the feline thyroid gland: a model for endocrine disruption by polybrominated diphenyl ethers?
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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 PresentationTRANSCRIPT
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
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)
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)
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”
Where are PBDEs? Where are PBDEs?
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
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
?
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
Future ResearchFuture Research
ADME:Half-life studies
Enzyme Induction
TR Effects:RC3/Neurogranin
Thyroid Effects:cAMPmRNA
Broader Implications
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
ILLINOIS SUSTAINABLE TECHNOLOGY
CENTER
THANKS!!!