Industrial incidents dioxins Risks to live in an

Industrial incidents: dioxins Risks to live in an industrialized world. Acute and Chronic Dioxin Poisoning. 30/09/2020 janna koppe 1

Industrial incidents: dioxins Acute Dioxin Toxicity v Seveso (1976) v Yusho and Yucheng (1968 and 1978) v Two Austrian secretaries (1997) v Yushchenko (2004) 30/09/2020 janna koppe 2

Industrial incidents: dioxins Acute dioxin poisoning Yushchenko autumn 2004, before and after. 30/09/2020 janna koppe 3

Industrial incidents: dioxins Acute Dioxin Toxicity p Clinical Effects p Laboratory Effects 30/09/2020 janna koppe 4

Seveso 1976 a few days after. 30/09/2020 janna koppe 5

Industrial incidents: dioxins Exposure routes of humans after the Seveso accident. v Absorption from dermal contact with soil v Inhalation of contaminated dust v Contribution of drinkable water v Ingestion of vegetables grown in home gardens v Consumption of animal products (chickens and rabbits) from the area v Casual ingestion of soil 30/09/2020 janna koppe 6

Industrial incidents: dioxins Acute dioxin poisoning CLINICAL EFFECTS v v v Chloracne Nausea Vomiting Epigastric pain Appetite loss Weight loss 30/09/2020 janna koppe 7

Industrial incidents: dioxins Acute dioxin poisoning v v Abnormal liver function tests in Seveso children: increase in γ-glutamyltransferase (GGT) v Alanine aminotransferase (ALT) v In induced abortions in the period 1976 -78 the incidence of aberrant cytogenetic findings was increased as was the number of miscarriages in general. 30/09/2020 janna koppe 8

Industrial incidents: dioxins Acute dioxin poisoning Follow-up Seveso v v 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 pleura) 30/09/2020 janna koppe 9

Industrial incidents: dioxins SEX RATIO after SEVESO Fathers Number concentration children Sex ratio Unexposed 271 15. 1 -31. 3 80 31. 9 -60. 7 81 61. 4 -117. 0 81 118. 0 -264. 0 80 281. 0 -26400. 0 81 0. 557 0. 438 0. 506 0. 469 0. 400 0. 383 30/09/2020 janna koppe 10

Industrial incidents: dioxins Acute Dioxin Poisoning Coca-cola coloured baby stillborn after YUSHO Placental transfer of PCBs and Furans (1968) 30/09/2020 janna koppe 11

Industrial incidents: dioxins Acute Dioxin Poisoning Two secretaries in Austria 1997 Secretary nr. 1, 30 years old v TCDD-level: 144. 000 pg/g fat in blood v Intake: 1, 5 mg dioxin v Soon (few days) after moving in a new office in autumn 1997 : centro-facial chloracne and 30/09/2020 janna koppe 12

Industrial incidents: dioxins Acute Dioxin Poisoning Secretary nr 1: v v Epigastric pain, gastritis, nausea Chloracne auricular area, eyelids, genital region, limbs and trunk affected by hundreds of cysts and comedones, Palmoplanar keratoderma Secundary amenorrhoea 30/09/2020 janna koppe 13

Industrial incidents: dioxins Acute dioxin poisoning Secretary nr. 1 30/09/2020 janna koppe 14

Industrial incidents: dioxins Acute dioxin Poisoning Laboratory effects in secr. 1 : v v v v Anemia, normochromic, normocytic Trombocytopenia Leucocytosis Natural killer cells slightly lower Triglycerides (7 x increased) Liver tests slightly abnormal TSH normal, FT 4: normal 30/09/2020 janna koppe 15

Industrial incidents: dioxins Acute dioxin poisoning Secretary nr. 2: 27 years old v TCDD-level : 26. 000 pg/g fat in blood, Intake: 0, 4 mg dioxin v Gastro-intestinal symptoms during several months since autumn 1997 v Not so severe chloracne on the cheeks 30/09/2020 janna koppe 16

Industrial incidents: dioxins Acute dioxin poisoning Laboratory effects in nr. 2 v v v v Marginally elevated cholesterol Triglycerides increased 2 x Anemia Trombocytopenia Leukocytosis NK cells lower TSH increased, FT 4 normal 30/09/2020 janna koppe 17

Industrial incidents: dioxins Acute dioxin poisoning Two year Follow-up of both secretaries Nr 1: v Severe chloracne after one year on the back of the trunk v Big problems with chloracne in the face with inflammation v Depressed Nr 2: v Chloracne disappeared within one year. 30/09/2020 janna koppe 18

Industrial incidents: dioxins Back of secretary nr. 1 shortly after (c) and one year after the intoxication (d) 30/09/2020 janna koppe 19

