Janna G. Koppe * Gavin ten Tusscher** Marike Leijs** Pier de Boer * *NGO Ecobaby

1. Authors: Janna G. Koppe * Gavin ten Tusscher** Marike Leijs** Pier de Boer * *NGO Ecobaby ** Emma children’s hospital/AMC, University of Amsterdam

2. Severe Dioxin Poisoning • Yushchenko (2004) • Two Austrian secretaries (1997)

3. Acute Dioxin Poisoning Yushchenko autumn 2004, before and after.

4. Acute Dioxin Poisoning Two secretaries in Austria 1997 Secretary nr. 1, 30 years old • TCDD-level: 144.000 pg/g fat in blood • Intake: 1,5 mg dioxin • Soon (few days) after moving in a new office in autumn 1997 : centro-facial chloracne

5. Acute Dioxin Poisoning CLINICAL EFFECTS • Chloracne • Nausea • Vomiting • Epigastric pain • Appetite loss • Weight loss

6. Acute Dioxin Poisoning Secretary nr. 1

7. Acute Dioxin Poisoning Secretary nr.2: 27 years old • TCDD-level : 26.000 pg/g fat in blood, Intake: 0,4 mg dioxin • Gastro-intestinal symptoms during several months since autumn 1997 • Not so severe chloracne on the cheeks

8. Acute Dioxin Poisoning Secr. 1 • more chloracne, more abnormal hematological effects • more abnormal lipid spectrum than nr. 2 • no effect on TSH-level Secr. 2 • less chloracne , • less abnormal hematological effects • less abnormal lipid spectrum • effect on TSH-level (increase) much more

9. Acute Dioxin Poisoning Bone marrow • Anemia • Trombocytopenia, • NK cells decreased Lipid spectrum • Triglycerides increased • Cholesterol increased

10. Acute Dioxin Poisoning Trombocytopeniacharacteristic for dioxin poisoning • BASF workers 1953 • Japanese workers • Two secretaries 4. Dutch children perinatally exposed tobackground levels

11. Heme synthesis Glycine Succinyl CoA ALA-synthetase Pos.PCBs etc. ALA ALA-dehydratase -------------- NEG. Lead, Heavy metals PBG URO’GEN URO-decarboxylase --------------- NEG. PCBs etc, Mercury, Lead, Hexachlorobenzene COPRO’GEN Ferrochelatase --------------- NEG. Lead,Heavy Metals HEME Bilirubin HEMOPROTEIN P450

12. Back of secretary nr.1 shortly after (c) and one year after the intoxication (d)

13. AcuteDioxin PoisoningIn the Long Run • Chloracne improves during 25 years • More cancer and 8 years earlier. • More diabetes and earlier in life. • More hypertension. • More miscarriages, prematurity, congenital malformations: congenital hydrocephalus and renal agenesis, and altered sex ratio. • More auto-antibodies to different tissues.

14. Hotspots of Dioxin Poisoning congenital malformations • Seveso (1976) • Open burning of Chemical waste in Amsterdam (1963-1968) • Yusho and Yucheng (1968 and 1978) • Vietnam 1975 • Chapaevsk • Bashkortostan

15. Seveso 1976 a few days after.

16. SEVESO 1976-1978 • Abnormal liver function tests in Seveso children: increase in • γ-glutamyltransferase (GGT) • Alanine aminotransferase (ALT) • In induced abortions in the period 1976-78 the incidence of aberrant cytogenetic findings was increased as was the number of miscarriages in general.

17. SEX RATIO after SEVESO

18. Acute Dioxin Poisoning Follow-up Seveso • Sex, distance from the accident site and meat consumption were significantly associated with an increased TCDD concentration. • Abnormal sex ratio (more girls) in relation to paternal exposure. • TCDD- concentration in breastmilk after 25 years still twice as high. • Increase in all cancers (rectum, lympho-hemopoietic, myeloid, thyroid gland and pleura)

19. More cleft lip and palate after open burning of chemicals.

20. MEG/EEG

21. MEG mapping

22. Acute PCB and Furan Poisoning Coca-cola coloured baby stillborn after YUSHO Placental transfer of PCBs and Furans (1968)

23. Hotspots of Dioxin PoisoningBashkortostan • Bashkortostan:city close to the Ural with large-scale production of the herbicide 2,4,5 T in CHIMPROM a factory opening in 1965. Workers came in contact with high doses of dioxins, since the herbicide contained between 30-100 mg /kg dioxin. • Chloracne and toxic melanoderma were seen. • 8 years earlier dead due to cancer, aging fast. • More spontaneous abortions, more girls, chromosome aberrations in peripheral lymfocytes.

