1. Occupational toxicology Ass. Prof. Laith A. Alrudainy MBChB, MSc, PhD Lecture 2 Environmental toxicology

2. Lead Toxicity

3. Sources of lead - Extraction process - Lead-acid battery manufacture - Ship breaking - Car radiator repair - Welding - Paint manufacture or application - Plumbing - Petrol manufacture - Plastics manufacture

4. Biological Fate Once in blood stream, lead is primarily distributed among three compartments: Blood ( 1%). Soft tissues ( Kidney, bone marrow, liver, and brain). Hard tissue ( the bone and teeth - 95% of the total lead in the body).

5. Signs and Symptoms Acute Toxicity –Abdominal Colic/ Constipation –Anemia

6. Signs and Symptoms Chronic Toxicity: –Joint Aches (Arthralgias) –High Blood Pressure –Chronic Renal Failure –Increase spontaneous abortions... Lead can easily cross the placenta –Mental retardation and behavioral problems in children

7. Laboratory Evaluation The best screening and diagnostic test for lead poisoning is a Blood Lead Level (BLL).

8. Treatment and Management A symptomatic patients with BLL below 25 µg/ dl -- ------ separation from the source of exposure. Patient with blood lead level of 45 µg/ dl or greater - ----- chelating therapy immediately.

9. Treatment and Management Chelating Agents: 1) BAL (British Anti-Lewisite) or dimercaprol. 2) CaNa2 EDTA 3) DMSA or succimer. Mechanism: Binds and removes inorganic lead from the soft tissues and bones.

10. Mercury Toxicity

11. Types of Mercury Three Types of Mercury: 1) Elemental Mercury 2) Inorganic Mercury 3) Organic Mercury

12. Sources of mercury 1) Mining Operations 2) Paper Production 3) Medical Instruments: Thermometer, Blood Pressure Apparatus 4) Dental Fillings: Amalgams: 50% Mercury with Silver

13. Health Effects Elemental Mercury (mercury vapor): Lungs ----- Chemical Pneumonitis. Brain ----- Chronic exposure  Tremor, Psychological problems

14. Health Effects 2) Inorganic Mercury: Gastrointestinal tract: Corrosive to mucosal membranes  Hemorrhagic Necrosis and rapid fluid loss  Shock  Death Kidneys: Effects the Proximal Tubule  Acute Renal Failure can develop within 24 to 48 hours

15. Health Effects 3) Organic Mercury/ Methyl Mercury:  Due to high lipid solubility Methyl Mercury easily crosses the placental barrier and blood brain barrier.  Maternal exposure ----- ingestion of contaminated food (fish, grain).  Clinical Triad: Ataxia, Dysarthria, and constriction of visual fields

16. Clinical Triad: - Ataxia - Dysarthria - Constriction of visual fields

17. Laboratory Evaluation Blood is an appropriate specimen for analysis after acute mercury exposure. A 24-hour urine specimen is preferred in cases of chronic exposure.

18. Treatment and Management Chelation therapy has been used successfully in treating patients who have ingested inorganic mercury or inhaled elemental mercury. No antidote exist for patient with organic mercury; supportive care is recommended.

19. Cadmium Toxicity

20. Exposure pathway Smoking: –Cigarette = 1-2 ug Cd Industrial Uses: –Industries dealing with pigment, metal plating, plastics, batteries

21. Health Effect Acute Toxicity: –Inhalation of Cadmium Fumes Flu Like Illness that Resolves within 24 Hours

22. Chronic Toxicity: Kidneys –Cd ½ Life in Tubular Cells = 10 – 30 years –Proximal Tubule Dysfunction: Proteinuria Excretion of Glucose and Amino Acids Excretion of Minerals: Phosphate and Calcium Health Effect

23. Skeletal System: Due to increase Urinary Calcium exertion the bones mobilize calcium stores Osteoporosis & Osteopenia, "Itai – Itai" Health Effect

24. Laboratory Evaluation Blood Cadmium Urine Cadmium Urine Beta- 2 Microglobulin

25. Arsenic Toxicity

26. Exposure pathway Commercial Sources: –Wood Preservatives  Arsenic is an excellent pesticide, herbicide, and fungicide Occupational Sources: –used throughout the semi- conductor industry. –Arsine Gas is used in computer chips

27. Exposure pathway After absorption arsenic is bound to proteins in the blood and is rapidly distributed to the Liver, Kidneys, Lungs, and Gastro-Intestinal Tract within 24 hours. Two to four weeks after exposure arsenic can be identified in hair, skin and nails

28. Acute Toxicity: –1) Gastrointestinal Tract: Most prominent symptoms occur within minutes of ingestion Sloughs the entire GI Tract –Difficulty swallowing, intense abdominal pain, projectile vomiting, Rice- Water Stools, Severe Dehydration –Develop Shock due to Fluid loss Health Effect

29. Chronic Exposure: 1) Skin: Hyperkeratosis of Palms and Soles Increased risk for non-melanoma skin cancer 2) Peripheral Nervous System: Neuropathy of extremities with a sensory & motor component

30. Hyperkeratosis of Palms and Soles ( Arsenic Hand )

31. Laboratory Evaluation –Blood: Acute toxicity (24 hours) –Urine: Indicator of recent toxicity (48 hours) –Hair: Useful for Chronic Toxicity (Weeks)

32. Treatment and Management Acute Toxicity: –1) Supportive Care: Fluid Replacement Gastric Lavage –2) Chelating agents

33. Thank you