Title: Draft Guidance for Environmental Risk Assessment for Veterinary Medicinal Products: Aquatic Exposure
1Draft Guidance for Environmental Risk Assessment
for Veterinary Medicinal Products Aquatic
Exposures
- Joint Subcommittee on Aquaculture
- Quality Assurance Working Group
- Washington, DC
- December 3, 2003
- Charles E. Eirkson III, HFV-103,
- 301-827-8561
- ceirkson_at_cvm.fda.gov
2National Environmental Policy Act (NEPA)
- Categorical Exclusion
- Environmental Assessment
- Environmental Impact Statement
3- Existing Environmental Guidance
- 21 CFR Part 25 - FDA Environmental Considerations
- FDA Approval of New Animal Drugs for Minor Uses
and for Minor Species - CVM Number 61 - Environmental Impact Assessments (EIA'S) for
Veterinary Medicinal Products (VMP'S)- PHASE I - - CVM Guidance Number 89
- Organization for Economic Cooperation and
Development (OECD) Guidelines for the Testing of
Chemicals
4Guidance for Industry FDA Approval of New
Animal Drugsfor Minor Uses and for Minor
SpeciesNumber 614/99
- ENVIRONMENTAL CONSIDERATIONS general and
regulatory - the content and format of an EA for veterinary
drugs - Guidance for performing an environmental risk
analysis - format
5Content and format of an EA for veterinary drugs
- date, name, and address of the applicant
- description of the proposed use (including
disposal) - ID of the substances that are subject of the use
- description of the ecosystem at the site of
introduction - analysis section (analysis of the fate and
effects) - risk characterization based upon the exposures
and the hazards - description of any alternatives (including
mitigations) - preparers names
- signature block of responsible individual
- references
- Appendices
6Critical portions of the EA are 4, 5, 6, and 7.
- 4) description of the ecosystem at the site of
introduction (including a conceptual model with
assessment endpoints of the potential impacts at
exposed sites in the environment) - 5) analysis section (analysis of the fate and
effects) - 6) risk characterization based upon the
exposures and the hazards (derived from the
conceptual model and analysis of the fate and
effects information) - 7) description of any alternatives (including
mitigations)
7Data sources literature and laboratory
- Laboratory studies - GLP
-
- Literature 3 independent peer review sources
with similar endpoint results
8Guidance for environmental risk analysis includes
- Baker, J.L., et al., editors. 1994. Aquatic
Dialogue Group Pesticide Risk Assessment and
Mitigation. SETAC Press, Pensacola, FL. - 2. Cockerham, Lorris and Shane, Barbara, editors.
1994. Basic Environmental Toxicology. CRC, Boca
Raton, FL. - 3. Environmental Protection Agency. Proposed
Guidelines for Ecological Risk Assessment. the
FEDERAL REGISTER of September 9, 1996 (61 FR
47552). - 4. Suter, G.W. 1993. Ecological Risk Assessment.
Lewis Publishers, Boca Raton, FL.
