MEASURING THE POTENTIAL

IMPACTS OF THE UNINTENTIONAL

CONSEQUENCES

Jade Mitchell, PhD

Center for Research on Ingredient Safety (CRIS) Annual Meeting - October 5, 2016

East Lansing Marriot at University Place

R.A.M.A.D.A.

RISK ASSESSMENT MODELING AND DECISION ANALYSIS

Jade Mitchell, PhD

Principal Investigator

www.theramadagroup.com

We perform human health risk analysis to address risks associated with chemical

and microbial stressors in multimedia environments.

Our goal is to increase the utility of risk analysis for decision making and effective

management of legacy and emerging contaminants.

We develop approaches, frameworks, models and data sets to support risk

characterization of poorly described hazards and exposures.

Prescriptive

Predictive

Descriptive

Approaches

Sense -making

Solution - making

Decision - making

Data collection and analysis

Modeling and simulation

Mechanistic systems modeling

o Systems Modeling

Conceptual

Statistical

Environmental and process

o Risk Analysis

o Decision Analysis

o Value of Information

o Multi-criteria Decision

analysis

o Decision Making Under

Uncertainty

o Sensitivity Analysis

o Uncertainty Analysis

o Life-Cycle Assessment

General Research ApproachesResource

Needs and

Complexity of

Effort

Residual

Uncertainty

Fully mechanistic systems

modeling and risk analysis

Predictive, generalizable

and simulation based modeling

Screening based on inherent

chemical, physical and/biological

processes

SOURCE: http://web.bryant.edu/~dlm1/sc372/readings/toxicology/toxicology.htm Dan L. McNally, Associate Professor,

Department of Science and Technology, Bryant University, Smithfield, RI

• Chemical and microbial stressors

exists among and across multiple

sectors

• Many are interrelated

• Identifying and characterizing

relevant exposure pathways

• Integrating risk into decision

frameworks

Applications

“Origins and Fate of PPCPs” Illustration by C.G. Daughton, U.S. EPA, NERL, Las Vegas, NV, February 2001 (revised March 2006); Source:

http://www.epa.gov/ppcp/basic2.html

Applications

Consumer Products

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Release

Reaction

ProductUse

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Population

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Water

Outdoor

Air

Surface

Dust

A C

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Soil

Indoor

Air

Food

ChemicalManufacture

ChemicalTransportation

Production/Formulation

WorkplaceExposure

EnvironmentalRelease

EnvironmentalDisposal

Air

Water

Incineration

RecyclingSewage

Treatment

Food

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Land

Transport

HumanExposure

HumanExposure

Food

Water

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HumanExposureProductDisposal

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RELEASE FATE / TRANSPORT CONCENTRATION ACTIVITY EXPOSURE

EnvironmentalRelease

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ProductUse

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Water

Outdoor

Air

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Soil

Indoor

Air

Food

ChemicalManufacture

ChemicalTransportation

Production/Formulation

WorkplaceExposure

EnvironmentalRelease

EnvironmentalDisposal

Air

Water

Incineration

RecyclingSewage

Treatment

Food

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HumanExposure

HumanExposure

Food

Water

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HumanExposureProductDisposal

Air

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RELEASE FATE / TRANSPORT CONCENTRATION ACTIVITY EXPOSURE

EnvironmentalRelease

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ProductUse

Location

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Market Share

Location

FrequencyTiming

Population

Market Share

Water

Outdoor

Air

Surface

Dust

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T I

V I

T I

E S

Soil

Indoor

Air

Food

ChemicalManufacture

ChemicalTransportation

Production/Formulation

WorkplaceExposure

EnvironmentalRelease

EnvironmentalDisposal

Air

Water

Incineration

RecyclingSewage

Treatment

Food

A C

T I

V I

T I

E S

Land

Transport

HumanExposure

HumanExposure

Food

Water

Land

HumanExposureProductDisposal

Air

A C

T I

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E S

RELEASE FATE / TRANSPORT CONCENTRATION ACTIVITY EXPOSURE

EnvironmentalRelease

Exposure-based prioritization

• Focuses on chemicals (or byproducts) intentionally manufactured for commercial use

• Understanding the intersection of inherent properties, purpose, form and use.

