EDUCATIONAL COMMENTARY – LEAD TESTING

Educational commentary is provided through our affiliation with the American Society for Clinical

Pathology (ASCP). To obtain FREE CME/CMLE credits, click on Earn CE Credits under Continuing

Education on the left side of the screen.

Learning Objectives

On completion of this exercise, the participant should be able to

• characterize the biochemical effects of lead on human health;

• compare and contrast the methods used to detect the presence of lead in various samples;

• characterize the challenges involved in obtaining accurate lead screening data;

• outline the current regulations from the Centers for Disease Control and Prevention, the

Environmental Protection Agency, and the Department of Housing and Urban Development on

action levels for lead in blood, paint, dust, plumbing, and air; and

• discuss the best practices for preventing a recurrence of the Flint, Michigan, disaster.

Introduction

Lead is naturally found in soil at 50 to 400 parts per million (ppm) and is introduced into air and water by

natural and human activities that churn up the soil (e.g., mining, earthquakes, road construction), and

through the use of lead in gasoline, paint, ceramics, pipes, solders, batteries, toys, ammunition, and

cosmetics.1,2 Its malleability as a metal and its lower cost than iron has made it particularly appealing for

transporting water, a use that has been documented since the plumbing of ancient Roman times. In fact,

the chemical symbol for lead is Pb, from the Latin plumbum.3 All of the benefits associated with those

uses, however, come at the price of toxicity. A particularly disastrous example involving the city of Flint,

Michigan, made national news in 2015.

Flint, Michigan, as a Case Study on Misunderstandings and Mishandling of Lead Safety Realities

The Flint episode began on April 25, 2014, when city officials, in a cost-saving move, decided to use a

different distributor to obtain water from Lake Huron. The officials anticipated that the project would

require a 2-year temporary use of Flint River water while the new pipelines to Lake Huron were put into

place. Mandatory corrosion control treatments that would have prevented lead from leaching from the

entire Flint water pipe delivery system were not done. For months, city officials continued to claim that

the water met safe drinking water standards, despite turning “a rainbow of industrial colors—‘light yellow

to nasty, dark-looking cooking grease.’”4 Tests finally done by the city in February 2015 showed lead

levels of 104 parts per billion (ppb), seven times the Environmental Protection Agency (EPA) limit of 15

ppb. By August 2015, the Michigan Department of Environmental Quality admitted to dropping two

samples from its July 2015 report on lead levels in the city’s water, an action that had placed the results

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

below the action level. The omission was considered justified because the two samples did not meet

federal sampling criteria, as one involved a water filter and the second came from a business rather than

from a home.5 Independent tests by investigators from Virginia Tech University in September 2015

revealed water lead levels as high as 13,200 ppb, where 5000 ppb is considered hazardous waste.5 The

investigators also reported that the Flint River water, itself, did not contain an increased amount of lead.

A method required by the 2011 Reduction of Lead in Drinking Water Act6 had previously been used with

the Lake Huron water to decrease the chance of lead leaching from the water pipes into the water. A

water treatment chemical was added that would react with the lead to form scales, a deposit on the inner

lining of the pipe, coating the inside surface of the pipe. Many times, this added chemical would be

orthophosphate, resulting in a coating of crystalline Pb(II) orthophosphate compounds such as

hydroxypyromorphite, Pb9(PO4)6, or Pb3(PO4)2.7 The city’s decision not to add orthophosphate treatment

to the Flint River water for corrosion control,8 combined with the increased corrosivity of the Flint River

water compared with the Lake Huron water, resulted in deterioration of that protective scale, allowing the

lead from the pipes to leach into the water.

In September 2015, a local pediatrician, Dr. Mona Hanna-Attisha, released data from 1473 Flint children

younger than 5 years9 showing a significant increase in the proportion of children with elevated blood lead

levels in the period after the water system was changed (4.9% in January 1, 2015, to September 15,

2015) compared with the period before the change (2.4% in January 1, 2013, to September 15, 2013).

