives before slaughter. But because of the billions of farmed animals being given insecticides and anti-parasiticides the long-term harmful environmental consequences are considerable. (Manure runoff, including glyphosate and other herbicide residues from feed and fields along with other pesticides, have killed off many aquatic species of Trichoptera and other fresh water organisms, indicators of water quality, and, along with chemical fertilizers, have made lake waters toxic with Blue-green, Cyanobacteria algal blooms).
The adverse environmental impact of insecticide residues in animals’ excrement on scatophagous and other insects and dependent insectivores, avian, reptilian and amphibian, is incalculable. These drugs are used world-wide by the livestock and poultry industries along with antibiotics and other production-enhancing drugs and hormones that contaminate the environment and kill waste-recycling organisms. This disrupts the nexus of bio-cycles of ecosystem recycling and regeneration. All such excrement from treated animals should be collected for biodegradation/bioremediation in manure containment or non-leaching land-fill facilities. Many different chemicals and pharmaceutical products are also in our dogs’ feces and urine, as well as in our own, from prescription drugs to some manufactured pet food ingredients and contaminants that make such waste harmful to the organisms that make for healthful, living soils and inevitably our water quality. It should, therefore, be a public offense in every community to not pick up after one’s dog has defecated in any public open space.
Veterinarian Rosemary Perkins in her article “Are pet parasite products harming the environment more than we think?” (Veterinary Record, 15⁄12 Sept 2020, p 397) notes that few studies have been done on this issue but presents some references that indicate the external neonicotinoid insecticides applied externally to cats and dogs or in impregnated neck collars, notably neurotoxic fipronil and imidacloprid are highly toxic to a wide range of invertebrate species and have high environmental persistence.
The European Commission has banned fipronil and imidacloprid for agricultural use to kill insects because of the impact on honey bees and other beneficial insects, yet their widespread use as pet flea treatment has been ignored. She references studies showing the dust in homes with pets receiving these topical insecticides contains sufficient amounts of these chemicals to kill bees; also, these chemicals are found in urban rivers at levels exceeding published environmental toxicity limits most likely coming from dogs being bathed in -home along with their bedding, and from treated dogs being allowed to go into outdoor waterways.
Far too many dermatological problems in dogs especially—and a cause of much animal suffering—could be prevented because they are man-made; consequences of genetic susceptibility, iatrogenic veterinary problems, manufactured pet foods and toxic home environments. Many such factors impair the immune system leading to inflammatory, autoimmune and allergic diseases. Thirty percent of food-allergic dogs and cats are found to have another allergic skin condition according to the 2018 Sate of Pet Health report from Banfield Pet hospital. ( www.StateofPetHealth.com/allergies). Significantly, flea allergy has increased by 12.5 percent in dogs and 76.3 percent in cats over the past decade.
This is a driver for marketing unsafe systemic insecticides as profitable preventives for veterinarians to prescribe for their companion animal clients. But it would not be more ethical and responsible for veterinarians to avoid promoting these insecticides and pandering to convenience and expediency, but rather, educate clients on integrative pest control, a challenge but urgent issue with climate change: Also to encourage clients and communities to keep cats strictly indoors; and to always use a flea comb after taking the dog to the woods during tick season, along with proper nutrition and removing toxic chemicals and other petrochemical-derived synthetic materials from the home environment. Land owners can also employ Guinea fowl to control ticks.
The widespread over-use of insecticides and other anti-parasitic drugs to protect livestock in particular, (now being considered for human use in malaria and other insect-born disease “hot spots”) has resulted in the evolution of resistant strains, often more virulent and numerous where there is little natural biodiversity to regulate their numbers. Individual and ecosystem health correlate with optimal biodiversity. This creates the treadmill for ever more potent chemicals and combinations thereof.
While Stockholm tar is not applicable to companion animals, essential oils derived from pine and other botanicals are less toxic alternatives to fipronil and other synthetic insecticidal and biocidal chemical compounds when properly formulated and applied and many veterinarians are now offering these to their clients and home prepared lemon rind tea sprits as effective insect repellants. ( For safer ways to control and repel fleas, ticks and mosquitoes see the posting on this website “Preventing Fleas, Ticks and Mosquitoes.”
