Lovells LLP Endocrine Disrupters

Industries which may be affected by endocrine disrupters Chemicals Plastics Agrochemicals Water companies Farming Food Cosmetics

Endocrine system Hypothalamus Pituitary Thyroid Pancreas Adrenal glands Ovaries Testes

Hormone action and receptor binding Hormone Target Cell Receptor

Hormone feedback pathways and homeostasis

Example - control of spermatogenesis and testosterone secretion

Definition of endocrine disrupter An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations. A potential endocrine disruptor is an exogenous substance or mixture that possesses properties that might be expected to lead to endocrine disruption in an intact organism, or its progeny, or (sub)populations. [

Sites of endocrine disruption Hormone synthesis Hormone transport Hormone binding Hormone metabolism and excretion Hormone Target Cell Receptor

Mechanism of endocrine disruption EDCs can bind to a receptor and trigger the usual response. EDCs can bind to the receptor and not trigger a response but cause a blockage such that the appropriate hormone cannot bind Can interfere with the production, transportation, metabolism and excretion of hormones Many EDCs are capable of multiple, sometimes opposing, actions in different tissues

Effects of endocrine disruption - TBT ages/fs_marine_biology_dogwhelk.jpg

TBT Survey of the dogwhelk showed a high degree of imposex Observed to be in areas close to shipping activity Tissues of the dogwhelk were analysed for several compounds and showed high levels of tin Experiments conducted using TBT which demonstrated a causative link Mechanism by which the disruption is caused is still unclear

Effects of endocrine disruption - DES Given to pregnant women who were at risk of miscarriage or premature birth ( ) Synthetic estrogen

DES

Examples of established endocrine disrupters Dioxins PCBs DDT

Examples of chemicals which are potential endocrine disrupters in humans TBT Bisphenol A Atrazine Phthalates Phytoestrogens Alkylphenols Brominated flame retardants

Products which contain potential endocrine disruptiers Industrial chemicals Pesticides Herbicides Plastics (phthalates) Cosmetics (bisphenol A) Sunscreens (4MBC & OMC) Fire retardants (brominated compounds)

Problems associated with the management of endocrine disrupters Identification of potential disrupters Multigenerational effects Timing of exposure Combined exposures Multiple effects on different endocrine pathways Persistence and cumulative effects Appropriate and standardised tests for ED ability Low dose effects/threshold Dose-response

Attempts to identify ED chemicals EC –Priority list of substances for further evaluation of their role in endocrine disruption –CREDO research initiative –REACH EPA’s Endocrine Disruptor Screening Program (EDSP) –“Draft List of Chemicals for Initial Screening” June 2007 –Endocrine Disruptors Research Initiative WHO –2002 Global Assessment of the State of the Science of Endocrine Disruptors

Lovells LLP EMF

EMF spectrum

Frequency/wavelength affects properties of EM waves Very high frequency radiation –Lots of energy –Ionising radiation –Able to easily penetrate (and damage) biological material –X-rays and gamma rays Radiofrequency wavelengths (10MHz to 300GHz) –Less energy associated –Non-ionising radiation –Less able to penetrate biological materials –Mobile phones and microwave Low- and extra-low frequency radiation –Low power levels –Non-ionising –Power lines

Risks of EMF Ionising radiation – various adverse effects including cancer Ultraviolet and visible radiation – various adverse effects including skin cancer Radiofrequency radiation – exposure at greater than ICNIRP guideline levels can lead to thermal effects Low frequency radiation – exposure greater than ICNIRP guideline levels can lead to shocks and effects on the nervous system Magnetic fields – classified by IARC as possibly a human carcinogen on the basis of studies relating to childhood leukemia

How are electric and magnetic fields generated

Mobile phones le_telephony/background_info.htm

Guidelines for exposure to non-ionising radiation set by ICNIRP European power frequencyMobile phone base station frequency Microwave oven frequency Frequency50 Hz 900 MHz1.8 GHz2.45 GHz Electric field (V/m) Magnetic field (µT) Power density (W/m 2 ) Public exposure limits Occupational exposure limits ICNIRP, EMF guidelines, Health Physics 74, (1998)

Examples of typical maximum exposures Typical maximum public exposure (W/m 2 ) TV and radio transmitters 0.1 Mobile phone base stations 0.1 Radars0.2 Microwave ovens0.5 SourceTypical maximum public exposure Electric field (V/m)Magnetic flux density (µT) Natural fields20070 (Earth's magnetic field) Mains power (in homes not close to power lines) Mains power (beneath large power lines) Electric trains and trams TV and computer screens (at operator position) Source: WHO Regional Office for Europe

