The Feline Thyroid Gland: A Model for Endocrine Disruption by Polybrominated Diphenyl Ethers?

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The Feline Thyroid Gland: The Feline Thyroid Gland: A Model for Endocrine A Model for Endocrine Disruption by Disruption by Polybrominated Diphenyl Polybrominated Diphenyl Ethers? Ethers? Donna Mensching, DVM, MS, DABVT, Donna Mensching, DVM, MS, DABVT, DABT DABT September 29, 2010 September 29, 2010

description

The Feline Thyroid Gland: A Model for Endocrine Disruption by Polybrominated Diphenyl Ethers?. Donna Mensching, DVM, MS, DABVT, DABT September 29, 2010. Feline Hyperthyroidism. Autonomously functional thyroid adenoma(s). Analogous to toxic multinodular goiter (TNG). - PowerPoint PPT Presentation

Transcript of The Feline Thyroid Gland: A Model for Endocrine Disruption by Polybrominated Diphenyl Ethers?

Page 1: The Feline Thyroid Gland: A Model for Endocrine Disruption by Polybrominated Diphenyl Ethers?

The Feline Thyroid Gland:The Feline Thyroid Gland:A Model for Endocrine Disruption byA Model for Endocrine Disruption by

Polybrominated Diphenyl Ethers?Polybrominated Diphenyl Ethers?

Donna Mensching, DVM, MS, DABVT, DABTDonna Mensching, DVM, MS, DABVT, DABTSeptember 29, 2010September 29, 2010

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Autonomously functional thyroid adenoma(s)Autonomously functional thyroid adenoma(s)

Excess thyroid hormones Excess thyroid hormones

Hypermetabolic stateHypermetabolic state

New York City, 1979New York City, 1979

A geriatric disease A geriatric disease

Most common endocrinopathy in catsMost common endocrinopathy in cats

“ “Benign” but quality of life is poorBenign” but quality of life is poor

Feline HyperthyroidismFeline Hyperthyroidism

Analogous to toxic multinodular goiter (TNG)Analogous to toxic multinodular goiter (TNG)

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Epidemiologic Risk Factors for Feline HyperthyroidismEpidemiologic Risk Factors for Feline Hyperthyroidism

Canned food (2.5-5.64)Canned food (2.5-5.64)Pop-top cans in malesPop-top cans in males

Variety of flavors of food (3.8)Variety of flavors of food (3.8)Liver and giblets-flavored foodLiver and giblets-flavored food

Fish-flavored foodFish-flavored foodBaby food as kittens (5)Baby food as kittens (5)Lawn and flea productsLawn and flea products

Bedding treated with flea products (57.6)Bedding treated with flea products (57.6)Exposure to fly sprays (3.3)Exposure to fly sprays (3.3)

Use of litter box (2.57)Use of litter box (2.57)Indoor housingIndoor housing

Increased age (1.21/yr)Increased age (1.21/yr)Periodontal disease (5.5)Periodontal disease (5.5)

Female sex (3.3)Female sex (3.3)Non-Siamese Breed (0.44)Non-Siamese Breed (0.44)

Non-Himalayan Breed (0.29)Non-Himalayan Breed (0.29)Sleeping predominantly on floor (6.6)Sleeping predominantly on floor (6.6)

Drinking water from puddles (5.3)Drinking water from puddles (5.3)Regular use of organic fertilizers (5.3)Regular use of organic fertilizers (5.3)

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What are PBDEs? What are PBDEs? Polybrominated Diphenyl EthersPolybrominated Diphenyl Ethers

Flame Retardants: Manufactured since 1970sFlame Retardants: Manufactured since 1970s

209 Congeners209 Congeners3 Commercial Mixtures:3 Commercial Mixtures:““Penta” “Octa” “Deca”Penta” “Octa” “Deca”

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Where are PBDEs? Where are PBDEs?

