# Presentation: 005744

## Overview of Carbofuran Ecological Risk Assessment 

- Edward Odenkirchen, Ph.D.
- Environmental Fate and Effects Division
- Office of Pesticide Programs
- U.S. Environmental Protection Agency
- February 6, 2008

## Overview of Ecological Risk Presentations

**Overview of carbofuran ecological risk assessment****  **
- Overall conclusions regarding the Agency’s assessment of avian risks associated with carbofuran use
**Overview of field data and incident reports (Dr. Melissa Panger)**
- Conclusions that can reasonably be drawn from available incident reports
- Conclusions that can reasonably be drawn from the results from field and monitoring studies
**Avian probabilistic risk assessment (Dr. Christopher Salice)**
- Impact of PRA model version used in the assessment
- Impact of new data and model provided recently by FMC

**Notes:**
The next three presentations provide an overview of EPA’s ecological risk assessment and the impact of new data or tools provided to EPA throughout the past year on EPA ecological risk conclusions

.....

## Timeline of Risk Assessment Development

- The assessment of risks to terrestrial and aquatic biota has undergone multiple internal and external peer review steps
- Preliminary eco risk assessment: June – August 2005
- Internal branch review
- Internal division review
- External error correction
- Revised combined risk assessment: March – May 2006
- Public Comment
- Interim RED: August – Nov. 2006
- Public comment

## Objective of the Risk Assessment

- To estimate the risk to non-target organisms associated with the current registered uses of carbofuran
- Non-target taxa assessed include
- Freshwater and estuarine/marine vertebrates, invertebrates
- Terrestrial vertebrates

## Consistency with Ecological Risk Assessment Guidelines and Peer Reviewed Methods

- Hazard Evaluation Division, Standard Evaluation Procedure. Ecological Risk Assessment EPA-540.9-85-001 June 1986
- Guidelines for Ecological Risk Assessment.  Risk Assessment Forum.  Washington DC EPA/630/R-95/002F
- Progress Report for Advancing Ecological Assessment Methods in OPP: Overview Document.  Submitted to the FIFRA Scientific Advisory Panel, April 5-7, 2000: Implementing Probabilistic Ecological Assessments
- Technical Progress Report of the Implementation Plan for Probabilistic Ecological Assessments- Aquatic Systems.  Submitted to the FIFRA Scientific Advisory Panel, April 5-7, 2000: Implementing Probabilistic Ecological Assessments
- Technical Progress Report of the Implementation Plan for Probabilistic Ecological Assessments- Terrestrial Systems.  Submitted to the FIFRA Scientific Advisory Panel, April 5-7, 2000: Implementing Probabilistic Ecological Assessments

## Problem Formulation:Stressor Source

- Carbofuran-
- N-methyl carbamate insecticide/nematicide
- Cholinesterase inhibiting mode of action
- Potential reversibility of this inhibition if dose is not fatal*

***issue discussed further today**

## Problem Formulation:Use Characterization

- The Risk Assessment considered
- 26 agricultural uses
- 5 non-agricultural uses
- Flowable formulations
- Aerial and ground applications:
- Foliar
- Broadcast
- Banded
- In-furrow
- Drip irrigation

## Problem Formulation:Use Characterization

- The Risk Assessment considered
- Application rates ranging from lowest to maximum labeled rates
- Uses were usually grouped under common categories of agro-practices, application methods, and rates and surrogate uses selected

## Problem Formulation:Exposure Pathways

- Aquatic organisms:  exposure to residues of carbofuran in the water column
- Surface runoff
- Erosion
- Spray drift
- Terrestrial organisms: exposure to residues in food items and drinking water
- direct deposition of spray and spray drift,
- surface runoff and erosion

## Problem Formulation:Assessment Endpoints

- Non-target organism assessment endpoints are established at the individual organism level:
- Survival
- Growth
- Reproduction

## Problem Formulation:Measures of Effect RQ Process

- Avian effects measures:
- Bird acute oral LD50
- Bird 21-week reproduction dietary NOAEL
- Mammalian effect measures:
- Mouse acute oral LD50
- Rat 3-generation reproduction dietary NOAEL
- Freshwater and estuarine/marine vertebrate
- Fish 96-hour LC50
- Fish chronic early life stage or full life cycle NOAEC
- Freshwater and estuarine/marine invertebrate
- Invertebrate 48-hour LC50 or EC50
- Invertebrate chronic life cycle NOAEC

