Är hälso- och miljörisker relaterade till hormonstörande ämnen underskattade? Åke Bergman Stockholms Universitet, Stockholm

Transcription

1 Är hälso- och miljörisker relaterade till hormonstörande ämnen underskattade? Åke Bergman Stockholms Universitet, Stockholm UNEP/WHO report 2002 UNEP/WHO report 2012

2 WHO/IPCS Definition av EDCs 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. Hormonstörande substanser är kemikalier designade för en specifik funktion, men med sidoeffekten att störa funktionen av ett eller flera hormonsystem

3 Hormonsystem och hormoner Minst 50 hormonsystems finns i biota, med ca. 100 naturliga signalsubstanser System i fokus så här långt har varit östrogener, androgener och sköldkörtelhormoner - EAT Hormonsystemen har stor likhet mellan arter

4 EDCs agerar som hormoner Hormones Act via hormone receptors Some have multiple receptors Tissue-specific receptor classes and subtypes Hormones normally bind similarly to all receptor subtypes Active at low doses Blood levels do not always reflect activity May be bound to serum proteins in blood with a small percentage free No bioaccumulation Non-linear dose-response relationships Always saturable with variable dynamic range Can exhibit non-monotonic dose-response relationships High-dose effects not same as low-dose effects Tissue-specific and life stage-specific effects Developmental effects permanent Programs brain and endocrine system for adult function Endocrine Disruptors Some act via hormone receptors and multiple receptors Will cause abnormal receptor function Likely isoform-specific interactions Some act at low doses, others variable Blood levels do not always reflect activity May be bound to serum proteins Effects on hormone blood levels may not reflect effects on hormone action Possible bioaccumulation Non-linear dose-response relationships Always saturable with variable dynamic range Can exhibit non-monotonic dose-response relationships High-dose effects not same as low-dose effects Tissue-specific and life stage-specific effects Developmental effects permanent Interferes with programming processes Different end-points vary in sensitivity Different end-points vary in sensitivity

5 Lågdos-effekter och Icke-monotona dos-effektsamband

6 Mer än 800 kemikalier har visats ha ED-egenskaper De flesta av kemikalier i användning är inte testade Current use Pesticides Flame Retardants Plastics Herbicides Industrial byproducts Plasticizers Personal Care products Surfactants Cosmetics Solvents Sunscreens Antioxidants Heavy metals POPs Polycyclic Compounds

7 Flamskyddad asfalt, flamskyddade underkläder och amningskuddar Bisfenol A i avloppsledningar, färskvattenledningar och i kvitton

8 och så finns det bisfenoler som är klorerade eller bromerade och så finns det derivat av bisfenoler! Bisfenoler BPA

9 Exponering för EDCs från många olika källor och via olika vägar! Miljö-exponering

10 Blandningseffekter av EDCs

11 Känsliga exponeringsfönster under fosterutvecklingen Early Prenatal Mid- Late Prenatal Postnatal Heart (3-8) Limbs (4-8wks) Skeleton (1-12 wks) Ear (4-20 wks) Central nervous system (3wks - 20 years) Kidneys (4-40 wks) Immune system (8-40 wks; competence & memory birth-10yrs) Lungs (3-40 wks; alveoli birth-10yrs) Reproductive system (7-40wks; maturation in puberty) Week 1-16 Week Birth 25 years

12 Developmental Exposure EDCs påverkar livsstadiespecifikt Learning differences/behaviour Astma Increased sensitivity to infections Testicular dysgenisis syndrome Atherosclerosis Cardiovascular disease Infertility Breast cancer Altered puberty Obesity Fibriosis Premature menopaus Prostate cancer Alzheimer disease Parkinson disease Age (Years) EDC exponering under fosterutvecklingen manifesteras senare I livet

13 Sjukdomsrisker ökar med exponering under fosterutvecklingen Reproductive/Endocrine Breast/prostate cancer (BPA) Endometriosis (Dioxin, PCBs) Infertility (Phthalates, Estrogens, Pesticides) Diabetes/metabolic syndrome (BPA) Early Puberty (Estrogens, BPA) Obesity (BPA, Tributyl Tin, Organochlorine Pesticides) Immune/Autoimmune Susceptibility to infections (Dioxin, Perfluorinated compounds, arsenic) Autoimmune Disease (Dioxin) Pulmonocardiovascular Asthma (Air Pollution) Heart disease/ hypertension (BPA) Stroke (PCBs) Brain/Nervous System Alzheimer's disease (Lead) Parkinson s disease (Pesticides) ADHD/learning disabilities (PCBs, Lead, Ethanol, Organochlorine Pesticides)

14 Hormonrelaterade sjukdomar och effekter ökar Bröstcancer Övervikt (fetma)

15 Hormonrelaterade sjukdomar och effekter ökar Hypothyroidism There is sufficient evidence to conclude that thyroid diseases are increasing in the human populations (hypothyroidism and thyroid cancers). Currently insufficient evidence for causal role of EDCs in thyroid disorders focusing on altered thyroid hormone levels. There is sufficient evidence linking PCB body burden to cognitive function in children direct link via thyroid hormones not shown. However PCBs clearly reduce circulating levels of thyroid hormone, in animal studies. Many effects of EDCs are are not picked up by measuring thyroid hormone levels. WHO/UNEP SOS of EDCs 2012

16 Sjukdomstrender; Nervutveclkling och beteende Prevalence of ADHD (%) Since the 1970s there has been a dramatic increase in rare neurodevelopmental disorders. There are sufficient data linking developmental exposures to PCB s, lead, and methylmercury to neurodevelopmental effects in animals at doses similar to those of humans. Sufficient data in humans that PCBs during development are linked to lower global IQ and sexually dimorphic behaviors... ADHD is linked to lead, PCBs, and some organophosphate pesticides. WHO/UNEP SOS of EDCs 2012

17 Paraleller mellan människa och vilda djur Hormones and signaling pathways are often quite similar across species. The increasing incidence of human disorders is similar to those observed in wildlife. There is recent evidence that animals living near humans also have increasing body weight. Studies of PCB-exposed wildlife have provided important information on: exposure levels; early and subclinical effects; and clinical neurotoxicity of PCBs. Mechanisms underlying the effect and outcomes of EDC exposure in wildlife are often similar to those in humans. Grey seal skull with highly eroded bone tissue associated with high POP concentrations in the Baltic Sea during the 1970s and 1980s. Photo by Hans Lind. The antifouling agent tributyltin in ship paints has disrupted mollusc sexual development worldwide. Here, the common whelk (Buccinum undatum) has both male and female genitalia.

18 Biodiversitetsförluster och hormonstörningseffekter bland vilda djur - Hur ser sambanden ut? 1.4 million wildlife species Feminisation of wild fish Thyroid, immune & reproductive disorders in many wildlife species

19 Några nyckelpunkter i sammanfattning o The high incidence and the increasing trends of many endocrine-related disorders in humans; o Observations of endocrine-related effects in wildlife populations; o The identification of chemicals with endocrine disrupting properties linked to disease outcomes in laboratory studies; o Increased numbers of chemicals with endocrine disrupting properties (beyond E,A,T) along with new sites of action; o Increased body burden across the globe; o Disease risk likely underestimated; o Lack of knowledge of sources; o Inadequate testing.

20 TACK för uppmärksamheten!