166 
Guidance for Industry  
 
 
 
ENVIRONMENTAL IMPACT ASSESSMENTS (EIAs) FOR 
VETERINARY MEDICINAL PRODUCTS (VMPs) - PHASE II  
VICH GL38 
 
FINAL GUIDANCE 
 
This VICH guidance document provides guidance for the use of a single set of environmental fate 
and toxicity data to be used by applicants/sponsors to obtain marketing approval in all VICH 
regions for those veterinary medicinal products (VMPs) identified as recommending data during 
the Phase I process.   
Comments and suggestions regarding the document should be submitted to Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, 
MD  20852. Submit electronic comments to http://www.regulations.gov/.   All comments should be 
identified with the Docket No. 2004D-0156. 
 For questions regarding this document: Charles E. Eirkson, Center for Veterinary Medicine, (HFV-
103), Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, 240-276-8173, e-
mail: charles.eirkson@fda.hhs.gov. 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine 
January 9, 2006 
  Contains Non-Binding Recommendation 
 
VICH GL 38 (ECOTOXICITY PHASE II) 
October 2004 
For implementation at Step 7 
 
 
 
 
 
 
 
 
 
ENVIRONMENTAL IMPACT ASSESSMENT FOR 
VETERINARY MEDICINAL PRODUCTS  
 
PHASE II GUIDANCE 
 
 
 
 
 Recommended for Adoption 
at Step 7 of the VICH Process 
in October 2004 by the VICH SC for implementation in October 2005 
 
 
This Guidance has been developed by the appropriate VICH Expert Working Group and is subject 
to consultation by the parties, in accordance with the VICH Process.  At Step 7 of the Process the 
final draft was recommended for adoption to the regulatory bodies of the European Union, Japan 
and USA. 
Page 2 of 37  Contains Non-Binding Recommendation 
 
VICH-GL38 
ENVIRONMENTAL IMPACT ASSESSMENT FOR 
VETERINARY MEDICINAL PRODUCTS  
PHASE II  GUIDANCE 
 
TABLE OF CONTENTS  
1    INTRODUCTION............................................................................................................7 
1.1.......Purpose of this Guidance Document..............................................................7 
1.2.......Scope..............................................................................................................8 
2  GENERAL ELEMENTS........................................................................................8 
2.1.......Protection Goals.............................................................................................8 
2.2.......General Description and Use of Phase II.......................................................8 
2.3.......Exposure of VMPs to the Environment.........................................................9 
2.4.......Risk Quotient (RQ) Approach.......................................................................9 
2.5.......Test Guidelines............................................................................................10 
2.6.......Metabolites...................................................................................................10 
2.7.......Special Consideration for Biodegradation Data...........................................11 
3  RECOMMENDED STUDIES AT TIER A AND TIER B..................................11 
3.1.......Tier A Testing..............................................................................................11 
3.1.2......Tier A Environmental Fate Studies.........................................................12 
3.1.3......Tier A Effects Testing.............................................................................12 
3.1.3.1  Tier A Aquatic Effects Studies.................................................................12 
3.1.3.2  Tier A Terrestrial Effects Studies.............................................................13 
3.1.4......Risk assessment at Tier A.......................................................................14 
3.1.4.1  PEC refinement.........................................................................................14 
3.2.......Criteria for Tier B Testing...........................................................................15 
3.3.......Tier B Testing..............................................................................................15 
3.3.1......Tier B Physical-Chemical Properties Studies.........................................15 
3.3.2......Tier B Environmental Fate Studies.........................................................15 
3.3.3......Tier B Environmental Effects Studies.....................................................15 
3.3.3.1  Tier B Aquatic effects studies..................................................................15 
3.3.3.2  Tier B Terrestrial effects studies..............................................................16 
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4  AQUACULTURE BRANCH...............................................................................17 
4.1.......Introduction..................................................................................................17 
4.2.......Tier A...........................................................................................................18 
4.2.1......Data recommended in Tier A..................................................................18 
4.2.1.1  Physical-chemical properties studies........................................................18 
4.2.1.2  Environmental fate studies.......................................................................18 
4.2.1.3  Environmental effects studies...................................................................18 
4.2.2......Calculation and comparison of PEC .........................................18 
surfacewater
4.2.2.1  Calculation of PEC (PEC ).........................................18 
surfacewater-initial  sw-initial
4.2.2.2  Comparison of PNEC and PEC .....................................................19 
sw-initial
4.2.2.3  Calculation of PEC .......................................................................19 
sw-refined
4.2.3......Calculation and comparison of PEC .............................................19 
sediment
4.2.3.1  Calculation of PEC .........................................................................19 
sediment
4.2.3.2  Calculation of PEC  in cases of VMPs added to feed.....................19 
sediment
4.2.3.3. Comparison of PNEC and PEC...................................................................20 
4.3.......Tier B...........................................................................................................20 
4.3.1......Triggers for testing in Tier B..................................................................20 
4.3.2......Data recommended in Tier B..................................................................20 
4.3.2.1  Physical-chemical properties studies........................................................20 
4.3.2.2  Environmental fate studies.......................................................................20 
4.3.2.3  Environmental effects studies...................................................................20 
4.3.3......Further assessment..................................................................................20 
5  INTENSIVELY REARED ANIMALS BRANCH...............................................22 
5.1.......Introduction..................................................................................................22 
5.2.......Tier A...........................................................................................................22 
5.2.1......Data recommended in Tier A..................................................................22 
5.2.1.1  Physical-chemical properties studies........................................................22 
5.2.1.2  Environmental fate studies.......................................................................22 
5.2.1.3  Environmental effects studies...................................................................22 
5.2.2......Calculation and comparison of PEC ...................................................23 
soil
5.2.2.1  Calculation of PEC ........................................................................23 
soil-initial
5.2.2.2  Comparison of PNEC and PEC .....................................................23 
soil-initial
5.2.2.3  Calculation of PEC ......................................................................23 
soil-refined
Page 4 of 37  Contains Non-Binding Recommendation 
 
5.2.3......Calculation and comparison of PEC water.............................................24 
5.2.3.1  Calculation and comparison of PEC ..............................................24 
sw-initial
5.2.3.2  Calculation of PEC .....................................................................24 
groundwater
5.3.......Tier B...........................................................................................................24 
5.3.1......Triggers for further testing in Tier B.......................................................24 
5.3.2......Data recommended in Tier B..................................................................24 
5.3.2.1  Physical-chemical properties studies........................................................24 
5.3.2.2  Environmental fate studies.......................................................................24 
5.3.2.3  Environmental effects studies...................................................................25 
5.3.3......Further assessment..................................................................................25 
6  PASTURE ANIMALS BRANCH........................................................................27 
6.1.......Introduction..................................................................................................27 
6.2.......Tier A...........................................................................................................27 
6.2.1......Data recommended in Tier A..................................................................27 
6.2.1.1  Physical-chemical properties studies........................................................27 
6.2.1.2  Environmental fate studies.......................................................................27 
6.2.1.3  Environmental effects studies...................................................................27 
6.2.2......Calculation and comparison of PEC ...................................................28 
soil
6.2.2.1  Calculation of PEC ........................................................................28 
soil-initial
6.2.2.2  Comparison of PNEC with PEC ...................................................28 
soil-initial
6.2.2.3  Calculation of PEC ......................................................................28 
soil-refined
6.2.3......Calculation and comparison of PEC ..................................................29 
dung
6.2.3.1  Calculation of PEC ......................................................................29 
dung-initial
6.2.3.2  Comparison of PNEC with PEC ..................................................29 
dung-initial
6.2.3.3  Calculation of PEC .....................................................................29 
dung-refined
6.2.4......Calculation and comparison of PEC water.............................................29 
6.2.4.1  Surface water and groundwater................................................................29 
6.2.4.2  Aquatic Exposure Scenarios.....................................................................29 
6.2.4.3  Comparison of PNEC with PEC ....................................................31 
sw-initial
6.2.4.4  Calculation of PEC ................................................................31 
sw-initial-refined
6.3.......Tier B...........................................................................................................31 
6.3.1......Triggers for further testing in Tier B.......................................................31 
6.3.2......Data recommended for Tier B.................................................................31 
Page 5 of 37  Contains Non-Binding Recommendation 
 
6.3.2.1  Physical-chemical properties studies........................................................31 
6.3.2.2  Environmental fate studies.......................................................................31 
6.3.2.3  Environmental effects studies...................................................................31 
6.3.3......Further assessment..................................................................................32 
7  GLOSSARY (Definitions of Terms)....................................................................34 
8  OECD/ISO TEST Guidelines for recommended studies......................................35 
Section 1  OECD Physical-Chemical Properties....................................................35 
Section 2  OECD Effects on Biotic Systems..........................................................36 
Section 3  OECD Degradation and Accumulation..................................................36 
Section 4  ISO Guidelines.......................................................................................37 
 
Page 6 of 37  Contains Non-Binding Recommendation 
 
ENVIRONMENTAL IMPACT ASSESSMENT FOR VETERINARY 
 
MEDICINAL PRODUCTS  - PHASE II  
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on the subject matter.  It does 
not create or confer any rights for or on any person and does not operate to bind FDA or the public.  You can use an 
alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.  If you want 
to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance.  If you cannot 
identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.  
 