The use of systemic insecticides like fipronil and fluralaner on companion animals puts those living with them at risk, especially children and other animals in the same home who make contact with treated animals. Therefore, for public as well as legitimate and self-evident animal and environmental health reasons these insecticides should be prohibited for use except by public health and veterinary authorities in times of justified One Health emergency intervention and for bioremediation in ecosystem health care maintenance and recovery to optimize biodiversity.
Since there are dozens of companies marketing these chemicals from Hartz Ultra Guard and Sentry to Zodiac Spot On and ShieldTech for Cats, a blanket prohibition by responsible government of private use on companion animals is surely called for. For companion animals the use should be by prescription only under veterinary supervision. Company by company class-action law-suits by plaintiffs whose animals have suffered adverse reactions including seizures and death from any one of these products sold over the counter and supplied by veterinarians for the highly promoted and widely marketed long-term prevention of ectoparasites may help lower but not stop misuse and adverse consequences. More informative product labeling of risks is the U.S. government’s response, the FA posting on Sept 20, 2018, that it “is alerting pet owners and veterinarians to be aware of the potential for neurologic adverse events in dogs and cats when treated with drugs that are in the isoxazoline class. Since these products have obtained their respective FDA approvals, data received by the agency as part of its routine post-marketing activities indicates that some animals receiving Bravecto, Nexgard or Simparica have experienced adverse events such as muscle tremors, ataxia, and seizures. Another product in this class, Credelio, recently received FDA approval. These products are approved for the treatment and prevention of flea infestations, and the treatment and control of tick infestations. The FDA is working with manufacturers of isoxazoline products to include new label information to highlight neurologic events because these events were seen consistently across the isoxazoline class of products”.
The situation concerning the over-use and risks, especially environmental, and to aquatic life in particular, is similar in the U.K. Veterinarians K. Powell et al (2018) cite studies raising concerns about pyrethroids, avermectins and the 68 registered products containing neonicotinoids, concluding that “one river-swimming dog treated with a spot-on compound can destroy an ecosystem, and advise treated livestock be put in “sacrificial paddocks” for 3-4 days to protect the rest of the farmland from contamination, , most ivermectin and deltamethrin being excreted within the first 4 days after application.
Dogs treated with spot-on insecticides or wearing insecticide-releasing collars should not be allowed into lakes, ponds and streams which they can contaminate according to Perkins et al ( 2021). I would add such dogs should also be kept out of vegetation/brush which they could also contaminate especially when wet.
Dysbiotic intestinal, aquatic and terrestrial microbiomes are ecologically interconnected. The contribution of antiparasitic agents to such dysbiosis on several trophic levels needs to be seen from a One Health perspective and eco-systemic loss of biodiversity which all responsible parties, from manufacturers and suppliers to users and regulators need to address at home and abroad.
From Animal Doctor, syndicated newspaper column by Dr. Fox, April 6th 2021:
DEAR DR.FOX, I saw on an article I was reading where a woman had her dog act out of character and aggressive after using flea medication. I have a 13- week old puppy and we used Activyl on him and about 7 days later he has these aggressive outburst then he acts overly sweet and you can almost see the confusion in his eyes. This is not like him in any way I don’t know if it’s the medicine but that’s the only thing we have changed. Did you get anymore reports or any leeway on this? A.T., Tulsa OK.
DEAR A.T., I am shocked you treated such a young dog with this kind of product. If a veterinarian prescribed this, he/she should go back to school. Most likely you made the purchase in a local store which should be prohibited in every community and State. According to the manufacturers ( Merck Animal Health) of this insecticide Activyl Topical for Dogs and Cats. “Fleas don’t have to bite to take up Activyl, simply coming into contact with the skin is enough”. Various flea and tick insecticides have caused sudden, unprovoked aggression in dogs and until your communication I was not aware that this highly toxic, hazardous organochloride insecticide was approved for companion animal use. It is strictly regulated in Europe. Indoxacarb is an organochlorine insecticide and a methyl ester. Greenpeace, Germany, has put this chemical Indoxacarb on its Pesticide Blacklist. (PDF) The EU Pesticide Blacklist 2016 - ResearchGate www.researchgate.net › publication › 307601520_The_E…
NOTE: This product does not kill these insects before they have a chance to transmit any diseases they may be carrying once they penetrate the skin and start sucking the animals’ blood. According to one European report ( https://www.ema.europa.eu/en/documents/overview/activyl-tick-plus-epar-medicine-overview_en.pdf) “The most common side effects seen with Activyl Tick Plus (which may affect up to 1 in 10 animals) are transitory scratching, erythema (reddening of the skin) and hair loss at the application site. These effects usually resolve without treatment. The application of Activyl Tick Plus may produce a temporary oily appearance or hair clumping at the application site, or a dry white residue. This is normal and will generally resolve within a couple of days. Activyl Tick Plus must not be used in cats as adverse reactions and even death can occur. It must not be used in dogs which are known to be hypersensitive (allergic) to indoxacarb, permethrin or to any of the other ingredients. Fleas, ticks and sand flies might still be able to transmit any diseases which they may be carrying”.