## Problem Formulation:Risk Hypotheses

- Terrestrial and aquatic vertebrates and invertebrates are subject to adverse effects (i.e. reduced survival or reproduction) when exposed to carbofuran residues following application of pesticide at labeled use rates

## Problem Formulation:Analysis Plan

- Three Lines of Evidence
- Deterministic Screening Assessment for both terrestrial and aquatic organisms
- Uses Risk Quotient Model (Exposure/Effects)
- Refined Risk Assessments for acute avian risks and aquatic animal risks
- Use probabilistic techniques
- Field studies, incident reports and field monitoring programs

## Risk to Aquatic OrganismsDeterministic Assessment

- Focus of assessment—exposure in water compartment
- Surface water scenarios modeled—small vulnerable aquatic surface waters
- PRZM/EXAM Model
- Not all labeled uses were modeled directly
- Grouped uses and a single label use selected to represent the group (surrogate approach)

## Risk to Aquatic OrganismsDeterministic Results

- Freshwater Fish and  Invertebrates
- Acute and chronic risks to freshwater fish not an issue for most uses (except corn and sorghum)
- All uses exceed acute and chronic levels of concern for invertebrates (acute RQs 1.6-16; chronic RQs 6.0-36) except
- drip irrigation use on grapes
- lowest foliar rate on alfalfa
- small grains, soybeans, and sunflowers

## Risk to Aquatic OrganismsDeterministic Results

- Estuarine/Marine Fish and Invertebrates
- All uses had acute and chronic concerns for fish except:
- grapes,
- lowest foliar rate on potatoes and alfalfa
- small grains, soybeans, and sunflowers
- All uses exceed acute restricted and chronic LOCs for invertebrates

## Risk to Aquatic Organisms— Probabilistic Results

- Freshwater Fish and  Invertebrates
- Supported deterministic screening that acute risk is unlikely concern for fish
- Chronic risk concerns for the highest foliar application rates to corn and sorghum (warm water fish species-NOEC exceeded in over 60% of application years)
- Use on potatoes would infrequently exceed chronic NOEC for fish
- Supported deterministic screening for both acute and chronic adverse effects for invertebrates
- All modeled uses frequently resulted in at least 5% of exposed freshwater invertebrate species > 80% mortality; 25% of freshwater species were estimated to have > 28% mortality
- Reproduction effect levels, were exceeded for nearly all uses in all application years or highly frequently (>43% of years).

## Risk to Aquatic Organisms— Probabilistic Results

- Estuarine/Marine Fish and Invertebrates
- Mortality events for fish are of low magnitude and frequency (except for corn and sorghum uses)
- Corn and sorghum on average result > 18% mortality
- Potential for frequent disruptions in the function and quality of vulnerable estuarine/marine sites
- corn and sorghum highest use rates frequently resulted in close to 100% mortality
- coastal potatoes (Section 3 label) and broadcast applications on grapes frequently resulted in _>_67% mortality
- in-furrow application on cotton at plant and soil incorporated applications for tobacco result in _>_53% and _>_23% mortality, respectively (> 50% of modeled daily exposures were a problem)

## Deterministic Risk Approach for Terrestrial Vertebrates

- Emphasis on dietary route of exposure
- Point estimates of peak residue concentrations in avian and mammalian food items (Fletcher et al. nomogram)
- Upper bound estimates of exposure (EEC)
- Uses most sensitive tested animal endpoints of effects
- Avian acute LD50 (0.238 mg/kg-bw)
- Avian 21-wk reproduction LOAEC (2 mg/kg-diet, NOAEC not available)
- Mouse LD50 (2 mg/kg-bw)
- Rat 3-generation reproduction NOAEC (20 mg/kg-diet)
- Risk Quotient calculation EEC/endpoint
- Levels of Concern comparison
- acute lethal risk concern RQ_>_0.5
- reproduction risk concern RQ_>_1

## Deterministic Risk Approach for Terrestrial Vertebrates

- Crops assessed: alfalfa corn, cotton, grapes, potatoes, small grains, sorghum, soybeans, sugarcane, sunflowers and tobacco
- representative uses by application method and rate (model sensitive to these)
- Application rates range:0.125 lb ai/acre to 2 lb ai /acre (tobacco 6 lb ai/acre)

