Reflecting on the environmental impact of parasite treatments: what the EMA says
Reflecting on the environmental impact of parasite treatments: what the EMA says
In December 2022, the Committee for Veterinary Medicinal Products (CVMP) of the European Medicines Agency (EMA) published a “reflection paper” on the environmental impact of parasite treatments for cats and dogs (EMA 2022), which is open for public consultation, with a deadline to submit comments by 31 March 2023. The paper summarises very well the current state of knowledge about the environmental impacts of cat and dog parasiticides, and proposes some changes. We’ve summarised the key messages.
What does the reflection paper say about the environmental impact of parasite treatments?
Introduction, aim and scope
The paper discusses ectoparasiticide veterinary medicines, which aim to protect animals from ectoparasites such as fleas, mites, lice, ticks, or sand flies, and associated diseases. When used in companion animals (as opposed to animals being intensively reared), the environmental impact of the parasite treatments has been assumed to be low (EMA 2022). However, it has more recently been suggested that environmental pollution, including the use of pesticides and parasiticides, may impair non-target insect diversity, aquatic ecosystems and other wildlife. (Wagner 2020, Sánchez-bayo 2019, Sadaria et al. 2017; Teerlink et al. 2017; Cryder et al. 2019; STOWA, 2019, EFSA, 2013a, 2014, Guldemond et al. 2019).
In the paper the EMA aims to communicate the CVMP's view on the current state of the scientific discussion on the potential environmental impact of parasite treatments used in companion animals, and to provide an opportunity for discussion and clarification.
The scope of the paper is limited to cats and dogs (not other companion animals); systemically- and locally-acting ectoparasiticide and endectocide products authorised in the European Union (EU)/European Economic Area (EEA); and the outdoor environmental compartment (that is, not indoor or user/human safety). As the limited data on the exposure and the toxicity of parasiticide drugs do not allow for a quantitative assessment, the CVMP conducted a qualitative discussion. As sales of parasiticide products are not monitored, no conclusions can be drawn about the environmental impact of individual parasiticides.
EMA recommendations
The CVMP recommends:
Filling the knowledge gaps about parasiticide drugs used in companion animals.
When considering marketing authorisation applications for certain companion animal medicines, the current approach (to stop the environmental risk assessment in phase I should be revisited and adequate, targeted environmental data should be requested due to a well-justified environmental concern.
Monitoring environmental concentrations of parasiticides used in cats and dogs, including in surface water sediments and sewage sludge.
Studying the impact of excreta from treated animals on the terrestrial compartment of the environment.
Regulation of the sale of parasiticides (e.g. advertisement control) or the consideration of environmental safety when assigning prescription status.
Raising awareness on the environmental hazards these products may pose among veterinarians, pet owners, pet supply sellers, pharmacists, pet associations and operators of animal shelters.
Promoting the prudent use of veterinary medicines from the perspectives of efficacy and environmental sustainability, including individually tailored treatment plans to avoid overuse or off-label use (e.g. ensuring the correct duration of use of a product, and avoiding unnecessary use of combination products if they are not relevant to the individual animal).
Following recommendations for correct use as described in the product literature (e.g. avoiding washing animals or allowing them to swim in surface water soon after topical product application; correct administration of oral products in relation to food; disposal of containers and used collars; using disposable gloves when recommended for the application followed by disposal with solid waste.
Non-medical preventive measures (e.g. regular visual examination for ectoparasites and manual removal) (ESCCAP 2022).
Environmental hazard information should be declared in a standard way in the product literature of all veterinary medicines for cats and dogs (e.g. stating that the product is toxic for aquatic organisms).
Why is it important to us what the EMA thinks?
We use the same products here in the UK and the issues are the same.
The UK’s veterinary medicines regulator, the Veterinary Medicines Directorate (VMD) is likely to take account of the paper (both the evidence and the recommendations) in their own review of the environmental impact of parasite treatments
The pharmaceutical companies that market parasiticides are multinational, so regulatory changes at a EU level are likely to affect products available here because of the size of the international market relative to the UK.
There are recommendations in the paper that are not about regulatory change that we might wish to adopt here.
More on the background to these recommendations
Guidelines governing how the environmental impact of parasite treatments is assessed
In the EU and EEA (and in the UK to date), the environmental risk assessment of veterinary medicines is tier-based and conducted in two phases: phase I mainly consists of a decision tree focusing on qualitative and quantitative criteria to determine whether the environmental risk assessment for a veterinary medicine for which a marketing authorisation is applied for should progress to a higher tier assessment (i.e. phase II) or if it can end at the first phase. A phase I assessment for veterinary medicines intended to be used in companion animals typically does not require the provision of any information on fate, behaviour and effects of an (active) substance in the environment, as the overall conclusion is mostly based on exposure considerations only. Veterinary medicines intended for use in cats and dogs and other non-food-producing animals usually do not require a phase II environmental risk assessment.
The relevant guideline, the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) guideline (GL) 6 (EMA 2000), does contain the so-called "however clause", which states that, for some veterinary medicines for which the environmental risk assessment might otherwise stop in phase I, additional environmental information may be required to address particular concerns associated with their activity and use.
What are the ectoparasiticide veterinary medicines?