There are safer alternatives to repelling fleas, ticks and other biting insects which all responsible and caring dog and cat owners should adopt rather than continue using insecticides year-in and year-out on their animals which can cause seizures and death as with Bravecto. Short and long- term adverse health and environmental consequences can be avoided. For such preventive measures see the posting on my website www.drfoxonehealth.com
SERESTO FLEA COLLAR LAW SUIT From Johnathan Hettinger, Midwest Center for Investigative Reporting March 26, 2021 “Two pet owners who claim their dogs either died or developed problems after using Seresto flea and tick collars filed a class-action lawsuit this week against Elanco Animal Health, alleging it misrepresented the safety of its product”. “The lawsuit, filed in the U.S. District Court of California in Los Angeles, comes just days after a congressional subcommittee asked Elanco to voluntarily recall the flea and tick collars in the wake of reporting by the Midwest Center for Investigative Reporting and USA TODAY on thousands of incident reports about pet and human harm linked to the collar. The lawsuit cites the news outlets’ reporting. Elanco declined to voluntarily recall the product”.
HUMAN HEALTH RISKS FROM INSECTICIDES APPLIED TO COMPANION ANIMALS
I am concerned about the long-term adverse consequences of insecticides given to companion animals externally as spot-on applications or released from impregnated collars on both the animals’ health and in-home human exposure through petting contact and in the ambient environment.
Veterinarian Joe Cummins’ letter in the Journal of the American Veterinary Medical Association (“Parkinson disease and the veterinary profession” March 1st 2021, vol.258, p 454) questions if his later-in-life development of this incapacitating disease might be caused by “repeated exposure to flea and tick collars” in the animals he was attending to.
I would extend this questioning of exposure risk and better monitoring also to dog groomers and workers in tanneries and slaughterhouses/ animal processing facilities considering the fact that insecticides are widely used by the livestock and poultry industries.
It would seem that many autoimmune and neurodegenerative diseases like Parkinson’s and Alzheimer’s are multifactor/pluri-causal. Several studies have linked farmers’ exposure to insecticides, fungicides and herbicides as well as non-farming people living in communities close to agrichemical-treated fields. For a general overview see Pesticide-Induced Diseases: Brain and Nervous System … https://www.beyondpesticides.org and also, https://www.americanscientist.org/article/the-rise-of-parkinsons-disease.
In their extensive review of clinical and research studies of these concerns. authors Freya Kamel and Jane A. Hoppin conclude “ there is mounting evidence that chronic moderate pesticide exposure is neurotoxic and increases risk of Parkinson disease.” ( quote from Association of Pesticide Exposure with Neurologic Dysfunction and Disease Environmental Health Perspectives Vol. 112, No. 9 June 1st 2004https://doi.org/10.1289/ehp.7135).
The precautionary principle of risk reduction is an essential component of preventive health care maintenance. This means reducing the use of and human exposure to externally applied insecticides to companion animals in particular and to farmed animals with the adoption of Organically Certified husbandry practices that preclude and negate the need for such chemicals.
