Pesticide Health Effects Medical Education Database (PHEMED) Effects of Pesticides on the Endocrine System biology.clc.uc.edu

Definition 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 times Receptors respond at inappropriate times Block a receptor by competing with other hormones Block a receptor by competing with other hormones Stimulate or inhibit the endocrine system causing over or under production of natural hormones (thyroid) Stimulate or inhibit the endocrine system causing over or under production of natural hormones (thyroid)

Chemicals with established links to endocrine disruption DES – diethylstibesterol Dioxins – CDD’s polychlorinated dioxins PCB’s – polychlorinated biphenyls DDT mimics estrogen DDE (major byproduct) interferes with testosterone function

DES Vaginal CA in offspring of women taking DES as morning after pill or during pregnancy to avert SAB’s Vaginal CA in offspring of women taking DES as morning after pill or during pregnancy to avert SAB’s DES daughters increased risk for infertility, miscarriages, ectopic pregnancies. DES daughters increased risk for infertility, miscarriages, ectopic pregnancies. DES sons: evidence of increased risk: DES sons: evidence of increased risk: undescended testicles undescended testicles smaller penis size smaller penis size poorer sperm quality poorer sperm quality

Dioxins Formed during: Formed during: chlorine bleaching process at pulp and paper mills chlorine bleaching process at pulp and paper mills chlorination of waster and water treatment chlorination of waster and water treatment contaminant of chlorinated phenols ( ) none currently in use 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 currently 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-DAmitroleMetribuzin AlachlorAtrazineNitrofen* Trifluralin

Pesticides Suspected to be Endocrine Disruptors Fungicides: BenomylManebVinclozolin FenarimolMetiramZineb MancozebTributyltinZiram Fumigants: DBCP*

Pesticides Suspected to be Endocrine Disruptors Insecticides: AldicarbEndosulfanMethomyl Aldrin*Endrin*Methoxychlor CarbarylFenvalerateMirex* Chlordane*Heptachlor*Parathion* DicofolKepone*Pentachlorophenol Dieldrin*LindanePermethrin MalathionToxaphene*

Health Effects of Endocrine Disruptors (ED’s) in Humans Health Effects of Endocrine Disruptors (ED’s) in Humans No firm causal evidence w/low exposure Suggestive relationship with : Suggestive relationship with : Reproduction Reproduction Endometriosis Endometriosis Precocious puberty Precocious puberty Nural function Nural function Immune function Immune function Cancers: breast, endometrial, testicular, prostate, thyroid Cancers: breast, endometrial, testicular, prostate, thyroid Source: WHO/IPCS. Global assessment of the state-of-the-science of endocrine disruptors. WHO/PCS/EDC/02.2

Reproductive Decline in human sperm quality Decline 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’s Impaired fertility and increased SAB’s Relationship to ED’s speculative Relationship to ED’s speculative Declining sex ratios Declining sex ratios Evidence of unidentified external causes but mechanism unknown Evidence of unidentified external causes but mechanism unknown Developmental male reproductive tract abnormalities Developmental male reproductive tract abnormalities ED exposure evidence unclear ED exposure evidence unclear Experimental data with a number of chemicals demonstrate they can disrupt male reproductive tracts. Experimental data with a number of chemicals demonstrate they can disrupt male reproductive tracts.

Gynecological Endometriosis Endometriosis Association with ED reported but studies equivocal Association with ED reported but studies equivocal Precocious Puberty Precocious Puberty Concern regarding influence of ED’s on early onset of puberty Concern regarding influence of ED’s on early onset of puberty Role of other factors such as nutrition needs clarification Role of other factors such as nutrition needs clarification

Neural Function Prenatal exposure to ED’s (PCB’s) result in neurodevelopmental, behavioral and neuro-endocrine function problems. Prenatal exposure to ED’s (PCB’s) result in neurodevelopmental, behavioral and neuro-endocrine function problems. Human and animal data Human and animal data Effects more likely a result of altered thyroid or neuro-transmitters. Effects more likely a result of altered thyroid or neuro-transmitters. In most instances ED mechanism not demonstrated In most instances ED mechanism not demonstrated

Immune Function Some ED’s alter human and animal immunity Some ED’s alter human and animal immunity Unknown if these alterations due to an endocrine mediated mechanism Unknown if these alterations due to an endocrine mediated mechanism

Cancers of Hormonally Sensitive Organs Temporal association between rise in hormone sensitive organ cancers and wide spread use of industrial chemicals Temporal association between rise in hormone sensitive organ cancers and wide spread use of industrial chemicals Increase incidence not explained by improved diagnostic techniques. Increase incidence not explained by improved diagnostic techniques. Hypothesis – is it from ED’s? Hypothesis – is it from ED’s?

Breast Cancer Studies measuring DDE (DDT metabolite stored in fat tissue) in adult women do not support a causative relationship. Studies measuring DDE (DDT metabolite stored in fat tissue) in adult women do not support a causative relationship. New study measuring the more active metabolite in frozen blood from women at delivery from the 1950’s show a 5 fold relationship. * New study measuring the more active p,p´-DDT metabolite in frozen blood from women at delivery from the 1950’s show a 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)

Other Cancers Endometrial - limited data – no causal relationship established. Endometrial - limited data – no causal relationship established. Prostate – some associations positive and some negative. Mechanism unknown. Prostate – some associations positive and some negative. Mechanism unknown. Testicular – temporal rise without link to same time frame as use of ED’s Testicular – temporal rise without link to same time frame as use of ED’s Thyroid – no direct link to ED exposure has been demonstrated. Thyroid – no direct link to ED exposure has been demonstrated.

Future Adverse health outcomes appear biologically plausible given: Adverse health outcomes appear biologically plausible given: Known effects of endogenous and exogenous hormones sensitive organs Known effects of endogenous and exogenous hormones sensitive organs Demonstrated effects on wildlife and laboratory animals Demonstrated effects on wildlife and laboratory animals They are a high priority research area is required – They are a high priority research area is required – EPA required to screen products for potential effects on the endocrine system EPA required to screen products for potential effects on the endocrine system Other non-ED mechanisms must also be explored Other non-ED mechanisms must also be explored