1 INTRODUCTION  
1.1  Purpose of this Guidance Document 
The purpose of this document is to provide guidance for the use of a single set of environmental fate 
and toxicity data to be used by applicants/sponsors to obtain marketing approval in all VICH 
regions for those veterinary medicinal products (VMPs) identified as recommending data during the 
Phase I process.  It also aims to be a major contribution towards the common use of study methods 
used to generate these data.   
It needs to be kept in mind that guidances should not consist of rigid stipulations, but should make 
clear recommendations on the minimum information needed.  By their nature, guidances address 
most, but not all possible eventualities.  Each case has to be considered on its merits, and if in a 
particular circumstance an alternative approach, for example use of data published in the literature, 
is deemed more fitting, a reasoned argument for the deviation should be prepared and discussed 
with appropriate regulatory authorities before work is initiated.   
Besides serving as a common basis for the Environmental Impact Assessment (EIA), this document 
provides recommendations to protect the environment. The field of ecotoxicology is a complex 
science and gaps in data and knowledge exist. Notwithstanding these limitations, the Phase II 
recommendations should be based on science and strive for objectivity. The maximum amount of 
information should be extracted from each study to achieve an understanding of the potential for a 
given VMP to affect the environment.  
An important factor in the use of the guidance contained herein is professional judgement. Expertise 
in the appropriate scientific disciplines is a valuable prerequisite for designing an EIA program for 
VMPs. Such expertise is important in evaluating the relevance of available data, for predicting 
environmental exposures, for identifying the recommended studies, and interpreting exposures 
relative to endpoint values obtained in such studies. 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required. 
 
Page 7 of 37  Contains Non-Binding Recommendation 
 
1.2  Scope 
The mandate given by the VICH Steering Committee for developing this guidance is described in 
the Phase I document (http://www.vichsec.org/pdf/2000/Gl06_st7.pdf, 
http://fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustr
y/UCM052424.pdf). 
The scope of the guidance is for VMPs, as defined by the individual parties to VICH. Particular 
VICH regions may mandate legislatively that this guidance be applicable to new products only or to 
both new and old products. Therefore, it is incumbent upon the applicant/sponsor to determine what 
the case is for a particular VMP.  If an applicant/sponsor uses an alternative approach to conducting 
an EIA, then they should assess the suitability of the deviation from the guidance contained herein 
with the appropriate regulatory authority.  However, an alternative approach, depending on the 
nature of the deviation from the guidance and the justification for it, may result in a submission not 
being accepted by all parties to VICH. 
2  GENERAL ELEMENTS 
Phase II provides a common basis for EIA testing for VMPs between the EU, Japan, US, Canada 
and Australia/New Zealand.  It is recognized that significant regional differences (e.g. animal 
husbandry practices, climates, soil and water types, etc.) preclude fully harmonized guidance at this 
time.  Full harmonization on principles of fate, effects and risk assessment is possible; the 
parameterization and decision making is, however, the prerogative of the individual regulatory 
authority.  For this reason, the scope and extent of information recommended for EIAs for all 
regions cannot be completely specified.  To the extent possible, Phase II provides recommendations 
for standard datasets and conditions for determining whether more information should be generated 
for a given VMP. 
2.1  Protection Goals  
Legislation and policy on environmental quality in the VICH regions set out the protection goals 
reflected in the EIA. The overall target of the assessment is the protection of ecosystems. 
The aim of the guidance provided in Phase II (and in Phase I) is to assess the potential for VMPs to 
affect non-target species in the environment, including both aquatic and terrestrial species.  It is not 
possible to evaluate the effects of VMPs on every species in the environment that may be exposed 
to the VMP following its administration to the target species.  The taxonomic levels tested are 
intended to serve as surrogates or indicators for the range of species present in the environment. 
Impacts of greatest potential concern are usually those at community and ecosystem function levels, 
with the aim being to protect most species.  However, it may be important to distinguish between 
local and landscape effects.  There may be some instances where the impact of a VMP at a single 
location may be of significant concern, for example, for endangered species or a species with key 
ecosystem functions.  These issues should be handled by risk management at that specific location, 
which may even include restriction or prohibition of use of the product of concern in that specific 
local area.  Additionally, issues associated with cumulative impact of some VMPs may be 
appropriate at a landscape level.  These types of issues cannot be harmonized but should be 
considered as part of the EIA and if recommended, addressed by each region/local area. 
2.2  General Description and Use of Phase II 
This Phase II guidance contains sections for each of the major branches: (1) aquaculture, (2) 
intensively reared terrestrial animals and (3) pasture animals, each containing decision trees 
Page 8 of 37  Contains Non-Binding Recommendation 
 
pertaining to the branch.  The document also contains a section listing the recommended studies for 
physical/chemical properties, environmental fate and environmental effects, as well as a description 
of how to determine when studies may be relevant. 
The guidance uses a two-tiered approach to the environmental risk assessment.  The first tier, Tier 
A, makes use of simpler, less expensive studies to produce a conservative assessment of risk based 
on exposure and effects in the environmental compartment of concern.  If the EIA cannot be 
completed with such data, due to a prediction of unacceptable risk, then the applicant/sponsor 
progresses to Tier B to refine the EIA.  
In some cases, it may be possible to implement a risk management option instead of moving to Tier 
B.  In these cases, discussion with the regulatory authority is recommended.  It should be 
recognized that risk management may not be identical for all regions and where Tier B testing is 
omitted in one region, it may still be recommended in another. 
For certain VMPs, it may be recommended to go beyond Tier B because more complex studies, 
specific to issues being addressed or to a particular region, are recommended to complete the risk 
assessment.  Such studies cannot be comprehensively dealt with in a harmonized guidance 
document.  Therefore, these issues do not fall within the purview of this document, but should be 
addressed on a case-by-case basis with the appropriate regulatory authority.  Examples include 
exceeding relevant trigger values in Tier B, where further testing may be warranted and/or risk 
mitigation measures may be recommended.  As risk management measures are not within the scope 
of this guidance document, no guidance on these aspects is possible.  
2.3  Exposure of VMPs to the Environment 
The route and quantity of a VMP entering the environment determines the risk assessment scenarios 
that are applicable and the extent of the risk assessment.  This guidance sets out a number of 
emission scenarios, using various assumptions.  There may be some emission scenarios that are not 
applicable to a specific region.  Emission can occur at various stages in the life cycle of the product.  
However, with the exception of certain topicals or those added directly to water, most VMPs first 
pass through the animal to which it is administered.  Generally the most significant environmental 
exposure results from excretion of the active substance being the parent and/or its metabolites.  
Following excretion, residues are generally assumed to be uniformly distributed in the environment; 
even though distribution may be patchy. 
2.4  Risk Quotient (RQ) Approach 
The EIA is based on the accepted principle that risk is a product of the exposure, fate and effects 
assessments of the VMP for the environmental compartments of concern.  The Phase II EIA is 
based on a RQ approach, which is the ratio of the predicted environmental concentration (PEC) and 
the predicted no effect concentration (PNEC) on non-target organisms. The RQ (PEC/PNEC) is 
compared against a value of one, and a value less than one indicates that no further testing is 
recommended.  However, in some circumstances, professional judgement is needed for a final 
determination.    
The PEC of the RQ is defined as the concentration of the parent compound and metabolites 
predicted to be present in the soil, water and sediment compartment.  Worldwide harmonization of 
PEC calculations is not practical or possible at this time.  Regional differences in animal husbandry 
practices, different environmental conditions in the VICH regions, differences in treatment rates and 
frequency, should be taken into account when calculating PECs.  Therefore this document does not 
contain any examples of PEC calculations but gives some general qualitative guidance needed to 
determine PECs.  It is incumbent upon the applicant/sponsor to determine the most appropriate 
Page 9 of 37  Contains Non-Binding Recommendation 
 
method of estimating exposures for the region of interest for a particular VMP based on regulatory 
guidance. 
The PNEC of the RQ is determined from the experimentally determined effects endpoint divided by 
an appropriate assessment factor (AF). The AF is intended to cover uncertainties such as intra- and 
inter-laboratory and species variation, the need to extrapolate from laboratory study results to the 
field, and from short term to long term toxicity (acute:chronic ratios).  The value varies depending 
on the type of study conducted.  Variation in the AF applied should be clearly justified in the 
submission. 
AFs of between 1000 and 10 are used in the assessment.  A factor of 1000 is designed to be 
conservative and protective and is applied when only limited data are available; this value may be 
progressively reduced to 10 as more evidence becomes available.  Such evidence could include: 
(1)  availability of data from a wide variety of species including those which are considered  
       to represent the most sensitive species.  
(2)  information from structurally similar compounds, to suggest that the acute to chronic  
      ratio is likely to be lower than that for many other compounds; and 
(3)  information to suggest that the chemical is rapidly degraded and not repeatedly  
      administered so as to lead to chronic exposure. 
2.5  Test Guidelines 
The specific test guidelines/protocols recommended in Phase II are those finalized by OECD/ISO.  
This has the advantage of ensuring that environmental studies are current and broadly acceptable to 
regulatory authorities on a worldwide basis.  Lack of a specific study recommendation, however, 
does not eliminate the importance for data on the specific organism class identified.  In these 
situations, it is up to the applicant/sponsor to seek guidance from the appropriate regulatory 
authority.   
Finally, conducting EIA studies in accordance with Good Laboratory Practice (GLP) is a regional 
requirement.  It is preferred that studies should be conducted using methods that allow for a data 
audit as may be necessary for some regions.  It should be recognized that if studies are not 
conducted to GLP, they may not be accepted in some VICH regions. 
2.6  Metabolites 
In triggering a Phase II assessment, the exposure is based on the total residue approach, as described 
in question 11 and 17 of the Phase I document.  The fate of chemicals in the environment is 
dependent on their chemical/physical properties and degradability.  These properties will vary 
between the parent compound and the individual excreted metabolites, for example, the latter may 
be more water-soluble than the parent compound and may be more mobile and/or more persistent in 
the environment.    
In general, the data generated at Phase II will be on the parent compound, but the risk assessment 
should also consider relevant metabolites. This is especially the case for pro-drugs that are 
efficiently metabolized into a single metabolite for which testing may be more appropriate.  
Consideration of the excretion data is not initially recommended at Tier A, where a total residue 
approach should be taken and a PEC  should be estimated.  It should be assumed that the VMP is 
initial
excreted 100% as parent.   
If the RQ is 1 for one or more tested taxonomic levels, then metabolism/excretion data from the 
residues and ADME part of the dossier should be considered as part of the PEC refinement.  
Page 10 of 37  Contains Non-Binding Recommendation 
 
Excreted metabolites representing 10% or more of the administered dose and which do not form 
part of biochemical pathways should be added to the active substance to allow the PEC to be 
recalculated. 
If the RQ is still 1 after PEC refinement and testing at Tier B, then guidance should be sought 
from the regulatory authority, including whether testing of the major environmentally relevant 
metabolites should be considered. 
2.7  Special Consideration for Biodegradation Data 
At Tier A if the RQ is <1 for all taxonomic levels tested, the assessment should normally stop.  
However, for persistent compounds (e.g. DT90 > 1 year in soil based on the annual appication) it is 
recommended that the PECinitial be recalculated due to the possibility of accumulation in the 
environment. 
In case of specific concerns related to the persistence and/or mobility, further investigation of 
degradates formed during environmental fate studies may be important.  It should be noted that an 
individual substance may be both an excreted metabolite and a degradate in the environment. In 
both cases guidance should be sought from the regulatory authority. 
 
