There are two types of agents: the topical pipette, which works through the skin, and the systemic tablet, which works through the blood. Both do what they promise. But the way in which it is done has consequences that extend beyond the flea.
740x higher than the no-effect level: fipronil concentration in the coat of a treated dog [PAN Europe, 2021] | 86,8% of dogs treated with fluralaner (Bravecto) reported an adverse event [Dodds & Aronson, 2020] | 39.148 adverse event reports to the EMA for isoxazoline products 2013–2019, of which up to 55% were seizures |
Fipronil and permethrin: soaking on the skin
A spot-on pipette spreads through the sebaceous glands over the entire skin and coat. That sounds targeted, but the substance is also on the hands of everyone who strokes the animal, on the couch, and via bath or rainwater in the water drain.
Fipronil blocks GABA receptors in the nervous system of insects. The same receptors are present in mammals. The system is more selective for insects, but not exclusive. With repeated exposure, liver burden is documented and the EPA classifies fipronil as a possible human carcinogen.
Permethrin, which is found in many dog pipettes as a reinforcing substance, is acutely toxic to cats and significantly disrupts the gut microbiota with repeated exposure, including in dogs.
In households with both dogs and cats: A permethrin pipette on the dog can cause fatal neurological damage through body contact in a cat that shares the same sleeping surface.
Isoxazolines: months in the blood
The chewable tablet (Bravecto, NexGard, Simparica, Credelio) works differently: the active ingredient circulates through the blood for months. The flea only dies when it bites. The drug structurally loads kidneys, liver and nervous system during the entire period of action.
A 2023 study showed that fluralaner accumulates in the fat sheaths of cells and can reach high local concentrations in membranes and organs. In clinical practice, the most common complaints are atopy and behavioral changes. Epilepsy is reported, but in many cases seems to stem from the consequences at the microbiome and gut level.
In 2018, the FDA issued an official safety notice on isoxazoline products associated with neurological side effects, including muscle tremors, ataxia, and seizures. Manufacturers were obliged to adjust the labelling.
Microbiome, mitochondria and cells
Pesticides disrupt the gut microbiome through three mechanisms: direct inhibition of bacterial strains, damage to the tight junctions in the gut wall leading to increased permeability, and disruption of the production of short-chain fatty acids and other essential metabolites.
In addition, pesticides hit the mitochondria, the power plants of every cell. Permethrin has been shown to induce oxidative stress, leading to damage to mitochondrial DNA and reduced energy production. This partly explains the fatigue and lethargy that owners observe after treatment and rarely link to the flea remedy. In practice, this fatigue is sometimes visible for months after the treatment.
Research published in The ISME Journal (2023) shows that pesticide exposure in animal models consistently leads to negative effects on the gut microbiota, host physiology, and behavioral disturbances via the microbiome-gut-brain axis.
Beyond the animal
PAN Europe published hair analyses in 2021 that showed that fipronil and permethrin are detectable in the hair of people without professional pesticide exposure. The most likely source, the researchers said: veterinary pipettes. Hair stores exposure over six months and is therefore a direct biomarker for chronic, low-grade uptake via the treated animal.
Regarding the concentration on the animal itself, 18.5 mg/kg fipronil was measured in the coat of a treated dog, 740 times higher than the no-effect level of 0.025 mg/kg based on animal studies. Anyone who touches that animal comes into contact with that load.
The same substances reach surface water and groundwater via bath water and rainwater. Fipronil was detected in Dutch ditches and in treated sewage at concentrations that exceed the EPA limit values for aquatic organisms. The substance has been on the EPA candidate list for possible regulation in drinking water since 2021.
An alternative that works, without the chemical burden
You don’t have to choose between protecting your animal and protecting its health. NGD Care has developed two products that are effectively flea and tick repellent based on plant-based active ingredients, without pesticides, without burdening the microbiome and without systemic side effects.
For dogs & environment Flea & Tick Support IntenseHigher concentration of essential oils for effective protection of dog and immediate environment. Suitable as an environmental spray and for use on the dog. | Especially for cats Flea & Tick Support GentleFormulated with a microdosing of essential oils that is absolutely safe for cats. Effective and mild, without the risks of permethrin or isoxazolines. |
Don’t forget the environment: 95% of the flea life cycle takes place in the home, not on the animal. Both products can also be used as an environmental spray. Would you like to know more about a step-by-step plan to get fleas out of your home and animal in a natural way? Read our other blog here.
Would you like to read the full scientific substantiation, including all literature references to the FDA, EMA, EPA and peer-reviewed studies? The full article can be found on stefanveenstra.nl.
Sources: FDA (2018/2019), EMA adverse event database (2013–2019), PAN Europe hair research (2021), Dodds & Aronson (2020), Javurek et al. (2023), Garg et al. (2024), Goh et al. (2017), Tennekes (2018), Ccanccapa-Cartagena et al. (2024), Bexfield et al. (2021). Full bibliography via stefanveenstra.nl.