## Deterministic Risk Results for Mammals

- Mammalian RQ results
- Acute
- Herbivores (all body weights 15, 35, 1000g) :
- 	3.9 to 684
- Granivores (all body weights): 0.11 to 9.5
- Insectivores (all body weights): 4.7 to 365
- Chronic: 0.1 to 72
- Levels of Concern comparison
- acute lethal risk concern RQ_>_0.5
- reproduction risk concern RQ_>_1
- Carbofuran exposures via the dietary pathway are sufficient to cause mortality and reproduction effects

## Deterministic Risk Results for Birds

- Avian RQ results
- Acute
- Herbivores (all body weights 20, 100, 1000g) : 17 to 6897
- Granivores (all body weights): 0.6 to107
- Insectivores (all body weights): 20 to 3879
- Chronic: >1 to > 690
- Levels of Concern comparison
- acute lethal risk concern RQ_>_0.5
- reproduction risk concern RQ_>_1
- Carbofuran exposures via the dietary pathway are sufficient to cause mortality and reproduction effects

## Risks to Birds:  Probabilistic Assessment

- Goals
- Define the probability and magnitude of avian effects
- Explore key areas of variability and uncertainty in datasets underlying the deterministic approach
- Consider the potential for exposure routes other than food as risk drivers

## Risks to Birds:  Probabilistic Assessment

- Problem formulation
- Deterministic assessment identified acute lethal effects as an area of concern for birds
- Risk managers expressed a desire to have more information on these potential effects
- All registered uses were identified as being of concern with screening process
- Focus the refinements on a selected subset of uses:
- Large range of applications rates
- Large potential land area treated (greater opportunity for surrogacy)
- Additional biological information to support refinements regarding resident bird species and their behavior

## Risks to Birds:  Probabilistic Assessment

- Approach to the Analysis
- Focus on corn and alfalfa crops
- Use Terrestrial Investigation Model version 1.0 as the assessment tool
- Focus on species shown to use these crops as evidenced by incidents and field studies

## Problem Formulation: Focal Species

- Considered:
- census data from field studies of pesticide use on corn and alfalfa
- species found dead in such field studies
- open literature surveys of birds in and around corn and alfalfa fields
- Selection criteria:
- high frequency occurrence in Midwest corn or alfalfa areas
- high frequency of observation within the actual fields
- either observed mortalities or close to them in terms of size, nesting, and feeding characteristics

## Focal Species Corn

- Variety of dietary preferences
- Varied expected use of field and field margins

## Focal Species Alfalfa

- Variety of dietary preferences
- Varied expected use of field and field margins

## Risks to Birds:  Probabilistic Assessment

- Approach to the analysis
- Use full suite of carbofuran acute lethal effects data for birds
- Applications should consider minimum, typical and labeled maximum carbofuran application rates
- Allow for dissipation of carbofuran residues in diet, drinking water, and in the feeding bird*****

*** An issue more fully explored in today’s presentations**

## Introduction to TIM 1.0 

- The model can be characterized as a species specific model which addresses acute mortality over a defined exposure window
- (14 days for carbofuran with two 12-hour time steps per day)
- The spatial scale is at the field level, such that the field and surrounding area is assumed to meet habitat requirements for each focal species
- Temporal scale is for exposure immediate to and following a single application

## Introduction to TIM 1.0

**The major parameters addressed in the model are:**
- Food habits of select focal species
- Daily ingestion rates of food and water for selected focal species
- Frequency of feeding and drinking on sprayed fields
- Residues on focal species food and water sources
- Degradation rates of of food and water residues
- Inter and intra species toxicity estimates

## Introduction to TIM 1.0

- For each of the major exposure and effects variables,
- Distributions were developed and
-    combined using Monte Carlo
-    sampling techniques, and
- The probability and magnitude of acute lethal effects were estimated.