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PBDE Burdens in WildlifePBDE Burdens in Wildlife

Polar Bear ~70 ppb lipidHarbor seals (Dutch coast) >100 ppb w/wSperm whales (Dutch coast) ~100 ppb w/w

Whitebeaked dolphin (Dutch coast) >700 ppb w/wBeluga whales (Quebec) ~1,000 ppb w/w

Pilot whales (Faroe Islands) 3,160 ppb lipidOrca/Killer whale (Pacific NW) 8,560 ppb w/wBottlenose Dolphins (SE US) 22,780 ppb lipid

*Peregrine Falcon eggs (Sweden) 39,000 ppb lipid

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Endocrine Disruptive Properties of PBDEsEndocrine Disruptive Properties of PBDEs

Viberg et al., 2003-2007Viberg et al., 2003-2007

Impaired Spontaneous Impaired Spontaneous Behavior:Behavior:

Decreased HabituationDecreased HabituationHyperactivity Hyperactivity

Altered LearningAltered LearningAnd MemoryAnd Memory

?

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Endocrine Disruptive Properties of PBDEsEndocrine Disruptive Properties of PBDEs

Thyroid HormoneThyroid Hormone

vsvs

BrBr

Br Br

BrBr

BrBrBrBr

Hydroxylated Hydroxylated Metabolites of PBDESMetabolites of PBDES

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Endocrine Disruptive Properties of PBDEsEndocrine Disruptive Properties of PBDEs

Meerts et al., 2000Meerts et al., 2000

Induction Induction ofof

phase Iphase Iandand

phase IIphase IIenzymesenzymes(UDPGT)(UDPGT)

Norris et al., 1975Norris et al., 1975

Stoker et al., 2004Stoker et al., 2004

Kuriyama et al. 2007Kuriyama et al. 2007

Marsh et al. 1998Marsh et al. 1998

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Research ObjectivesResearch Objectives

Compare PBDE burdens in serum & adipose tissue in age-matched Compare PBDE burdens in serum & adipose tissue in age-matched euthyroid vs hyperthyroid cats to determine if hyperthyroidism euthyroid vs hyperthyroid cats to determine if hyperthyroidism

correlates with higher residuescorrelates with higher residues

Evaluate the PBDE content of commercial canned cat foods & Evaluate the PBDE content of commercial canned cat foods & household dust to identify predominant exposure sources household dust to identify predominant exposure sources

for domestic catsfor domestic cats

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Materials and MethodsMaterials and Methods

Silica Gel ChromatographySilica Gel Chromatography

GC/HRMS Analysis of Sample Extracts for PBDEs: GC/HRMS Analysis of Sample Extracts for PBDEs: Congeners 17, Congeners 17, 2828, , 4747, 49, 66, 71, 85, , 49, 66, 71, 85, 9999, , 100100, 138, , 138, 153153, , 154154, , 183183, 190, and , 190, and 209209

Sample Extraction:Sample Extraction:Liquid-liquid/PFELiquid-liquid/PFE

Gel Permeation ChromatographyGel Permeation Chromatography

Lipid Determination: Sulfo-Phospho-Vanillin ReactionLipid Determination: Sulfo-Phospho-Vanillin Reaction

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Blanks/Reagent BlanksBlanks/Reagent BlanksDuplicatesDuplicates

Spiked samplesSpiked samplesSurrogates: BDE-118R and 209RSurrogates: BDE-118R and 209R

Internal standards: FR-250 and BZ209Internal standards: FR-250 and BZ209

Quality Assurance/Quality ControlQuality Assurance/Quality Control

AccuracyAccuracy

PrecisionPrecision

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Total Serum PBDEs (ng/g lipid) Total Serum PBDEs (ng/g lipid)

Client-ownedClient-owned(n = 62)(n = 62)

Range: 370-51,000Range: 370-51,000Median: 2,615Median: 2,615

Euthyroid Euthyroid (n = 21)(n = 21)

Range: 470-16,000Range: 470-16,000Median: 2,851Median: 2,851

HyperthyroidHyperthyroid(n = 41)(n = 41)

Range: 370-51,000Range: 370-51,000Median: 2,517Median: 2,517

FeralFeral(n = 8)(n = 8)

Range: 460-3,700Range: 460-3,700Median: 759Median: 759

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Total Serum PBDEs (ng/g lipid) Total Serum PBDEs (ng/g lipid)

Client-ownedClient-owned(n = 62)(n = 62)

Range: 370-51,000Range: 370-51,000Median: 2,615Median: 2,615

Euthyroid Euthyroid (n = 21)(n = 21)