9- Guidance for Industry
- ENVIRONMENTAL IMPACT
- ASSESSMENTS (EIA'S)
- FOR VETERINARY MEDICINAL PRODUCTS (VMP'S)-
- PHASE I
- VICH GL6
- Final Guidance
- March 7, 2001
10Phase I
- Risk screen based on environmental exposures
- VMP's with limited use and limited environmental
exposure management methods - Phase I also identifies VMP's that may need a
more extensive EIA under Phase II - identifies VMP's that need additional
environmental information to address particular
concerns - Provides a default concentration of 1 ppb for
requiring additional data in Phase II for aquatic
exposures - Follows our categorical exclusions in 21 CFR Part
25.33 (http//www.access.gpo.gov/cgi-bin/cfrassemb
le.cgi?title200221)
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13VICHENVIRONMENTAL IMPACT ASSESSMENTS (EIAs) FOR
VETERINARY MEDICINAL PRODUCTS (VMPs) - PHASE II
DRAFT GUIDANCE
14Phase II
- Specific studies
- Tier A
- Tier B
- Decision-making criteria within and between
tiers -
- Risk Quotient Method
-
- Predicted Environmental Concentration (PEC)
-
- Predicted No Effect Concentration (PNEC)
- Assessment (safety) factors (AF)
- Still a risk screen that includes exposure and
effects
15Ecological and Assessment Endpoint
- Exposures generally in
- Water
- Soil / Sediment
- Exposure to and concern for
- Invertebrates
- Plants
- Vertebrates
- Microbial functioning
16Tier A Physical-chemical Tests
- Test Guideline
- Water Solubility OECD 105
- Dissociation Constant OECD 112
- UV-Visible Spectrum OECD 101
- Melting Temperature OECD 102
- Vapour Pressure (calc only) OECD 104
- n-Octanol/Water Partition OECD 107/117
17Tier A Environmental Fate Studies
- Test Guideline
- Adsorption/Desorption OECD 106
- (soil and/or sediment)
- Soil Biodegradation OECD 307
- Aquatic Degradation in OECD 308
- Photolysis (optional) Seek guidance
- Hydrolysis (optional) OECD 111
18Tier A Aquatic Effects Studies
- Tests Endpoint AF Guidelines
- Freshwater
- Algal growth EC50 100 OECD 201
- Daphnia EC50 1000 OECD 202
- Fish acute LC50 1000 OECD 203
- Seawater
- Algal growth EC50 100 ISO 10253
- Crustacean acute EC50 1000 ISO 14669
- Fish acute LC50 1000 Seek guidance
19Risk Quotient (RQ) Approach
- PEC/PNEC ratio
- where
- PEC predicted environmental concentrations
- PNEC predicted no-effect on non-target
organisms - PNEC is derived from the toxicity endpoint
divided by the AF - Assessment Factors (AF) - numerical factor that
is applied to the endpoint value of an effects
study to derive a predicted no-effect
concentration (PNEC)
20Application Factor
- Follow standard toxicology factor setting
- Inter/intra species 10
- Laboratory to field 10
- Acute to chronic 10
- Results in AF ranging from 1 to 1000
21PEC Refinement at Tier B
- metabolism/excretion information
- biodegradation in soil/aquatic systems
- use of regional values for the parameters in the
PEC estimation equations
22Criteria to go to Tier B testing
- Triggers Testing
- RQ ?1 Chronic toxicity for affected species
- logKow ? 4 Bioconcentration test in fish
- If RQ for aquatic invertebrate?1 then do
PECsediment/PNECaquatic invertebrate - If RQ?1, then toxicity test in sediment species
in Tier B - (if log Kow ?5, then the AF for aquatic
invertebrate is increased by 10)
23Tier B Testing
- No additional physical-chemical tests
24Tier B Aquatic Effects Studies
- Tests Endpoint AF Guidelines
- Freshwater
- Algae growth inhibition NOEC 10 OECD 201
- Daphnia magna reproduction NOEC 10 OECD 211
- Fish, early-life stage NOEC 10 OECD 210
- Sediment Invertebrate EC50 10 OECD 218,
219 - Seawater
- Algae growth inhibition NOEC 10 ISO 10253
- Crustacean chronic NOEC 10 Seek guide
- Fish chronic NOEC 10 Seek guide
- Sediment Invertebrate EC50 10 Seek guide
25PEC Surface Water (SW-initial)
- total amount of VMP used in within the
consecutive administration period for one
treatment - volume of the aquatic environment within a
defined distance of the treatment area which is
determined regionally - assumption that the VMP is diluted within the
system (dependent on practices), and then
introduced into the wider environment - for a partially closed system, depends on
dilution within the facility and upon release as
determined regionally and - for an open system, the extent of dilution is
dependent on the shape, width and depth of the
cultured area and water movement.
26PECsediment
- PECsediment
- PECsurfacewater X Kd
- Where
- PECsurfacewater is in (mg/L)
- Kd soil-water partitioning coefficient
- consider uneaten feed
27PEC calculations regional variables
- Surface water
- facility size and operation
- size of mixing zone
- shape, width and depth of the cultured area
-
- number of pens treated
- water movement