# Presentation: 438037

## Risk Assessment Overview-or-A Risk Assessment is Not a Number

**Risk Assessment Overview**-or-A Risk Assessment is Not a Number

- Michael S. Metzger

- HED Risk Assessment Training and Certification Program

**Notes:**
Welcome
Will cover many topics, provide vocabulary, but little detail – detail in later talks
Hold questions – don’t want to go into detail
There will be a contradictory example for almost everything I say, but the idea today is to provide an overview of RA issues providing information that will be applicable in most cases

## Objectives - To Understand:

- The risk assessment paradigm
- Required toxicity studies
- Route/duration effects on toxicity
- Standard HED risk assessments
- Endpoint selection
- Dietary assessment
- Occupational/residential assessment

## Objectives – To Understand:

- Drinking water assessments
- Aggregate assessment
- Cumulative assessment
- A risk assessment is not a number!

**Notes:**
Risk assessment is not a number – it’s a number combined with all of the scientific information describing our confidence in that number, and the associated uncertainties.

## The Risk Assessment Paradigm:  The ”Red Book”

- Hazard Identification

- Dose Response
-  Assessment

- Exposure
- Assessment

- Risk Characterization

- From the National Research
- Council’s *Risk Assessment in the*
*Federal Government: Managing the *
*Process,* 1983.

- http://books.nap.edu/books/030904894X/html/1.html

## Hazard Assessment:  Typically Required Guideline Studies

- Acute toxicity battery
- Subchronic oral toxicity study in rats
- Subchronic dermal toxicity study in rats and rabbits
- Subchronic inhalation toxicity study in rats
- Developmental toxicity studies in rats and rabbits
- 2-Generation reproduction study in rats

## Hazard Assessment:  Required Studies

- Chronic / carcinogenicity studies in rats, dogs, and mice
- Acute (ACN) and subchronic (SCN) neurotoxicity studies in rats
- Delayed neurotoxicity study in hens
- Mutagenicity testing battery (*in vitro*)
- Developmental neurotoxicity study (DNT) in rats
- Dermal absorption study
- Rat metabolism study

## Hazard Characterization

- Important toxicological effects observed including developmental / fetal, reproductive, endocrine, carcinogenic, and other effects

- Any critical exposure periods and routes

- Metabolism and potential for bioaccumulation

- Quality of the data and uncertainties

- Studies which provide conflicting results, and why a particular study might be deemed to be the most appropriate to rely on

## Hazard Characterization

- Toxicity data available for related chemicals

- Pertinence of the toxicity observed to humans

- Availability of epidemiological data which supports or does not support other hazard information

- Adverse effects on wildlife that may be pertinent to human health risk assessment

-  Toxic mode of action information

- Confidence in the conclusions, alternative conclusions which could be drawn, significant data gaps, and highlights of major assumptions

## Hazard Characterization

- Each characterization factor describes our confidence in the hazard assessment, and therefore our confidence in the risk assessment
-     without transparent, clear, consistent, and reasonable characterization, the assessment has little meaning
- _A risk assessment is not a number!_

## Dose-Response Assessment and Endpoint Selection

- Provides a quantitative description of the hazard potential which can be used to assess the concern for effects to people who may be exposed.

## Dose-response Assessment and Endpoint Selection:  Definitions

**Endpoint:**  Toxic Effect upon which the risk assessment is based

**Lowest Observed Adverse Effect Level (LOAEL):**  Lowest dose from a study at which adverse toxic effects were observed

**No Observed Adverse Effects Level (NOAEL):**  The dose below the LOAEL at which no adverse toxic effects are observed

**Point of Departure (POD):**  Any dose level used to quantify risk (generic)

## *NOAEL / LOAEL Dose Spacing

- NOAEL / LOAEL dose spacing usually ranges between 2X and 10X.
- True NOAEL will be somewhere between the NOAEL and LOAEL

-    Will always lead to a conservative (protective) hazard estimate

- _A risk assessment is not a number!_

## Dose-response Assessment and Endpoint Selection:  Adverse

**LOAEL** = Lowest Observed ***Adverse*** Effect Level

**LOEL** = Lowest Observed Effect Level

- Effects are of concern only if they are “adverse”  =  “harmful”