Range: 470-16,000Range: 470-16,000Median: 2,851Median: 2,851

HyperthyroidHyperthyroid(n = 41)(n = 41)

Range: 370-51,000Range: 370-51,000Median: 2,517Median: 2,517

FeralFeral(n = 8)(n = 8)

Range: 460-3,700Range: 460-3,700Median: 759Median: 759

p = 0.008p = 0.008

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Comparison of Log PBDEs (lipid weight) in Serum of Comparison of Log PBDEs (lipid weight) in Serum of Client-Owned Euthyroid (a) and Hyperthyroid (b) Cats vs AgeClient-Owned Euthyroid (a) and Hyperthyroid (b) Cats vs Age

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Research ObjectivesResearch Objectives

Compare PBDE burdens in serum & adipose tissue in age-matched Compare PBDE burdens in serum & adipose tissue in age-matched euthyroid vs hyperthyroid cats to determine if hyperthyroidism euthyroid vs hyperthyroid cats to determine if hyperthyroidism

correlates with higher residuescorrelates with higher residues

Evaluate the PBDE content of commercial canned cat foods & Evaluate the PBDE content of commercial canned cat foods & household dust to identify predominant exposure sources household dust to identify predominant exposure sources

for domestic catsfor domestic cats

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PBDEs in Commercial Canned Cat FoodsPBDEs in Commercial Canned Cat Foods

Brand and FlavorBrand and Flavor ΣPBDEs ΣPBDEs (ng/g w/w)(ng/g w/w)Fancy Feast Cod, Sole & Shrimp FeastFancy Feast Cod, Sole & Shrimp Feast 3.09 3.09 Meijer Main Choice Salmon DinnerMeijer Main Choice Salmon Dinner 3.01 3.01Fancy Feast Trout FeastFancy Feast Trout Feast 1.90 1.90Purina Friskies Pacific Salmon Dinner in Sauce 1.90 Purina Friskies Pacific Salmon Dinner in Sauce 1.90 9 Lives Ocean Whitefish Dinner (n = 2)9 Lives Ocean Whitefish Dinner (n = 2) 1.80 1.80Fancy Feast Tuna in GravyFancy Feast Tuna in Gravy 1.70 1.70Fancy Feast Ocean Whitefish & Tuna Feast Fancy Feast Ocean Whitefish & Tuna Feast 1.70 1.70 Meijer Main Choice Ocean Whitefish & Tuna Dinner 0.75Meijer Main Choice Ocean Whitefish & Tuna Dinner 0.75Purina Friskies Ocean Whitefish & Tuna DinnerPurina Friskies Ocean Whitefish & Tuna Dinner 0.42 0.42

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Summary of Total PBDEs in DustSummary of Total PBDEs in Dust

Total of Total of Dust Samples Dust Samples

(n = 19)(n = 19)Range: 510-95,000Range: 510-95,000

Median: 1,959Median: 1,959

Hyperthyroid CatsHyperthyroid Cats(n = 7) (n = 7)

Range: 1,100-95,000Range: 1,100-95,000Median: 17,177Median: 17,177

Euthyroid CatsEuthyroid Cats(n = 12) (n = 12)

Range: 510-4,900Range: 510-4,900Median: 782Median: 782

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Summary of Total PBDEs in DustSummary of Total PBDEs in Dust

Total of Total of Dust Samples Dust Samples

(n = 19)(n = 19)Range: 510-95,000Range: 510-95,000

Median: 1,959Median: 1,959

Hyperthyroid CatsHyperthyroid Cats(n = 7) (n = 7)

Range: 1,100-95,000Range: 1,100-95,000Median: 17,177Median: 17,177

Euthyroid CatsEuthyroid Cats(n = 12) (n = 12)

Range: 510-4,900Range: 510-4,900Median: 782Median: 782 ≠≠

p = 0.002p = 0.002

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From Canned Food:From Canned Food:Assumes 5 oz of food/day and 5 kg BWAssumes 5 oz of food/day and 5 kg BW

Mean: 51 ng/kg/dayMean: 51 ng/kg/dayRange: 12-91 ng/kg/dayRange: 12-91 ng/kg/day

From Dust:From Dust:Assumes 200 mg of dust ingested/dayAssumes 200 mg of dust ingested/day

