Endocrine Disrupting Chemicals: Health Effects and Moving Forward - PowerPoint PPT Presentation

Endocrine Disrupting Chemicals: Health Effects and Moving Forward Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S. Director National Institute of Environmental Health Sciences National Toxicology Program Pesticides & The Chesapeake Bay Watershed Project Conference 18 September 2019 Reisterstown, Maryland National Institutes of Health U.S. Department of Health and Human Services

What is the NIH? • The National Institutes of Health is the primary Federal agency for conducting and supporting medical research in the U.S. More than $39 billion invested annually in medical research • • 50,000 competitive grants awarded to more than 300,000 researchers at over 2,500 universities, medical schools, and other research institutions in every state -- and around the world National Institutes of Health NIH Budget webpage, accessed July 2019 U.S. Department of Health and Human Services

The National Institute of Environmental Health Sciences • One of the 27 National Institutes of Health, located in RTP, NC • Wide variety of programs supporting our mission of environmental health: ‒ Intramural laboratories ‒ Clinical research program ‒ Extramural funding programs ‒ National Toxicology Program ‒ Disease prevention ‒ Public health focus Office of the Director Director: Linda S. Birnbaum, PhD, DABT, ATS Deputy Director: Rick Woychek, PhD Division of Division of the Division of Office of Extramural National Toxicology Intramural Management Research and Program Research Training Executive Officer: Chris Scientific Director: Scientific Director: Darryl Long, MPA Brian Berridge, DVM, Director: Zeldin, MD PhD, DACVP National Institutes of Health Gwen Collman, PhD U.S. Department of Health and Human Services

Our Health Genetics National Institutes of Health Image adapted from: NHGRI U.S. Department of Health and Human Services

Diet Our Health Microbiome Pesticides Medicines Synthetic materials Combustion Stress by-products Genetics + Environment Chemicals in Personal care electronics products National Institutes of Health Image adapted from: NHGRI U.S. Department of Health and Human Services

The Endocrine System • Extremely complex, many controls, interacting parts • Multiple points of regulation for finely-tuned responses • Sensitive to perturbations • Naturally operates at low doses • Effects can be activational and/or organizational National Institutes of Health U.S. Department of Health and Human Services

Endocrine Disrupting Chemicals: A Global Health Problem Hormones • “An exogenous substance or mixture EDCs Nuclear Receptors that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub) populations.” • Report from The United Nations Environment Programme (UNEP) and the World Health Organization (WHO), “ State of the Science of Endocrine Disrupting Chemicals (EDCs)” – EDCs are becoming a "global threat" that needs to be addressed National Institutes of Health WHO. State of the Science of Endocrine Disrupting Chemicals . 2013 U.S. Department of Health and Human Services

Endocrine Disrupting Chemicals (EDCs) Known EDCs: • Dioxin and dioxin-like compounds • Polychlorinated biphenyls (PCBs) • Some pesticides • Plasticizers, such as BPA Health outcomes associated with EDC exposure: • Developmental • Reproductive How do EDCs work? EDCs can mimic the body's natural • Neurological hormones or alter the natural • Immune production of hormones National Institutes of Health NIEHS, 2019 U.S. Department of Health and Human Services

Lifelong Effects of Early-Life Exposures Developmental Origins of Health and Disease (DOHaD) National Institutes of Health U.S. Department of Health and Human Services

Chemical Contaminants in the Chesapeake Bay Common contaminants: Almost three-quarters of the – Polychlorinated biphenyls Bay’s tidal waters are impaired (PCBs) by chemical contaminants, – Pesticides which can harm the health of both humans and wildlife – Polycyclic aromatic hydrocarbons (PAHs) – Mercury – PFAS Sources of contamination: – Air pollution – Agricultural runoff – Stormwater runoff – Wastewater discharge Chesapeake Bay Program, 2019

Pesticides, Sources, and Health Effects • Includes herbicides, fungicides, insecticides, and disinfectants • Sources include agricultural, residential, and occupational • Many health effects associated with exposure, including: – Cancer – Neurological (Parkinson’s disease, autism, IQ) – Endocrine and metabolic effects (diabetes) – Respiratory effects National Institutes of Health NIEHS, 2019. CDC, 2019 U.S. Department of Health and Human Services