- Very minimal or adaptive effects may not be considered adverse, so would not be suitable endpoints for risk assessment

## Dose-response Assessment and Endpoint Selection:  Dose

- “All substances are poisons; there isnone which is not a poison.  The right dose differentiates a poison froma remedy.”
- Paracelsus (1493-1541)

- Lower dose    lower toxicity

- Higher dose    Higher toxicity

- No exposure    No risk

## Hazard Assessment:  Hazard vs. Risk

- Hazard = toxicity
- Risk = toxicity  x  exposure

## Dose-response Assessment and Endpoint Selection:  Duration

- Longer duration exposure
- 		  more severe toxicity
- 		 toxicity seen at lower doses

- Range of potential exposure durations must be considered in risk assessments
- 		  	One dose to lifetime

## Dose-response Assessment and Endpoint Selection:  Route

- 3 major routes:  oral, dermal, inhalation

- Toxic effects seen –and- severity of toxic effects can vary by route
- Of particular concern for portal-of-entry effects

- Must assure that route of dosing in animal study matches human exposure route – or characterize any mismatch

## Dose-response Assessment and Endpoint Selection

- Endpoints selected for risk assessment must be the most sensitive endpoint for each population, and relevant to humans.

- Most sensitive (protective)    Most protective POD (e.g. lowest NOAEL, highest q*)

- Relevant  Toxicity seen in animal studies could also occur in humans

## Dose-response Assessment and Endpoint Selection:  Exposure Scenarios

- Dietary
- Oral food and water (all ages)
- Residential
- Incidental oral ingestion (children, adult swimmers)
- Dermal exposure (all ages)
- Inhalation exposure (adults, children indoors)
- Occupational
- Dermal and inhalation exposure (adults)

## Major Risk Assessments

| 
Assessment | Duration of Continuous Exposure |
| --- | --- |
| Acute | 1-day |
| Short-term (ST) | 1-30 days |
| Intermediate-term (IT) | 1-6 months |
| Chronic | 6 months - lifetime |
| Cancer | Chemical-specific |

## Major Risk Assessments:  “Continuous” Exposure

**“****Continuous Exposure”**
- Exposure sufficiently often that cumulative toxicity from the chemical is expected to occur
- -or-
- Exposure sufficiently often that recovery from the toxic effects is unlikely to occur between doses

**Notes:**
Recovery and the continuity of exposure range over a wide spectrum – another example of “A risk is not a number”.

## Major Risk Assessments: Acute

- One-day dietary (oral) exposure
- Food and water
- One-day occupational or residential assessments (oral, dermal, and inhalation)
- Used to refine ST assessments

## Major Risk Assessments: Acute

- Endpoints typically used:
- Developmental (teratogenic) effects
- Applicable to females of child-bearing age only
- Neurotoxicity
- Applicable to everyone

**Notes:**
- acute 6-pack primarily looks only at LD-50s – not useful for RA.

## Major Risk Assessments: Acute

| Study Type | Approximate Percent of time used |
| --- | --- |
| Acute neurotoxicity, rat | 30 |
| Developmental, rat | 30 |
| Developmental, rabbit | 22 |
| Subchronic, dog |   7 |
| Special studies |   4 |
| Subchronic, rat |   1 |
| Subchronic neurotoxicity, rat |   1 |
| Reproduction, rat |   1 |
| Developmental neurotoxicity, rat | <1 |
| Developmental, mouse | <1 |
| Chronic, rat | <1 |
| Chronic, monkey | <1 |
| Subchronic, mouse | <1 |

## Major Risk Assessments: Short Term (ST)

- Duration:  1-30 days continuous exposure
- Scenarios:
- Single-source occupational and residential assessments
- When residential assessments are needed, aggregate assessments for food, water and residential
- Routes:  Oral, dermal, and inhalation

## Major Risk Assessments: Short Term (ST) - Typical Endpoints

**Incidental oral**
- (children, adult swimmers)
- Maternal effects from developmental studies (14-days dosing)
- Neurotoxicity and other effects from subchronic studies
- Fetal developmental effects not appropriate for children