3  RECOMMENDED STUDIES AT TIER A AND TIER B 
Exposure to both the terrestrial and aquatic compartment may be applicable to a particular VMP 
depending on its route of environmental introduction.  For instance, VMPs administered to 
intensively reared animals have the potential to impact terrestrial non-target species directly and 
non-target species in surface waters indirectly due to transport in water, including when adsorbed to 
soil particles and organic matter.  Likewise, VMPs used to treat pasture animals may impact aquatic 
as well as terrestrial non-target species.  Therefore, there should be a common set of criteria and 
studies that will be used when it is determined that testing is recommended.  These can be 
applicable to all three branches or just two, e.g. intensively reared and pasture animals and are 
cross-referenced (as appropriate) in later sections of this document.  If there is evidence that there 
will be no exposure to a particular compartment (i.e. water, soil/sediment and dung), then it may be 
possible to waive studies for that compartment.  However, sound scientific evidence should be 
presented in the dossier in support of the omission of these studies. 
This section summarizes the studies that are recommended at Tier A, and which should be 
conducted once it has been determined at Phase I that testing at Phase II is recommended.  It also 
outlines the process that should be followed to determine whether testing at Tier B may be relevant 
and lists the studies recommended at this level. 
All testing should be carried out on the parent compound, with the possible exception of VMPs such 
as pro-drugs as already discussed in section 2.6.  
3.1  Tier A Testing 
3.1.1  Tier A Physical-Chemical Properties Studies 
Table 1 gives the studies recommended in this area in Tier A for all three Branches.  Except where 
noted, all studies should be conducted. 
Page 11 of 37  Contains Non-Binding Recommendation 
 
  Table 1.  Physical-chemical Properties Studies at Tier A 
Study  Guideline  
Water Solubility  OECD 105 
Dissociation Constants in Water  OECD 112 
UV-Visible Absorption Spectrum  OECD 101 
Melting Point/Melting Range  OECD 102 
Vapour Pressure*  OECD 104 
n-Octanol/Water Partition Coefficient **  OECD 107 or 117 
*   Calculation only, though a study is recommended when other physical-chemical properties, e.g. molecular 
weight, melting temperature, thermogravimetric analysis suggest that the vapour pressure may exceed 10-5 Pa at 
20C. 
**  This criterion is not directly applicable to ionisable substances at environmental pH. If appropriate, the 
logKow for such substances should be measured on the non-ionised form at environmentally relevant pHs. 
3.1.2  Tier A Environmental Fate Studies 
Table 2 gives the recommended studies in this area in Tier A for all three branches.  The 
degradation study should only be performed in soil or aquatic systems, depending on whether the 
initial exposure is to the terrestrial or aquatic environment.  The photolysis and hydrolysis studies 
are optional (see comments under sections 4.2.1.2, 5.2.1.2 and 6.2.1.2) for the three branches. 
Table 2. Environmental fate studies at Tier A 
Study  Guideline 
Soil Adsorption/Desorption*  OECD 106 
Soil Biodegradation (route and rate)**  OECD 307 
Degradation in aquatic systems**  OECD 308 
Photolysis (optional)  Seek regulatory guidance*** 
Hydrolysis (optional)  OECD 111 
*Adsorption/desorption studies should report both the K  and K  values for a range of soils. Care should be 
oc d
taken in extrapolating the study results from soil to sediment, especially for substances which are ionized at 
environmentally relevant pHs.  
  **  These studies are recommended only for the terrestrial and aquaculture branches, respectively.  It may be 
appropriate to do the latter studies under saltwater conditions (regulatory guidance should be sought). 
*** Draft OECD test guidelines for both aquatic and soil photolysis are in preparation. 
3.1.3  Tier A Effects Testing 
3.1.3.1  Tier A Aquatic Effects Studies 
Table 3 gives the studies and AFs recommended in Tier A for both direct and indirect aquatic 
exposures.  Testing of three taxonomic levels is recommended.  At least one fish, one aquatic 
invertebrate and one algal species should be tested and the PNEC estimates for all taxonomic levels 
used individually for the RQ calculations.   
Page 12 of 37  Contains Non-Binding Recommendation 
 
VMPs to be used in freshwater should be studied using fresh water species and under freshwater 
conditions.  Those used in saltwater should be studied using saltwater species and under saltwater 
conditions.  Only the freshwater studies should be conducted for VMPs used on terrestrial animals.  
Species used should be characteristic of the environmental conditions (temperature range 
especially) in the region of use. 
Table 3. Aquatic effects studies at Tier A 
Toxicity 
Medium  Studies  endpoint   AF   Guideline 
EC  
Algal growth  50 100  OECD 201 
Freshwater 
inhibition* 
EC  
Daphnia  50 1000  OECD 202 
Freshwater 
immobilization 
Fish acute  LC   1000  OECD 203 
Freshwater  50
toxicity 
Algal growth  EC   100  ISO 10253 
Saltwater  50
inhibition 
Crustacean acute  EC   1000  ISO 14669 
Saltwater  50
toxicity 
Fish acute  LC   1000  Seek regulatory 
Saltwater  50
toxicity  guidance 
*  For substances with anti-microbial activity, some regulatory authorities prefer a blue-green algae rather than a green 
algae species be tested. 
3.1.3.2  Tier A Terrestrial Effects Studies 
Table 4 gives the studies and AFs recommended in Tier A for soil exposures.  These are generally 
only applicable to VMPs used for terrestrial treatments.  All studies should be done and the PNEC 
estimates for all taxonomic levels used individually for the RQ calculations.  For 
endo/ectoparasiticides used in intensively reared animals only, some regulatory authorities may 
seek additional information on the toxicity to non-target arthropods (e.g. Collembola).  
In general, endo/ectoparasiticidal substances are not considered to be toxic for plants and 
microorganisms. Therefore for endo/ectoparasiticides used on pasture animals studies on plants and 
microorganisms are only recommended in case the trigger value given in Phase I is exceeded. 
Table 4. Terrestrial effects studies at Tier A 
Study  Toxicity endpoint   AF  Guideline 
Nitrogen Transformation (28 days)*  < 25% of control  **  OECD 216 
Terrestrial plants   EC   100  OECD 208 
50
Earthworm Subacute/reproduction  NOEC  10  OECD 220 / 
222 
*   Studies should be conducted at 1X and 10X the maximum PEC. 
** An assessment factor is not relevant to this end point  when the difference in rates of nitrate formation between the 
lower treatment (i.e. the maximum PEC) and control is equal to or less than 25% at any sampling time before day 28, the 
Page 13 of 37  Contains Non-Binding Recommendation 
 
VMP can be evaluated as having no long term influence on nitrogen transformation in soils.  If this is not the case, the study 
should be extended to 100 days  at Tier B (see Table 8). 
 
In the specific case of endo/ectoparasiticides used in pasture treatments, the studies listed in Table 5 
are also recommended for dung exposures.  Regulatory guidance should be sought to determine the 
appropriate test guidelines to be used to conduct the toxicity studies for dung fauna. Both dung 
beetle larval and dung fly larval data are recommended to assess the effects on dung fauna of 
endo/ectoparasiticides excreted in dung.  Regulatory guidance should be sought to determine the 
appropriate study guidelines to be used to conduct the effects studies for dung fauna. If sound 
scientific reasons can be advanced, for example evidence of nil absorption for topicals or extensive 
excretion in the urine, then these studies may be waived. 
Table 5. Additional effects studies recommended for endo/ectoparasiticides used 
for pasture treatments at Tier A 
Study  Toxicity endpoint   AF  Guideline 
Dung fly larvae  EC   100  Seek regulatory 
50
guidance* 
Dung beetle larvae  EC   100  Seek regulatory 
50
guidance* 
*  There are currently no internationally accepted guidelines or processed drafts available for these 
studies, but the VICH WG noted the ongoing work in developing standardised studies for dung fly and 
dung beetle larvae and their inclusion into the OECD Test Guidelines Program. 
 
