Pesticide Health Effects Medical Education Database (PHEMED) Effects of Pesticides on Effects of Pesticides on the Endocrine System the Endocrine System biology.clc.uc.edu
Dec 23, 2015
Pesticide Health Effects Medical Education Database (PHEMED)
Effects of Pesticides on the Effects of Pesticides on the Endocrine SystemEndocrine System
bio
log
y.cl
c.uc
.ed
u
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