## Major Risk Assessments: Short Term (ST) - Typical Endpoints

- Dermal
- Toxicity seen in 21-day dermal toxicity study
-  	Dermal studies not always available
-  	Only a limited range of endpoints is 	measured in 21-day dermal studies

## Major Risk Assessments: Short Term (ST) - Typical Endpoints

- Dermal
- From oral studies:
- Developmental endpoints (adult females only)
- Same as incidental oral (adults and children)
-   Must be corrected for % dermal absorption

## Major Risk Assessments: Short Term (ST) - Typical Endpoints

- Inhalation
- Toxicity seen in 28- or 90-day inhalation studies
-  Inhalation studies not always available
-  Only a limited range of endpoints is 	measured in most inhalation studies

## Major Risk Assessments: Short Term (ST) - Typical Endpoints

- Inhalation
- From oral studies:
- Developmental endpoints (female adults only)
- Same as incidental oral (adults and children)
- 	Must be corrected for % inhalation 	absorption

## Major Risk Assessments: Intermediate Term (IT)

- Duration:  1- 6 months continuous exposure
- Scenarios:
- Single-source occupational and residential assessments
- Aggregate assessments for food, water and residential
- Routes:  Oral, dermal, and inhalation

## Major Risk Assessments: Intermediate Term (IT) - Typical Endpoints

**Incidental oral**
- (children, adult swimmers)
- Toxic effects from subchronic or chronic studies

## Major Risk Assessments: Intermediate Term (IT) - Typical Endpoints

- Dermal
- Toxicity effects from 21-day dermal studies
- Matches exposure route
- Toxic effects from subchronic and chronic oral studies
- Matches exposure duration
- Developmental
- If most sensitive
- Must determine whether using route-specific or duration-appropriate study is best for each chemical

## Major Risk Assessments: Intermediate Term (IT) - Typical Endpoints

- Inhalation
- Toxic effects from 90-day inhalation study
- Correct route and duration
- Toxic effects from subchronic and chronic oral studies
- Matches exposure duration
- Developmental
- If most sensitive

## Major Risk Assessments: Chronic

- Long-term dietary (oral) exposure
- Food and water
- Long-term occupational assessments
- dermal and inhalation
- Long-term residential assessments
- inhalation

## Major Risk Assessments: Chronic – Typical Endpoints

- Oral and Dermal
- Toxic effects from chronic studies
- Reproductive effects
-  % dermal absorption correction required for dermal

## Major Risk Assessments: Chronic – Typical Studies Used for cPAD

| Study Type | Approximate Percent of time used |
| --- | --- |
| Chronic, dog | 36 |
| Chronic, rat | 36 |
| Reproduction, rat | 7 |
| Subchronic, dog | 6 |
| Chronic, mouse | 5 |
| Subchronic, rat | 5 |
| Chronic, monkey | 1 |
| Special studies | 1 |
| Acute neurotoxicity, rat | <1 |
| Developmental, rat | <1 |
| Subchronic, rabbit | <1 |
| Subchronic, mouse | <1 |
| Developmental, rabbit | <1 |

## Major Risk Assessments: Chronic – Typical Endpoints

- Inhalation
- Toxic effects seen in 90-day inhalation study
- Toxic effects from chronic and reproduction studies (corrected for % inhalation absorption)

## Major Risk Assessments: Cancer

- Non-threshold   (default)
**Any exposure leads to some probability of risk**
**Regulated with a q****1*******

- Threshold   (only when Mode of Toxic Action is known)
**Risk only when exposure exceeds threshold**
**Regulated with an MOE, RfD, or PAD**

- 2 major types:

## Expressing Risk

- Risks in OPP are generally expressed in the following ways:
- % Reference Dose (%RfD)
- % Population Adjusted Dose (%PAD)
- Margin of Exposure (MOE)
- Cancer Probability
- Units used in all assessments are mg/kg body weight/day

## Expressing Risk:  % Reference Dose (%RfD)

- Used to express risks in acute (aRfD) and chronic (cRfD) dietary assessments

- RfD =       Point of Departure (e.g. NOAEL)
- 	   Uncertainty Factors (except Special FQPA)
- %RfD =   exposure   x   100
- 	          RfD

