State of the Science of Endocrine Disrupting Chemicals – 2012 UNEP and WHO published in February, 2013 From ”Global Assement of EDCs” published 2002 to … Åke Bergman (coordinator of the 2012 document) Swedish toxicology sciences research center

What is “Endocrine Disruption”? It is a change to the normal function of endocrine glands and hormone action, in any living species, imposed by external (anthropogenic) stressors. Endocrine disruptors, are chemicals designed for a specific function…with a side effect of altering the function of the endocrine system. UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Drivers for an update of the ”Global Assement of EDCs” from 2002 It has been a decade since the global IPCS assessment was published Important to take stock in new findings Identify Key Concerns Identify Future Needs In recognition of human health and biodiversity Improving the global knowledge regarding EDCs (SAICM), for improved risk reductions UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Major changes re. endocrine disruption since 2002 Many more chemicals with ED effects, many more potential EDCs Many more hormones than yet addressed in research Mixture effects addressed ”New” exposure routes Windows of exposure – Effects during development or manifested later in life; transgenerational effects Low dose effects discussed Non-monotonic dose response Increasing biodiversity threats UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Strength of evidence Effects can be explained by endocrine mode of actions (mechanisms) The identification of chemicals with endocrine disrupting properties linked to disease outcomes in laboratory studies Observations of endocrine-related effects in wildlife populations The rate of incidence of many endocrine-related diseases or disorders in humans UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Endocrine disruption is associated with: female reproductive health male reproductive health sex ratio in humans thyroid related disorders and diseases neurodevelopment in children and wildlife hormone related cancers adrenal disorders in humans and wildlife immune function, immune diseases and disorders metabolic disorders wildlife population sustainability loss UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

EDCs and female reproductive health DES – the most well-known chemical affecting female reproductve health Downward trends in the age at breast development in girls from Europe to substantiate USA data. Increasing experimental evidence that chemicals can interfere with endocrine signaling of: Pubertal timing Fecundity Fertility Menopause. Evidence linking phthalate exposure to endometriosis UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Key concerns The high incidence and the increasing trends of many endocrine-related disorders in humans; Observations of endocrine-related effects in wildlife populations; The identification of chemicals with endocrine disrupting properties linked to disease outcomes in laboratory studies; Increased numbers of chemicals with endocrine disrupting properties (beyond E,A,T) along with new sites of action; Increased body burden across the globe; Disease risk likely underestimated; Lack of knowledge of sources; Inadequate testing. UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Key Concerns Three strands of evidence fuel concerns over endocrine disruptors: the high incidence and the increasing trends of many endocrine-related disorders in humans; observations of endocrine-related effects in wildlife populations; the identification of chemicals with endocrine disrupting properties linked to disease outcomes in laboratory studies. Disease risk due to EDCs may be significantly underestimated. UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Key Concern The speed with which the increases in disease incidence have occurred in recent decades rules out genetic factors as the sole plausible explanation. Environmental and other non-genetic factors, including nutrition, age of mother, viral diseases and chemical exposures, are also at play, but are difficult to identify. Despite these difficulties, some associations have become apparent. 143'000 substances were pre-registered, indicating an actual use of theses substances. But since many exemptions apply, far from all substances must be registered resulting in a much larger number of substances we are actually exposed to. And if one take into consideration degradation products, unintentionally produced substances and metabolites, the figure might actually reach one million or more UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Two main messages on ”Exposure to Chemicals” EDCs & potential EDCs are everywhere - EDCs are chemically diverse, primarily include human-made chemicals, and are used in a wide range of materials and goods. EDCs are present in food, nature and human beings. They can also be formed in the environment and in humans, wildlife and plants. Increasing number of EDCs & potential EDCs – Unlike ten years ago, it is better understood that humans and wildlife are exposed to far more EDCs than just persistent organic pollutants (POPs). However, only a fraction of the potential EDCs in the environment are currently understood. UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Future needs Strengthening knowledge of EDCs Improved testing for EDCs Identifying EDCs Reducing exposures and thereby vulnerability to disease Creating enabeling environments for scientific advances, innovation and disease prevention Methods for evaluating evidence UNEP/WHO 2013 EDC report Bergman, Geneva May 5, 2015

Thank you Ake Bergman Executive Director Professor, PhD Postal address: Forskargatan 20, SE-151 36 Södertälje, Sweden Phone +46-8-5248 8510 Email: ake.bergman@swetox.se Web: www.swetox.se