Pesticide Health Effects Medical Education Database (PHEMED)

Effects of Pesticides on the Effects of Pesticides on the Endocrine SystemEndocrine System

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DefinitionDefinition

Synthetic chemicals that mimic hormones Synthetic chemicals that mimic hormones Disruption by:Disruption by:

Receptors over-respond to the mimic Receptors over-respond to the mimic Receptors respond at inappropriate timesReceptors respond at inappropriate times Block a receptor by competing with other hormonesBlock a receptor by competing with other hormones Stimulate or inhibit the endocrine system causing over Stimulate or inhibit the endocrine system causing over

or under production of natural hormones (thyroid)or under production of natural hormones (thyroid)

Chemicals with established links to Chemicals with established links to endocrine disruptionendocrine disruption

DES – diethylstibesterol Dioxins – CDD’s polychlorinated dioxins

PCB’s – polychlorinated biphenyls DDT

mimics estrogen DDE (major byproduct) interferes with

testosterone function

DESDES

Vaginal CA in offspring of women taking DES as Vaginal CA in offspring of women taking DES as morning after pill or during pregnancy to avert morning after pill or during pregnancy to avert SAB’sSAB’s

DES daughters increased risk for infertility, DES daughters increased risk for infertility, miscarriages, ectopic pregnancies. miscarriages, ectopic pregnancies.

DES sons: evidence of increased risk: DES sons: evidence of increased risk: undescended testicles undescended testicles smaller penis sizesmaller penis size poorer sperm qualitypoorer sperm quality

Dioxins

Formed during:Formed during: chlorine bleaching process at pulp and paper millschlorine bleaching process at pulp and paper mills chlorination of waster and water treatmentchlorination of waster and water treatment contaminant of chlorinated phenols (contaminant of chlorinated phenols (2,4,5-TCP, PCP)

chlorinated pesticides or herbicides (such as 2,4,5-T, older 2,4-D, hexachlorophene, Silvex® ) none ) none currently in usecurrently in use

Agent Orange (combination of Agent Orange (combination of 2,4,5-T+ 2,4-D) Interferes with sex hormones Interferes with sex hormones

PCB’s Persists in the environment + body (lipophylic) Banned uses that would disperse PCB’s:

plasticizers in paints and cements fire retardant fabric treatments heat stabilizing additives for PVC electrical insulation Adhesives/ paints and water-proofing railway ties

Continued use in ‘closed systems’ capacitors and insulating fluids in transformers vacuum pump fluids and hydraulic fluids

Human exposure appliances, fluorescent light fixtures, electrical equipment > 30 years

old Contaminated food (contaminated fish, dairy, meat) Air from hazardous waste sites Workplaces where closed systems are repaired

Minics estrogen + interferes with thyroid hormones

Pesticides Suspected to be Endocrine Disruptors

Herbicides:

2,4-D Amitrole Metribuzin

Alachlor Atrazine Nitrofen*

Trifluralin

http://www.nrdc.org/health/kids/ocar/chap5e.asp

Pesticides Suspected to be Endocrine Disruptors

Fungicides:

Benomyl Maneb Vinclozolin

Fenarimol Metiram Zineb

Mancozeb Tributyltin Ziram

Fumigants:DBCP*

http://www.nrdc.org/health/kids/ocar/chap5e.asp

Pesticides Suspected to be Endocrine Disruptors

Insecticides:

Aldicarb Endosulfan Methomyl

Aldrin* Endrin* Methoxychlor

Carbaryl Fenvalerate Mirex*

Chlordane* Heptachlor* Parathion*

Dicofol Kepone* Pentachlorophenol

Dieldrin* Lindane Permethrin

Malathion Toxaphene*

http://www.nrdc.org/health/kids/ocar/chap5e.asp

Health Effects of Endocrine Disruptors (ED’s) in Humans

No firm causal evidence w/low exposureNo firm causal evidence w/low exposure Suggestive relationship with : Suggestive relationship with :

Reproduction Reproduction EndometriosisEndometriosis Precocious pubertyPrecocious puberty Nural functionNural function Immune functionImmune function Cancers: breast, endometrial, testicular, prostate, Cancers: breast, endometrial, testicular, prostate,

thyroidthyroid

Source: WHO/IPCS. Global assessment of the state-of-the-science of endocrine disruptors. WHO/PCS/EDC/02.2