IARC classification of static electric and magnetic and extremely low-frequency electric fields “Evaluation There is limited evidence in humans for the carcinogenicity of extremely low-frequency magnetic fields in relation to childhood leukaemia. There is inadequate evidence in humans for the carcinogenicity of extremely low-frequency magnetic fields in relation to all other cancers. There is inadequate evidence in humans for the carcinogenicity of static electric or magnetic fields and extremely low-frequency electric fields. There is inadequate evidence in experimental animals for the carcinogenicity of extremely low- frequency magnetic fields. No data relevant to the carcinogenicity of static electric or magnetic fields and extremely low-frequency electric fields in experimental animals were available. Overall evaluation Extremely low-frequency magnetic fields are possibly carcinogenic to humans (Group 2B). Static electric and magnetic fields and extremely low-frequency electric fields are not classifiable as to their carcinogenicity to humans (Group 3).”

World Health Organisation Factsheet – June extremely low frequency fields “ In 2002, IARC published a monograph classifying ELF magnetic fields as "possibly carcinogenic to humans". This classification is used to denote an agent for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence for carcinogenicity in experimental animals (other examples include coffee and welding fumes). This classification was based on pooled analyses of epidemiological studies demonstrating a consistent pattern of a two-fold increase in childhood leukaemia associated with average exposure to residential power-frequency magnetic field above 0.3 to 0.4 µ T. The Task Group concluded that additional studies since then do not alter the status of this classification. However, the epidemiological evidence is weakened by methodological problems, such as potential selection bias. In addition, there are no accepted biophysical mechanisms that would suggest that low-level exposures are involved in cancer development. Thus, if there were any effects from exposures to these low-level fields, it would have to be through a biological mechanism that is as yet unknown. Additionally, animal studies have been largely negative. Thus, on balance, the evidence related to childhood leukaemia is not strong enough to be considered causal. ”

Research into potential effects of RF radiation on humans World Health Organisation - The International EMF Project REFLEX MTHR - UK Mobile Telecommunications and Health Research Programme Interphone

Reports on EMF/RF 1999 Canadian Report Royal Society of Canada's Expert Panel's review of the potential health risks of radiofrequency fields from wireless telecommunication devices 2000 Zmirou Report French Health General Directorate 2000 Stewart Report UK Independent Expert Group 2002 Dutch Report Health Council of the Netherlands, advisory report 2003 Swedish Report Swedish Radiation Protection Authority (SSI) First annual report from SSI's Independent Expert Group on Electromagnetic Fields 2003 AGNIR Report NRPB's Independent Advisory Group on Non-Ionising Radiation Report 'Health Effects from Radiofrequency Electromagnetic Fields' 2004 Dutch Report Health Council of the Netherlands Electromagnetic Fields Annual Update Review by ICNIRP Standing Committee on Epidemiology A comprehensive review of the epidemiology of health effects of radiofrequency exposure 2004 Swedish Report Swedish Radiation Protection Authority (SSI) Second annual report from SSI's Independent Expert Group on Electromagnetic Fields 2005 NRPB Report W65 A Summary of Recent reports on Mobile Phones and Health ( ) 2005 NRPB Report Documents of the NRPB - Mobile Phones and Health Volume 15 No French Agency for Environmental Health Safety Opinion on Mobile Telephony 2005 Dutch Report Health Council of the Netherlands Electromagnetic Fields Annual Update Swedish Report Swedish Radiation Protection Authority (SSI) Third annual report from SSI's Independent Expert Group on Electromagnetic Fields 2007 Dutch Report Health Council of Netherlands 2007 Swedish Report Swedish Radiation Protection Authority (SSI) 2007 June Canadian Report Update report by the Royal Society of Canada's Expert Panel on Potential Health Risks of Radiofrequency Fields from Wireless Telecommunication Devices

World Health Organisation Factsheet – May Base stations and wireless technologies “ Considering the very low exposure levels and research results collected to date, there is no convincing scientific evidence that the weak RF signals from base stations and wireless networks cause adverse health effects. ” “ While no health effects are expected from exposure to RF fields from base stations and wireless networks, research is still being promoted by WHO to determine whether there are any health consequences from the higher RF exposures from mobile phones. ” “ The International Agency for Research on Cancer (IARC), a WHO specialized agency, is expected to conduct a review of cancer risk from RF fields in and the International EMF Project will then undertake an overall health risk assessment for RF fields in ”