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).
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.
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 fiprinil and other synthetic insecticidal and biocidal chemical compounds when properly formulated and applied and many veterinarians are now offering these to their clients such as PetzLife’s Herbal Defense and home prepared lemon rind tea sprits as effective insect repellants.
The use of systemic insecticides like fiprinil 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.
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.
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 email@example.com
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 - ConsumerAffairs.com
and 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.
Powell, K., Foster, C., and Evans, S. Environmental dangers of veterinary antiparasitic agents, Veterinary Record, Nov.17th, 2018, p 599-600.
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
Marie Miglianico, Maarten Eldering, Hannah Slater, Neil Ferguson, Pauline Ambrose, Rosemary S. Lees, Karin M. J. Koolen, Katerina Pruzinova, Magdalena Jancarova, Petr Volf, Constantianus J. M. Koenraadt, Hans-Peter Duerr, Graham Trevitt, Baiyuan Yang, Arnab K. Chatterjee, John Wisler, Angelika Sturm, Teun Bousema, Robert W. Sauerwein, Peter G. Schultz, Matthew S. Tremblay, and Koen J. Dechering
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.
The author appreciates the helpful suggestions of Dr. W. Jean Dodds in preparing this review.
* Michael W. Fox BVetMed, PhD, DSc, MRCVS Website: www.drfoxvet.net Email firstname.lastname@example.org