The effect of The effect of environmental environmental pollutants on pollutants on thyroid and thyroid and reproductive reproductive

functionfunctionWalter J. Crinnion NDWalter J. Crinnion ND

Xenobiotics and ThyroidXenobiotics and Thyroid

PCBs, Thyroxine, Bisphenol A all PCBs, Thyroxine, Bisphenol A all have two joined benzene rings with have two joined benzene rings with attached halogens (at similar sites).attached halogens (at similar sites).

PCBs, PCDDs, PCDFs bind PCBs, PCDDs, PCDFs bind transthyrethrin in vitro, but not transthyrethrin in vitro, but not thyroxine-binding globulin.thyroxine-binding globulin.

Also adversely effect thyroid Also adversely effect thyroid hormone metabolizing enzymes in hormone metabolizing enzymes in liver and brain liver and brain

PBDE and ThyroidPBDE and Thyroid

Reduced thyroid hormone serum Reduced thyroid hormone serum levelslevels PBDE metabolites interfere with PBDE metabolites interfere with

binding to thyroid hormone transport binding to thyroid hormone transport protein.protein.

PBDE increases metabolism of thyroid PBDE increases metabolism of thyroid hormonehormone

Effect additive if PCBs also presentEffect additive if PCBs also present

PCBs and ThyroidPCBs and Thyroid

PCB plant workersPCB plant workers Elevated anti-TPOElevated anti-TPO Elevated anti-thyroglobulinElevated anti-thyroglobulin No out-of-range T4 or TSHNo out-of-range T4 or TSH

Female Swedish fish eaters (Baltic fish)Female Swedish fish eaters (Baltic fish) Inverse correlation with TT3 (significant)Inverse correlation with TT3 (significant) Inverse correlation with TT4 (insignificant)Inverse correlation with TT4 (insignificant)

Polyhalogens and Polyhalogens and ThyroidThyroid

German ChildrenGerman Children Pos. correlation PCB and TSH Pos. correlation PCB and TSH

(significant)(significant) Inverse correlation PCB & fT4 Inverse correlation PCB & fT4

(significant)(significant) Canadian NewbornsCanadian Newborns

PCP inversely correlated with fT4PCP inversely correlated with fT4 German womenGerman women

PCP inversely correlated with basal T3PCP inversely correlated with basal T3

Acute OP poisoningAcute OP poisoning

31.8 % experience sick euthyroid 31.8 % experience sick euthyroid syndromesyndrome Low FT3, FT4 or TSHLow FT3, FT4 or TSH

Other hormonal abnormalitiesOther hormonal abnormalities Elevated cortisol, ACTH, prolactinElevated cortisol, ACTH, prolactin

Pesticides and thyroidPesticides and thyroid

Pesticide (OP) formulatorsPesticide (OP) formulators Low TT3 (significant)Low TT3 (significant) Elevated TSH (non-significant)Elevated TSH (non-significant)

Pesticide (OP) applicators – low TSH Pesticide (OP) applicators – low TSH (seasonal)(seasonal)

Persons using dithiocarbamates Persons using dithiocarbamates from backpack sprayerfrom backpack sprayer Increased TSHIncreased TSH

TCDD and ThyroidTCDD and Thyroid

Operation Ranch Hand Air Force Operation Ranch Hand Air Force personnelpersonnel

Serum levels of TCDD and TSHSerum levels of TCDD and TSH Those with highest TCDD had Those with highest TCDD had

significantly elevated TSH.significantly elevated TSH.

Heavy Metals and Heavy Metals and ThyroidThyroid

Cadmium serum levelsCadmium serum levels Elevated TSH and low FT4 (non Elevated TSH and low FT4 (non

significant)significant) Lead Serum levelsLead Serum levels

Low T4, TSH and TRH (significant)Low T4, TSH and TRH (significant) Hg vapor – workersHg vapor – workers

Increased rT3Increased rT3

Female Fertility and Female Fertility and Reproductive OutcomesReproductive Outcomes

Reproductive Outcomes Reproductive Outcomes

Associated WithAssociated WithDifferent OccupationsDifferent Occupations

Female Navy PersonnelFemale Navy Personnel

Exposed to petroleum products, Exposed to petroleum products, solvents, heavy metals.solvents, heavy metals.