Studies for toxicity to vertebrates (e.g. mammals and birds) are not recommended.  However, there 
may be cases where there is both high toxicity and potential exposure through the food chain and a 
consequent risk.  An example is risk to birds feeding on the backs of animals that have been treated 
with pour-on formulations of endo/ectoparasiticides with potentially high mammalian/avian 
toxicity.  In these cases, the applicant should consider the mammalian and (if available) avian 
toxicity data and seek regulatory guidance as to whether additional data are recommended.   
3.1.4  Risk assessment at Tier A 
The risk assessment approach that is recommended is to compare the PEC  based on the total 
initial
residue with the PNEC derived for each of the tested taxonomic levels as described above.  Where 
the RQ for all taxonomic levels is < 1 it should be sufficient to conclude that the VMP does not 
pose a risk for the environment, unless based on the persistence of the active substance there is a 
potential for it to accumulate in the environment (see section 2.7). Where the RQ is  1 a risk for 
the environment can not be excluded and further assessment is recommended.   
3.1.4.1  PEC refinement 
The first step should be to refine the PEC  based on the total residue at Tier A through 
initial
consideration of the metabolism/excretion information and the data on biodegradation in 
manure/soil/aquatic systems data (see section 2.6 and 2.7).  The PEC  should then be compared 
refined
with the PNEC for the affected taxonomic level and a new RQ determined for each.  If the RQ is 
now <1 for all taxonomic levels, the assessment stops. 
If the RQ is still 1 for any of the taxonomic levels tested, then the VMP moves to Tier B and 
testing for the affected taxonomic level is recommended.  
Page 14 of 37  Contains Non-Binding Recommendation 
 
For pasture treatments if the RQ is 1 for dung insects for the PEC , then the excretion data 
dung-initial
should be examined and the PEC  used to recalculate the RQ.  The PEC  assumes 
dung-refined dung-initial
that all of the dose is excreted in a single days dung.  The PEC  is more realistic as it takes 
dung-refined
account of how many days the active substance is excreted in dung and at what concentrations (see 
Section 6.2.3.3).  If the RQ is still 1, further regulatory guidance should be sought. 
3.2  Criteria for Tier B Testing 
The main criteria for advancing to Tier B is when the RQ is 1 or in the case of soil micro-
organisms an effect > 25%. Effects studies at Tier B are only recommended for affected taxonomic 
levels. There are two other cases relating to bioaccumulation and sediment invertebrate toxicity 
where Tier B testing is recommended. 
The logK  4 is used as a criterion for an assessment of bioaccumulation. This criterion is not 
ow
directly applicable to ionisable substances at environmental pH. If appropriate, the logK  for such 
ow
substances should be measured on the non-ionised form at environmentally relevant pHs. 
If the RQ for aquatic invertebrate is 1 it is recommended to consider the PEC /PNEC
sediment sediment 
ratio. The PNEC  is calculated using equilibrium partitioning. This method uses the 
sediment
PNEC  and the sediment/water partitioning coefficient as input. If the RQ is 1, then 
aquatic invertebrate
testing of sediment organisms is recommended. For substances with a log K  >5, the RQ is 
ow
increased by an extra factor of 10 to take account of possible uptake via ingestion of sediment.  If 
the RQ is >1, then a study, preferably long-term, with benthic organisms using spiked sediment is 
recommended. 
3.3  Tier B Testing 
3.3.1  Tier B Physical-Chemical Properties Studies 
Usually, there are no additional physical-chemical studies recommended in Tier B. 
3.3.2  Tier B Environmental Fate Studies 
If the logK  is 4, evidence from metabolism/residues/excretion, biodegradation studies and 
ow
molecular mass should be considered to see whether there is the potential for bioaccumulation to 
occur.  If so, then the study listed in Table 6 is recommended to be carried out at Tier B. To assess 
the risk for secondary poisoning, the use of a predicted BCF based on QSARs may be considered. If 
in doubt, regulatory guidance should be sought. 
Table 6.  Environmental fate study at Tier B 
Study  Guideline 
Bioconcentration in fish  OECD 305 
If the BCF is >1000, regulatory guidance should be sought. 
3.3.3  Tier B Environmental Effects Studies 
3.3.3.1  Tier B Aquatic effects studies 
The studies in Table 7 are recommended only for those cases where the RQ for the affected 
taxonomic level is 1 following use of the PEC  (see section 3.1.4). 
refined
Page 15 of 37  Contains Non-Binding Recommendation 
 
Table 7.  Aquatic effects studies at Tier B 
Toxicity 
Environment  Study  Endpoint  AF   Guideline 
Freshwater   Algae growth inhibition* NOEC  10  OECD 201 
Freshwater  Daphnia magna  NOEC  10  OECD 211 
reproduction  
Freshwater  Fish, early-life stage**  NOEC  10  OECD 210 
Freshwater  Sediment invertebrate  NOEC  10  OECD 218, 
species toxicity  219*** 
Saltwater   Algae growth inhibition* NOEC  10  ISO 10253 
Saltwater  Crustacean chronic  NOEC  10  Seek regulatory 
toxicity or reproduction  guidance 
Saltwater  Fish chronic toxicity  NOEC  10  Seek regulatory 
guidance  
Saltwater  Sediment invertebrate  NOEC  10   Seek regulatory 
species toxicity  guidance 
*   Using the same study and species as in Tier A but the NOEC is used in Tier B. 
**  Alternative studies for fish: Fish short term toxicity test on embryo and sac-fry stage (OECD TG 212) and Fish 
juvenile growth test (OECD TG 215) are not favoured, noting inter alia that the first page of the former suggests why this 
may not be the first choice guideline and that OECD TG 210 is preferable. 
*** It is suggested that if entry into the environment is through water, OECD TG 219 is used, if exposure is through 
sediment or adsorbed to soil in run-off, OECD TG 218 should be used. 
 
If after the Tier B testing the RQ is >1, regulatory guidance should be sought. 
3.3.3.2 Tier B Terrestrial effects studies 
The studies in Table 8 are recommended only for those cases where the RQ for the affected 
taxonomic levels is 1 or in the case of soil micro-organisms an effect > 25% following use 
of the PEC  (see above). 
refined
 
Page 16 of 37  Contains Non-Binding Recommendation 
 
Table 8.  Terrestrial effects studies at Tier B 
Study  Endpoint  AF  Guideline  
Nitrogen Transformation (100 days  < 25% of  *   OECD 216 
 extension of Tier A study)  control 
Terrestrial plants growth, more  NOEC 
10   OECD 208  
species** 
Earthworm    
  None  
*    An assessment factor is not relevant to this end point - when the difference in rates of nitrate formation between the 
lower treatment (i.e., the maximum PEC) and control is equal to or less than 25% at any sampling time before day 100, 
the VMP can be evaluated as having no long term influence on nitrogen transformation in soils. 
**   The study should be repeated on two additional species from the most sensitive species category in the Tier A study, 
in addition to repeating the study on the most sensitive species. 
If after the Tier B testing the RQ is >1 or in the case of soil micro-organisms an effect > 25%, 
regulatory guidance should be sought. 
For pasture treatments, if the RQ is still 1 for dung fauna from the PEC , no additional 
dung-refined
studies are recommended at Tier B, but regulatory guidance should be sought.  
 
4  AQUACULTURE BRANCH  
4.1  Introduction 
This section of the Phase II guidance deals with the environmental risk assessments for VMPs used 
in aquaculture.  A variety of VMPs are administered to aquatic organisms.  In many cases these are 
added to the organisms food or directly to their water, or they may be injected directly into the 
organism.  
Aquaculture practices may vary widely between the VICH regions, but the generic types of 
aquaculture facilities are: 
  net pens and cages in ocean, coastal and inland areas such as bays, estuaries, fjords, lakes 
and lochs;  
  raceways, ponds or tanks/baths taking from, and returning water to, streams or rivers; 
  raceways, ponds or tanks/baths discharging to a sewage treatment facility; and 
  isolated ponds or tanks with limited discharge to a river or sewage treatment facility. 
The above give an indication of the spectrum of aquaculture facilities, which range from systems 
fully open to essentially closed to the aquatic environment.  However, in the majority of cases there 
will be dilution of treated water/effluent on release into the environment.   
Even with fully open systems during treatment with a VMP the net pen is often raised, e.g. so that 
the fish are contained in 2-3 m depth of water and enclosed in a tarpaulin to achieve the required 
concentration for a specified time period.  At completion of the treatment, the used drug is assumed 
to be equally distributed within the reduced volume of water in the net pen.  Following removal of 
the tarpaulin, the released active substance may initially be distributed evenly within an area of 
water around the facility.  Eventually more widespread distribution in the environment of the active 
Page 17 of 37  Contains Non-Binding Recommendation 
 
substance may occur due to passive diffusion/current movement.  In other cases release may be 
more direct as no impervious barrier will be in place, or the tarpaulin is placed as a skirt around the 
net pen so that the bottom is open. 
For systems that are partially closed to the environment, at the end of the VMP treatment release of 
effluent to the environment will occur together with other untreated water from the aquaculture 
facility.  Again there will initially be dilution in receiving waters for a limited distance, followed by 
more widespread distribution.  In some cases, effluent will pass through a sewage treatment facility, 
where there is the opportunity for the active substance to be removed by adsorption/degradation, 
prior to discharge to surface waters. 
A decision tree/flow diagram is presented in Figure 1 at the end of this section as an overview of the 
risk assessment process for various types of VMPs used in aquaculture.  The diagram provides a 
summary of the text, which is intended as a quick reference to the recommendations.  However, the 
diagram should always be referred to in conjunction with the main text. 
4.2  Tier A 
4.2.1  Data recommended in Tier A 
If a VMP used in aquaculture has failed to meet Phase I criteria, the following is the minimum 
testing data set recommended to be conducted in Tier A. 
4.2.1.1  Physical-chemical properties studies 
Table 1, Section 3.1.1 gives the studies recommended in Tier A.  Except where noted, all studies 
should be conducted. 
4.2.1.2  Environmental fate studies 
Table 2, Section 3.1.2 gives the studies recommended in this area in Tier A.  The degradation study 
should only be performed in aquatic systems.  If initial chemical studies indicate a potential for the 
active substance to photolyse or hydrolyse, then photolysis or hydrolysis studies may be conducted.  
4.2.1.3  Environmental effects studies 
Table 3, Section 3.1.3.1 gives the studies and AFs recommended in Tier A.  At least one species 
should be studied from each of the three taxonomic levels, i.e. fish, invertebrates and algae in the 
relevant medium (fresh or saltwater), and the PNEC to be used for the RQ estimated for each 
taxonomic level.   
4.2.2  Calculation and comparison of PEC  
surfacewater
4.2.2.1  Calculation of PEC (PEC ) 
surfacewater-initial  sw-initial
The initial risk assessment should be conducted for a PEC .   
sw-initial
The calculation should be based on: 
  the total amount of VMP used in the aquaculture system within the consecutive 
administration period for one treatment (see Glossary); 
  the volume of the aquatic environment within a defined distance of the treatment area (e.g. 
net pens), which is determined by the typical facility for the species and the country/region 
where the VMP is to be used; 
Page 18 of 37  Contains Non-Binding Recommendation 
 