-  Because the Special FQPA SF must be applied in HED assessments, the RfD is now used in OPP primarily in calculating a Population Adjusted Dose (PAD)

## Expressing Risk:  % Population Adjusted Dose (%PAD)

- Used to express risks in acute (aPAD) and chronic (cPAD) dietary assessments

- PAD  =  Point of Departure (e.g. NOAEL)
-       Uncertainty  Factors (inc. Special FQPA)

- %PAD =	exposure	x  100
- 		   PAD

## Expressing Risk:  Margin of Exposure (MOE)

- Used to express risk for ORE assessments, any aggregate assessment which includes an ORE component, and some cancer risks

- MOE =  _Point of Departure  (e.g. NOAEL)_					   exposure

## Expressing Risk:  RfD/PAD vs. MOE

- RfD/PAD
- Risk = exposure
-              POD
-  As exposure increases, %RfD/%PAD _increases_

- MOE
- Risk =     POD
-            Exposure
-   As exposure increases,       MOE _decreases_

## Expressing Risk:  Cancer Probability

- Used to express cancer risks when a non-threshold mechanism is assumed (q1*)

- q1* = a measure of dose response seen in cancer studies
- Risk  =   q1*  x  exposure

## Dermal Absorption

- “Route-to-route extrapolation” – oral to dermal
- Use of an endpoint from an oral study for 	dermal risk assessment
- Must correct dermal exposure to account for less than 100% of the pesticide being absorbed through the skin into the body
- Multiply dermal exposure x % dermal absorption (expressed as a fraction)

## Inhalation Absorption

- “Route-to-route extrapolation” – oral to inhalation

-  Math is identical to that used for dermal absorption

-  However, since always assume 100% inhalation absorption, use of an oral endpoint is mathematically the same as using an inhalation endpoint

## Uncertainty and Safety Factors

- “**One of several, generally 10-fold factors, used in operationally deriving the RfD and RfC from experimental data”****    ****(**_[http://www.epa.gov/iris/gloss8.htm](http://www.epa.gov/iris/gloss8.htm)_**)**
**Intraspecies – variability among humans**
**Interspecies – extrapolating animal data to humans**
**Extrapolating from less-than-lifetime to lifetime exposures**
**LOAEL to NOAEL**
**Incomplete data base**

## Uncertainty and Safety Factors

- Generally 10X unless:
- A smaller factor can be shown to be protective, or
- A larger factor is clearly needed
- Maximum = 3000

## Uncertainty Factors

## Special FQPA Safety Factor

- Used when:
- There is concern that the NOAEL used in the risk assessment may cause risks to be underestimated because of:
- Poor dose-response
- Small difference between NOAEL and LOAEL
- Concern that exposure may be underestimated

## Uncertainty Factors

- What if:
- No interspecies differences
- Minimal intra-species variability

-   Risk estimates will significantly exaggerate real risks!

- _A risk assessment is not a number!_

## Exposure Assessment: Chemistry and Dietary Exposure Assessment

- Three major Areas:
- Product Chemistry
- Residue Chemistry
- Dietary Exposure Assessment

## Product Chemistry

- Manufacturing and Impurities
- Identifies important contaminants in pesticide products which could be of risk concern

- Physical / chemical property data
**Water solubility**
**Octanol-water partition coefficient**
**Vapor pressure**

## Residue Chemistry

- Major areas include:
- Metabolism (plant and livestock)
- Residue analytical methods
- Residue Field Trials
- Rotational crop studies
- Livestock feeding studies
- Food processing studies
- Residue monitoring studies

## Metabolism in Plants and Livestock

- Nature of the Residue (NOR) studies
- Purpose:  Used to **identify** metabolites or degradates which might occur in foods as a result of the pesticide use, specifically:
- Which metabolites must be included in dietary risk assessment
- Which metabolites must be included in tolerance expression

## Metabolism in Plants and Livestock

- Study design:
- Radiolabel the pesticide
- Apply to plant or livestock (in feed or directly) consistent with how pesticide will be used
- Harvest crop or livestock consistent with how pesticide will be used
- Identify and quantify radioactive products in foods