For an earlier analysis of the risks of these products go to the Natural Resources Defense Council’s report
Flea-Control Products Threaten Pets and Children. November 01, 2000 https://www.nrdc.org/media/2000/001101
For details about these chemicals go to www.pesticideinfo.org and the National Pesticide Information Center at nipc@acc.orst.edu
See also CBC Marketplace: Pet Safety - Paws for Concern
Cat and dog flea treatments can be toxic to pets, humans. CBC Marketplace investigates risks to humans and pets from popular pet products Megan Griffith-Greene / Marketplace · CBC News · Posted: Dec 05, 2014
This 2012 article talks about banning highly toxic organophosphate-containing flea collars in France and England which also puts humans at risk
Over 44,000 reports of adverse reactions to topical anti-flea and tick products were compiled by the US government’s Environmental Protection Agency in 2008. For details, see www.Biospotvictims.org
In the U.S. regulation of these pesticides is divided between two agencies. According to the Food and Drug Administration’s website “Flea and tick products for pets are regulated by either Food and Drug Administration or the Environmental Protection Agency (EPA). FDA is responsible for regulating animal drugs; however, some products to control external parasites come under the jurisdiction of EPA. FDA and EPA work together to ensure adherence to all applicable laws and regulations. In general, flea and tick products that are given orally or by injection are regulated by FDA. Before an animal drug is allowed on the market, FDA must “approve” it. Before a pesticide can be marketed, EPA must “register” it. Both agencies base their decision on a thorough review of detailed information on the product’s safety and effectiveness provided by the manufacturer or other product sponsor”.
EPA Evaluation of Pet Spot-on Products: Analysis and Plans for Reducing Harmful Effects ( From https://www.epa.gov/pets/epa-evaluation-pet-spot-products-analysis-and-plans-reducing-harmful-effects).
Summary of Findings
EPA found that the products could be used safely but that some additional restrictions are needed. EPA’s team of veterinarians learned that most incidents were minor, but unfortunately some pet deaths and “major incidents” have occurred. The Agency learned that the most commonly affected organ systems were skin, gastrointestinal (digestive), and nervous.
For more information, refer to Review of Enhanced Reporting of 2008 Pet Spot-on Incidents (EPA-HQ-OPP-2010-0229-0023)
EPA’s report on the evaluation of products and incidents is available at: https://www.epa.gov/pesticides/health/petproductseval.html . See also U.S. EPA confirms problems exist with spot-on flea, tick treatments - VIN news.vin.com/vinnews.aspx?articleId=15367EPA recommends that veterinarians use the National Pesticide Information Center’s Veterinary Pesticide Adverse Effects Portal to report incidents: http://npic.orst.edu/vet
The division of regulatory and approval authority between the FDA and EPA facilitates the continued marketing of many of these products even after the sellers and manufacturers have been informed of thousands of adverse reactions in dogs and cats as well as many fatalities. The fundamental question of the health consequences of long-term/lifetime use of these insecticides on companion animals has not been addressed by the manufacturers but may be a significant factor in the rising incidence of cancer and other chronic, degenerative and systemic diseases in dogs and cats. It should be noted that fleas and ticks carrying disease could infect dogs and cats on whom they feed before they are killed by these chemicals, flea bites also triggering allergic reactions in many animals.
For some social media links go to www.hartzvictims.org/
Flea and Tick Product Risks and Recalls - From Consumer Affairs: https://www.consumeraffairs.com/flea-and-tick-product-risks-and-recalls
See also yourpetsneedthis.com and facebook.com/groups/411371212394679/. Also https://www.change.org/p/petition-for-the-immediate-withdrawal-of-simparica-flea-tick-treatment-from-the-market and Beware of Seresto flea collars - Page 1 - Pedigree Database www.pedigreedatabase.com/community.read?post=859429-beware-of-seresto-flea…Mar 10, 2016.
Jennings KA1, Canerdy TD, Keller RJ, Atieh BH, Doss RB, Gupta RC. Human exposure to fipronil from dogs treated with frontline. Vet Hum Toxicol. 2002 Oct;44(5):301-3.
This investigation determined fipronil residues on gloves worn while petting dogs after Frontline application. Repeated exposure to such contamination can pose human health risks.
See also: https://www.publicintegrity.org/environment/health-and-safety/perils-new-pesticides
And https://www.nrdc.org/stories/nontoxic-ways-protect-your-pet
Powell, K., Foster, C., and Evans, S. Environmental dangers of veterinary antiparasitic agents, Veterinary Record, Nov.17th, 2018, p 599-600.