Mean: 320 ng/kg/dayMean: 320 ng/kg/dayRange: 20-3,800 ng/kg/dayRange: 20-3,800 ng/kg/day

Calculated Daily Intake of PBDEs in CatsCalculated Daily Intake of PBDEs in Cats

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Both Sources:Both Sources:Mean: 371 ng/kg/dayMean: 371 ng/kg/day

Range: 32-3,900 ng/kg/dayRange: 32-3,900 ng/kg/day

Calculated Daily Intake of PBDEs in CatsCalculated Daily Intake of PBDEs in Cats

At the high end,At the high end, this represents 1.3% of the this represents 1.3% of the lowestlowest singlesingle acutelyacutely toxictoxic

PBDE dose known to disrupt thyroid function PBDE dose known to disrupt thyroid function in laboratory animals.in laboratory animals.

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Domestic cats are highly exposed to PBDEs Domestic cats are highly exposed to PBDEs with the highest recorded levels on the planet:with the highest recorded levels on the planet:51,063 vs previous high of 39,000 ng/g lipid51,063 vs previous high of 39,000 ng/g lipid

ConclusionsConclusions

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Domestic cats are highly exposed to PBDEs Domestic cats are highly exposed to PBDEs with the highest recorded levels on the planetwith the highest recorded levels on the planet::51,063 vs previous high of 39,000 ng/g lipid51,063 vs previous high of 39,000 ng/g lipid

Total PBDE serum burdens do not significantly Total PBDE serum burdens do not significantly differ between client-owned differ between client-owned

euthyroid and hyperthyroid cats. euthyroid and hyperthyroid cats.

ConclusionsConclusions

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Feral cats have significantly lower PBDE burdens Feral cats have significantly lower PBDE burdens in serum than both euthyroid and in serum than both euthyroid and

hyperthyroid client-owned (older) cats.hyperthyroid client-owned (older) cats.

ConclusionsConclusions

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Feral cats have significantly lower PBDE burdens Feral cats have significantly lower PBDE burdens in serum than both euthyroid and in serum than both euthyroid and

hyperthyroid client-owned (older) cats.hyperthyroid client-owned (older) cats.

Dust is likely the primary route of Dust is likely the primary route of exposure of domestic cats to PBDEs.exposure of domestic cats to PBDEs.

ConclusionsConclusions

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Feral cats have significantly lower PBDE burdens Feral cats have significantly lower PBDE burdens in serum than both euthyroid and in serum than both euthyroid and

hyperthyroid client-owned (older) cats.hyperthyroid client-owned (older) cats.

Dust is likely the primary route of Dust is likely the primary route of exposure of domestic cats to PBDEs.exposure of domestic cats to PBDEs.

Total PBDEs were significantly higher in dust from Total PBDEs were significantly higher in dust from homes of hyperthyroid cats versus homes of euthyroid cats.homes of hyperthyroid cats versus homes of euthyroid cats.

ConclusionsConclusions

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The Feline Thyroid Gland:The Feline Thyroid Gland:A Model for Endocrine Disruption byA Model for Endocrine Disruption by

Polybrominated Diphenyl Ethers?Polybrominated Diphenyl Ethers?

X

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The Feline Thyroid Gland:The Feline Thyroid Gland:A Model for Endocrine Disruption byA Model for Endocrine Disruption by

Polybrominated Diphenyl Ethers?Polybrominated Diphenyl Ethers?

X

MAYBEMAYBE

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Future ResearchFuture Research

ADME:Half-life studies

Enzyme Induction

TR Effects:RC3/Neurogranin

Thyroid Effects:cAMPmRNA

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Broader Implications

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THANKS!!!

My Committee:Dr. Val BeasleyDr. Duncan FergusonDr. Susan SchantzDr. Thomas Graves

Dr. Colleen Currigan & Staff, Cat Hospital of ChicagoDr. Robert Badertscher & Staff, Arboretum View Animal Hospital

Dr. Stephen Gardner & Staff, VCA of Albany, CaliforniaVeterinary Information Network

University of Illinois Campus Research BoardDr. David SchaefferDr. Margaret Slater

VB Departmental Staff

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ILLINOIS SUSTAINABLE TECHNOLOGY

CENTER

THANKS!!!