33% experienced adverse birth 33% experienced adverse birth outcomes compared to 0% in civilian outcomes compared to 0% in civilian control group.control group. Fetal distressFetal distress - low birth weight- low birth weight Preterm deliveryPreterm delivery - Birth defects- Birth defects Small for gestational age babiesSmall for gestational age babies

Female Vietnam VetsFemale Vietnam Vets

OR 1.46 for having children with OR 1.46 for having children with moderate to severe birth defectsmoderate to severe birth defects 2,4-D and 2,4,5-T ?2,4-D and 2,4,5-T ? Controls were contemporary female Controls were contemporary female

vetsvets

Ontario farmersOntario farmers

Pesticide exposure and infertility RR Pesticide exposure and infertility RR 3.83.8

Dicamba – FR 0.51Dicamba – FR 0.51 Glyphosate – FR 0.61Glyphosate – FR 0.61 2,4-D – FR 0.712,4-D – FR 0.71 OP – FR 0.75OP – FR 0.75 Thiocarbamates – FR 0.76Thiocarbamates – FR 0.76

Reproductive OutcomeReproductive OutcomeAssociated With Associated With

Different XenobioticsDifferent Xenobiotics

Organophosphates (OPs)Organophosphates (OPs)

Higher spontaneous abortion rates Higher spontaneous abortion rates in Spanish greenhouse workers.in Spanish greenhouse workers. Also more depression and headachesAlso more depression and headaches No reduction in acetylcholinesteraseNo reduction in acetylcholinesterase

In California higher fetal death due In California higher fetal death due to congenital anomalies (wk 3-8)to congenital anomalies (wk 3-8) OR 1.4 if spraying within 8 sq milesOR 1.4 if spraying within 8 sq miles OR 2.2 if spraying within 1 sq milesOR 2.2 if spraying within 1 sq miles

Organochlorine Organochlorine compoundscompounds

Serum HCH levels sign assoc w/ Serum HCH levels sign assoc w/ miscarriage and uterine fibroids.miscarriage and uterine fibroids. HCH and PCB assoc w/ anti-thyroid and ANAHCH and PCB assoc w/ anti-thyroid and ANA

PCP assoc increased miscarriage and ANAPCP assoc increased miscarriage and ANA Incr FSH, cortisolIncr FSH, cortisol Decr T3, DHEA, Test, 17-OH progest, 17-OH-Decr T3, DHEA, Test, 17-OH progest, 17-OH-

pregnenpregnen PCB assoc endometriosis and miscarriagePCB assoc endometriosis and miscarriage DDT assoc reduced conception, preterm DDT assoc reduced conception, preterm

births and small for gestational age births and small for gestational age babiesbabies

Generational Effects of Generational Effects of DDT/EDDT/E

Women giving birth in Oakland, CAWomen giving birth in Oakland, CA Serum frozen, later checked for DDT/DDESerum frozen, later checked for DDT/DDE

Daughters followed 28-31 yearsDaughters followed 28-31 years Maternal levels of serum DDT assoc. Maternal levels of serum DDT assoc.

with reduced daughter fecundity (32% with reduced daughter fecundity (32% less).less).

Maternal levels of serum DDE assoc. Maternal levels of serum DDE assoc. with increased daughter fecundity with increased daughter fecundity (16%)(16%)

Cohn BA, Lancet 2003;361:2205-2206Cohn BA, Lancet 2003;361:2205-2206

SolventsSolvents

OR 1.76 for infertility with occup OR 1.76 for infertility with occup exposureexposure

OR 1.95 for tubal factor infertility “OR 1.95 for tubal factor infertility “ FR 0.47 with toluene workersFR 0.47 with toluene workers FR 0.79 with occup organic solvent FR 0.79 with occup organic solvent

exp.exp. Acetone FR 0.72Acetone FR 0.72

FR 0.36 for wives of solvent workersFR 0.36 for wives of solvent workers

SolventsSolvents

Chinese chemical workersChinese chemical workers OR 2.9 for spontaneous abortionsOR 2.9 for spontaneous abortions

OR 2.5 benzeneOR 2.5 benzene OR 1.8 gasolineOR 1.8 gasoline OR 2.3 hydrogen sulfideOR 2.3 hydrogen sulfide

Pharmaceutical workersPharmaceutical workers Increased risk spontaneous abortion Increased risk spontaneous abortion

from multiple solvent exposure (4 or from multiple solvent exposure (4 or more greatest)more greatest)

Still more on solventsStill more on solvents

Pharmacy assistantsPharmacy assistants Incr risk spontaneous abortions and Incr risk spontaneous abortions and

perinatal death with solvent exposureperinatal death with solvent exposure Forest workersForest workers

Miscarriage OR 2.77 and 2.82 for use of Miscarriage OR 2.77 and 2.82 for use of certain paints to mark treescertain paints to mark trees

Miscarriage OR 1.87 for herbicide exp.Miscarriage OR 1.87 for herbicide exp.

Environmental Tobacco Environmental Tobacco SmokeSmoke(ETS)(ETS)

Reduced fertility (FR 0.66) (OR 1.64)Reduced fertility (FR 0.66) (OR 1.64) Higher rates ectopic pregnancyHigher rates ectopic pregnancy Higher rates spontaneous abortionsHigher rates spontaneous abortions Higher rates stillbirths (OR 2.0)Higher rates stillbirths (OR 2.0) Higher rates infant mortality (OR Higher rates infant mortality (OR

1.8)1.8) Same even for moms who quit smoking Same even for moms who quit smoking

in the first trimester.in the first trimester.