## RQ Process
Exposure is a point estimate selected to be an expected conservative level from a distribution

Effects endpoint is the LD50

Effects uses lowest LD50 from species tested

Assessment process is division of exposure estimate by effects endpoint

Output is a single number

**Exposure is a point estimate selected to be an expected conservative level from a distribution**
**Effects endpoint is the LD50**
**Effects uses lowest LD50 from species tested**
**Assessment process is division of exposure estimate by effects endpoint**
**Output is a single number**

_***Probabilistic Process***_
**Exposure varies with variable inputs; entire distribution of exposure values is considered***** **
**Effects considers entire dose-response relationship to account for variability in sensitivity among individuals*******
**Effects estimates interspecies variability in sensitivity; uses scenarios to express uncertainty about sensitivity of a given species**
**Assessment is integration of exposure distribution with entire dose response curves **
**Output is a distribution of the probability and magnitude of adverse effects**

*** An issue more fully explored in today’s presentations**

## An issue more fully explored in today’s

**An issue more fully explored in today’s**
** ****presentations**

## What Variables are Explicitly Considered in TIM 1.0 ?

**What Variables are Explicitly Considered in TIM 1.0 ?**

***issue discussed further today**

## What Variables are Explicitly Considered in TIM 1.0 ?

**Bird variables considered in exposure model**
**What does the bird weigh?**
**What does the bird eat?**
**How much does the bird eat? *******
**Where does the bird eat****? *******
**How much does the bird drink?**
**Where does it drink?**

**What Variables are Explicitly Considered in TIM 1.0 ?**

***issue discussed further today**

## Following A Bird in the Model

- TIM 1.0 can be run in two modes
- X iterations of Y birds in a cohort
- Track number of dead in each cohort
- X individual birds
- Calculates mean risk of mortality for individuals
- Central tendency results of cohort mortality predictions is very close if not identical to mean mortality risk in individual birds (SAP 2000)
- In either case central tendency value is post-processed in a binomial distribution for probability/magnitude of effects for cohorts of Y birds

## TIM Avian Exposure ModelSimplified (food ingestion)...

- Species

- Randomly pick an
- individual bird from
- body weight CDF
**BW**   (grams)

- Based on BW, calculate
- Free-living metabolic
- Rate **FMR** (kcal/day)

- For each food group, calculate
- Fraction Metabolized Energy
**ME **=** Frac X GE X AE**
- (kcal/gram)

- For each food group, randomly
- pick Gross Energies
**GE**  (kcal/gram)

- For each food group, randomly
- pick Assimilation Efficiency
**AE**   (unitless)

- Calculate total daily
- metabolized  intake rate
**TMIR = FMR/ME**
- (gram/day)

- For each food group,
- Calculate daily uptake rate
**U****K**** = Frac X TMIR*******
-  (gram/day)

- For each food group, randomly
- generate residue
**CON**   (ug/gram)*****

- For each food group,  calculate
- residue ingestion rate*****
**CIR****K**** = CON X U****K**** **(gram/day)

- Calculate total daily
- intake of pesticide
**TCIR = sum CIR****K****   **(ug/day)

- Is bird feeding in
- treated field?*****
- Yes, =1
- No, =0

- TIM Avian Exposure ModelSimplified (food ingestion)...
***issue discussed further** **today**

- Calculate total residue ingestion from
- Treated Field

## Biological Parameters for Exposure Modeling:Frequency in Treated Field

- Available data are limited to counts of birds inside and out of a particular crop field
- Data do not represent time budgets of individuals
- EFED and the SAP believe that use of census data to represent daily time budgets of individual birds has limitations

## Biological Parameters for Exposure Modeling:Frequency in Treated Field

- The model does not dilute exposure in a time step *****
- The model uses census data to determine the likelihood that a bird will be in treated area*****

*******issue discussed further** t**oday**

**Notes:**
The exposure model therefore does not dilute exposure in a time step by using census data to determine fraction of food from a treated area
Model  uses census data to determine the likelihood that an individual bird will be in treated area during a time step

## Retention of Chemical In Birds*

- Purpose: to account for pesticide body burden from one exposure time step to another
- Relied on metabolism data in chickens
- Adjusted single oral dose 24-hour retention factor to appropriate time step
- 24-hour period retention 17%
- 12-hour retention set constant at  41 %

***issue discussed further**** ****today**

## Residues in Vegetative Food Items

- EFED relied on the summary statistical information provided by Fletcher et al. (1994)
- Limited data from field studies
- Log normal distributions for residues in each vegetative food item normalized to application rate*****

***issue discussed further**** ****today**

## Residues in Insect Food Items

- EFED relied on the data of Fischer and Bowers (1997)
- Data cover a variety of application methods, pesticides, and crop areas
- Log normal distributions for residues normalized to application rate*****

