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Flea product use and limiting environmental risks

The active ingredients imidacloprid and fipronil used in a range of AVM-GSL, NFA-VPS and POM-V parasiticides, until recently were also used in agriculture as insecticides. Imidacloprid is a neonicotinoid. The name means "new nicotine-like insecticides". They are chemically similar to nicotine. Clothianidin, imidacloprid, and thiamethoxam are included in this class. Fipronil is a phenylpyrazole. In 2017/18 for Neonicotinoids and 2013 for fipronil, they were banned as agricultural chemicals in the UK and EU. As they are not selective molecules they kill not only the pests but can also harm useful helper insects.

Fipronil was used as seed coatings and granules in agriculture to control a range of relevant pests such as termites and aphids. Imidacloprid was used in a similar fashion.  In January 2022, the Government authorised an emergency application in England of the use of thiamethoxam which is a neonicotinoid (the same class as Imidacloprid) to tackle the threat to sugar beet crops from the Yellows Virus, carried by aphids. It was stated by the government that by 2023, it is hoped that the sugar beet industry will no longer rely on neonicotinoids through the development of pest resistant varieties and greater use of Integrated Pest Management, a key focus for future UK pesticides policy. 

Imidacloprid and fipronil are still licensed for use in veterinary medicine in companion animals, where they are used in a more targeted way (i.e. in individual animals rather than herds or flocks) to agriculture, namely as spot-ons applied directly to the companion animal skin.

Today there is increased scrutiny on these actives and how they are being assessed and used and their possible impact on the environment.

There is a great deal of opinion in this area with some information starting to come through from within the UK and also EU and USA, with publications focusing on appearance of these molecules in waterways.  Harm to non-target species of invertebrates as well as secondary impacts on insectivores are considered the primary concerns, along with impacts not only on terrestrial, but also aquatic insects and insect species that spend part of their life cycle in the water. 

In 2020 the European medicines agency published a Concept paper to reflect on and look at the environmental risk assessment for parasiticide veterinary medicinal products used in companion animals.

With Britain’s departure from the EU we will no longer have the opportunity to contribute to this specific reflection as a member state, however the UK has subsequently formed the Pharmaceuticals in the Environment (PiE) Group. This is a UK cross-government platform to enable discussion and knowledge exchange relating to pharmaceuticals in the environment from human, veterinary and, where there is crossover, agricultural and non-agricultural sources. 

The following text is extracted and adapted where appropriate from the EMA concept paper produced in 2020 which gives some oversight:

The environmental risk assessment for veterinary medicinal products (VMPs) is tier-based and conducted in two tiers (Phase I and Phase II), in line with VICH guideline 6  and VICH guideline 38 for Phase I and Phase II, respectively. Products for which the environmental risk assessment is concluded in Phase I are those for which the environmental emissions resulting from their use are considered to be negligible and, therefore, their exposure level in the environment is not expected to cause a risk to non-target organisms. The Phase I guideline (VICH GL 6) makes use of a decision tree to determine if the VMP fulfills the criteria for a higher tier assessment (Phase II) or if the risk assessment can end at Phase I. 

The environmental risk assessment for products used in companion animals usually ends at Phase I, as the decision tree concludes that the use of products for companion animals does not lead to environmental risks, as environmental exposure from their use is assumed to be low. Furthermore, a Phase I assessment for veterinary products used in companion animals does not require information on fate, behaviour and effect data as the overall conclusion is based on exposure considerations only.  

Since 2000, when VICH GL 6 came into force, applicants and regulators have accepted that risks due to environmental exposure to active substances from products used in companion animals will be low.  However, recent publications on the environmental effects of certain parasiticides as well as environmental monitoring data (Sadaria et al., 2017; Cryder et al., 2019; Perkins et al.,2021), suggest that this situation might have changed since the guideline was developed, and came into force in 2000. Indeed, not only the number of companion animals (i.e., dogs and cats in urban areas) is reported to have increased (Statista and PDSA Paw report) but also the use of certain ectoparasiticides in companion animals and the pattern of use is reported to be higher (Curtis et al., 2016). Thus, the combination of a larger number of treated animals, together with an increased pattern of use might be leading to an increase in the overall environmental exposure for some type of substances, in target compartments. Hence, the resulting environmental exposure may be higher than that which was estimated in 2000, and may need further or different evaluation.

It is clear that the CVMP GL in support of VICH GL 6 and GL 38  already considered that for ectoparasiticides applied topically to dogs, specific risk mitigation measures, as outlined in the SPC guideline should be applied to the product information as a standard statement. An example of a  risk mitigation measure to be included in the SPC is :

“Do not allow treated animals to swim in water courses until at least 2 days after administration”.  

Perhaps it should be acknowledged that this statement could be regarded as a minimum i.e. ‘at least 2 days’ could encompass a longer period.

Where Phase II ERA studies are carried out on relevant products such as ectoparasiticides used in farm animals and where these may show that the use of the medicine will create an unacceptable risk for the environment, the applicant/MAH is obliged to propose mitigation measures to reduce the risk to an acceptable level.

It is crucial that prescribing and supplying of these products is carried out conscientiously, with awareness of the possible impact and that prescribers remind pet owners to be  responsible and observe the conditions and restrictions placed .  It is essential that all products are prescribed and supplied prudently and responsibly with sufficient information to ensure the products are used correctly which will ensure both Efficacy and limit Down The Drain (DTD) water contamination to a minimum (or ideally prevent it).

As much as necessary, as little as possible with thorough advice at the time of supply on correct use and any restrictions in place.

Glossary

CVMP – Committee for Veterinary Medicinal Products
ERA – Environmental Risk Assessment.
GL – Guideline
MAH – Marketing Authorisation Holder
SPC – Summary or product Characteristics
VMP – Veterinary Medicinal Product
VICH - International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products

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