  the assumption that the active substance is diluted within the system (the extent of which is 
dependent on the aquaculture practices and the facility and how it is operated), and then 
introduced into the wider environment; 
  for a partially closed system,  the extent of dilution within the fish farm and how much 
further dilution occurs in receiving waters such as running river/stream water when effluent 
is discharged from the fish farm; and 
  for an open system, the extent of dilution is dependent on the shape, width and depth of the 
cultured area and water movement. 
4.2.2.2  Comparison of PNEC and PEC  
sw-initial
At this stage, the PNEC for all taxonomic levels determined during aquatic effects testing should be 
compared with the PEC .  If the RQ is <1 for all taxonomic levels, no further assessment is 
sw-initial
recommended.  However, if the RQ is 1, the PEC  should be refined, using a number of 
sw-initial
mitigations as described in Section 4.2.2.3.   
4.2.2.3  Calculation of PEC   
sw-refined
The PEC  calculations assume that all of the active substance is retained within the facility 
sw-initial
until released, and then is diluted only within a defined distance.  The effect of further dispersal in 
open systems should be considered.  Dispersal may be influenced by external factors such as wind, 
currents, tide and the extent of mixing of water as affected by temperature or salinity.  The effect of 
adsorption onto sediments should be considered.  There may also be a number of discrete 
applications within the one treatment period, which in open systems would be released as a series of 
pulses that will have largely dispersed prior to the next application.  
4.2.3  Calculation and comparison of PEC  
sediment
4.2.3.1  Calculation of PEC   
sediment
If the RQ for the aquatic invertebrate study is still 1 following the calculation of PEC , the 
 sw-refined
PEC should be calculated to compare with the PNEC (see section 3.2) to indicate 
sediment  sediment -
whether an effects study for sediment species is triggered and should be conducted at Tier B.  As for 
PEC , this should initially be carried out at a basic level, and then further refined if 
surfacewater
necessary.  At the basic level PEC , it should be assumed that partitioning processes 
sediment-initial
between sediment and water are complete, and that sediment and water are in equilibrium in the 
aquatic environment.   
4.2.3.2  Calculation of PEC  in cases of VMPs added to feed 
sediment
It is often convenient to administer VMPs in the fish feed, particularly where a treatment has to be 
given for several days in succession.  In such systems, the VMP may remain associated with waste 
feed which usually settles to the sediment under the net pens and for a distance beyond the net pens.  
For such VMPs it is also appropriate to calculate the PEC , using the following parameters: 
sediment
  Percentage administered feed not eaten by fish and subsequently deposited on sediment; 
  Total amount of VMP in fish feed; 
  Percentage of dose excreted in faeces (in absence of data to the contrary assume this is 
100% minus the percentage of uneaten feed); 
  Area of sediment directly beneath the net pen(s) and distance beyond net pen(s) in which 
uneaten feed and faeces are deposited;  
Page 19 of 37  Contains Non-Binding Recommendation 
 
  Depth to which the active substance is distributed in sediment; and 
  Density of sediment. 
Therefore, the concentration of the active substance in the sediment is a function of the amount 
reaching sediment in uneaten feed, the amount reaching sediment in excreted faeces and the 
weight/volume of sediment in which the active substance is distributed. 
4.2.3.3. Comparison of PNEC and PEC
 
Once the PEC  has been calculated, it should be compared with the PNEC as described 
sediment sediment 
in Section 4.2.3.1 to indicate whether an effects study for sediment species is triggered and should 
be conducted at Tier B. 
4.3    Tier B 
4.3.1  Triggers for testing in Tier B 
 
The criteria for further testing at Tier B are given in Section 3.2. 
4.3.2  Data recommended in Tier B 
4.3.2.1  Physical-chemical properties studies 
Usually, there are no additional physical-chemical studies recommended in Tier B. 
4.3.2.2  Environmental fate studies 
As noted in Section 3.3.2, if the logK  is 4, and following the consideration given in that section, 
ow
the bioconcentration study in fish listed in Table 6 is recommended for VMPs used in aquaculture at 
Tier B.   
4.3.2.3  Environmental effects studies 
If the RQ is still 1 for one or more aquatic taxonomic levels, when the PEC  is compared 
sw-refined
with the PNECs calculated for the acute studies conducted in Tier A, chronic testing for that 
particular taxonomic level is recommended as indicated in Table 7 of Section 3.3.3.1. 
If following refinement, the RQ for an aquatic invertebrate in surface water is 1, the 
PEC /PNEC  should be considered.  If RQ is 1, a sediment invertebrate effects 
sediment-refined sediment
study is recommended in Tier B.  
4.3.3  Further assessment 
If there is still an indication of risk on completion of the Tier B assessment, e.g. for VMPs which 
still have an RQ >1 or the BCF  1000, then the applicant is recommended to discuss their dossier 
and proposals for further data or risk mitigation with the regulatory authority. 
Page 20 of 37  Contains Non-Binding Recommendation 
 
  Figure 1. Decision tree/Flow diagram for VMPs used for aquaculture  
 
Physical-Chemical Studies Environmental FateStudies Environmental Effects Studies
-UV/VISabsorptionspectra Freshwater
-Degradationinaquatic systems
-Meltingpoint/Meltingrange -Algaegrowth inhibition
-Photolysis(optional)
-Watersolubility -Daphniaimmobilization
-Hydrolysis(optional)
-K -Fishacutetoxicity
ow -K/K ofsoil
-Dissociationconstant in water d oc Saltwater
-Vapourpressure(calculation) -Algae growth inhibition
-Crustacean acute toxicity
-Fishacutetoxicity
Calculate PEC and compare the PEC with each PNEC, calculate RQsfor all taxonomic levelstested.  
surfacewater-intial
If all RQsare <1 and other criteria are met*, STOP. If not, consider PEC refinement
RefinePEC andrecalculateRQusing PEC .
sw-initial refined
Ifall RQs are now<1 and other criteria are met*,STOP.
Ifnot, do additionaltesting only for the relevant species below.
* RQfrom PEC for  Environmental effect studies * LogKow4, and 
swrefined
aquatic invertebrate1.  following consideration 
Freshwater
Consider given in Section 3.2.2 
-Daphnia magnareproduction 
PECsediment/PNECsediment. -Fish, early-life stage toxicity 
IfRQ 1, do sediment  -Algae growth inhibition 
study. (use NOEC from Tier A study)
Saltwater
-Crustacean chronic toxicity 
Environmental fate studies
-Fish chronic toxicity or reproduction 
-Algae growth inhibition   -Bioconcentrationin fish
(use NOEC from Tier A study)
Environmental effect 
studies
If BCF<1000 STOP
Freshwater/saltwater Ifall RQsisnow<1 STOP.
-Sediment invertebrate  Ifnot, seekregulatory guidancefor furtherstudies If 1000 seek regulatory 
species toxicity  orrisk managementoptions
guidance
Page 21 of 37  Contains Non-Binding Recommendation 
 
5  INTENSIVELY REARED ANIMALS BRANCH 
5.1  Introduction 
This section of the Phase II guidance deals with the risk assessments for VMPs used in intensively 
reared animal systems.   
Intensively reared animal systems consist of areas where animals are kept and raised in confined 
situations, which may include housed animals or animals kept in feedlots.  Producers confine 
animals, feed, manure and urine in a relatively small land area (feed-yard).  Feed is brought to the 
animals rather than the animals only grazing or otherwise seeking feed in pastures, fields, or on 
rangelands.  Waste is usually disposed of off-site by spreading on adjacent fields.  Facilities that 
have feedlots with constructed floors, such as solid concrete or metal slots would be considered 
intensive rearing practices.  If a facility maintains animals in an area without vegetation, including 
dirt lots, the facility would also be considered an intensive animal feeding operation.  Feedlots with 
nominal vegetative growth along the edges while animals are present or during months when 
animals are kept elsewhere are also considered to be intensive rearing operations.  Beef cattle, dairy 
cattle, pigs, chickens, and turkeys are examples of species that may be reared in an intensive 
terrestrial system. 
A decision tree/flow diagram is presented in Figure 2 at the end of this section as an overview of the 
risk assessment process for various types of VMPs used in intensively reared animals.  The diagram 
provides a summary of the text, which is intended as a quick reference to the recommendations.  
However, the diagram should always be referred to in conjunction with the main text. 
5.2  Tier A 
5.2.1  Data recommended in Tier A 
If a VMP used in intensively reared animal systems has failed to meet Phase I criteria, the following 
is the minimum testing data set recommended to be conducted in Tier A. 
5.2.1.1  Physical-chemical properties studies 
Table 1, Section 3.1.1 gives the studies recommended in Tier A.  Except where noted, all studies 
should be conducted. 
5.2.1.2  Environmental fate studies 
Table 2, Section 3.1.2 gives the studies recommended in Tier A.  For VMPs used in intensively 
reared animal systems the biodegradation study should be conducted only in soil.  If initial chemical 
studies indicate a potential for the active substance to photolyse or hydrolyse, then photolysis or 
hydrolysis studies may be conducted. 
5.2.1.3  Environmental effects studies 
Table 3, Section 3.1.3.1 gives the aquatic effects studies and AFs recommended in Tier A.  For 
VMPs administered to intensively reared animals at least one species should be tested from each of 
the three taxonomic levels e.g. fish, invertebrates and algae, and the PNEC is estimated for each 
taxonomic level to be used for the RQ.  
Table 4, Section 3.1.3.2 gives the terrestrial effects studies and AFs recommended in Tier A.  The 
studies provide data on the potential effects to organisms representing three environmental 
Page 22 of 37  Contains Non-Binding Recommendation 
 