## Metabolism in Plants and Livestock

- Include metabolites in risk assessment if:
- They are likely to be of _risk_ concern (i.e., both toxic and likely to result in significant exposure)
- Separate assessments may be required for metabolites likely to have significant toxicity which is different from parent compound

- Include metabolites in tolerance expression if:
- They are present in significant amounts and will be a good measure of misuse of pesticide

## Residue Analytical Methods

- Designed for 3 purposes:
- Data collection in field trials (less validation required)
- Tolerance enforcement (ease of use and robustness are important; may be MRMs)
- Monitoring: Multi-Residue Methods (MRMs) for use in generating monitoring data for dietary risk assessment (measure many pesticides in one analysis)

## Residue Field Trials

- Purpose:  To **quantify** residues in crops under a range of field conditions
- While typically 1-3 plant metabolism studies would be required to represent all crops for a chemical, 3-20 field trials will be required for *each* crop.

## Residue Field Trials

- Study design:
- Prepare representative formulated products
- Apply each product to the crops in the field per label directions (generally 3-20 diverse fields for each formulation)
- Harvest the plants per label directions
- Measure residues (those required for both the tolerance and risk assessment) in all plant parts used for food or feed

## Rotational Crop Studies

- A rotational crop is one which is planted in a field following harvest of the primary crop.
- Rotational crops can contain residues resulting from pesticide applications made to the primary crop
- Both confined (radiolabeled) and field (cold)  rotational crop studies may be required to identify and measure these residues

## Livestock Feeding Studies

- Purpose:  To **quantify** residues in meat, milk, poultry and eggs resulting from livestock consumption of treated feed, or direct application to livestock
- While 1 livestock metabolism study is required for each type of livestock (typically chickens and ruminants), several feeding studies are required for each

## Livestock Feeding Studies

- Study design:
- Apply formulated pesticide to livestock either directly or in feed, in a manner similar to which the livestock will actually be exposed (multiple animals)
- Analyze samples of meat, milk, poultry, and eggs for residues (both those required for risk assessment and tolerance enforcement)

## Food Processing Studies

- Purpose:  To estimate a processing factor which describes the concentration or reduction in residue level going from the raw to processed commodity
- Required for all major processed foods

## Food Processing Studies

- Study design:
- Obtain sample of raw commodity containing residues, measure residues
- Process using methods simulating commercial processing methods
- Measure residues in processed foods

- Processing Factor (PF) = Residue in proc. Food_  _
- 			            Residue in raw food

## Residue Monitoring Studies

- Not generally required, but frequently used in risk assessment
- Purposes:
- Enforcement (targeted, less useful for risk assessment)
- Risk assessment
- Usually generated by government agencies and pesticide registrants

## Residue Monitoring Studies

- Samples collected at various points in commerce
- Farm gate, warehouses and food distribution points, grocery stores

- Sample collection closer to consumer
-          More accurate risk estimates

- Monitoring data most frequently used:
- USDA PDP data
- FDA Surveillance Monitoring
- Registrant-generated special studies

## Dietary Exposure Assessment

- Two components
- Food residues
- Food consumption

## Dietary Exposure:  Food Residues

- Residue estimates obtained from
- Field trials (plants)
- Livestock feeding studies (MMPE)
- Monitoring data (various foods)
- Processing factors (factors used in combination with field trial or monitoring data)

## Dietary Exposure:  Food Consumption

- Food consumption data obtained from the USDA’s Continuing Survey of Food Intake by Individuals (CSFII)(1994-96, 1998 supplemental data)
- Consumption data may be grouped by various factors including age, sex, region, ethnicity, others

## Dietary Exposure:  Food Consumption

- CSFII Survey data represent 2 non-consecutive days for each respondent
- Used to calculate long-term averages for each population subgroup

- Longitudinal (long-term) consumption data for individuals not available

## Dietary Exposure:  Calculations

- Exposure = _Residue  x  Consumption_
-                          Body Weight

- _mg pest_   =  _mg pest_  x  _g food  _  x  _  kg food  _  x   _1_
- kgbw-day     kg food        day        1000 g food    kgbw