***issue discussed further**** ****today**

## Toxicity Endpoint

- Problem Formulation: Acute lethal effects
- Two sets of data for evaluating acute lethal effects
- Acute single oral dose studies LD50 (selected for use)*
- Dose response relationships largely clear
- Allows for extrapolation across pathways
- Robust data set for species
- Does not account for dietary matrix
- Very short term exposure window
- Acute dietary exposure studies LC50 (not selected for use)
- Dose response relationships obscure
- Limited dietary matrix consideration
- More protracted exposure window, relevance to field not known

*** issue discussed further**** ****today**

**Notes:**

Both these studies have limitations for estimating the risk to wild avian species exposed to pesticides in the environment.  Both studies have a fixed exposure period, not allowing for the differences in response of individuals to different duration of exposure.  Further, for the acute oral study, the dose administered in a single dose all at one time does not mimic wild birds’ exposure.  Also, for exposure through different environmental matrices, it does not account for the effect of the matrices on the absorption rate of the chemical into the animal.  This latter criticism also applies to the dietary test for other food matrices consumed in the wild.

For the dietary test, as it is currently designed, there are several other aspects of this test that limits its utility for refining an assessment. The endpoint of this test is reported as the concentration mixed with food that produces a response rather than as the dose ingested. Although food consumption is some times measured allowing for the estimate of a dose, calculations of the mg/kg/day are confounded by undocumented spillage of feed, how often consumption is measured, mortality within a treatment group, rapid growth rates of test subjects, and the willingness of the birds to consume treated food.
More importantly, there is evidence that the laboratory derived  LC50 ChemX values are  poor predictors of effects.

## Results of Probabilistic Risk Assessment

- 360 different scenarios were examined for corn and alfalfa uses
- For broadcast application to corn and alfalfa, and for each focal species, 27 separate scenarios were examined

## Slide 46

## Carbofuran Foliar Application to Corn

**Carbofuran Foliar Application to Corn**

| Species | Percent Mortality (cohorts of 20 birds) |  |  |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  | High Sensitivity Assumption1 |  |  | Medium Sensitivity Assumption1 |  |  | Low Sensitivity Assumption1 |  |  |
|  | Mean | 5% | 95% | Mean |  5% |  95% | Mean |  5% |  95% |
| Carbofuran Foliar Application to Midwest Corn (0.25 lbs/a.i./A) Minimum Application |  |  |  |  |  |  |  |  |  |
| K | 87 | 100 | 75 | 10 | 20 | 0 | 0 | 0 | 0 |
| HL | 79 | 95 | 65 | 4 | 15 | 0 | 0 | 0 | 0 |
| VS | 35 | 50 | 20 | 1 | 5 | 0 | 0 | 0 | 0 |
| MD | 25 | 40 | 10 | 1 | 5 | 0 | 0 | 0 | 0 |
| EM | 66 | 85 | 50 | 7 | 15 | 0 | 0 | 0 | 0 |
| WM | 28 | 45 | 10 | 1 | 5 | 0 | 0 | 0 | 0 |
| RWB |  |  |  | 24 | 40 | 10 |  |  |  |

## Carbofuran Foliar Application to Corn

**Carbofuran Foliar Application to Corn**

| Species | Percent Mortality (cohorts of 20 birds) |  |  |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  | High Sensitivity Assumption1 |  |  | Medium Sensitivity Assumption1 |  |  | Low Sensitivity Assumption1 |  |  |
|  | Mean | 5% | 95% | Mean |  5% |  95% | Mean |  5% |  95% |
| Carbofuran Foliar Application to Midwest Corn (0.75 lbs/a.i./A) Typical Application |  |  |  |  |  |  |  |  |  |
| K | 98 | 100 | 90 | 58 | 75 | 40 | 1 | 5 | 0 |
| HL | 96 | 100 | 90 | 46 | 65 | 25 | 0 | 5 | 0 |
| VS | 62 | 80 | 45 | 15 | 30 | 5 | 0 | 0 | 0 |
| MD | 51 | 80 | 30 | 9 | 20 | 0 | 0 | 0 | 0 |
| EM | 84 | 95 | 70 | 40 | 60 | 25 | 1 | 5 | 0 |
| WM | 49 | 70 | 30 | 13 | 25 | 0 | 0 | 0 | 0 |
| RWB |  |  |  | 57 | 75 | 40 |  |  |  |