taxonomic levels in the terrestrial environment that are expected to be exposed, e.g. invertebrates, 
plants, and micro-organisms.  Again the PNEC estimated for each taxonomic level is to be used for 
the RQ.   
5.2.2  Calculation and comparison of PEC  
soil
PECs of residues introduced to soil as a result of use of VMPs in the intensively reared animal 
systems are usually based on: 
  The total amount of product administered; its dose and frequency of use per animal and 
pattern of use within a flock or herd; 
  Metabolism in the treated animal, together with the pattern of excretion of parent and 
relevant metabolites; 
  The manure output of the animal on a weight basis; 
  Animal husbandry with respect to the number of animal cycles, length of individual animal 
cycles and proportion of year animals are housed; 
  Manure storage times in relation to product usage; and 
  Manure spreading practices in relation to any restrictions on time of spreading, whether 
manure is spread on an area once a year or on several occasions during the year, and legal 
or advisory limits to amounts spread. 
5.2.2.1  Calculation of PEC  
soil-initial 
In Phase II Tier A the PEC  is first calculated and used in the risk assessment.  As noted in 
soil-initial
Section 2.6 this will assume 100% excretion of the administered dose as parent and will have been 
calculated as part of the Phase I assessment.   
PEC  should give consideration under spreading practices to the possibility of repeat 
soil-initial
applications of manure containing a active substance to the same area of land.  As noted in Section 
2.7, this will be of particular concern for persistent compounds, where repeat applications over 
several years could lead to elevated soil concentrations with consequent effects on soil function and 
possibly other environmental impacts.   
5.2.2.2  Comparison of PNEC and PEC  
soil-initial
At Tier A, the PNEC for all the taxonomic levels determined during terrestrial effects testing should 
be compared with the PEC .  If the RQ is <1 for all taxonomic levels tested no further 
soil-initial
assessment is recommended.  However, if the RQ is 1 for one or more taxonomic levels, the worst 
case PEC  should be refined, as described in Section 5.2.2.3, and the RQ recalculated.   
soil-initial
5.2.2.3  Calculation of PEC  
soil-refined
The refinement of PEC  should occur prior to consideration of conducting any testing in Tier B.  
soil
Any refinement should be carried out using appropriate calculations and methods.   
PEC  can be refined by determining the actual composition of the dose excreted by the treated 
soil-initial
animal.  As noted in Section 2.6, where excretion data are available then the active substance and 
relevant metabolites (defined as representing 10% or more of the administered dose and which do 
not form part of biochemical pathways) should be added to allow an estimate of the PEC . 
soil-refined
The PEC may be refined further by several adjustments, including but not limited to the following:   
Page 23 of 37  Contains Non-Binding Recommendation 
 
  accounting for any degradation of the active substance during storage of manure before 
spreading on fields, as appropriate; and 
  by degradation of the parent and relevant metabolites in the field, using the results of the 
laboratory soil degradation study from Tier A.  Time to mineralization, formation of bound 
residue or degradation to substances that are part of biochemical pathways can be used to 
refine the PEC in this case.   
5.2.3  Calculation and comparison of PEC water  
As noted in the introduction to section 3, VMPs administered to intensively reared animals have the 
potential to impact non-target species in surface waters indirectly due to transport in water, 
including when adsorbed to soils.  Therefore, it is appropriate to calculate PECs for both surface 
and groundwater. 
5.2.3.1  Calculation and comparison of PEC  
sw-initial 
PEC  will be calculated from any form of indirect entry into surface water.  PEC  is 
sw-initial sw-initial
calculated from the PEC .   
soil-initial
The factors that affect the likelihood of movement to surface water include the physical and 
chemical properties of the active substance, the amount of rainfall and the proportion that is likely 
to run off, and soil hydrology. 
The PNEC for all tested aquatic taxonomic levels should be determined and compared with the 
PEC .  If the RQ is <1 for all taxonomic levels, no further assessment is recommended.  
sw-initial
However, if the RQ is 1 for one or more taxonomic levels, the PEC  should be refined, using 
sw-initial
a number of mitigations as described in Section 5.2.2.3, and the RQ recalculated. 
5.2.3.2  Calculation of PEC  
groundwater 
The factors important in movement to groundwater include the physical and chemical properties of 
the active substance, the amount of soil organic matter, amount of rain, depth to the aquifer or 
seasonally saturated layer and preferential flow. 
The PEC  should be considered on a regional level for additional testing and/or mitigation 
groundwater
for public health concerns.  Groundwater is a natural resource and should not only be assessed with 
regards to public health but also to possible harmful effects to the biota of groundwater. 
5.3  Tier B 
5.3.1  Triggers for further testing in Tier B 
The criteria for further testing at Tier B are given in Section 3.2.  
5.3.2  Data recommended in Tier B 
5.3.2.1  Physical-chemical properties studies 
Usually, there are no additional physical-chemical studies recommended in Tier B. 
5.3.2.2  Environmental fate studies 
If the logK  is 4, and following the consideration given in Section 3.3.2, the bioconcentration 
ow
study in fish listed in Table 6 is recommended for VMPs at Tier B.   
Page 24 of 37  Contains Non-Binding Recommendation 
 
   
5.3.2.3  Environmental effects studies 
If the RQ is still 1 or in case micro-organisms an effect > 25% for one or more taxonomic levels 
(both aquatic or terrestrial) when the PEC  is compared with the results of the studies 
soil/sw-refined
conducted in Tier A, testing for that particular taxonomic levels should be carried out as indicated in 
Tables 7 and 8 of Section 3.3.3. 
If following refinement, the RQ for an aquatic invertebrate in surface water is 1, the 
PEC /PNEC  should be considered.  If RQ is 1, a sediment invertebrate effects 
sediment-refined sediment
study is recommended in Tier B. For calculation PEC  see section 4.2.3.1.  
sediment
5.3.3  Further assessment  
If there is still an indication of risk on completion of the Tier B assessment, e.g. for VMPs which 
still have an RQ >1 or BCF >1000, then the applicant is recommended to discuss their dossier and 
proposals for further data or risk mitigation with the regulatory authority. 
Page 25 of 37  Contains Non-Binding Recommendation 
 
 
Figure 2. Decision tree/Flow diagram for VMPs used for intensively-reared animal systems 
Physical-Chemical Studies Environmental Fate Studies Environmental Effect Studies
-UV/VIS absorption spectra
-Melting point/Melting range -Biodegradation in soil Terrestrial
-Water solubility -Kd/Kocof soil -Nitrogen transformation*
-K -Photolysis (optional) -Terrestrial plants growth 
-Doiswsociation constant in water -Hydrolysis (optional) -Earthworm subacute/reproduction
-Vapourpressure (calculation)  Aquatic
-Algae growth inhibition 
-Daphniaimmobilization 
-Fish acute toxicity
Calculate the PECs and compare the PECswith each PNEC, calculate RQsfor all taxonomic levels tested.  
intial
If all RQsare <1 and other criteria are met*,STOP.  If not, consider PEC refinement
Refine PEC for compartment(s) of concern and recalculate RQ using PEC .  
initial refined
If all RQsare <1 and other criteria are met*, STOP. 
If not, do additional testing from lists below only for the relevant species below.
* RQ from PEC for  Environmental effect studies * LogKow4, and 
swrefined
aquatic invertebrate 1.  following consideration 
Consider  Terrestrial given in Section 3.2.2
PEC /PNEC -Nitrogen transformation test (100 days)
sediment aqinvert.
If RQ 1, do sediment  -Terrestrial plants growth test (more species)
Aquatic
study
-Daphniareproduction
-Fish early-life stage Environmental fate studies
-Algal growth inhibition 
-Bioconcentrationin fish
(use NOEC of Tier A  test)
Environmental effect 
studies
Freshwater If all RQsis now <1 and other criteria are met STOP.   If BCF<1000 STOP
-Sediment invertebrate  If not, seek regulatory guidance for further studies or 
species toxicity  risk management options If 1000 seek 
regulatory guidance 
Page 26 of 37  Contains Non-Binding Recommendation 
 
