1. Introduction
This guideline sets out the considerations that applicants should make when submitting environmental data as part of applications for:
- registration of a veterinary chemical product (VCP)
- variation or extension of a registration of a veterinary chemical product
- a permit to use a veterinary chemical product.
The Australian Pesticides and Veterinary Medicines Authority's (APVMA) Risk Assessment Manual, Environment is a useful document that provides a general explanation of how data are used in the environmental risk assessment framework.
The International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) publishes internationally harmonised guidance on the determination of the environmental impacts of veterinary chemical products. The APVMA has adopted the VICH harmonised guidance.
The VICH environmental safety guidelines apply to veterinary chemical products other than biologicals (e.g. immunologicals). Two phases (Phase I and Phase II) of environmental assessment have been agreed upon. The route and quantity of VCP entry into the environment determines which phase of assessment is required, and the scenarios to be used. Dosage, route of administration, type of target animals, excretion, route of entry into the environment, and agricultural practice all influence the point at which environmental exposure occurs.
2. VICH Phase I
A Phase I assessment examines the potential for environmental exposure. VCPs with limited uses and limited environmental exposure will usually have limited environmental effects, and thus only require a Phase I assessment. Products that are applied as individual treatments are considered to have limited environmental exposure (e.g. companion animals, anaesthetics, sedatives, injectable corticosteroids or non-steroidal anti-inflammatories). Some injectable antibiotics or hormones applied to a small number of animals in a flock or herd may also fall into this category.
Environmental data are not required for a Phase I assessment, however, linkages to some data can be made to justify stopping further assessment during Phase I. For example, an ADME (absorption, distribution, metabolism, excretion) study could be supplied to demonstrate the VCP is extensively metabolized in the treated animal, thereby stopping assessment at Question 6. For terrestrial animals, a manure fate study could be submitted to enable the assessment to stop assessment at Question 18 (see the Guideline on determining the fate of veterinary medicinal products in manure).
Information on animal husbandry and other relevant factors specific to the proposed use of a product can also be supplied to inform the environmental exposure assessment (e.g. body weight of treated animals, ploughing depth of manure when applied to land, etc.). These assumptions could be carried through to a Phase II assessment, if necessary.
3. VICH Phase II
A Phase II environmental risk assessment requires a base data set as detailed in Tier A Testing in the VICH Phase II guidance document which describes the fate and effects of the VMP. If acceptable risks cannot be concluded following the assessment of the Tier A data, Tier B data are then required. Studies should be performed according to OECD test guidelines.
Although the APVMA has adopted the VICH guidance, there are certain differences reflecting Australia’s unique environment.
For VCPs with anti-microbial activity intended for use in aquaculture, the APVMA prefers to use blue-green algae (cyanobacteria) as the test species (see OECD 201).
For endo/ectoparasiticides intended for the treatment of terrestrial animals, the APVMA requires additional information on the toxicity to non-target arthropods (see OECD 232: collembolan reproduction test).
APVMA assessment factors for effects endpoints do not align with those described in the VICH Phase II guidance document. Please refer to the APVMA Risk Assessment Manual, Environment for the assessment factors applied in Australian assessments (see Appendices B (aquatic species), E (soil organisms), and F (non-target terrestrial plants).
Since the VICH phase II guidance document was published, the following test guidelines are now available, which are preferred by the APVMA.
- OECD 203 now also covers saltwater fish
- OECD 228: dung flies
- OECD 122: dung beetle
- OPPTS 850.4500: saltwater algae
- OPPTS 850.1035: saltwater crustaceans
- ASTM E1611-00: saltwater sediment invertebrates
If additional fate and effects data are available, these must also be supplied.
4. Biologicals
Veterinary biologicals represent a diverse range of microorganisms, and as such not all studies or data requirements may be appropriate for a specific agent. The environmental data requirements are based on the survival of the biological product in the environment, the potential pathogenicity to non-target organisms, the potential to disrupt natural ecosystem dynamics, and adversely affecting environmentally significant biota.
Applicants should consider the unique characteristics of their proposed microorganism when addressing specific data requirements and protocols and are encouraged to consult the APVMA prior to commencing data collection. Exemptions from certain data requirements can be considered when accompanied by sound, scientific rationale.
5. Relevant data for applications
Quality of submitted studies
Data quality directly influences how confident our risk assessors can be in the results of a study, and the conclusions they may draw from it. Therefore, environmental fate and toxicity studies should be of sufficient quality for the study to be relied upon for regulatory decision-making and must be performed according to GLP. The process of determining the quality of data takes into consideration three aspects – adequacy, reliability, and relevance of the available information to describe a given assessment endpoint.