Dr. Hanna-Attisha and colleagues published these findings in February 2016 in the American Journal of

Public Health.10 The Centers for Disease Control and Prevention (CDC) reported in July 2016 that their

records of 9422 tests from April 2013 to March 2016 showed the adjusted probability of children younger

than 6 years having a blood lead level greater than 5 μg/dL (50 ppb) was 46% higher after the switch from

Detroit-supplied Lake Huron water to Flint River water.11 In addition, Flint residents were experiencing

symptoms of rashes, hair loss, and abdominal pain.4 This data finally led Michigan governor Rick Snyder,

President Obama, and the EPA to declare a state of emergency in January 2016. Unfortunately,

consensus in the medical community was that, because there is no “safe” degree of lead exposure,12 the

damage had already been done, especially to children exposed to the lead.10 There was also agreement

that any of the studies done during the crisis most likely underestimated the true level of lead exposure in

the affected Flint population.5,10,11

By July 2016, two state regulators had resigned and nine state and city employees faced felony charges

ranging from misconduct in office to conspiracy, willful neglect of duty, and tampering with evidence. Two

corporations hired as consultants were sued for “failing miserably in their job.”5

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

The Flint details highlight sampling errors, multiple reporting units for lead, toxic effects in children and

adults, detection method differences, and inadequacies of state and federal reporting guidelines.

Sampling Error

There were numerous reasons why the water sampling techniques used during the Flint crisis were

inadequate to provide accurate data. In December 2015, Flint reintroduced orthophosphates to the water

to rebuild the protective scales within the pipes. The EPA guidelines at that time required residents to

preflush the night before, beginning a 6 to 8 hour “stagnant” period of no water flow before sampling.

Residents were still being charged for the water wasted in the preflush, however, and thus would not do

that step, thereby preventing the corrosion control from reaching the very pipes it was intended to rescale.

One reporter stated that “people in Flint don’t want to pay for contaminated water that they can’t use.”5 In

addition to this, those who did follow the instructions had been provided with sample collection bottles

with small openings, requiring a low-flow rate during collection. This led to reduced levels of lead in the

samples.13 There was evidence that only 71 of the 100 samples required by the 1991 Lead and Copper

Rules were collected by city officials for analysis.

The EPA protocols were updated in light of the Flint experience on February 29, 2016. Changes include

eliminating the practice of flushing the tap before the mandatory 6- to 8-hour stagnation period, use of

kitchen or bathroom cold-water faucets for testing, avoiding faucets with water softeners if possible,

ensuring that faucet aerators are not removed before tap sampling, and encouraging the use of wide-

mouth bottles for collection of tap samples to avoid the loss of any of the first-draw sample.14

Multiple Lead Reporting Units

Reporting units used for lead concentrations differ depending on the sample being tested. As a

conversion reference, for water, blood, or paint, 1 μg/dL = 0.01 ppm = 10 ppb = 10,000 μg/m3; 1 ppm =

100 μg/dL = 1 mg/L; 1 ppb = 1 μg/L.15

The Reduction of Lead in Drinking Water Act of 20117 applies to an estimated 68,000 public water

systems in the United States.14 It specifies that the maximum allowable lead content in plumbing

products is 0.25%. In 1986, those guidelines specified a lead content of 8.0%. The regulation affects

kitchen, bar, and lavatory faucets, water dispensers, drinking fountains, water coolers, glass fillers,

residential refrigerator ice makers, supply stops, and end point control valves. Exempt from the 0.25%

maximum are pipes, fittings, and fixtures for nonpotable water, and “fill valves, flushometer valves, tub

fillers, shower valves, service saddles, or water distribution main gate valves that are 2 inches in diameter

or larger.”7 A 2013 update also exempted fire hydrants.7

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

Regarding regulations for lead in drinking water, the 1991 Lead and Copper Rules (LCR) specified a goal

of zero for acceptable concentration of lead in drinking water. The previously allowable level was 50 ppb,

measured at the entry point to the distribution system.16 The 2007 revision of the LCR established an

action level of 0.015 mg/L (15 ppb) for lead in drinking water, measured at the customer tap.7