## Carbofuran Foliar Application to Corn

**Carbofuran Foliar Application to Corn**

| Species | Percent Mortality (cohorts of 20 birds) |  |  |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  | High Sensitivity Assumption1 |  |  | Medium Sensitivity Assumption1 |  |  | Low Sensitivity Assumption1 |  |  |
|  | Mean | 5% | 95% | Mean |  5% |  95% | Mean |  5% |  95% |
| Carbofuran Foliar Application to Midwest Corn (1.0 lbs/a.i./A) Maximum Application |  |  |  |  |  |  |  |  |  |
| K | 99 | 100 | 95 | 72 | 90 | 55 | 3 | 10 | 0 |
| HL | 97 | 100 | 90 | 61 | 75 | 45 | 1 | 5 | 0 |
| VS | 64 | 80 | 45 | 23 | 40 | 10 | 0 | 0 | 0 |
| MD | 57 | 75 | 40 | 15 | 30 | 5 | 0 | 0 | 0 |
| EM | 86 | 95 | 70 | 51 | 70 | 30 | 2 | 1 | 0 |
| WM | 52 | 70 | 35 | 18 | 35 | 5 | 0 | 5 | 0 |
| RWB |  |  |  | 64 | 80 | 45 |  |  |  |

## For untested species: Three curves are presented, representing 

- For untested species: Three curves are presented, representing
- predicted mortality for low, medium, and high sensitivity assumptions

## For all species and sensitivity 

- For all species and sensitivity
- assumptions modeled, mean
- predicted mortalities are
- ranked and graphed.

- Mean mortality is the fraction of dead birds in 20-bird cohorts.

- In this case, 65% of the species/sensitivity combinations had at least 10% mortality, with mortality as severe as 98%.

## Results of Probabilistic Risk Assessment

- Potentially high mortality in at least some avian species for all scenarios
- 55% to 95% of the bird species modeled exhibit mortality
- Results dependent upon:
- application rate (>rate >mortality),
- method (banded and in-furrow less than aerial broadcast),
- target crop (likely a result of differing extent of bird use of fields)
- assumption of sensitivity to pesticide (>sensitivity > level of mortality)

## Incident and Field Studies

- Third line of evidence
- Do observations in the field comport with risk assessment predictions?
- Are one or more exposure routes complete?
- Are laboratory-based predictions of effects manifested in the field?

## Ecological Incident Reports: CONCLUSION

- When carbofuran is used as currently registered, wildlife mortality can and does occur

## Avian Field Studies

- Conclusion:
- Carbofuran is measurable in avian diet
- Carbofuran use at current application rates can adversely impact wildlife (mortality incapacitation, reproduction impairment)

## Overall Conclusions

- Deterministic Model
- One or more exposure pathways are complete
- Exposure levels meet or exceed levels shown to cause adverse effects (mortality and reproduction) in the laboratory
- Probabilistic Model
- Exposure is variable but one or more pathways are complete
- Exposure levels are sufficient to cause mortality based on laboratory effects data
- Mortality is frequent and under some situations severe
- Incident, Monitoring, Field Data
- One or more exposure pathways are complete
- Exposure levels are sufficient to result in field-observable effects (mortality, incapacitation, and reproduction)

## Key Scientific Issues from TIM 1.0 SAP

- Focal Species Selection,
- Frequency of Birds in Treated Fields Use in the Model,
- Frequency of Birds in Treated Fields, Setting Parameters,
- Consideration of Drinking Water Source Selection,
- Puddle Persistence,
- Concentrations in Drinking Water,
- Residues in Food Items,
- Residue Clearance in Focal Species,
- Selection of Exposure Time Steps,
- Selection of Acute Toxicity Standard,
- Defining the Distribution of Species Sensitivity, and
- Other Factors Affecting Sensitivity

## Scientific Issues Addressed by New Data

- Residues in Food Items,
- Residue Clearance in Focal Species,
- Selection of Acute Toxicity Standard, and
- Other Factors Affecting Sensitivity

## Scientific Issues Addressed by New Model (TIM 2.1)

- Focal Species Selection,
- Frequency of Birds in Treated Fields, Setting Parameters,
- Consideration of Drinking Water Source Selection,
- Puddle Persistence,
- Concentrations in Drinking Water, and
- Selection of Exposure Time Steps

## Scientific Issues Addressed by Alternative Input Assumptions

- Frequency of Birds in Treated Fields, Setting Parameters,
- Residues in Food Items,and
- Selection of Exposure Time Steps