Level of documentation
The documentation you provide should be complete, well organised, and presented in sufficient detail (for example, the inclusion of raw data on concentrations measured or individual animal responses) to allow independent scientific assessment.
Copies of original reports should be supplied. Summaries, or reprints of published material usually do not contain sufficient detail, and therefore would only be accepted if they allowed independent scientific assessment and achieved an acceptable reliability rating.
Adverse reports
You should not omit reports or published material that may adversely influence the outcome of an environmental risk assessment. If you consider that a report reaches an unsupportable conclusion, you should justify this within the application via scientific argument.
Details of other regulatory applications
Your application should include details of any regulatory applications you have made for the same active constituent and/or product to other regulatory bodies in Australia, or overseas. Where available, you should provide the results of those applications and subsequent regulatory decisions (for example, copies of assessment reports, or links to where these and/or regulatory decisions may be found). If any data in those submissions have been rejected by an overseas regulatory body, you should identify this and provide scientific justification as to why you have included the study in question in your application.
Formulation data
Most VCPs first pass through the animal to which they are administered and, in general, the most significant environmental exposure results from the excretion of the active constituent, which is usually the parent and/or its metabolites. Therefore, test data on the active constituent are most important.
However, for certain topical products (for example, applications of ectoparasiticides to sheep) or products added directly to water bodies, formulation data may be most relevant. For example, in aquaculture products may be directly applied to the aquatic environment for therapeutic use on target organisms. Unconsumed product may have a direct effect on non-target aquatic organisms, particularly if the product is used in an open environment. In this situation, formulation data would be highly relevant, including for combination products.
Metabolites
VICH Phase II guidance notes that the fate of chemicals in the environment is dependent on their chemical and physical properties, and degradability. These properties will vary between a parent compound and individual, excreted metabolites. For example, excreted metabolites may be more water soluble than the parent compound and may also be more mobile and/or more persistent in the environment.
In general, data is generated on the active constituent, but a risk assessment should also consider relevant metabolites. This is particularly important for pro-drugs that are efficiently metabolised into a single biologically active metabolite for which testing may be more appropriate.
Excreted metabolites that are 10% or more of the administered dose and do not form part of biochemical pathways should be added to the percentage of active substance excreted to allow the Predicted Environmental Concentration (PEC) to be recalculated. If the RQ is still 1 or more after this PEC refinement and testing at Tier B, then guidance should be sought from the APVMA, including guidance on whether testing of major environmentally relevant metabolites should be considered.
Combination toxicity testing
In aquaculture where a product is applied directly to the aquatic environment and particularly if used in an open environment, formulation data is important. For products containing more than one active constituent, the combined effect of the active constituents on non-target aquatic organisms should be considered, and thus combination toxicity data for the aquatic compartment is relevant (for further details refer to Part 7 – Environment (agricultural chemical products).
Product disposal
The applicant should consider developments in waste management and provide Information on the intended disposal of:
- empty containers
- unused product
- diluted-for-use chemical.
The National Farmers Federation, CropLife Australia, Animal Medicines Australia, the Veterinary Manufacturers & Distributors Association, and the Australian Local Government Association have together developed the following initiatives:
- drumMuster as one solution to the safe collection and recycling of cleaned chemical containers
- ChemClear for the collection of unwanted rural and agricultural and veterinary chemicals
General label statements for the proper disposal of product and used containers can be obtained from the Veterinary Labelling Code.
Spent dipping solution disposal
Estimation of environmental exposure using the following criteria for disposal of spent dipping solutions to land have been adopted by the APVMA. The criteria were developed based on 10 active constituents used in dips, and have been endorsed by the APVMA’s Registration Liaison Committee:
- The half-life in soil is less than 10 days at likely concentrations following dip disposal
- The active constituent(s) should be able to be denatured safely, quickly and completely (more than 98% in 2 hours) prior to disposal
- If repeat applications are to be made at the same site and denaturing is not possible, these should not occur until 4 half-lives have passed
- The spent dip should be evenly spread over flat land at a rate not exceeding 100,000 litres per hectare for spent sheep dips and 20,000 litres per hectare for spent fruit dips
- The disposal site must be dedicated and adequately bunded (the soil should at least be 15 centimetres high)
While an examination of the data holdings and label statements relating to all current active constituents and their associated products used in dipping is being undertaken, any application for new active constituents or extension of existing actives and associated products to be used in dips should be accompanied by:
- data in the above areas, to allow assessment of whether disposal to land is feasible
- the drafting of suitable label statements.
6. More Information
Applicants seeking further information on relevant environmental data for specific uses may wish to apply for pre-application assistance or make an application for a technical assessment.