Discussions and recommendations from multiple stakeholders led to the publication of the Lead and

Copper Rule Revisions White Paper by the EPA in 2016.17 Among proposals currently being considered

are a “household action level” approach recommended by the National Drinking Water Advisory Council,

enhanced public education requirements, and rules related to schools and other priority locations.17

Lead-based paints were legally banned in 1978; therefore, houses built before that year have the highest

likelihood of having lead on walls, baseboards, and windowsills (Figure 1).18,19 The paint itself is not a

problem, but its deterioration into paint chips and dust increases the exposure of vulnerable populations

to the lead. The EPA estimates that 24 million homes have such paint deterioration, with 4 million of

these homes being the residences of young children.18

Figure 1. Percentage of homes that are likely to contain lead. Reprinted from The Lead-Safe Certified Guide to Renovate Right. Environmental Protection Agency, 2011.19

Analysis of paint flakes for lead should be reported in mg/cm2 if the surface area can be accurately

measured and if all paint within that area is collected.19 Methods must be able to detect at least 1 mg/cm2

(0.5% lead in total weight).20 Lead in dust is hazardous if greater than 40 μg/ft2 on floors, 250 μg/ft2 on

interior windowsills, 400 ppm in bare soil in children’s play areas, or 1200 ppm in bare soil in the rest of

the yard.21 For air quality, the EPA in 2016 recommended that action levels for lead be greater than 0.15

µg/m3 in total suspended particles as a 3-month average.22

Establishment of action levels for blood lead in children has varied widely over the years. Before 2012,

the US Department of Housing and Urban Development (HUD) held that the level should be 20 μg/dL (0.2

ppm) and the CDC posed an action level of 10 μg/dL (0.1 ppm). In 2012, to identify more children at risk

for lead exposure more quickly, the CDC reduced the level to 5 μg/dL (0.05 ppm), and HUD has adopted

this lower level.23 When a HUD housing provider is notified of a child’s elevated blood lead level, they

must test the child’s surroundings within 15 days, and control for any lead hazards within 30 days.23

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

Toxic Effects in Children and Adults

The EPA has published, both on its website and in print, the summary of medical research defining the

risks of lead exposure.1 Children are vulnerable because they have a tendency to place objects possibly

contaminated with lead into their mouths, their food and drink may be in containers containing lead (lead-

glazed ceramics or lead-soldered containers), they may inhale lead dust from paint or soil, and toys may

be coated with lead-based paint. Compared with adults in the final absorption of the same amount of

ingested lead, children will absorb more.24 In addition, their nervous systems and brains are more

sensitive to lead toxicity before the age of 2 years when the blood-brain barrier has not completely

developed, and in utero exposure can affect the development of the central nervous system.

Flora et al25 attribute the major effect of lead to be oxidative stress produced by inactivating glutathione,

δ-amino levulinic acid dehydratase, glutathione reductase, glutathione peroxidase, and glutathione-S-

transferase.26 The fetal brain capillaries have a lower resistance to lead, allowing it to enter the brain.27

Lead easily damages the immature astroglial cells and obstructs the formation of a myelin sheath, both

factors in the development of the blood brain barrier.25 Within the cells, lead can compete with calcium as

a second messenger,27 and block the N-methyl-D-aspartate subtype of the glutamate receptor, which is

involved in the maturation of brain plasticity.28 Markowitz29 reported that approximately one-fourth to one-

half of an IQ point is permanently lost per 0.04826 μmol/L increase in blood lead level during the

preschool years. Toscano30 estimated an IQ deficit of 0 to 5 points for every 10 μg/dL (0.1 ppm) increase

in blood lead levels. Khan’s findings31 suggest that the effects may be reversible if the lead exposure

happens after the child is 2 years old.