Perkins, R et al Potential role of veterinary flea products in widespread pesticide contamination of English rivers. Sci Total Environ 2020; doi : 10.106/j.scitotenv.2020.143560
Survey of canine use and safety of isoxazoline parasiticides by Valerie Palmieri W. Jean Dodds | Judy Morgan et al Vet Med Sci. 2020;00:1–13. Abstract —-
A veterinarian and pet owner survey (Project Jake) examined the use and safety of isoxazoline parasiticides given to dogs. Data were received during August 1–31, 2018 from a total of 2,751 survey responses. Forty-two percent (1,157) reported no flea treatment or adverse events (AE), while 58% (1594) had been treated with some parasiticide for flea control, and of those that received a parasiticide, the majority, or 83% (1,325), received an isooxazoline. When any flea treatment was given, AE were reported for 66.6% of respondents, with no apparent AE noted for 36.1%. Project Jake findings were compared to a retrospective analysis of publicly available Food and Drug Administration (FDA) and European Medicines Agency (EMA) reported AE. The number of total AE reported to FDA and EMA were comparable, although a 7 to 10 times higher occurrence of death and seizures was reported from the EMA or from outside the United States (US). Serious AE responses for death, seizures and neurological effects reported in our survey were higher than the FDA but moderately lower than the EMA reports. These sizable global data sets combined with this pre and post-parasiticide administration survey indicated that isoxazoline neurotoxicity was not flea- and tick-specific. Post-marketing serious AE were much higher than in Investigational New Drug (IND) submissions. Although the labels have recently been updated, dogs, cats and their caregivers remain impacted by their use. These aggregate data reports support the need for continued cross-species studies and critical review of product labelling by regulatory agencies and manufacturers.
FOIA FDA: Total Nexgard Reports = 14,116 that contain 47,550 Events; Deaths = 341⁄14116 ( 2.4%); Seizures = 981⁄14116 ( 6.97%) Total Bravecto Reports = 16,896 that contain 45,924 Events; Deaths = 416⁄16896 (2.5%); Seizures = 468⁄16896 (2.8%) Total Simparica Reports = 1,361 that contain 5,977 Events; Deaths = 44⁄1361 (3.2%); Seizures = 279⁄1361 ( 20.5%) 1–8FOIA: CVM ADE Comprehensive Clinical Detail Report Listing, Cumulative Date Range:-Jan-2013 - Sept-2017. Adverse consequences include:: Death. Seizures. Shaking/Tremors/Ataxia. Behavioural Issues. Neurological/Cognitive. Muscular/Balance Issues. Skin Problems/Itching. Internal Bleeding. Anaemia. Vomiting/Nausea. Not Eating/Drinking. Diarrhea
Receiving a query from a CNN reporter I was alerted to this proposal to use these kinds of drugs in poor communities at risk from insect born diseases, which gives pause for thought:
Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases by Marie Miglianico, Maarten Eldering, Hannah Slateret al PNAS July 2, 2018. 201801338; published ahead of print July 2, 2018. https://doi.org/10.1073/pnas.1801338115
Reduction in clinical cases of vector-borne diseases is strongly dependent on the ability to reduce the number of infectious insect bites. Here we describe a treatment concept based on single-dose administration of an insecticidal isoxazoline drug to a human population, which leads to killing of blood-fed insect vectors and a predicted sharp decline in disease transmission. Based on the long half-life observed in preclinical species, a single human dose of <500 mg is predicted to provide plasma exposure above the insecticidal threshold for longer than 2 months. Importantly, we show that isoxazolines are active against a range of vector species, which holds promise for expanding the concept of drug-based vector control from malaria to leishmaniasis and arboviral diseases.
CANINE BREED SUSCEPTIBILITY
According to veterinarian Dr. W. Jean Dodds “Some breeds of dogs have the MDR1 gene mutation. This gene undergoes one or more mutations that allow a higher absorption of drugs and toxic substances to enter the central nervous system and then can breach the blood-brain barrier and create adverse reactions. Plus, we know that this gene mutation is most commonly found in dog breeds of herding breed ancestry. According to the Washington State Veterinary Clinical Pharmacology Lab, nearly three of every four Collies in the US have the mutant MDR1 gene. The frequency is about the same in France and Australia, so it is likely that most Collies worldwide have the mutation. The MDR1 mutation has also been found in Shetland Sheepdogs (Shelties), Australian Shepherds, Old English Sheepdogs, English Shepherds, German Shepherds, Long-haired Whippets, Silken Windhounds, and a variety of mixed breed dogs”. ( From https://drjeandoddspethealthresource.tumblr.com/post/178817671296/fda-warning-flea-tick-products#.X5WsBIhKjY0).
