A NEW CHALLENGE : ASSESSMENT of Metallic Toxicity. Professeur F. DESCHAMPS Dept of Occupational Health (IMTECA) Medicine Faculty REIMS- FRANCE

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1 3 rd International Summit on Toxicology CHICAGO Oct 2014 TRACK 4 : Industrial and Metallic Toxicology A NEW CHALLENGE : ASSESSMENT of Metallic Toxicity Professeur F. DESCHAMPS Dept of Occupational Health (IMTECA) Medicine Faculty REIMS- FRANCE 1

2 INTRODUCTION (Environmental exposure) - Cobalt is a hard lustrous, gray metal - Cobalt is naturally found in rocks, soil, water, plants, animals.. 2

3 INTRODUCTION (Environmental exposure) - Cobalt is present in trace amounts in human diet -(fish, vegetable, drinking water ) 3

4 PHYSIOLOGY - cobalt is a part of vitamin B 12 (necessary for neurological function, brain function, and blood formation ) - Require for oxygen transport in metabolism 4

5 USES - cobalt containing products include corrosion and heat resistant alloys (metal industries) - hard metal alloy : cobalt tungsten - carbide 5

6 OTHER USES - magnet - grinding/ cutting tools - pigments / paint - colored glass - catalyst / batterie - cobalt coated metal - surgical implants 6

7 OCCUPATIONAL EXPOSURE - hard metal industry - diamond polishing - ceramic industry 7

8 INDUSTRIAL PROCESS First step : forming wolfram carbide (WC) from the ore WC is then milled to fine powder secondly mixed with metallic cobalt (size 1 2 mm) 8

9 INDUSTRIAL PROCESS mixed powder is pressed to obtain desired shapes after heated under pressure to 1000 this «product» could be drilled finelly heated again (1500 C) 9

10 End of the PROCESS pieces obtained are ground to very exact shapes ( material is very hard and only diamond grinders can be used) 10

11 Mechanism of cobalt toxicity high affinity for sulfhydryl groups inhibition of crucial enzymes (oxidative phosphorylation) inhibition and competition with calcium binding generation of oxygen species direct cyto-toxicity 11

12 Effects of cobalt on cells inhibit osteoblast function reducing alkaline phosphatase activity inducing secretion of proteins IL8 and MCP ( osteoblasts) 12

13 Chronic systemic exposure accumulation liver accumulation Kidney 13

14 Adverse effects of cobalt and pulmonary diseases (intertitial fibrosis) tightening of the chest cough shortness of breath fatigue production of sputum weight loss 14

15 Adverse effects of cobalt neurological symptoms severed headaches cognitive decline memory difficulties (remembering names) poor concentration depression 15

16 Adverse effects of cobalt metal taste in the mouth anorexia weight loss 16

17 Adverse effects of cobalt hearing loss visual changes arrhythmias and cardiopathy endocrine symptoms ( hypothyroïdism ) abnormal lymphocyte function 17

18 Adverse effects releasing micro particulate metal debris : development of pseudotumors hypersensitive reaction nanoparticles consequences * cytotoxic * genotoxic * immunological (vigilance after long latency) 18

19 Hip prostheses conventional total hip prostheses : metal head fits into polyethylene cup ( but with time require revision) 19

20 Hip prostheses metal on metal bearing (made with cobalt and chromium) release a variety of metal ions into : local tissue general circulation 20

21 Metal hip assessment well fixed (x-rays) well aligned implant mild osteopenia around acetabular component 21

22 Case report 60 years old women total hip prosthesis containing cobalt three years ago 22

23 Case report clinical symptoms none symptom 23

24 Case report routinebiomonitoring 1) Blood cobalt level : 3.2 ug/l (non exposed population < 0.6 ug/l) 2) Blood cobalt level : 4.64 ug/l ( three months later) 3) Blood cobalt level increases : 8.29 ug/l ( patient with cobalt hip : 7 ug/l) 24

25 References biomonitoring - Problem from : 60 ug / l (up to 100 times that of physiologic levels) 25

26 Intravenous injection - 40 % eliminated within first 24 hours - 70 % eliminated within one week - 80 % eliminated one month - 90 % eliminated one year 26

27 Treatment of cobalt toxicity - No consensus - To treat the systemic symptoms : * thyroid replacement therapy * beta-blockers * angiotensin-converting. (no established indication for chelation therapy) 27

28 Conclusion - No current consensus regarding managment of patients with cobalt alloy, hip prostheses and elevated circulating cobalt metal ion levels - Removal of implanted hardware if : * endocrinopathy * cardiopathy ( persistance of neurologic symptoms) - Improved surveillance is needed 28

5. Summary of Data Reported and Evaluation

METALLIC COBALT PARTICLES 129 5. Summary of Data Reported and Evaluation 5.1 Exposure data Cobalt is widely distributed in the environment, occurring in the earth s crust mainly in the form of sulfides,