Although it is acknowledged that the best action for managing lead poisoning is to reduce lead exposure,

chelation therapies (succimer, dimercaprol [BAL] and/or CaNa2EDTA) are available and can be provided

based on whether the child is symptomatic and the blood lead level.32 Children with blood lead levels >70

µg/dL (with or without symptoms) have an acute medical emergency and both BAL and CaNa2EDTA are

given. Chelation treatment for asymptomatic children with blood lead levels between 45 and 69 µg/dL

should be limited to CaNa2EDTA only. Less evidence is available for effectiveness of chelation therapy in

children with blood lead levels of 20 to 44 µg/dL.32

Encephalopathy can be directly attributed to lead exposure, with symptoms including dullness, irritability,

poor attention span, headache, muscular tremor, loss of memory, and hallucinations. More severe

manifestations occur at very high exposure and include delirium, lack of coordination, convulsions, ataxia,

paralysis, and coma.33

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A CDC infographic document34 targeted to families

mentions only the neural effects of lead poisoning.

There are other effects, however, including

nephropathy35 (Figure 2), hypertension, gout, future

kidney failure, decreased sperm count and

increased abnormal sperm forms, myocardial

morphologic abnormalities, irregular systolic and

diastolic numbers, electrocardiographic

disturbances,36 hearing loss, abdominal pain,

vomiting, constipation, weight loss, and seizures.37

Physical examination could include gingival lead

lines (Figure 3) wrist drop (Figure 4), and bone

growth arrest lines (Figure 5)38. In 2007, Stewart

and Schwartz suggested “a significant proportion of

what is considered to be ‘normal’ age-related cognitive decline may, in fact, be due to past exposure to

neurotoxicants such as lead.”39

Figure 3. Lead line on the gingival border of an adult with lead poisoning. Image reprinted with permission from Steven Marcus.38

Figure 4. Wrist-drop in adult with lead poisoning and renal failure. Image reprinted with permission from Steven Marcus.38

The effect of lead on red blood cells, leading to anemia, is infrequently mentioned in the literature. In

1899, Behrend first reported the nonspecific finding of erythrocyte stippling (Figure 6) associated with

lead.40

Figure 2. Kidney biopsy results from a patient with chronic lead nephropathy show nonspecific tubular atrophy and interstitial fibrosis. Note the absence of an interstitial infiltrate. The one glomerulus included in the section is normal. Image reprinted with permission from Vecihi Batuman.35

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

Figure 5. Growth arrest lines, also known as lead lines, in bones of a child who recovered from lead poisoning. Image reprinted with permission from Steven Marcus.38

Figure 6. Basophilic stippling of red blood cells in lead poisoning. Image reprinted with permission from Steven Marcus.38

Lead downregulates δ-aminolevulinic acid dehydratase, aminolevulinic acid synthetase, and

ferrochelatase.41 This results in the plasma/urine increase of aminolevulinic acid (ALA) and higher levels

of zinc protoporphyrin (ZPP) in red blood cells. The increased ALA originally inside the red blood cells

can lead to hemolysis.42 Although measurement of blood lead levels is the usual way to assess lead

exposure, assessing these porphyrin compounds in plasma, urine, and red blood cells can be helpful for

monitoring levels in adults who regularly work with or have hobbies using lead. An advantage of red

blood cell ZPP measurements is that there is no interference if lead is present as a skin contaminant at

the time of sample collection.43

Detection Method Differences

Table 1 summarizes methods for analyzing lead levels in various samples.19,44 Included in the chemical

tests in Table 1 are point-of-care blood tests. The only tests approved by the U.S. Food and Drug

Administration (FDA) are manufactured by Magellan Diagnostics; products include LeadCare, LeadCare

II, LeadCare Plus, and LeadCare Ultra. LeadCare II is listed on the company’s website as a CLIA-waived

test. On May 17, 2017, the FDA issued a warning regarding all of these instruments: “The FDA’s warning

is based on currently available data that indicate Magellan lead tests, when performed on blood drawn

from a vein, may provide results that are lower than the actual level of lead in the blood. Currently, the

FDA believes the issue may date back to 2014. The warning includes all four of Magellan Diagnostics’

lead testing systems: LeadCare; LeadCare II; LeadCare Plus; and LeadCare Ultra.”45 When testing is

performed with capillary samples, no error occurs. Magellan Diagnostics’ own investigation uncovered a

possible cause: a curing agent in the caps of blood-collection tubes leached into the venous samples.