Examples of the parasiticide ingredient and their chemical classes are:
fipronil (a phenylpyrazole; e.g. Broadline, Frontline)
imidacloprid (a neonicotinoid; e.g. Advantage, Advocate)
permethrin (a pyrethroid; e.g. Activyl, Vectra 3D)
dimpylate (an organophosphate; e.g. Beaphar, Johnson’s collars)
afoxolaner (an isoxazoline; e.g. Nexgard)
selamectin (an endectocide macrocyclic lactone; e.g. Selehold) (Veterinary Prescriber 2023).
Use of some classes of parasiticide such as organophosphates and neonicotinoids has been restricted for other indications (e.g. as biocides or plant protection products) due to environmental (e.g. toxicity to pollinators) and health concerns. However, in veterinary medicines use, while many of the older organophosphate or pyrethroid class substances have been replaced by newer ones, many older molecules are still on the market, possibly due to their low cost.
Whereas locally-acting spot-on products (e.g. pyrethrins and pyrethroids) originally dominated the market (Beugnet and Franc 2012), followed by collars and sprays (e.g. organophosphorous compounds), the number of available ectoparasiticide veterinary medicines for companion animals has significantly increased in recent years, including the use of oral systemic treatments (e.g. isoxazolines), longer-lasting formulations, and combination products for concurrent treatment of multiple ecto- and endoparasites (e.g. endectocide macrocyclic lactones).
How much of the products are sold and used?
There is no surveillance system in place on the veterinary sales of (ecto-)parasiticides in the EU/EEA, so the overall amounts of the chemicals sold cannot readily be calculated. Freedom of Information (FOI) requests to the Veterinary Medicines Directorate (VMD) show that in the UK, the total amount of imidacloprid in veterinary medicines in 2015 (for example) was 3,910kg/year (Anthe et al. 2020).
Estimates suggest there are around 75 million pet cats and 63 million pet dogs in the EU/EEA, not counting abandoned and stray animals (FEDIAF 2020). Pet ownership is increasing in Europe (FEDIAF 2020), but data are limited on stray, feral or shelter animals and whether animals are free-roaming or not, which might influence the use-patterns and the exposure of the environment to ectoparasiticides.
This means that the environmental impact of parasite treatments may no longer be negligible (EMA 2022).
Which type of product releases the most active substances in which species?
Although spot-on products and tablets are the most common formulations, collars contain greater amounts of parasiticide drug. The amounts released from the collars to the animal and subsequently to the environment before disposal are unknown, although it is estimated that more than half of the active substance remains in the collar at disposal (Stanneck et al. 2012).
For similar numbers of cats and dogs, the volume of parasiticide drug is influenced more by use in dogs, due to their larger size and therefore higher doses used (Montforts et al. 2021).
Where do the chemicals end up?
Most exposure pathways for systemically- and locally-acting veterinary medicines end up in surface waters (including sediments), so these are likely the most important destination (e.g. due to dogs swimming, or wastewater systems after washing dog bedding etc.) (Mul et al. 2021). Pathways into the terrestrial compartment and potential impacts on wildlife have not yet been quantified (e.g. the relevance of animal excreta not connected to urban sewage systems) or understood (e.g. the potential impact of dog hair in bird nests and exposure of nestlings) (Guldemond et al. 2019).
What are the potential hazards?
Hazard data and Persistent, bioaccumulative and toxic (PBT) assessments exist for older parasiticides (e.g. due to their use in food-producing animals), but environmental data are scarce for newer substances that are only used in companion animals (e.g. isoxazolines).
Examples are given showing that parasiticide ingredients (e.g. imidacloprid and fipronil, for which monitoring data are most abundant and non-pet medicine uses are being more and more restricted) contained in ectoparasiticide medicines for cats and dogs are present in waterways in the UK and elsewhere and are toxic to the environment at very low levels.
The specific hazards and environmental behaviour of selected substances are:
Imidacloprid is an insecticide with effects on the nervous system, so can be toxic towards species such as aquatic invertebrates (e.g. crustaceans), pollinating insects (e.g. bees) and soil-dwelling organisms such as springtails. To protect especially pollinators from exposure, neonicotinoids have been banned in Europe from use as pesticides in non-closed agricultural systems. It has high solubility in water and is stable to hydrolysis but sensitive to photolysis (EFSA 2008).
Fipronil blocks GABAA-gated chloride channels in the central nervous system, prevents the uptake of chloride ions, and causes excessive neuronal stimulation and death of insects. It has low solubility in water, is persistent in soil and water-sediment systems and is insecticidal and acaricidal.
Data on the environmental hazards or the environmental behaviour of isoxazolines are scarce. They have high lipophilicity and are classified as persistent/very persistent in soil and aerobic freshwater sediment. The major elimination pathway is excretion of the unchanged parent compound via faeces. They are insecticidal and acaricida
What is an EMA “Reflection paper”?
The EMA website states: “A reflection paper may be developed to communicate the current status of discussions or to invite comment on a selected area of medicinal product development or a specific topic. It can provide a framework for discussion or clarification particularly in areas where scientific knowledge is fast evolving or experience is limited. A reflection paper does not provide scientific, technical or regulatory guidance, but may contribute to future development of such guidelines, or related documents.”
You might also be interested to read Is there a pet parasiticide that is safer for the environment?
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References
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