• Identifying high-throughput methods and models to estimate exposure potential

Antibiotic Resistance

■ The World Health Organization cites antibiotic resistance as one of the most critical health challenges of the next century.

■ Antibiotic use plays a major role in the emerging public health crisis of antibiotic resistance.

– Majority of antibiotic use in the United States occurs in agricultural settings,

– Relatively little research regarding how antibiotic use in farm animals contributes to the overall problem of antibiotic resistance.

■ Use of antibiotics and discharge into the environment may encourage horizontal gene transfer to human commensal gut bacteria and/or pathogens

Risk assessment models across food safety pathway

HGT ???

Multi-criteria Decision Analysis for Antibiotic Usage

•Properties

•Withdrawal periods

•Degradation rates

•Bioavailability

•Disposal

•Irrigation

•Treatment

•Associated disease prevalence

•Regional population analysis

•Production

•Availability

•Indications

•Administration

Usage Excretion

FatePractices

LINKING ANTIBIOTIC USAGE ON DAIRY FARMSTO PROLIFERATION OF ANTIMICROBIAL

RESISTANCE

Objectives

Evaluates the usage of a β-lactam antibiotic (Cephalosporin) at the Kellogg Biological Station (KBS) Pasture Dairy

■ To investigate the fate and transport of antimicrobial resistance in agricultural lands.

■ To determine the effects of manure management practices on the delivery of antimicrobial resistance in the environment.

■ To identify the conditions promoting the transport of antimicrobialresistant genes to environment.

■ To monitor temporal and spatial variations in the abundance of antimicrobal resistant genes in manure, soil, and groundwater.

■ To identify the correlations in the co-occurrence of clusters of identical antimicrobial resistance genes in impacted soils and groundwater.

Kellogg Biological Station

The W.K. Kellogg Biological Station is Michigan State University’s largest off-campus education complex close to

Kalamazoo in south west Michigan.

Manure application methods at KBS farms

■ Slurry surface application

■ Compost surface application

■ Bed-pack surface application

KBS

■ KBS Pasture Dairy primarily administered ceftiofur, a β-lactam antibiotic (a class of cephalosporins deemed critically important in human medicine) to treat mastitis and foot rot.

■ The use of ceftiofur antibiotics at the KBS Dairy did require a blanket veterinary prescription, however, individual treatment decisions were made by lay farm workers in accordance with manufacturer’s guidelines.

■ Other antimicrobials intermittently administered at the dairy include tulathromycin for respiratory infection and oxyteracyclinefor conjunctivitis.

■ The herd, consisting of approximately 160 milking-age cows, was predominantly maintained on rotationally grazed pastures from April-November, with access to the barn, and then housed exclusively in the barn during winter months.

Sampling

■ Animal feces

■ Several wells nearby

■ Animal feed and drinking water before animal contact

■ Animal feed and drinking water after animal contact

■ Lakes nearby

■ Manure compost

■ Slurry

■ Animals drinking water

■ Soils at three depths in fields where manure in slurry, compost, and bed-pack forms were applied last year

■ Soils at three depths in fields where manure in slurry, compost, and bed-pack forms were applied an hour before sampling

Proportion of positive qPCR assays to total assay (%)

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Stagnat slurry Compost Agitated lagoon Beded-pack Feces

Proportion of positive assays in slurry, compost, bed-pack and cow feces

Proportion of positive assays in water samples

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Potable water from a well adjacent to the dairy barn

Non-potable (for human) water from cistern

Water from where cows drink

Prairieville Creek

Well beside Field 508

Duck Lake

Future Work

■ Studying the physical, chemical, and microbiological processes affecting the fate and transport of antimicrobial resistance in dairy farms.

■ Modelling the fate and transport of antimicrobial resistance in the farm environment.

■ Studying the mitigation strategies associated with antimicrobial resistance from agricultural lands through risk-based manure management strategies.

Acknowledgements

■ Dr. Sina Akram

■ Dr. Robert Stedtfeld

■ Alexandre Chabrelie, BAE Graduate Student

■ Center for Health Impacts of Agriculture