- Correction factor

## Dietary Risk:  Calculations

- Risk (%PAD)   =   _Exposure_  x  100
-                                PAD
- Equation applies to both acute and chronic dietary risk assessments

## Dietary Risk:  Acute

**Acute Dietary Risk**:
-  Risk resulting from 1-day dietary exposure
- Residue level, food consumption, and endpoint all must represent 1-day exposure or dosing

## Acute Dietary Risks:  Two Assessment Methods

- Deterministic – less refined  (lower tier)
- Entire range of food consumption with only single, high-end residue estimate
- Screening-level, high-end risk estimate

- Probabilistic – more refined  (higher tier)
- Entire range of both food consumption and residue levels
- More accurate risk estimate

## Acute Dietary Risk Assessment

- Outputs for both deterministic and probabilistic assessments include exposure and risk estimates for different exposure percentiles for each population
- Deterministic assessments:  Regulatory target is risk associated with 95th percentile exposure
- Probabilistic assessment:  Regulate target is risk associated with 99.9th percentile exposure

## Acute Dietary Risk Assessment:  Percentiles

**Number of People**

- Exposure / Risk Level

- Everyone

- 95’th percentile

- 99.9’th percentile

## Chronic Dietary Risk Assessment

- Risks resulting from 6 months to lifetime exposure

- Residue levels, food consumption: must be average values

- Only deterministic assessments are done since longitudinal consumption data are not available

- Output:  Average exposure and risk for each population subgroup

## Dietary Risk Assessment:  Models

- Two models routinely used:

- Dietary Exposure Evaluation Model - Food Commodity Intake Database (DEEM-FCID)
- Models entire range of single day exposures or population averages

- Lifeline
- Models longitudinal exposures to individuals (single day, seasonal, and lifetime)

## Dietary Risk Characterization

- What factors determine how closely the risk estimates approximate real population risks?
-  Estimated risks can differ by orders of magnitude when different data or methods are used.

## Dietary Risk Characterization

- Were field trial or monitoring data used for risk drivers (foods with highest risks)?  Source of monitoring data?

- Were residues detectable or based on limits of detection?

- Were residues surface of systemic?

- What processing data were used (commercial/washing/ cooking/peeling, or high-end defaults)?

## Dietary Risk Characterization

- Were high-end or a distribution of residues used?

- Are residues primarily parent or more/less toxic metabolites?

- Was percent crop treated used?

## Dietary Risk Characterization:Example

- Assume risk at 99.9’th percentile exposure = 125% aPAD
- Does this mean that 0.1% of the population will get sick from exposure to pesticide residues?

## Dietary Risk Characterization:Example

**More potential concern exists if:**
**Monitoring data rather than FT or feeding study data used**
**A distributional rather than deterministic assessment was done**
**Refined processing, cooking, washing or other data were used**

- NO!
- It means that our regulatory target has been exceeded.

-   Even with the most refined exposure data, hazard conservatisms lead to protective assessments.

## Dietary Risk Characterization:Example

- Does this mean that we’re never concerned with risks at 125% aPAD?

**No!**

-          It means that:
- Our regulatory target, designed to be protective in virtually all situations, has been exceeded
- We must consider the elements of the hazard and exposure characterizations to determine our degree of concern

## Occupational and Residential Exposure

**Occupational - job-related exposures**
**Handler:  Mix, load and apply pesticide (agricultural, professional residential, others)**
**Post-application: Reentry after application (e.g., pickers, thinners) **
**Dermal and inhalation routes**

## Residential - non-job-related exposures
Handler: Mix, load, and apply by homeowner
Post-application:  Reentry after application (e.g., playing on lawns, playing golf, rolling on rug)
Dermal, inhalation, and oral routes

**Handler: Mix, load, and apply by homeowner**
**Post-application:  Reentry after application (e.g., playing on lawns, playing golf, rolling on rug)**
**Dermal, inhalation, and oral routes**

- Occupational and Residential Exposure

## Occupational Handlers

- Application Rate:  Label or usage information (lbs. A.I./A)

- Acres treated: Standard values from data and surveys

- Unit exposure:  exposure per pound of active ingredient handled from the Pesticide Handlers Exposure Database (PHED)

- Three Major Inputs:

## Pesticide Handlers Exposure Database (PHED)

- PHED aggregates data for different chemicals into scenarios representative of each activity / formulation type / PPE / etc  unit exposures
**e.g., mix/load dry flowables, apply granules**

- Concept:  Handler exposure is less dependent on chemical structure, more dependent on the physical processes of mixing and loading, the type of formulation, Personal Protective Equipment (PPE), packaging, application equipment, etc.