This explanation has not been confirmed by the FDA.46

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Table 1. Methods for Analyzing Lead in Various Samples.a

Method Sample Type Strengths Limitations

Flame atomic absorption

spectrometry (FAAS)

Blood Paint

Requires only basic lab expertise Rapid analysis Small sample size with Delves

cup Low cost Few interferences Most accurate for paint

Detection limit, approx. 10 µg/dL Time needed to process sample Large sample size if no Delves cup Should not run unattended Paint surface must be disturbed Results not immediately available

Graphite furnace atomic

absorption spectrometry

Blood Water Paint

Detects < 1-2 µg/dL Small sample size Moderate cost Few interferences

Longer analysis time Needs more lab experience than

FAAS Greater potential spectral interference

than FAAS

Anodic stripping

voltammetry (ASV)

Blood

Detection limit 2-3 µg/dL Low cost Rapid Small sample size Portable ASV detection limit 3.3

µg/dL

Needs more lab experience than FAAS

Sample pretreatment needed Copper may affect measurement Becoming less available Portable ASV levels above 8 µg/dL

should be confirmed by another method

Inductively coupled

plasma mass spectrometry

Blood Water Paint

Detects approx. 0.1 µg/dL Rapid Small sample size Few interferences Multi-element capability Economic if large number of

samples

High cost High skill needed

Portable x-ray fluorescence spectrometry

Paint

Good accuracy Immediate results Low use costs No damage to paint surface Rapid

Potentially large margin of error compared with laboratory analysis

Requires certification High purchase cost Cannot measure lead in small

objects, curved surfaces, including toys

Chemical tests Blood Water Paint

Immediate results Inexpensive Simple to use

Limited accuracy Qualitative or semiquantitative Tests mainly top layers of paint May need to damage paint surface Difficult to observe color change for

dark paints Abbreviations: ASV, anodic stripping voltammetry; FAAS, flame atomic absorption spectrometry aData from Environmental Protection Agency19 and World Health Organization.44

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

Jennifer Lowry, a pediatrician at Children’s Mercy Hospital in Kansas City, Missouri, noted that physicians

may not be using the point-of-care devices properly. “A child’s finger needs to be cleaned well before

sample collection because a tiny speck of lead on the skin can cause a high reading.”47

A new testing sample type may be helpful in the future. Gardner et al48 tested the correlation between

lead assays using blood versus oral fluid and found a 100% negative predictive value using the oral

sample, eliminating the need for blood for lead screening in more than half of the 407 children tested.

Inadequacies of State and Federal Reporting Guidelines

The CDC recommends blood lead screening for high-risk populations and for children insured by

Medicaid at age 1 and 2 years.49 This recommendation does not include fetuses in utero (as prenatal

testing is currently not done) or infants younger than 12 months.10 Hanna-Attisha reported that her own

studies on the Flint children had that as a limitation, as well as the reality of housing instability, in which

the lead level of a child may reflect exposure from a previous residence.10

Although there is quite an exhaustive set of references, laws, and regulations mandating testing, plus

helpful aids for all citizens describing the dangers of lead, a review of the literature strongly suggests that

reporting guidelines are not universal, not followed, and results are manipulated and/or underreported. A

comprehensive summary of state requirements was compiled in 2015 by Genevieve Sykes at the

University of Alaska.50 Among the important findings is that only Iowa, Massachusetts, Delaware, and

Maryland require proof of lead testing for school-aged children.

