# Presentation: 895728

## Health Effects of Lead Exposure

- Susan K. Cummins, MD, MPH
- Senior Science Advisor
- Pediatric & Maternal Health Staff
- Office of New Drugs

## Today’s Talk

- Blood lead distribution & trends over time
- Trends in measurement and modeling of exposure
- Health effects in children and adults

## Lead in Arctic Snow Strata 

- Lead in Arctic Snow Strata

**Year **

**Percent of Current Concentration**

## Geometric Mean Blood Lead Levels by Gender & AgeNHANES III, 1991 to 1994

**Age (years)**

**Geometric mean ****blood lead level (ug/dL)**

**Env Health Perspect, 1998**

**Females**

**Males**

## Geometric Mean Blood Lead Levels in Children 1 to 5 yearsNational Health & Nutrition Surveys

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**14**

**16**

**1976-1980**

**1988-1991**

**1991-1994**

**1999-2000**

- Geometric Mean Blood Lead Levels
- in ug/dL whole blood

**NHANES II**

**NHANES **III

**NHANES **III

**NHANES IV**

- Source: CDC

**14.9**

**3.6**

**2.7**

**2.2**

## 13 ug/dL

**13 ug/dL**

**3 ug/dL**

**2 ug/dL**

## Common Lead Sources

- Children
- Deteriorated paint
- Contaminated dust, water, soil, food
- Occupational take-home exposure
- Folk remedies
- Imported ceramic pots, toys
- Many others

- Adults
- Occupational (90%)
- Hobbies (stained glass, packing shot)
- Folk remedies
- Imported ceramic pots
- Contaminated food
- Many others

## Uptake, Distribution, Metabolism and Excretion

## Primary Routes of Lead Exposure

- Inhalation
- Only particles of respirable size (< 1um)
- Ingestion
- Inhaled lead particles > 2.5 um in diameter
- Absorption influenced by:
- Presence of other nutrients (iron, zinc, calcium)
- Age—Children ~ 50%     Adults ~ 10-20%

## Exposure Scenarios

**Time**

- Blood
-  Lead
- Level** **

**Brief Acute Exposure**

**Long Term Chronic Exposure**

## Lead Uptake, Deposition & Excretion

- Source: EPA

## Circulating Lead Increases with:

- Physiologic states that heighten bone resorption--
- Pregnancy & lactation
- Prolonged bed rest (fracture in traction)
- Postmenopausal osteoporosis
- Hyperthyroidism
- Weightlessness

## Measuring Human Lead Exposure  and Body Burden

- Blood Lead Level
*If brief exposure* – half-time 35 days
*If long term exposure* – slower clearance, ongoing lead exposure equilibrates with stores in soft tissue & bone
- Bone Lead Level -- by K X-Ray Florescence
- Measures cumulative body burden
- Cortical bone (tibia) – clearance half-time decades
- Trabecular bone – clearance half-time years to decades
- Cumulative Blood Lead Index (CBLI)
- Area under the curve of blood lead levels over time, estimates cumulative lead dose

## Blood Lead TrendsTreatment Lead Exposed Children Trial 

**NEJM, 2001**

- First year— small BLL drop
- Three years– No IQ impact

## Health Effects in Children

## Lead is a Systemic ToxicantHealth Effects in Children

**CDC Level**
**of Concern**

**1978**
**1985**
**1991**

## Slide 17

## Slide 18

## Slide 19

## IQ Impairment from Blood Leads < 10 ug/dL

- Canfield & Colleagues, NEJM in April, 2003
- 172 children
- Serial Blood Lead measured every 6 months from 6 to 36 months, then at 48 & 60 months
- Stanford-Binet IQ scales at 3 and 5 years
- Impact of Blood Lead on IQ measured, after adjustment for maternal IQ and covariates

## IQ vs. Lifetime Average Blood Lead Concentration

- Canfield, NEJM 2003

## Effect Size

- Linear Model, all Blood Leads:  4.6 point IQ decline for every 10 ug/dL increase in Blood Lead
- Non-linear Model, only Blood Leads below 10 ug/dL: IQ decline of 7.4 points

