Ulrike Luderer, M.D., Ph.D., M.P.H.
Professor, Division of Occupational and Environmental
Medicine, Dept. of Medicine, University of California ,
Irvine

• Face powders, rouges, and mascaras
• Paint pigment in many paints ("crazy as a painter“)t
• Spermicide for informal birth control;
• Cold metal for use in the manufacture of chastity belts;
• Sweet and sour condiment popular for seasoning and adulterating food
• Wine preservative perfect for stopping fermentation or disguising inferior vintages
• Malleable and inexpensive ingredient in pewter cups, plates, pitchers, pots and pans, and other household artifacts
• Basic component of lead coins
• Partial ingredient in debased bronze or brass coins as well as counterfeit silver and gold coins.
• EPA Lead Poisoning: A Historical Perspective

• 5 year history of progressive cognitive decline, largely involving short-term memory, wordfinding, worsening over the last 2 years
• Depression, anxiety, fatigue, irritability, headaches, poor sleep quality
• Abdominal pains, diarrhea
• Early retirement 1.5 years ago- medical disability
• Internist, neurologist, and psychiatrist
• His medications included clonazepam, escitalopram, topiramate, and ramelteon

• Physical examination
• Diagnostic studies for metabolic, endocrine, and auto-immune conditions were negative.
• Neuroimaging studies, including two brain MRIs and a FDG PET/CT, were normal.
• EEG and EMG readings were normal.
• Neuropsychological testing -conclusions as to whether findings represented deficits or problems with test performance that may possibly have resulted from emotional factors.

• Baseline blood lead level was 48 μg/dL
• Succimer (19 days total: 2,800 mg/day for 5 days, 4 divided doses; 1,400 mg/days for 14 days, twice daily)
• decreased to 10.3 μg/dL. He reported marked symptom improvement.
• His urine lead was 28 μg/L. His urinary lead excretion increased to 1,265 μg/day
• One month after chelation, his blood lead levels increased to
28.5 μg/dL, consistent with lead redistribution from skeletal and soft tissue stores. He reported a worsening of symptoms.
• Second course of chelation his blood lead level decreased to
5.9 μg/dL.
• Blood lead levels increased again to 36.4 μg/dL about 4 months after the second chelation.
• No subsequent lead exposures were identified,
• No change in hobby activity or additional chelation, his blood lead levels over the next several months diminished to 16.9
μg/dL. Marked improvement of symptoms

• H/o gunshot wound to spine at age 14 with transection resulting in paraplegia and retained bullet in T10-T11 interspace.
• PhD, scientist at pharmaceutical company.
• Anxiety, depression, difficulty sleeping, fatigue, intermittent diffuse abdominal pain lasting a few hours at a time, constipation, increased appetite, weight gain, left sided tinnitus, numbness and tingling in 3 rd and 4 th fingers of left hand that resolved when he stopped playing the violin.
• Asked PMD to check blood lead levels about 2 years ago

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• Physical examination
• BP 138/95, HR 100, decreased to 90
• HEENT: No lead lines
• Neurological: upper extremity motor and sensory intact
• CBC within normal limits; no basophilic stippling of nucleated RBCs on examination of peripheral smear.
• Renal function:
• Normal BUN, Cr.
• Urinary β-2-microglobulin and α-1-microglobulin within reference ranges.

Case 2: Source of lead exposure
(A) Anterior and (B) lateral x-rays of lumbar spine showing elution of lead particles in peridiskal region with “diskogram” like effect (Scuder et al, 2004, J Spine Disord Tech).

• 99% of bullets sold in the US still contain lead.
• Lead content of cast bullets is 80-95%.
• Due to lead’s softness, fragmentation on impact is likely.
• Systemic absorption of lead and lead toxicity are unlikely with retained fragments in soft tissues.
• Blood lead levels more likely to rise if bullet/fragments are bathed in fluid - located in joint space or intervertebral space, a cyst forms around the fragment – and if the bullet caused a bone fracture
(Eward, William C., et al. 2010, J surgical orthopaedic advances 20.4:
241-246; Scuderi et al, 2004, J Spinal Disorder Tech 17:108-111;
McQuirter et al, 2001, J Trauma , Injury, Infection, Critical Care 50:892-
899)

Sandeep Ravindran, National Geographic , October 14, 2013

Ayurveda, a Sanskrit word that means
"knowledge of life and longevity," is based on principles and rhythms found in nature

≥μg/dL
No. (%)
(MMWR, 2013, 62:927-71)

Chronic BLLs at or above 10 μg/dL:
• Hypertension
• Kidney dysfunction
• Reduced birth weight
Chronic BLLs less than 10 μg/dL:
• Increased blood pressure and risk of hypertension
• Increased incidence of essential tremor
Chronic BLLs less than 5 μg/dL:
• Decreased kidney filtration rate
• Reduced fetal growth
EHP review (2007)
U.S. Environmental Protection Agency (2013). Integrated Scientific Assessment for Lead (EPA/600/R-10/075F). Research Triangle Park, NC: US EPA.
National Toxicology Program (2012). NTP Monograph on Health Effects of Low-
Level Lead

Impairment of renal function with increasing blood lead concentration in the general population
Staessen JA et al. NEJM 327:151-6;
1992
 Random population sample of 965 men and
1016 women (age 20 to 88)
 Blood lead range 1.7 - 72.5 ug/dL; geometric mean ≈ 10 ug/dL
 Significant correlation between age-adjusted creatinine clearance and blood lead
 Relationship persisted after excluding subjects with occupational Pb exposure, or those with highest tercile of PbB (geom. mean 18.4 ug/dL)
 “Reverse Causation” remains unresolved question

The Relationship of Bone and Blood
Lead to Hypertension.
The Normative Aging Study
[ Hu H et al, JAMA 1996; 275:1171-1176]
• Case control study: 146 hypertensive men; 444 controls selected from large, ongoing prospective study of aging.
Mean age = 66.6 ±7.2 y
• Exposure reflected that of general population. (Mean PbB
= 6.3 μg/dL)
• Final logistic model yielded 3 significant risk factors for hypertension: BMI, family history of hypertension, tibia bone lead concentration
• From the lowest quintile of bone lead to the highest quintile (≥29 μg/g) , the odds of being hypertensive increased by 50 %

Decrease in Birth Weight in Relation to
Maternal Bone-Lead Burden
[Gonzalez-Cossio T et al.
Pediatrics 100:856-862; 1997]
• Study of 272 full-term, parturient women in Mexico City and birth weight of their infants Maternal blood lead 8.9 ±
4.1 μg/dL Maternal tibia bone lead 9.8 ± 8.9 μg/g (range
12 – 38 μg/g)
• In a multivariable regression model, every increase of 10
μg/g in maternal tibia bone lead was associated with a
73 gram (95% CI, 25 -121) decrease in birth weight.
• The relationship was nonlinear and most pronounced in highest quartile of bone lead (> 15 – 38 μg/g), where birth wt decrement relative to first quartile was 156 g.
“Because lead remains in bone for years to decades, mobilization of bone lead during pregnancy may pose a significant fetal exposure with health consequences, long after maternal external lead exposure has declined.”

Time required to return to <10 μg/dl

Recommendations for chelation based on BLL
• Current recommendations from the Centers for
Disease Control (2010) state that chelation should be possibly considered in adults for blood lead levels between 50-79 mcg/dL if symptoms are present, strongly considered for levels between 80-
99 mcg/dL, and recommended for levels greater than 100 mcg/dL.