ReproductiveReproductive

Decline in human sperm qualityDecline in human sperm quality Meta analysis studies reached different conclusions Meta analysis studies reached different conclusions Not necessarily due to endocrine disrupters (ED’s)Not necessarily due to endocrine disrupters (ED’s)

Impaired fertility and increased SAB’sImpaired fertility and increased SAB’s Relationship to ED’s speculativeRelationship to ED’s speculative

Declining sex ratiosDeclining sex ratios Evidence of unidentified external causes but mechanism Evidence of unidentified external causes but mechanism

unknownunknown Developmental male reproductive tract Developmental male reproductive tract

abnormalitiesabnormalities ED exposure evidence unclear ED exposure evidence unclear Experimental data with a number of chemicals Experimental data with a number of chemicals

demonstrate they can disrupt male reproductive tracts. demonstrate they can disrupt male reproductive tracts.

GynecologicalGynecological

EndometriosisEndometriosis Association with ED reported but studies Association with ED reported but studies

equivocalequivocal Precocious PubertyPrecocious Puberty

Concern regarding influence of ED’s on early Concern regarding influence of ED’s on early onset of pubertyonset of puberty

Role of other factors such as nutrition needs Role of other factors such as nutrition needs clarification clarification

Neural FunctionNeural Function

Prenatal exposure to ED’s (PCB’s) result Prenatal exposure to ED’s (PCB’s) result in neurodevelopmental, behavioral and in neurodevelopmental, behavioral and neuro-endocrine function problems. neuro-endocrine function problems.

Human and animal dataHuman and animal data Effects more likely a result of altered Effects more likely a result of altered

thyroid or neuro-transmitters.thyroid or neuro-transmitters. In most instances ED mechanism not In most instances ED mechanism not

demonstrated demonstrated

Immune FunctionImmune Function

Some ED’s alter human and animal Some ED’s alter human and animal immunityimmunity

Unknown if these alterations due to an Unknown if these alterations due to an endocrine mediated mechanismendocrine mediated mechanism

Cancers of Hormonally Sensitive OrgansCancers of Hormonally Sensitive Organs

Temporal association between rise in Temporal association between rise in hormone sensitive organ cancers and hormone sensitive organ cancers and wide spread use of industrial chemicalswide spread use of industrial chemicals

Increase incidence not explained by Increase incidence not explained by improved diagnostic techniques. improved diagnostic techniques.

Hypothesis – is it from ED’s? Hypothesis – is it from ED’s?

Breast CancerBreast Cancer

Studies measuring DDE (DDT metabolite Studies measuring DDE (DDT metabolite stored in fat tissue) in adult women do not stored in fat tissue) in adult women do not support a causative relationship.support a causative relationship.

New study measuring the more active New study measuring the more active p,p´-DDT metabolite in frozen blood from metabolite in frozen blood from women at delivery from the 1950’s show a women at delivery from the 1950’s show a 5 fold relationship. *5 fold relationship. *

*Cohen et al. (2007) DDT and Breast Cancer in Young Women: New Data on the Significance of Age at Exposure. EHP. 115(10) 1406-1414.

Other CancersOther Cancers

Endometrial - limited data – no causal Endometrial - limited data – no causal relationship established. relationship established.

Prostate – some associations positive and Prostate – some associations positive and some negative. Mechanism unknown.some negative. Mechanism unknown.

Testicular – temporal rise without link to Testicular – temporal rise without link to same time frame as use of ED’s same time frame as use of ED’s

Thyroid – no direct link to ED exposure Thyroid – no direct link to ED exposure has been demonstrated. has been demonstrated.

Future Future

Adverse health outcomes appear biologically Adverse health outcomes appear biologically plausible given: plausible given: Known effects of endogenous and exogenous Known effects of endogenous and exogenous

hormones sensitive organshormones sensitive organs Demonstrated effects on wildlife and laboratory Demonstrated effects on wildlife and laboratory

animals animals They are a high priority research area is They are a high priority research area is

required – required – EPA required to screen products for potential EPA required to screen products for potential

effects on the endocrine systemeffects on the endocrine system Other non-ED mechanisms must also be Other non-ED mechanisms must also be

explored explored