According to W.J. Dodds & J.P.Kimball (Updated Summary on Use and Safety of Flea and Tick Preventives for Animals. J Vet Med Surg. Vol 5 No 52:005.2021) “Unlike the Food and Drug Administration (FDA) which regulates parasiticides, such as the isoxazoline compounds, the Environmental Protection Agency (EPA) regulates pesticides like the imidacloprid+flumethrin collar. This difference in regulatory authority in the USA has caused confusion among veterinarians and companion animal owners….Current Class Action lawsuits include one in Quebec and a second in New Jersey involving fluralaner (Bravecto®) and related compounds, due to the incidence of serious AR (Adverse Reactions) including death, that have a duration of treatment lasting from one to 3 months. A third Class Action lawsuit was filed in March 2021 against the imidacloprid+flumethrin product (Seresto Collar®). The collar was introduced in 2012, and is touted to last for 8 months…..The number of adverse reports was highest for spinosad+milbemycin+oxime (TriFexis®) (200,941) followed by afoxalaner+milbemycin+oxime (NexGard Spectra®) (190,802). The smallest reported number was for the more recently introduced lotilaner (Credelio®, 2018) at 3.302. With regard to the number of reported deaths, the largest number was for sar olaner+moxidectin+pyrantel+pamoate (Simparica Trio®) at 6,717 (approved in 2020), followed closely by spinosad+milbemycin+o xime(TriFexis®) with 6,662 (approved in 2011) and ivermectin+py rantel+pamoate+praziquantel (Iverhart Max®, approved in 2018) at 6,207….. The vast majority of reports involved dogs (86%) with cats accounting for 13%, and 1.5% involving humans…. Updated results from the USA and European Union indicate a notable increase in the number of particularly serious adverse events reported for the flea and tick preventives including seizures, behavioural aggression, and death. The actual number of adverse incidents is likely much higher than those reported to regulatory agencies.”
The author appreciates the helpful suggestions of Dr. W. Jean Dodds in preparing this review.
SERESOTO ANTI-FLEA COLLARS CALL FOR GOVERNMENT BAN
Now, at last, we are seeing our better government under President Biden addressing this isse with a major report: Seresto Flea and Tick Collars: Examining Why a Product Linked to More Than 2,500 pet Deaths Remains on the Market. House Committee on Oversight and Reform: Subcommittee on Economic and Consumer Policy Staff Report June 2022 .I commend all involved in producing this well referenced report which begins with this statement:
“This staff report presents the findings of a 16-month investigation by the Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy into the safety of the Seresto flea and tick collar that contain the insecticides Flumethrin 4.5%, Imidacloprid 10.0%. Bayer Animal Health—the original owner and manufacturer of the collar—and Elanco Animal Health, which purchased Bayer Animal Health in 2020, have sold millions of Seresto collars since the product entered the market in 2013. Pet owners embraced the convenience of the eight-month flea and tick protection offered by the collar—for under $70—when many other flea and tick treatments must be re-applied monthly. In March 2021, a report from USA Today revealed that, as of June 2020, there had been more than 75,000 incidents—what the Environmental Protection Agency (EPA) calls unexpected effects from the use of a pesticide—and approximately 1,700 pet deaths linked to the Seresto collar. Since the USA Today report was published, the reported numbers have increased to more than 98,000 incidents and 2,500 pet deaths. The Subcommittee’s investigation found that EPA knew about the dangers posed by the collar—and the many consumer complaints about the collars—for several years yet failed to take action.”