## Blood Lead & IQ

- Blood lead _>_ 10 ug/dL lowers IQ by 2 to 4 points
**Doubles low IQ**
**Halves high IQ**
- Blood lead 1 to 10 ug/dL lowers IQ by 7 points

## Lead Poisoning Causes Anemia

- Hypochromic, microcytic red blood cells
- Mimics & may occur with iron deficiency
- Rare with Blood Lead Levels < 35 ug/dL
- High Free Erythrocyte Protoporphyrin (FEP)

## Other Health or Behavioral Effects in Children & Youth

- Executive function disorders
- Complications of ADHD & school failure
- Delayed onset of puberty
- Dental carries
- Reduced linear growth

## Health Effects in Adults:Adult WorkersGeneral Population

## Lead is a Systemic ToxicantHealth Effects in Adults

## Health Effects in Adult Workers

- Hematological: Microcytic anemia
- Neurological:
- Irritability, headache, poor memory, tremor, depression
- Acute encephalopathy
- Peripheral neuropathy-- slowed nerve conduction, motor > sensory
- Gastrointestinal: colic, constipation, anorexia, nausea, vomiting
- Renal toxicity:
- Gradual decline in renal function & interstitial fibrosis
- Hypertension, hyperuricemia with/without gout

## Reproductive Effects in Adult Workers

- Males
- Impotence
- Reduced sperm counts & production
- Malformed sperm with reduced motility
- Females
- Menstrual disturbances
- Sterility
- Spontaneous abortions
- Stillbirths
- Both -- genetic damage to germ cells

## Carcinogenesis

- 2004—National Toxicology Program
- Found Lead & Lead Compounds, “*Reasonably anticipated to be human carcinogens”*
- 2006—WHO, IARC Monograph
*Inorganic Lead Compounds* —*probably carcinogenic to humans*
*Organic Lead Compounds* —*not classifiable **as to their carcinogenicity to humans*

## Health Effects in Adults From Low Level Exposure

- Hypertension & Renal Disease
- Cardiovascular Disease
- Cognition

## Lead Exposure and HypertensionAdults

- Multiple Reviews and Meta-Analyses of..
- 30 original observational studies with
- Approximately 60,000 participants
- Conclusion: Low level lead exposure is associated with hypertension
- For every 2-fold increase in blood lead (e.g. from 5 to 10 ug/dL) 0.6 to 1.25 mmHg increase in systolic blood pressure
- Findings supported by animal studies

## Lead Exposure and Cognitive Function

- Meta-Analysis conducted in 2007
- Study participants had environmental exposure or current or past occupational exposure to lead
- Supported an association between lead dose and decrements in cognitive function in all three cohorts
- Affected cognitive domains:  verbal & visual memory, motor & psychomotor speed, manual dexterity, attention, executive functioning, peripheral motor strength
- Dose-response relationship in nearly all studies

- EHP, 115:483, 2007

## Lead Effect Studies within the Normative Aging Study

- From cohort of 2,280 Boston resident men, selected a subset of 719 men without occupational exposure at entry
- Enrollment began 1961
- 21 to 80 years old at enrollment
- Few employed in lead occupations
- No chronic diseases or HTN at entry
- Follow up every 3 to 5 years (survey, physical exam, laboratory work)

## Lead Burden Assessment Normative Aging Study

- 1991: Blood lead & bone lead measured
- Blood Lead Distribution (n and percent):
- Below 5 ug/dL 	(270)	38%
- 5 to 10 ug/dL   	(361)	50%
- 11 to 20 ug/dL 	(80)	11%
- _>_ 20 ug/dL          	(8) 	8%
- Bone Lead Burden (range and geometric mean):
- Tibia: (<1-51 ug/g bone) & 20.8 ug/g bone
- Patella: (3-77 ug/g) & 29.8 ug/g bone
- Bone lead level correlated with & was the major contributor to blood lead level

## Conclusions

- Lead is a systemic toxicant with no evidence for a “safe” exposure threshold
- Integration of bone lead with blood lead measurements allows for more precise categorization of lead exposure
- Recent evidence demonstrates harm in the from low level lead burdens in children & adults