A 2017 report in Pediatrics, describing the Public Health Institute’s research on lead screening from 1999

to 2010, revealed “1.2 million cases of elevated blood lead levels among children under 6 … only half of

those were reported to the Centers for Disease Control and Prevention. In some states, as many as 80

percent of lead-burdened children were not diagnosed at all.”51 Figure 7 shows the geographic distribution

of the Pediatrics data.50,52

Figure 7. Percent of lead-poisoned children missed, by region. From Cabrera 2017.52

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

Of the roughly 600,000 children not reported in the Pediatrics study, Roberts et al51 noted that “∼45%

(278,299) occurred in years during which the child’s state was not reporting to the CDC, and 55%

(337,405) were not reported because of incomplete case ascertainment in states engaged in reporting

efforts.”51 A listing of CDC data provided by states can be found at

https://www.cdc.gov/nceh/lead/data/state.htm. The following states do not submit lead surveillance data

to the CDC: Alaska, Arkansas, Hawaii, Idaho, Montana, North Dakota, Nebraska, Nevada, South

Carolina, South Dakota, Utah, and Wyoming.

Policies that defer to state and local health agencies to mandate blood lead testing for children in their

jurisdictions make the following assumptions: (1) good communication with stakeholders and (2)

mechanisms and resources for enforcement. Roberts and colleagues conclude that “both of these

assumptions have proven to be false, with the effect that large numbers of children with [elevated blood

lead levels] (indeed, the majority of these children in many parts of the country) have been missed by

clinicians.”51 Added to this, the National Center for Healthy Housing reported that “the budget for the

CDC Childhood Lead Poisoning and Healthy Homes program was itself reduced from $29 million to $2

million in 2012, leading to a loss of 57% of state positions responsible for primary prevention,

environmental assessments, enforcements of lead-safe building laws, and outreach and education to lay

and professional audiences, as well as for surveillance itself.”53 This would suggest that a more proactive

physician initiative, to learn about lead exposure risks and rely less on state and even national data, will

provide better service to their local patients in identifying those at risk and decreasing the effects of lead

exposure.

References

1. Environmental Protection Agency. Learn about lead: what is lead? Lead website. https://www.epa.gov/lead/learn-about-lead#lead. Updated May 26, 2017. Accessed August 9, 2017.

2. EarthJustice. Under pressure, FDA agrees to review lead in hair dye. EarthJustice website. http://earthjustice.org/news/press/2017/under-pressure-from-health-advocates-fda-agrees-to-review-lead-in-hair. February 27, 2017. Accessed August 9, 2017.

3. RWL Water News Team. A very brief history of lead in water supplies.

https://www.rwlwater.com/brief-history-lead-water-supplies. May 9, 2016. Accessed July 16, 2017.

4. McQuaid J. Without these whistleblowers, we may never have known the full extent of the Flint water crisis. Smithsonian. December 2016. http://www.smithsonianmag.com/videos/category/innovation/whistleblowers-marc-edwards-leeane-walters-flint/. Accessed August 9, 2017.

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5. Kennedy M. Lead-laced water in Flint: A step-by-step look at the making of a crisis. National Public

Radio. http://www.npr.org/sections/thetwo-way/2016/04/20/465545378/lead-laced-water-in-flint-a-step-by-step-look-at-the-makings-of-a-crisis. April 20, 2016. Accessed July 18, 2017.

6. Environmental Protection Agency. Summary of the Reduction of Lead In Drinking Water Act and Frequently Asked Questions, EPA 815-S-13-003. http://www.iapmort.org/Documents/epaLEADFAQs%2010-13.pdf. Published December 19, 2013. Accessed July 22, 2017.

7. Environmental Protection Agency. Optimal Corrosion Control Treatment Evaluation Technical

Recommendations for Primacy Agencies and Public Water Systems, EPA 816-B-16-003. https://www.epa.gov/sites/production/files/2016-03/documents/occtmarch2016.pdf. Published March 2016. Accessed July 20, 2017.

8. Edwards MA, Pruden A. The Flint water crisis: overturning the research paradigm to advance science and defend public welfare. Environ Sci Technol. 2016;50(17):8935-8936.