EPA Learned in 2016 That the Seresto Collar Was Deemed Too Dangerous to Be Sold in Canada. Canada’s Pest Management Regulatory Agency (PMRA) Seresto report—which EPA received in July 2016 and which has not been made public prior to this Report—contained a number of striking findings. PMRA closely reviewed 961 “Death and Major” pet incidents using enhanced data provided by Bayer, and found that the Seresto collar probably or possibly caused 737—or 77%—of them. More broadly, PMRA expressed great concern over the “number and severity” of animal incidents linked to the Seresto collar. The PMRA report revealed that from 2012 through 2015, there were over 19,000 reported pet incidents in the United States, including 381 deaths and 1,342 major incidents. Several people had serious adverse reactions associated with putting the Seresto collars on their animals. For more details do go to 2022.06.15 ECP Seresto Staff Report FINAL.pdf (house.gov)
It is notable that the use of Elanco’s recombinant bovine growth hormone injected widely in America’s dairy cows has been banned in Canada, Australia, New Zealand, Japan and all 27 nations of the European Union for reasons of consumer safety and cow health and welfare. Elanco’s branded ractopamine hydrochloride products, Paylean for pigs and Optaflexx for beef cattle, are not approved, available or sold within China. This is a psychotropic drug causing animals stress and distress, details posted at https://drfoxonehealth.com/post/pharmaceutical-cruelty-in-animal-farms-consumer-beware/
MORE DOCUMENTED EVIDENCE OF ENVIRONMENTAL RISKS OF SPOT-ON INSECTICIDES ON PETS
After spot-on application, imidacloprid and fipronil spread over the surface of the skin where they are incorporated into the superficial epidermis and sebaceous glands, and slowly released via hair follicles. From here they disperse widely throughout the household environment through pet hair, shed skin and direct transfer. People, especially children, are at risk from these neurotoxins when they pet and snuggle with treated animals. Significantly, hand-washing resulted in these chemicals going down the drain for at least 28 days after an owner’s spot-on application to their pet and an estimated 4.9 % of imidacloprid and 3.1 % of fipronil applied in dog spot-ons passing down-the-drain. Also, bathing the dog and washing contaminated bedding lead to environmental contamination. These insecticides have lethal and sublethal effects on aquatic insects that are a vital part of the food-chain. Governments need to take action to prohibit the use of these insecticides on companion animals.For details see Perkins R et al. Down-the-drain pathways for fipronil and imidacloprid applied as spot-on parasiticides to dogs: Estimating aquatic pollution. Sci Total Environ. 2024 Mar 20;917:170175. doi: 10.1016/j.scitotenv.2024.170175
UPDATES AUG 2024
ANTIPARASITIC PRODUCTS AND THE GUT MICROBIOME
Addressing the widespread use of parasiticides and advocating oral or injectable rather than topical products in companion animals on a case-by-case rather than routine, blanket approach, because of concerns over environmental contamination, as reported by Loeb and Scally (1) is a positive initiative. The potential risks to the environment are considerable, however, even with the oral and injectable products. (2).
But oral and injectable parasiticides, including some known to cause seizures and unprovoked aggression in dogs, may cause other health and behavioral issue by adversely impacting the gut microbiome. (3). Conspecific aggression has been correlated with changes in the gut microbiome in rescued dogs. (4). Some dogs are reported to have become aggressive after treatment with parasiticides which was theorized several years ago by veterinarian Dr. Margo Roman (personal communication) to have been caused by oxytocin depletion, and improved after she provided microbiome restorative therapy. More research is called for on this issue considering the widespread use of antiparasitic drugs in companion animals.
Research has found that certain gut microbiota in the intestinal microbiome can affect the production of oxytocin in the intestinal epithelium. Oxytocin regulates social behavior and feeding, and is usually produced in the hypothalamus. However, gut bacteria can stimulate the production of oxytocin through the gut hormone secretin, which is produced in enteroendocrine cells. This process has been called “upregulation” of endogenous oxytocin. The probiotic Limosilactobacillus reuteri (formerly known as Lactobacillus reuteri) has been shown to not only increase circulating oxytocin levels but also oxytocin expression in the brain in rodents, effects which have been linked with metabolism, wound healing, sociability, and behavior. (5, 6, 7).
It is notable that treatment with probiotics to boost oxytocin levels helped reduce obesity, an all-too-common problem in dogs. (8). Prescribing probiotics, therefore, to dogs being given parasiticides on a case-by-case basis is a hypothetical proposition that might prove beneficial in maintaining a healthy gut microbiome and gut-brain axis and in preventing aggression and other behavioural problems. The benefits including so-called postbiotics in fermented foods in the human and canine diets should also be considered. (9, 10).
Microbiome restorative therapy for various behavioural and health issues in human and non-human patients is also being recognized more widely (11,12,13), notably the finding that overweight cats have changes in their gut microbiome like how diet affects the human gut, potentially helping researchers better understand how gut bacteria influence diseases like obesity and type 2 diabetes. (14). Of course, dietary ingredients, additives, and contaminants such as Bisphenol A impact the biodiversity of the gut microbiome. (15). Also, since glyphosate and other herbicide residues harm the gut-brain-microbiome (16), current widespread agricultural use calls for more restricted applications, and screening especially of corn and soy products.