6  PASTURE ANIMALS BRANCH 
6.1  Introduction 
This section of the Phase II guidance deals with the environmental risk assessment for VMPs used 
in animals kept at pasture.  
Pasture is defined as land covered with grass or herbage and grazed by or suitable for grazing by 
livestock.  Pasture animals are those livestock reared for part or all of the year on grassland, and 
refers only to the time spent at pasture.  Excretion occurs directly onto the pasture or onto other 
habitats within the grazed area.  This is in contrast to intensive systems such as feedlots where 
manure is collected and later spread onto agricultural or grassland.  At pasture, grazing provides the 
primary source of food for livestock.   
The types of pasture where animals are grazed will vary according to their situation within a region, 
for instance in different parts of the EU, and also between regions, e.g. there will be differences 
between Japan and Australia.  The number of animals that can be maintained on an area of land will 
be limited; and the number of animals/hectare is referred to as the stocking density that will vary 
both within and between regions.  
For animals reared on pasture, there are specific concerns for certain types of products related to 
their direct entry to the aquatic environment.  There are also some specific areas of environmental 
concern relating to endo/ectoparasiticides used in animals at pasture and both of these are described 
in this guidance.   
A decision tree/flow diagram is presented in Figure 3 at the end of this section as an overview of the 
risk assessment process for various types of VMPs used in pasture animals.  The diagram provides a 
summary of the text, which is intended as a quick reference to the recommendations.  However, the 
diagram should always be referred to in conjunction with the main text. 
6.2  Tier A 
6.2.1  Data recommended in Tier A 
If a VMP used on pasture animals has failed to meet Phase I criteria, the following is the minimum 
testing data set recommended to be conducted in Tier A. 
6.2.1.1  Physical-chemical properties studies 
Table 1, Section 3.1.1 gives the studies recommended in Tier A.  Except where noted, all studies 
should be conducted. 
6.2.1.2  Environmental fate studies 
Table 2, Section 3.1.2 gives the studies recommended in this area in Tier A.  For pasture animal 
VMPs the biodegradation study should be conducted only in soil.  If initial chemical studies 
indicate a potential for the active substance to photolyse or hydrolyse, then photolysis or hydrolysis 
studies may be conducted. 
6.2.1.3  Environmental effects studies 
Table 3, Section 3.1.3.1 gives the aquatic effects studies and AFs recommended in Tier A.  For 
VMPs administered to pasture animals at least one species should be tested from each of the three 
Page 27 of 37  Contains Non-Binding Recommendation 
 
taxonomic levels i.e. fish, invertebrates and algae, and the PNEC estimated for each taxonomic 
level is to be used for the RQ calculations.   
Table 4, Section 3.1.3.2 gives the terrestrial effects studies and AFs recommended in Tier A.  The 
studies provide data on the potential effects to organisms representing three environmental 
taxonomic levels in the terrestrial environment that are expected to be exposed, e.g. invertebrates, 
plants, and micro-organisms. However, for endo/ectoparasiticides used on pasture animals studies 
on plants and microorganisms are usually recommended only in the case the trigger value given in 
Phase I is exceeded. If data are available to show a concern for these taxonomic levels the studies 
are recommended. Again the PNEC estimated for each taxonomic level is to be used for the RQ 
calculations.  
Both dung beetle larval and dung fly larval data are recommended to assess the effects on dung 
fauna of endo/ectoparasiticides excreted in dung. Regulatory guidance should be sought on the 
appropriate study guidelines to use to assess toxicity to dung fauna. An earthworm study, listed in 
Table 4, is also recommended in regions where dung is colonised by earthworms. 
6.2.2  Calculation and comparison of PEC   
soil
VMPs may be used on animals that are kept at pasture, rather than being housed or kept in feedlots.  
Consequently, any excretion of the active substance in urine or faeces will occur at pasture, rather 
than being collected, stored and spread onto land as manure. The proportion of the year livestock 
spend on pasture, in relation to the timing of treatment, is an important consideration when 
calculating the range of PEC values. 
6.2.2.1  Calculation of PEC  
soil-initial 
At Tier A, an initial calculation of PEC  is recommended for all VMPs used in pasture 
soil-initial
animals, including topical products that are absorbed and excreted.  Even though a later calculation 
will be done for PEC , at this stage the worst case calculation of PEC  should take 
dung-initial soil-initial
account of active substance excreted in both faeces and urine.  While in general, there will be 
excretion data available to determine the percentage of the administered dose of VMP excreted, and 
the relative contribution of parent and metabolites, initially it should be assumed that 100% of the 
administered dose is excreted onto pasture.  
The PEC  is based on: 
soil-initial
  100% excretion of the administered dose;  
  an assumption regarding depth of soil to which residue is distributed;  
  livestock stocking density; and 
  an even distribution of the active substance across the field. 
6.2.2.2  Comparison of PNEC with PEC  
soil-initial
At this stage, the PNECs for all taxonomic levels determined from terrestrial effects testing should 
be compared with the PEC .  If the RQ is <1 for all taxonomic levels tested no further 
soil-initial
assessment is recommended.  However, if the RQ is 1, the PEC  should be refined, using a 
soil-initial
number of mitigations as described in Section 6.2.2.3, and the RQ recalculated.   
6.2.2.3  Calculation of PEC  
soil-refined
The refinement of PEC  should occur prior to consideration of conducting any testing in Tier B.  
soil
Any refinement should be carried out using appropriate calculations and methods.  Further 
Page 28 of 37  Contains Non-Binding Recommendation 
 
refinement of PEC  can be done as described in Section 5.2.2.3 of the Intensively Reared Animals 
soil
Branch. 
6.2.3  Calculation and comparison of PEC   
dung
6.2.3.1  Calculation of PEC  
dung-initial
Some VMPs are excreted predominantly in the dung rather than in urine.  Where such VMPs 
remain associated with the dung they are unlikely to be distributed in the soil initially, though there 
may be subsequent incorporation into soil by dung/soil fauna or by leaching. 
For active substances excreted predominantly in dung, the PEC  should be estimated.  This is 
dung-initial
the maximum concentration of the active substance in dung, and initially it should be assumed that 
there are no excretion data of the active substance in dung.  Therefore, the PEC  should be 
dung-initial
calculated assuming that 100% of the dose is excreted in dung on a single day.  
This is relevant in particular to endoparasiticides and ectoparasiticides that will be excreted at 
pasture following oral, parenteral or topical administration.  For these products, the PEC  
soil-initial
should also be estimated.  However, there is also a need to estimate the concentration in dung as 
these products have the potential to affect dung fauna. 
6.2.3.2  Comparison of PNEC with PEC  
dung-initial
At this stage, the PNECs derived for dung fly, dung beetles and if applicable for earthworms should 
be compared with the PEC .  If the RQ is <1 for all taxonomic levels tested no further 
dung-initial
assessment is recommended.  However, if the RQ is 1, the PEC  should be refined, as 
dung-initial
described in Section 6.2.3.3, and the RQ recalculated.   
6.2.3.3  Calculation of PEC   
dung-refined
In Tier B, the concentration in dung, PEC , is not expressed as a single value.  Excretion studies 
dung
may be used to produce more realistic estimates of the PEC .  Data should be obtained on the 
dung
concentrations of active substance in fresh dung excreted by treated animals.  Dung concentrations 
should be measured by an appropriate method and for a period adequate to determine the 
concentrations of ecotoxicological significance. 
The maximum PEC in dung excreted at each time point is compared to the PNEC for dung fauna.  
An assessment can then be made of the time period after treatment during which dung is toxic to 
dung fauna. 
6.2.4  Calculation and comparison of PEC water  
6.2.4.1  Surface water and groundwater  
VMPs administered to pasture animals have the potential to impact non-target species in surface 
waters indirectly due to transport in water, including when adsorbed to soils.  Therefore it is 
appropriate to calculate PECs for both surface and groundwater (see Section 5.2.3 of this guidance). 
However, the PEC  should be considered at a regional level.  
groundwater
In addition there are other routes of exposure to the aquatic environment that are specific to animals 
reared at pasture.  These are described in Section 6.2.4.2 and should also be referred to. 
6.2.4.2  Aquatic Exposure Scenarios 
There are a number of ways that contamination of the aquatic environment may occur and more 
than one of the scenarios below may be relevant to an individual product.  Therefore it may be 
Page 29 of 37  Contains Non-Binding Recommendation 
 
appropriate to add the PEC values from the different routes of exposure to arrive at a PEC .  
total
Alternatively the different routes of exposure may mean that contamination of surface water occurs 
over a longer period of time.  These factors should be considered when estimating the PEC .   
sw-initial
An initial risk assessment can be conducted at Tier A using the PEC  based on the 
sw-initial
concentration estimated in the scenarios below. 
6.2.4.2.1  Direct excretion of active substance into surface waters from pasture animals 
This is relevant in pasture situations where livestock have direct access to surface waters as a source 
of drinking water.  In addition, it is only relevant to those livestock species, e.g. cattle, that spend 
time standing in the water.   
6.2.4.2.2  Contamination of hard-standing areas during application of topical 
ectoparasiticides, leading to indirect exposure of the aquatic environment 
through run-off from these surfaces following rainfall 
This exposure scenario applies in situations where animals are gathered together in a specific area 
of the farm for application of topical ectoparasiticides.  This may be an area of pasture, an area of 
bare ground, or an area of concrete.  Such areas will become contaminated with VMPs as a result of 
mixing concentrate, splashing during administration, or from excess liquid draining from animals.  
During subsequent rainfall events there is potential for surface run-off of the active substance from 
this area to surrounding soil and nearby surface waters. 
6.2.4.2.3  Entry of animals treated with high volume ectoparasiticides into surface waters 
leading to direct exposure of the aquatic environment 
Animals treated with high volume VMPs include those that have been dipped, jetted or showered.  
After a period of time to allow excess liquid to drain off, treated animals will be returned to pasture.  
If they enter surface waters before the active substance has dried and adsorbed onto the greasy part 
of the fleece or hide, it will be readily lost into surface waters where the treated part of the body 
comes into direct contact with water.  This will generally involve shallow surface waters and it may 
only be the legs, and possibly also the underbelly, that come into contact with water.  
In general, animals that have been treated with a pour-on product (i.e., low volume) will not 
contaminate surface waters in this way, due to the low volumes used and the area of the animal to 
which the product is applied.   
6.2.4.2.4  Use and disposal of sheep dip 
Disposal of dilute dip to vegetated areas will lead to exposure of the soil and associated vegetation, 
as well as groundwater.  High volume disposal of ectoparasiticides to land represents a potential 
impact in the environment and risk management may be important1 to prevent this impact.  Where 
this practice is allowed, data should enable an assessment of the risk to the environment to be 
performed, as part of the authorization process for these VMPs.  These situations should be 
addressed by the applicant in consultation with the appropriate regulatory authority on a case-by-
case basis. 
                                                 
1 This guidance document, developed under the VICH process, has been revised to conform to FDAs good guidance 
practices regulation (21 CFR 10.115).   
 