9. Roy S. Pediatric lead exposure presentation from Hurley Medical Center doctors concerning Flint

MI. Flint Water Study website. http://flintwaterstudy.org/2015/09/pediatric-lead-exposure-presentation-from-hurley-medical-center-doctors-concerning-flint-mi/. September 24, 2015. Accessed July 18, 2017.

10. Hanna-Attisha M, LaChance J, Sadler RC, Champney Schnepp A. Elevated blood lead levels in children associated with the Flint drinking water crisis: a spatial analysis of risk and public health response. Am J Public Health. 2016;106(2):283-290.

11. Kennedy C, Yard E, Dignam T, et al. Blood lead levels among children aged <6 years – Flint Michigan 2013-2016. MMWR Morb Mortal Wkly Rep. 2016;65(25):650-654.

12. Centers for Disease Control and Prevention. Lead website. https://www.cdc.gov/nceh/lead/. Updated February 9, 2017. Accessed August 9, 2017.

13. Pieper KJ, Tang M, Edwards MA. Flint water crisis caused by interrupted corrosion control: Investigating “ground zero” home. Environ Sci Technol. 2017;51(4):2007-2014.

14. Delaware Health and Social Services, Office of Drinking Water Programs. Homeowner Lead & Copper Tap Sample Collection Procedures. http://www.dhss.delaware.gov/dph/hsp/files/odwsamcollproc.pdf. Published March 10, 2016. Accessed August 9, 2017.

15. Microgram/deciliter ↔ Part per million conversion. EndMemo website. http://www.endmemo.com/sconvert/ug_dlppm.php. Accessed August 9, 2017.

16. Environmental Protection Agency. Lead and Copper Rule page. Drinking Water Requirements for States and Public Water Systems website. https://www.epa.gov/dwreginfo/lead-and-copper-rule. Updated March 15, 2017. Accessed August 9, 2017.

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

17. Environmental Protection Agency. Lead and Copper Rule Revisions White Paper.

https://www.epa.gov/sites/production/files/2016-10/documents/508_lcr_revisions_white_paper_final_10.26.16.pdf. Published October 2016. Accessed August 9, 2017.

18. Centers for Disease Control and Prevention. Prevention tips: how are children exposed to lead? Lead website. https://www.cdc.gov/nceh/lead/tips.htm. Updated June 19, 2014. Accessed August 9, 2017.

19. Environmental Protection Agency. The Lead-Safe Certified Guide to Renovate Right. https://www.epa.gov/sites/production/files/documents/renovaterightbookletbwsept2011.pdf. Revised September 2011. Accessed August 9, 2017.

20. Environmental Protection Agency. Lead Abatement for Workers: Identifying Lead-based Paint Hazards. https://www.epa.gov/sites/production/files/documents/wkrch4_stu_eng.pdf. Accessed August 9, 2017.

21. Environmental Protection Agency. Hazard Standards for Lead in Paint, Dust and Soil (TSCA Section 403) page. Lead website. https://www.epa.gov/lead/hazard-standards-lead-paint-dust-and-soil-tsca-section-403. Updated May 8, 2017. Accessed August 9, 2017.

22. Environmental Protection Agency. NAAQS table. National Ambient Air Quality Standards website. https://www.epa.gov/criteria-air-pollutants/naaqs-table. Originally published November 15, 1990. Web page last updated December 20, 2016. Accessed August 9, 2017.

23. Sullivan B. Press Release: HUD issues final rule to help children exposed to lead paint hazards. HUD No.17-006. https://portal.hud.gov/hudportal/HUD?src=/press/press_releases_media_advisories/2017/HUDNo_17-006. Published January 13, 2017. Accessed August 9, 2017.

24. Kathuria P, Rowden AK, O’Malley RN, Lorenzo N. Lead toxicity: clinical presentation. http://emedicine.medscape.com/article/1174752-clinical?src=refgatesrc1. Updated January 31, 2017. Accessed August 9, 2017.