Repeated treatments with ivermectin to prevent heart worm disease can alter the microbiome, facilitating the proliferation of beneficial bacteria. (17). However, the antibacterial properties of ivermectin, although evidence of this is based mainly on in vitro tests, are of concern as prolonged use may lead to gut dysbiosis. In-depth studies are need to be done to determine the effect prolonged use has on gut microbiota and the possibility of developing resistant strains. (18). Our understanding of the gut microbiome and its role in physical and mental health-maintenance is progressing significantly (19), calling for the precautionary principle and more research on the influence of various medications.
References 1. Loeb J, Scally P. Corporate advises against spot-on treatment. Vet Rec 2014; 195: 4. 2. Wells C, Collins C.M.T. A rapid evidence assessment of the potential risk to the environment presented by active ingredients in the UK’s most commonly sold companion animal parasiticides. Environ Sci Pollut Res 2022; 29: 45070–45088 3. Doolin ML, Dearing MD. Differential Effects of Two Common Antiparasitics on Microbiota Resilience. J Infect Dis. 2024: 14;229(3):908-917. 4. Kirchoff NS, Udell MAR, Sharpton TJ. The gut microbiome correlates with conspecific aggression in a small population of rescued dogs (Canis familiaris). PeerJ. 2019 9;7:e61033 5. Cuesta-Marti C, Uhgil F, Muguerza B, et al et al Microbes, oxytocin and stress: Converging players regulating eating behavior. J. Neuroendocrinology 15 February 2023 https://doi.org/10.1111/jne.13243 6. Erdman SE, Poutahidis T. Microbes and Oxytocin: Benefits for Host Physiology and Behavior. Int Rev Neurobiol. 2016; 131: 91-126. 7. Buffington SA, Di Prisco GV, Auchtung TA, et al. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016; 165(7): 1762-1775. 8. Varian BJ, Levkovich T, Poutahidis T, et al. Beneficial dog bacteria up-regulate oxytocin and lower risk of obesity. J Probiotics Health. 2016; 4: 1-9. 9. Liang B, Xing D. The Current and Future Perspectives of Postbiotics. Probiotics Antimicrob Proteins. 2023;15(6):1626-1643. 10. Sabahi S, Homayouni Rad A, Aghebati-Maleki L, et al. Postbiotics as the new frontier in food and pharmaceutical research. Critical Reviews in Food Science and Nutrition, 2022; 63:(26), 8375–8402. 11. Chinna Meyyappan A, Forth E, Wallace CJK, et al. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry 2020; 20, 299.https://doi.org/10.1186/s12888-020-02654-5 12. Tan Q, Orsso CE, Deehan EC, Kung JY, et al. Probiotics, prebiotics, symbiotic, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review. Autism Research 2021; 14:(9), 1820–1836. 13. Collier AJ, Gomez DE, Monteith G, et al Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study. PLoS One. 2022; 17:(10):e0276295. 14. Rowe JC, Winston JA, Parker VJ. et al. Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats. Sci Rep 2024; 14:11901. 15. Lopez-Moreno A, Cerk K, Rodrigo L. et al. Bisphenol A exposure affects specific gut taxa and drives microbiota dynamics in childhood obesity. mSystems 2024; 9:e00957-23.https://doi.org/10.1128/msystems.00957-23
Additional Concerns About Antiparasiticides
The inclusion of PFAS (“forever” chemicals) in some anti-flea and tick formulations applied to companion animals calls for more research and application of the precautionary principle. Short and long-chain PFAS (per-and polyfluoroalkyl substances) such as PFOA, PFOS, and perfluorohexanesulfonic acid (PFHxS)—are known to harm the immune system, weaken the antibody response to vaccinations, and increase the risk of infectious disease. According to a report by Donley et al (1) they have been detected in some pesticides given to pets, notably Front Line Plus and Seresto collars. They also reported that fipronil was found to be one of the most prevalent contaminants in nearly 500 streams across five regions of the United States. Reference 1. Donley, N. Cox, C. Bennett, K. et al. Forever Pesticides: A Growing Source of PFAS Contamination in the Environment. Environmental Health Perspectives, 2024; 132:7 CID: 075003 https://doi.org/10.1289/EHP13954