1. Lead-Induced Renal Disease Mark Huang Rachel Lipper Shannon Sullivan Carrie Ziehl

2. What is the Diagnosis? End stage renal disease Pathologic diagnosis of active acute and chronic interstitial nephritis; glomerulosclerosis

4. What is the Exposure? Lead compounds (found in printing ink): –ingestion (primary route of exposure) –inhalation Glycol ether EE acetate (found in solvent): –transdermal (primary route of exposure) –inhalation

5. Mr. SO worked with: –Oil based ink containing lead. –Printing solvent containing glycol ether EE acetate. Duration: –Working 5 days a week, 12 hours shifts. Working a sixth day for 8 hours and twice monthly a seventh day for 6 hours. Intensity: –He would add solvent or ink at least hourly to his pan utilizing a gallon of solvent and ink each hour. –Pouring the solvent over his head with the solvent dripping down onto his exposed arms and his gloves. –He wore gloves that were wet with solvent a minimum of 20 minutes of every hour.

6. Frequency –At least 2 times a week, he would use rags saturated with the solvent to clean his press and the ink pan. When the production demand changed in 1988, he would clean the ink pan 4 times a day. Other conditions: –He stated that vapor odor was strong at his work site. –The only PPE worn was gloves, and the solvents and ink were constantly spilling onto his clothing in the areas of arms, chest, and legs.

7. Does This Exposure Cause This Disease at any Dose? YES!!!!!! Chronic lead exposure can lead to chronic interstitial kidney disease. This, in turn, leads to renal failure. Glycol ether EE acetate can cause acute and chronic effects: CNS changes, GI bleeds, and renal failure.

8. The Kidney Functional unit = nephron Nephron has 2 basic parts: –glomerulus (filter) –tubule (passageway for urine, where reabsorption occurs)

10. Damage to the Kidney Glomerulus (filter) –Often caused by infection or autoimmune disease. –Causes protein spillage into urine. Interstitium (tubules) –Caused by heavy metals, toxins, drugs. –Acute toxic exposure is reversible (tubules). –Chronic toxic exposure is irreversible (interstitium) => CHRONIC RENAL FAILURE

11. Lead Toxicology Cumulative poison: found in lead-based paint, lead dusts. Chronically exposed develop interstitial fibrosis, and tubular atrophy, and eventually chronic renal failure. Other toxic lead symptoms include hypertension, anemia, GI disturbances, nausea, vomiting, musculoskeletal, and CNS changes.

12. Lead-Induced Kidney Disease Male smelter workers employed between 1940 - 1965: Large cohorts of heavily exposed lead workers followed through 1980 showed 3X excess deaths due to chronic nephritis or “other hypertensive disease”, primarily kidney disease. Risk of death from renal disease increased with length of employment. (Steenland, 1992).

13. Acute Tubulointerstitial Nephropathy Often caused by toxins or drugs, including glycol ether EE acetate. Acute pathology is different than that of a chronic process, showing interstitial edema.

14. Was This Patient Exposed Sufficiently to Lead? Symptoms of severe lead intoxication occur at and above blood lead levels of 80µg/100g. Blood lead levels were not determined on Mr. So. 1910.1025(c)(1) “employer shall assure that no employee is exposed to lead at concentrations greater than 50 ug/m3 averaged over an 8-hour period” Solvent sampling showed levels below the OSHA PEL, but lead sampling is done using a different method so the true levels of lead in the air are unknown.

15. Was This Patient Exposed Sufficiently to Lead? Possible routes of exposure: –Handling food, cigarettes, chewing tobacco, or make-up with hands contaminated with lead will contribute to ingestion (OSHA) –Mr. So smoked a half pack of cigarettes a day –Lead scattered in the air as a dust, fume, or mist can be inhaled and absorbed through lungs and upper respiratory tract (OSHA) –Mr. So added ink hourly to his press and cleaned the ink pans from 2 times a week to 4 times a day.

16. Was This Patient Exposed Sufficiently to Glycol Ether EE Acetate? OSHA PEL: 100 ppm (540 mg/m3) [skin] for an 8-hour time weighted average NIOSH REL: TWA 0.5 ppm (2.7 mg/m3) [skin] Mr. So used a gallon of solvent an hour, pouring solvents over his head, dripping them onto his exposed arms. His gloves were wet with solvent 20 minutes of every hour. NIOSH recommendations for personal protection: –(1) Prevent skin contact –(2) Wash skin when contaminated –(3) Remove PPE when wet or contaminated

17. Are There Any Mitigating Factors? 1967 - Childhood injury resulting in glomerulosclerosis, which led to chronic protein spillage 1975 and 1981 - Protein observed in urine Failure to wear adequate protective clothing: –Wore gloves, a form of PPE. –HOWEVER - MSDS recommends wearing rubber boots, gloves, and apron.

18. Are There Alternative Explanations? There are no likely alternate explanations for the interstitial component of his renal disease. Baseline glomerulosclerosis is likely due to a childhood injury.

19. Is This Individual’s Disease Due to His Exposure? YES!!!!!!