Industrial incidents: dioxins Acute Dioxin Poisoning Secr. 1 v more chloracne, more abnormal hematological effects v more abnormal lipid spectrum than nr. 2 v no effect on TSH-level Secr. 2 v less chloracne , v less abnormal hematological effects v less abnormal lipid spectrum v effect on TSH-level (increase) 30/09/2020 janna koppe 20

Industrial incidents: dioxins Acute dioxin poisoning Bone marrow v v v Anemia Trombocytopenia, NK cells decreased Lipid spectrum v v Triglycerides increased Cholesterol increased 30/09/2020 janna koppe 21

Industrial incidents: dioxins Acute Dioxin Poisoning, follow-up Chloracne in YUSHO-patient a: shortly after the incident b: after 25 years 30/09/2020 janna koppe 22

Industrial incidents: dioxins Acute and Chronic Dioxin Poisoning Trombocytopenia characteristic for dioxin poisoning 1. BASF workers 1953 2. Japanese workers 3. Two secretaries 4. Dutch children perinatally exposed to background levels 30/09/2020 janna koppe 23

Industrial incidents: dioxins Acute Dioxin Poisoning In the Long Run v v v v 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. Earlier decline in cognitive functions. 30/09/2020 janna koppe 24

Industrial incidents: dioxins Therapy v v v There is no effective therapy. So primary prevention is warranted. 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 dioxinmolecules that are excreted in the gall Antioxidants like vitamin C and vegetables high in antioxidants, like broccoli, olive oil, berries, tea, grapes, beats and green vegetables high in chlorophyl. Lactation and liposuction are other possibilities to remove dioxins. 30/09/2020 janna koppe 25

Industrial incidents: dioxins Acute Dioxin Poisoning Conclusion v Clinical signs: chloracne, nausea and vomiting, gastrointestinal effects. Weight loss. v Laboratory signs: anemia, trombocytopenia, leukocytosis, increased liver enzymes, dyslipidaemia, TSH increased (not at high dose), NK cells decreased. 30/09/2020 janna koppe 26

Industrial incidents: dioxins Chronic Dioxin poisoning v Background levels of dioxins are levels found in human milk in non-contaminated areas. v In Europe background levels of dioxins were and are a problem. v Dioxins are a collective of dioxins and furans and dioxinlike PCBs, expressed as Toxic Equivalent Quantities (TEQ’s). 30/09/2020 janna koppe 27

Industrial incidents: dioxins Chronic Dioxin Poisoning Background concentrations are levels in human milk in non-contaminated areas caused by: v Incineration of municipal waste (79% Netherlands) v By-products of chlorinated phenol production, v Other waste incineration, v Metal smelting, v Traffic 30/09/2020 janna koppe 28

Industrial incidents: dioxins Chronic toxicity of dioxins. v Thyroid Hormone Disruptors, v Estrogen/Androgen v Direct 30/09/2020 janna koppe Disruptors, effects on cells. 29

Industrial incidents: dioxins Chronic toxicity of dioxins. Effects in humans. v Liver function, v Brain function, v Adipose tissue, v Lung function, v Puberty. v Bone marrow, cancer v Longer follow-up is needed for reproductive effects. 30/09/2020 janna koppe 30

Industrial incidents: dioxins Chronic Dioxin Poisoning v In the Amsterdam-Zaandam region in the Netherlands a prospective study was started to effects of background levels of dioxins in the perinatal period in the years 1987 -1991. v In the following slides a negative effect on neurofysiologic parameters is described. 30/09/2020 janna koppe 31

Industrial incidents: dioxins Chronic Dioxin Poisoning Characteristics of subjects. Amsterdam study started in 1987/1991 Follow-up: 41 healthy 7 -12 year old children optimal pregnancies, single births. Dioxin-levels ( I-TEQ dioxin): prenatal exposure 8. 74 -88. 8 ng postnatal exposure 4. 34 -384. 51 ng 30/09/2020 janna koppe 32

Industrial incidents: dioxins Chronic Dioxin Poisoning MEG/EEG methods. v Cognitive functioning was assessed with help of a visual oddball paradigm. The subject has the task to count the times the oddball is seen, during a continuous presentation of a visual stimulus. ( about 60 times during a session) v Strongly associated with N 200 (passive attention) and P 300 (active attention), subdivided in P 3 a and P 3 b. N 200 and P 3 b were analysed. 30/09/2020 janna koppe 33

Industrial incidents: dioxins Chronic Dioxin Poisoning Results The latencies of the N 200 and P 3 b component (pooled EEG- and MEG data) were significantly prolonged (p-value: 0. 002) and the amplitude was decreased (p-value: 0. 01) in relation to perinatal dioxin exposure 30/09/2020 janna koppe 34

Industrial incidents: dioxins Acute and Chronic Dioxin Poisoning Author: Janna G. Koppe CHEST-project. Leaders: Peter van den Hazel Moniek Zuurbier 30/09/2020 janna koppe 35