## Occupational Handlers: Calculations

- exposure   =    unit       x    app     x    _acres_  x    _1_
-                    exposure        rate           day        BW
- _     __mg     _  =  _  mg       _   x   _lbs a.i._  x    _A_   x    _1_
- kgbw day      lb a.i applied       A           day    kgBW

- Correction may be needed for % dermal absorption

## Occupational Post-Application Workers

- Three major inputs:

- Dislodgable Foliar Residue (DFR):  Residue on foliage which can rub off onto worker’s skin

- Transfer Coefficient (TC):  Measure of contact with foliage while performing a specific activity

- Time spent working

## Occupational Post-Application Workers

- The amount of contact with foliage while working (TC) is not dependent on the chemical structure, but depends on the type of work, and the type and growth stage of the crop - a table of standard TCs is available for specific activities and crop types/growth stages
- Over 4000 activity/growth stage combinations

- The amount of residue which can rub off onto skin (DFR) is chemical-specific - DFRs must be generated for each chemical

- Concept:

## Occupational Post-Application:  Calculations

- Exposure =  DFR  x  TC  x  hours  x  correction  x  _1_
-                                                        factor        BW
-     _mg_      =   _ug_   x  _cm_2  x   _hours_   x    _mg_      x   _1_
- Kgbw day      cm2     hour       day        1000 ug    kgbw

- DFRs decline over time  exposure declines over time:  Used to establish reentry intervals (REIs)

## Residential Risk Assessments

- Standard Operating Procedures for Residential Exposure Assessment (“Residential SOPs”)

**Residential lawns**
**Gardens (vegetable, ornamental)**
**Trees (fruit, nut, ornamental)**
**Swimming pools**
**Painting / wood preserv.**
**Fogging**

**Crack and crevice tx**
**Pet uses**
**Detergents/hand soap**
**Impregnated mat.**
**Termiticides**
**Indoor inhalation**
**Rodenticides**
**U-pick**

## Occupational and Residential Exposure

- All data conditionally required
- 40 CFR 180.390, 180.440
- May change in next revision of Part 158

- Less robust data than for dietary exposure

- Much of data is not chemical-specific, so generated by task forces

## Occupational and Residential Exposure:  Task Forces

**ARTF (Agricultural Reentry TF):**
**Occupational TCs**
**ORETF (Outdoor Residential Exposure TF): **
**Lawn use exposure data**
**NDETF (Non-dietary Exposure TF):  **
**Indoor exposure and residue data**
**REJV (Residential Exposure Joint Venture):**
**Use and usage information**
**AHETF (Agricultural Handlers Exposure TF):**
**PHED replacement data**

## Occupational and Residential Exposure:  Data Call-Ins (DCIs)

- 1984:	Field worker DCI
- 1995:	Generic Post-app DCI (TCs)
- No generic request for DFR data
- 1995:	Lawn uses DCI (TCs, activity 			pattern, etc.)
- Handlers – No DCI ever issued

## Drinking Water

- Two sources:
- Surface water:  lakes, reservoirs, rivers
- Ground water:  underground sources

##   Surface Water (SW) Sources of Drinking Water:  Monitoring

- Preferred data source - directly measures what people could be exposed to

- Rarely sufficient because of inadequate sampling, particularly for acute assessments
- Geographical representation
- Frequency of sampling

- NAWQA, STORET, registrant-generated studies

## Surface Water (SW) Sources of Drinking Water:  Models

- Used for most risk assessments

- Input: phys/chem properties, 1/2-lives

- Tier 1:  FQPA Index Reservoir Screening Tool (FIRST)
- high end values for DWLOC calculations