24. Hotspots of Dioxin PoisoningChapaevsk • Chapaevsk: city close to UFA in the Ural,poisoned by dioxins due to a factory of lindane, an insecticide. • Significantly more congenital hydrocephalus and renal agenesis and dysgenesis in the offspring.

25. Congenital malformations per 1000 births. RANGE (BAND) EUROCAT 1997;Columns Chapaevsk (1982-1997) *4:cong. Hydrocephalus 8:cardiac malformations 14:kidneys a/dysgenesis

26. Congenital hydrocephalus

27. Congenital hydrocephalus and type 1 diabetes Lecorché in 1895 published on two cases of congenital hydrocephalus in the offspring of mothers with type 1 diabetes. 173 mothers with type 1 diabetes (University of Amsterdam 1963-1979): 10 % congenital malformations: 2 congenital hydrocephalus, 2 sacral agenesis, 4 vitium cordis, a.o.

28. Vitamin A • Dioxins, PCBs and PBBs interfere (blocks) Vitamin A metabolism. Vitamin A is necessary for the monoglycosylation of proteïns. • Disturbance in the glycosylation is also the cause of congenital malformations in the offspring of mothers with type 1 diabetes. Both situations lead to the same sort of congenital malformation. In animal experiments effects of PAH’s are reversed with extra Vitamin A. Retinoic acid is essential for a good balance in the cardiac progenitor pool. (see notes)

29. Vitamin A In the Netherlands 48 % of women, that want to become pregnant have a diet deficiënt in Vitamin A. Advice: Better control of Vitamin A in nutrition preconceptionally; especially in women with type 1 diabetes.

30. Preconceptional CounselingandEnvironmental HazardsWhat future parents must know!

31. Secondary prevention effects of PBT’s(Persistent Bioaccumulating Toxicants) • Control thyroid hormone status of the woman, that wants to become pregnant. All PBT’s can interfere with thyroid hormone status and may promote the development of auto-antibodies against the thyroid. • Recommend breastfeeding and loving care to mitigate and cure effects of PBTs. • Avoid environmental tobacco smoke, stop smoking, no alcohol. • Use a multivitamin with the vitamins A, B12, folic acid, and eat food high in anti-oxidants.

32. Three months conceptional leave for fathers • Semen is produced during a three month cycle. • Three months before conception the father has to stop smoking, drinking, working (with solvents or other hazards), and move out an air polluted region to avoid PAH’s.

33. Waste Landfill sites • Living close to (within 3 km) of a landfill site more congenital malformations are found. (EUROHAZCON project). • Significant increase in neural tube defects, malformations of the cardiac septa and anomalies of great arteries and veins. • Borderline significant increase in Tracheo-oesophageal anomalies, hypospadias and gastroschizis • Advice : Use Folic Acid supplementation, because these anomalies can be prevented with help of Folic Acid.

34. gastroschizis

35. hypospadie

36. Acute Dioxin Poisoning Therapy • There is no effective therapy. • Acne therapy with isotretinoin creme may help to treat chloracne • Olestra, a resin that absorbs fat in the intestines, interferes with the entero-hepatic cycle and helps removing dioxin-molecules that are excreted in the gall • Lactation and liposuction are other possibilities to remove dioxins.

37. Multiple Exposure 1. • Faroe-islands (mercury and PCBs) • Slovakia (lead and PCBs) • Netherlands (lead and PCBs and Dioxins) • Anti-epileptic drugs (phenobarbital)

38. Multiple Exposure 2. • Alspac study (11 cleaning products) • Multiple exposure to pesticides, • Multiple exposure to air pollution • Smoking and asbestos Guillette paper • Primary pollutants mixture • Oxidant pollutants mixture

39. Na-onderzoek bij 13 - 18 jaar. Results: Exposure Prenatal: ADHD 4 Geen ADHD 16 54.68 TEQdioxng/kgmilkfat35.35 TEQdiox ng/kgmilkfat ExposurePostnatal: ADHD 4 Geen ADHD 15 227.5 ng dioxinen gegeten69.41 ng dioxinen gegeten