Page 30 of 37  Contains Non-Binding Recommendation 
 
6.2.4.2.5  Sheep wool processing effluent 
This issue is a concern for certain regions, but not for all regions that are party to VICH.  Therefore, 
this issue will not form part of this guidance document.  Applicants should approach the relevant 
regulatory authority for guidance. 
6.2.4.3  Comparison of PNEC with PEC  
sw-initial
The PNECs for all the taxonomic levels determined during the aquatic effects testing should be 
compared with the PEC .  If the RQ is <1 no further assessment is recommended.  However, if 
sw-initial
the RQ is 1, the PEC  should be refined, as described in Section 6.2.4.4, and the RQ 
sw-initial
recalculated. 
6.2.4.4  Calculation of PEC  
sw-initial-refined
For PEC  it would be more realistic to assume that there is dilution and dispersion following 
sw-initial
entry into surface waters and there is the option to revise the PEC  in this way if the RQ are 
sw-refined
>1 for any aquatic taxonomic level.  This should take account of the volume of the receiving water 
and the water flow-rate to estimate the extent of dispersion and dilution.  The resulting PEC  
sw-refined
will be lower, due to degradation, dilution, adsorption and dispersion, but will cover a larger area.  
Estimates should be made of the area affected and the resulting concentration.  These estimates will 
tend to be region specific and advice may be sought from the regulatory authority.  However, they 
are only empirical models at this stage, based on simple estimates, which can be refined later if 
necessary.   
6.3  Tier B 
6.3.1  Triggers for further testing in Tier B 
The criteria for further testing at Tier B are given in Section 3.2. 
6.3.2  Data recommended for Tier B 
6.3.2.1  Physical-chemical properties studies 
Usually, there are no additional physical-chemical studies recommended in Tier B. 
6.3.2.2  Environmental fate studies 
If the logK  is 4, and following the consideration given in Section 3.3.2, the bioconcentration 
ow
study in fish listed in Table 6 is recommended for VMPs at Tier B.   
6.3.2.3  Environmental effects studies 
If following refinement of the PECs the RQ is still 1 for one or more taxonomic levels (both 
aquatic or standard terrestrial) when the PEC  is compared with the PNEC derived from 
soil/sw-refined
Tier A or in case of micro-organisms an effect > 25%, additional testing for the particular 
taxonomic levels should be carried out as indicated in Tables 7 and 8 of Section 3.3.3. 
For the studies on dung fauna, if the RQs at Tier B, i.e. comparison of PEC and PNEC, are 
dung-refined 
still 1 for one or more taxonomic levels, then further testing should be conducted to determine the 
risk.  Regulatory guidance should be sought on appropriate studies.   
Page 31 of 37  Contains Non-Binding Recommendation 
 
If following refinement, the RQ for an aquatic invertebrate in surface water is 1, the 
PEC /PNEC  should be considered.  If RQ is 1, a sediment invertebrate effects 
sediment-refined sediment
study is recommended in Tier B. For calculation PEC  see section 4.2.3.1.  
sediment
6.3.3  Further assessment 
If there is still an indication of risk on completion of the Tier B assessment, e.g. for VMPs which 
still have an RQ >1 or BCF  1000, then the applicant is recommended to discuss their dossier and 
proposals for further data or risk mitigation with the regulatory authority. 
 
Page 32 of 37  Contains Non-Binding Recommendation 
 
  Figure 3. Decision tree/Flow diagram for VMPs used for pasture animals 
Physical-Chemical Studies Environmental Fate Studies Environmental Effect Studies
-UV/VIS absorption spectra
-Melting point/Melting range -Biodegradation in soil Terrestrial
-Water solubility -Kd/Kocof soil -Nitrogen transformation* 
-K -Photolysis (optional) -Terrestrial plants growth 
-Doiswsociation constant in water -Hydrolysis (optional) -Earthworm subacute/reproduction
-Vapourpressure (calculation)
Aquatic 
-Algae growth inhibition 
Dung fly and beetle tests -for 
endo/ectoparasiticidesonly -Daphniaimmobilization 
-Fish acute toxicity
Calculate PECs and compare the PECswith each PNEC, calculate RQsfor all taxonomic levels tested.  
intial
If all RQsare <1 and all other criteria are met*, STOP. If not, consider PEC refinement
If RQ 1 for one or more taxonomic levels , refine PEC for compartment(s) of concern and 
initial
recalculate RQ using PEC .  If all RQsare now <1 and all other are criteria met*, STOP.
refined
If not, do additional testing from lists below only for the relevant species.  
For effects on dung insects seek regulatory guidance.
* RQ from PEC for  Environmental effect studies * LogKow4, and 
swrefined
aquatic invertebrate 1.  following consideration 
Consider: Terrestrial given in Section 3.2.2
PEC /PNEC -Nitrogen transformation test (100 days)
sediment sediment.
If RQ 1, do sediment test -Terrestrial plants growth test (more species)
Aquatic
-Daphniareproduction
Environmental fate studies
-Fish early-life stage
-Bioconcentrationin fish
-Algal growth inhibition 
(use NOEC of Tier A  test)
Environmental effect 
studies
Freshwater If all RQsare <1and other criteria are met  STOP.   If BCF<1000 STOP
-Sediment invertebrate  If not, seek regulatory guidance for further studies 
species toxicity or risk management options If 1000 seek regulatory 
guidance 
Page 33 of 37  Contains Non-Binding Recommendation 
 
7  GLOSSARY (DEFINITIONS OF TERMS) 
 
Active substance  =   parent and/or its metabolites 
ADME    =  Absorption, Distribution, Metabolism, Excretion 
BCF    =  Bioconcentration Factor 
DT =  Time to degradation of 90% of original concentration of the compound in  
90   
    the tested soils.
 
EC =  The concentration of a test substance which results in 50% of the test  
50   
    animals being adversely affected, i.e., both mortality and sub-lethal effects. 
K =  Sorption/desorption coefficient 
d    
K =  Sorption/desorption coefficient, normalized to organic carbon content 
oc    
K =  n-Octanol/water partitioning coefficient 
ow    
=  The concentration of a test substance which results in a 50% mortality of  
LC50   
    the test species. 
NOEC    =  No-observed effect concentration, i.e., the test concentration at which no  
    adverse effect occurs. 
OECD    =  Organization for Economic Co-operation and Development 
One treatment    =  is considered to be administration of the VMP in accordance with the  
    proposed marketing authorisation/registration, taking into account  
    indication, amount administered and method of administration. A treatment  
    can consist of multiple applications (e.g. once a day for seven consecutive  
    days). 
QSAR    =  Quantitative Structure Activity Relationship 
 
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8  OECD/ISO TEST GUIDELINES FOR RECOMMENDED STUDIES  
 
OECD Guidelines for the Testing of Chemicals  
(http://www.oecd.org/en/home/0,,en-home-524-nodirectorate-no-no-no-8,00.html) 
 
Section 1  OECD Physical-Chemical Properties 
ADOPTED TEST GUIDELINES 
TG No.  Title 
101  UV-VIS Absorption Spectra (Original Guideline, adopted 12th May 1981)  
102  Melting Point/Melting Range (Updated Guideline, adopted 27th July 1995)  
104  Vapour Pressure (Updated Guideline, adopted 27th July 1995)  
105  Water Solubility (Updated Guideline, adopted 27th July 1995)  
106  Adsorption/Desorption Using a Batch Equilibrium Method (Updated Guideline, 
adopted 21st January 2000)  
107  Partition Coefficient (n-octanol/water): Shake Flask Method (Updated Guideline, 
adopted 27th July 1995)  
111  Hydrolysis as a Function of pH (Original Guideline, adopted 12th May 1981)  
112  Dissociation Constants in Water (Original Guideline, adopted 12th May 1981)  
117  Partition Coefficient (n-octanol/water), HPLC Method (updated Guideline, adopted 1st 
February 2004)  
 
Page 35 of 37  Contains Non-Binding Recommendation 
 
 
Section 2  OECD Effects on Biotic Systems 
ADOPTED TEST GUIDELINES 
TG No.  Title 
201  Alga, Growth Inhibition Test (Updated Guideline, adopted 7 June 1984)  
202  Daphnia sp. Acute Immobilisation Test and Reproduction Test (updated Guideline, 
adopted 1st February 2004) 
203  Fish, Acute Toxicity Test (Updated Guideline, adopted 17th July 1992)  
208  Terrestrial Plants, Growth Test (Original Guideline, adopted 4th April 1984)  
210  Fish, Early-Life Stage Toxicity Test (Original Guideline, adopted 17th July 1992)  
211  Daphnia magna Reproduction Test (Original Guideline, adopted 21st September 
1998)  
216  Soil Microorganisms, Nitrogen Transformation Test (Original Guideline, adopted 21st 
January 2000)  
218  Sediment Water Chironomid Toxicity Test Using Spiked Sediment (Original 
Guideline, adopted 1st February 2004) 
219  Sediment Water Chironomid Toxicity Test Using Spiked Water (Original Guideline, 
adopted 1st February 2004) 
220  Enchytraeidae Reproduction Test (Original Guideline, adopted 1st February 2004) 
222  Earthworm Reproduction Test (Eisenia fetida/Eisenia Andrei) (Original Guideline, 
adopted 1st February 2004) 
 
 
Section 3  OECD Degradation and Accumulation 
ADOPTED TEST GUIDELINES 
TG No.  Title 
305  Bioconcentration: Flow-through Fish Test (Updated Guideline, adopted 14th June 
1996)  
307  Aerobic and Anaerobic Transformation in Soil (Original Guideline, adopted 24 April 
2002) 
308  Aerobic and Anaerobic Transformation in Aquatic Sediment Systems (Original 
Guideline, adopted 24 April 2002) 
 
 
Page 36 of 37  Contains Non-Binding Recommendation 
 
Section 4  ISO Guidelines   
ADOPTED TEST GUIDELINES 
ISO No. Title 
10253  Marine algae growth inhibition test with Skeletonema costatum and Phaeodactylum 
tricornutum 
14669  Determination of acute lethal toxicity to marine copepods (Copepoda, Crustacea) 
 
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