Maternal Pesticide Exposure and Autism in Children • Finnish Prenatal Study of Autism – Mothers with the highest DDE blood levels in early pregnancy were 32% more likely to have a child who developed autism (p=0.03) • CHARGE Study (CA) – Mothers living near agricultural pesticide applications had a 60% increased risk for a child developing autism National Institutes of Health Brown et al., Am J Psychiatry, 2018. Shelton et al., EHP, 2014. U.S. Department of Health and Human Services

Prenatal Organophosphate (OP) Exposure and Decreased Infant Motor Function • 30 OPs measured in umbilical cord blood • Motor function assessed at 6-weeks and 9-months in Chinese infants (N=199) • Prenatal naled and chlorpyrifos were associated with decreased motor function at 9-months National Institutes of Health Silver et al., Environ Int, 2017 U.S. Department of Health and Human Services

Pesticides Associated with Neurobehavioral Effects in Ecuadorian Children N = 308 children 4-9 years old • Conducted behavioral tests between 63 and 100 Neurobehavioral Score days after Mother’s Day • Children tested closer to Mother’s Day had lower neurobehavioral performance • Periods of peak pesticide use may transiently affect child neurobehavior Days after Mother’s Day Harvest Suarez-Lopez et al., NeuroToxicology, 2017 National Institutes of Health U.S. Department of Health and Human Services

Developmental Pesticide Exposure Induces Neuroinflammation, Reduces Spatial Learning • Rats exposed from Pesticide Dose (mg/kg/day) GSD 7 to PND 21 Cypermethrin 1.5 Endosulfan 0.5 • All pesticides induced Carbaryl 15 neuroinflammation, Chlorpyrifos 0.1, 0.3, & 1 increasing IL-1b in Working Memory hippocampus Working errors • Effects were pesticide and sex-specific Gómez-Giménez et al., IL-1b (% control) Food and Chem Toxicol, 2017 National Institutes of Health U.S. Department of Health and Human Services

Exposure to Agricultural Pesticides and Cancer Among participants enrolled in the Agricultural Health Study: • Use of chlorpyrifos and terbufos was associated with increased breast cancer risk among farmer’s wives (Engel et al., Environ Health Perspect, 2017) • Use of pendimethalin, dieldrin, parathion, and chlorimuron ethyl associated with lung cancer risk in farmers (Bonner et al., Environ Health Perspect, 2017) • Use of the herbicide alachlor was associated with laryngeal cancer and myeloid leukemia in pesticide applicators (Lerro et al., J Natl Cancer Inst, 2018)

Pesticides and Respiratory Symptoms in Farmers • Assessed pesticide exposures and wheeze among male participants in the Agricultural Health Study (N=22,134) • Of 78 pesticides examined, 21 were significantly associated with non-allergic wheeze, and 19 with allergic wheeze • Dose-response relationships observed for three commonly used herbicides: glyphosate, 2,4-D, and atrazine National Institutes of Health Hoppin et al., Environ Health Perspect, 2017 U.S. Department of Health and Human Services

DDT and Breast Cancer: The Timing of Exposure Matters • Evaluated timing of DDT exposure and breast cancer • DDT was associated with breast cancer through age 54 • Risk depended on timing of first exposure • DDT may be an endocrine disruptor with responsive breast targets from in utero to menopause DDT associated breast cancer by age at first exposure and age at diagnosis Cohn et al., J Natl Cancer Inst, 2019

Pesticides and Endocrine Effects Organochlorine pesticides: Associated with reduced BMI and height in 8 to 19-year-old boys (Sergeyev et al., Rev Environ Health, 2017) Organophosphate pesticides : Associated with altered testosterone levels in Thai farmworkers (Panuwet et al., Arch Environ Occup Health, 2018) Pesticide residue on food: May reduce probability of pregnancy and live birth following assisted reproduction approaches (Chiu et al., JAMA Intern Med, 2018) National Institutes of Health U.S. Department of Health and Human Services Photo by Josh Vogel, Maryland Dept. of Natural Resources

Polychlorinated Biphenyls (PCBs) • Used in hundreds of industrial and commercial applications • Banned in U.S. in 1979 • Mobile, persistent, and accumulate in the environment and wildlife • Associated with a range of health effects: – Cancer – Immune – Reproductive – Nervous – Endocrine EPA, 2018