Outdoor air pollutionOutdoor air pollutionPAHsPAHs

Ambient air pollution sign assoc with Ambient air pollution sign assoc with PAH-DNA adducts in maternal and PAH-DNA adducts in maternal and cord WBCscord WBCs

Higher PAH-DNA adducts sign assoc Higher PAH-DNA adducts sign assoc w/ lower birth rates, birth length and w/ lower birth rates, birth length and head circumference.head circumference.

Inverse correlation with serum Inverse correlation with serum cotinine and birth length and weightcotinine and birth length and weight

PAH-DNA adducts higher in infertile PAH-DNA adducts higher in infertile malesmales

PhthalatesPhthalates

DEHP in serum was highly DEHP in serum was highly significant in women with significant in women with endometriosis.endometriosis.

DEHP in cord blood gave a small but DEHP in cord blood gave a small but statistically significant increased risk statistically significant increased risk of pre-term delivery. of pre-term delivery.

Love Potion # 9Love Potion # 9

Musk ketoneMusk ketone Higher in women using perfume 4x Higher in women using perfume 4x

wklywkly Greater PMS complaintsGreater PMS complaints

Musk xyleneMusk xylene Lower estradiol and progesteroneLower estradiol and progesterone Greater luteal insufficiency and Greater luteal insufficiency and

infertilityinfertility Higher in women with miscarriage hx. Higher in women with miscarriage hx.

Hong Kong Seafood Hong Kong Seafood and Infertility & Hg and Infertility & Hg

levelslevelsInfertileGroup

Semen abn40 Unexp Infertility

Control 26

MalesN=176

40.6 44.2 31.2

FemalesN=181

33.2 37.0 17.5

Chlorination by-productsChlorination by-products

TrihalomethanesTrihalomethanes ChloroformChloroform BromodichloromethaneBromodichloromethane ChlorodibromomethaneChlorodibromomethane BromoformBromoform

Increased risk of stillbirth OR 2.6Increased risk of stillbirth OR 2.6 Increased risk miscarriages OR 1.98 Increased risk miscarriages OR 1.98

BDCMBDCM

Jeanette Sherman MD Jeanette Sherman MD Takes on Chlorpyrifos Takes on Chlorpyrifos

(Dursban)(Dursban) Four children w/ multiple congenital Four children w/ multiple congenital

defectsdefects Each with:Each with:

Ventricular, eye & palate defects, growth Ventricular, eye & palate defects, growth retardationretardation

Three with:Three with: Hydrocephaly, microcephaly, mental Hydrocephaly, microcephaly, mental

retardation, blindness, hypotonia, wide-retardation, blindness, hypotonia, wide-spread nipples, deformities of teeth, ears, spread nipples, deformities of teeth, ears, genitalsgenitals

Jeanette Sherman MDJeanette Sherman MD

Reviewed ALL known possible Reviewed ALL known possible causative agentscausative agents

All were exposed in utero to All were exposed in utero to chlorpyrifoschlorpyrifos

Chlorpyrifos exposure previously Chlorpyrifos exposure previously associated with similar human associated with similar human defects in one published case.defects in one published case.

EPA banned chlorpyrifos for non-EPA banned chlorpyrifos for non-agricultural use.agricultural use.

What to do in situations of What to do in situations of infertilityinfertility

Review of exposure/burdenReview of exposure/burden Environmental QuestionnaireEnvironmental Questionnaire Diet (EWG.org)Diet (EWG.org) Scorecard.orgScorecard.org Other s&s associated with chemical Other s&s associated with chemical

overloadoverload

Direct toxin Direct toxin measurementmeasurement

Flushed urine test for heavy metalsFlushed urine test for heavy metals Solvent & chlorinated serum levels Solvent & chlorinated serum levels

for those with high exposure (Accu for those with high exposure (Accu Chem 800-451-0116)Chem 800-451-0116) Genetic polymorphismsGenetic polymorphisms

T1/2T1/2

OP exposureOP exposure

Metabolite urine testingMetabolite urine testing Avoidance of exposure (food)Avoidance of exposure (food) High antioxidantsHigh antioxidants

Hg and heavy metal Hg and heavy metal burdenburden

DMSA or DMPS or EDTA/DMPS DMSA or DMPS or EDTA/DMPS combocombo

SupplementationSupplementation CleansingCleansing

Solvent OverloadSolvent Overload

Removal from exposure sourceRemoval from exposure source Masks & air purifiersMasks & air purifiers

Enhancement of clearanceEnhancement of clearance Glycine, glutamine & taurineGlycine, glutamine & taurine NACNAC Ascorbic acidAscorbic acid

Colonic irrigationsColonic irrigations