25. Flora G, Gupta D, Tiwari A. Toxicity of lead: a review with recent updates. Interdiscip Toxicol. 2012;5(2):47-58.

26. Ahamed M, Siddiqui MKJ. Low level lead exposure and oxidative stress: current opinions. Clin Chim Acta. 2007;383:57-64.

27. Kursula P, Majava V. A structural insight into lead neurotoxicity and calmodulin activation by heavy metals. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:53-66.

28. Marchetti C. Molecular targets of lead in brain neurotoxicity. Neurotox Res. 2003;5:221-236.

29 Markowitz M. Lead poisoning. Pediatr Rev. 2000;21:327-335.

30. Toscano C, Guilarte T. Lead neurotoxicity: from exposure to molecular effects. Brain Res Rev. 2005;49:529-554.

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EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

31. Khan A. Lead poisoning imaging. http://www.emedicine.com/radio/topic386.htm. Updated

December 2, 2015. Accessed August 9, 2017.

32. Centers for Disease Control and Prevention, Advisory Committee on Childhood Lead Poisoning Prevention. Chapter 7, Diagnostic evaluation and medical management of children with blood lead levels > or = to 20 µg/dL. In: Preventing Lead Poisoning in Young Children. https://www.cdc.gov/nceh/lead/publications/books/plpyc/chapter7.htm#Treatment guidelines. Originally published October 1, 1991. Accessed July 23, 2017.

33. Flora SJS, Flora G, Saxena G. Environmental occurrence, health effects and management of lead poisoning. In: José SC, José S., eds. Lead. Amsterdam: Elsevier Science B.V; 2006:158-228.

34. Centers for Disease Control and Prevention. Infographic: prevent childhood lead poisoning. Lead website. https://www.cdc.gov/nceh/lead/infographic.htm. Updated January 26, 2017. Accessed August 9, 2017.

35. Batuman V. Lead nephropathy. http://emedicine.medscape.com/article/242605-overview. Updated January 12, 2016. Accessed August 22, 2017.

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American Proficiency Institute – 2017 3rd Test Event

EDUCATIONAL COMMENTARY – LEAD TESTING (cont.)

45. Food and Drug Administration. FDA warns against using Magellan Diagnostics LeadCare testing

systems with blood obtained from a vein: FDA Safety Communication. https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm558733.htm. Published May 17, 2017. Accessed August 9, 2017.

46. Rabin RC. F.D.A warns of inaccurate blood tests for lead poisoning in children and mothers. New York Times. May 18, 2017: A17.

47. Kirkwood J. Preventing the next Flint: lead crisis reveals opportunities to improve testing. Clin Lab News. 2016;43(11):12-15.

48. Gardner SL, Geller RJ, Hannigan R, Sun Y, Mangla A. Evaluating oral fluid as a screening tool for lead poisoning. J Anal Toxicol. 2016;40(9):744-748.

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50. Sykes G. Pediatric Lead Screening in the United States: A Comparative Analysis. Anchorage, AK: University of Alaska School of Nursing; 2015. https://scholarworks.alaska.edu/bitstream/handle/11122/4792/Sykes%20manuscript.pdf. Accessed August 9, 2017.

51. Roberts EM, Madrigal D, Valle J, King G, Kite L. Assessing child lead poisoning case ascertainment in the US, 1999–2010. Pediatrics. 2017;135(5).

52. Cabrera Y. In some states, 80 percent of kids with lead poisoning don’t get tested. ThinkProgress website. https://thinkprogress.org/lack-of-testing-leaves-a-third-of-u-s-children-with-lead-poisoning-undiagnosed-and-untreated-46fe3388c75f. Published May 3, 2017. Accessed August 9, 2017.

53. National Center for Healthy Housing. State and Local Childhood Lead Poisoning Prevention Programs: The Impact of Federal Public Health Funding Cuts. http://nchh.org/Portals/0/Contents/State-and-Local-Childhood-Lead-Poisoning-Prevention-Programs_2013-08-01.pdf. Published July 2013. Accessed August 9, 2017.

© ASCP 2017

American Proficiency Institute – 2017 3rd Test Event