- Tier 2:  Pesticide Root Zone Model - Exposure Analysis Modeling System (PRZM-EXAMS)
- high end values for DWLOC calculations
- direct use in distributional and chronic assessments

## Ground Water (GW) Sources Of Drinking Water:  Monitoring

- Useful for risk assessment more often than SW monitoring

- Prospective GW monitoring studies
- controlled studies at vulnerable sites

- National Water Quality Assessment (NAWQA) program, STORET

## Ground Water Sources of Drinking Water:  Models

- Model (SCIGROW)
- Often used for risk assessment
- Screening Concentration In GROund Water (SCIGROW)
- Input:  p-chem properties, 1/2-lives, chemical-specific data
- regression model
- Can be used in DWLOC calculations, or directly as a single input value

## Aggregate Exposure / Risk Assessment

- FQPA defines “safe” as:
-  “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposure and all other exposure for which there is reliable information.”

## Aggregate Exposure / Risk Assessment

- Aggregate typically includes:
- Food
- Drinking water
- Other non-occupational exposures (e.g. residential, playing golf)

- Oral, dermal, and inhalation routes

## Five Standard Aggregate Durations / Scenarios:

- Acute (_<_1-day)
**usually dietary food and DW, occasionally includes refined residential exposures**

- Short (1-30 days) and Int.-term (1-6 months)
**food, DW, residential - only done when residential scenarios exist**

- Chronic (6 months - lifetime)
**usually dietary food and DW, occasionally includes residential exposures**

- Cancer:
**food, DW, residential**

## Aggregate Risk Calculations:Population Adjusted Doses

- Used when only dietary (oral) components are included:

- %PADagg  =  %PADfood  +  %PADDW

## Aggregate Risk Calculations:MOE Approach

- Used when residential scenarios are included, and target MOEs are the same for all routes of exposure (or for cancer assessment using MOE approach)

- MOEagg  =                         1
-                    1         +       1          +       1
-                  MOEoral          MOEderm        MOEinhal

## Aggregate Risk Calculations:ARI Approach

- Aggregate Risk Index (ARI):  Used when residential scenarios are included, and target MOEs are NOT the same for all routes of exposure

- ARI  =      MOE
-            Target MOE

- ARIagg  =                         1
-                   1         +       1          +       1
-                 ARIoral            ARIderm          ARIinhal

## Aggregate Risk Calculations:Cancer (q1*) Assessment

- When cancer is quantified using a q1*, aggregate by adding the cancer risk probabilities for all scenarios
- When using a q1*, risks quantified for general population only

## Cumulative Risk

- Combined aggregate risks from all chemicals which have a common mode of action
-                           -or-
- Combined risks from food, drinking water, and residential exposure, for all pesticides which have common toxic effects produced in the same way

## Risk Characterization / Risk Management

**Risk management** is the **decision-making process** involving considerations of political, social, economic and engineering factors with relevant risk assessments relating to a potential hazard so as to develop, analyze and compare regulatory options and to select the optimal regulatory response for safety from that hazard.

- A major purpose of risk assessment is **to** **inform risk management decisions**

## The Risk Characterization Handbook

- Transparency
- Clarity
- Consistency
- Reasonableness

- http://www.epa.gov/osp/spc/rchandbk.pdf

## Risk Characterization:  Transparency

- Clearly understood assumptions and extrapolations, impact on risk assessment
- Use of modeled vs. measured data, data gaps
- Confidence in major conclusions
- Uncertainties

## Risk Characterization:  Clarity

- The final product should:
- Be as brief as possible
- Use plain language
- Be understandable to the target audience

## Risk Characterization:  Consistency

- Follow statutory requirements
- Follow Agency guidance and policies
- Puts the risk assessment in context with other assessments
- Necessary in a regulatory context to assure a level playing field

## Risk Characterization:  Reasonableness

- Is deemed to be sound by interested parties, using generally-accepted scientific knowledge
- Based on best available science
- Provides plausible alternative estimates of risk
- Consistent with common sense

## HED Risk Assessment Training and Certification Program

- Thanks for Coming