Also Known As
ZPP
ZP
Free Erythrocyte Protoporphyrin
FEP
ZPP/Heme Ratio
This article was last reviewed on
This article waslast modified on May 28, 2019.
At a Glance
Why Get Tested?

To screen for and monitor chronic exposure to lead in adults; to detect iron deficiency in children

When To Get Tested?

When you have been chronically exposed to lead, as part of a program to monitor industrial lead exposure, and/or when your healthcare provider suspects lead poisoning; as part of screening and diagnosing iron deficiency in children and adolescents

Sample Required?

A blood sample drawn from a vein or from a fingerstick

Test Preparation Needed?

None

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The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Zinc protoporphyrin (ZPP) is normally present in red blood cells in small amounts, but the level may increase in people with lead poisoning and iron deficiency. This test measures the level of ZPP in the blood.

To understand how lead poisoning and iron deficiency affect the ZPP level, it is necessary to know about heme. Heme is an essential component of hemoglobin, the protein in red blood cells that carries oxygen from the lungs to the body's tissues and cells.

Heme formation occurs in a series of steps that concludes with the insertion of an iron atom into the center of a molecule called protoporphyrin. When there is not enough iron available, as in iron deficiency, or when the insertion of iron is inhibited, as in lead poisoning, then protoporphyrin combines with zinc instead of iron to form zinc protoporphyrin. ZPP serves no useful purpose in red blood cells since it cannot bind to oxygen.

Erythrocyte protoporphyrin (EP) accumulates in red blood cells when there is insufficient iron present for proper heme synthesis. A small percentage of EP may be unbound and can be measured as free erythrocyte protoporphyrin (FEP), with the remainder EP (about 90%) measured as zinc protoporphyrin (ZPP).

Accordion Title
Common Questions
  • How is it used?

    Zinc protoporphyrin (ZPP) is used to monitor chronic exposure to lead in adults. It is also elevated in iron deficiency and maybe ordered to help detect this deficiency in children. A ZPP level can be compared with the hemoglobin level to form a ZPP/heme ratio that is sensitive to diagnosing iron deficiency.

    Lead exposure in adults

    ZPP testing may be ordered along with a lead level to test for chronic lead exposure. Hobbyists who work with products containing lead and people, especially children who live in older houses built prior to 1960, may have been exposed to lead-based paint products and can be at increased risk for lead poisoning. Inhaling or ingesting lead dust particles from lead batteries, lead pipe-contaminated water, certain leaded fuels, and foods that have been transported in lead-soldered containers, can may also cause elevated lead levels.

    In an industrial setting, the Occupational Safety & Health Administration (OSHA) mandates the use of the ZPP test and strongly recommends that a ZPP test is ordered every time a lead level is ordered in order to monitor an employee's exposure. Both are necessary because ZPP will not reflect recent or acute lead exposure because it does not change quickly when a person's source of lead exposure is removed. ZPP is best at detecting a person's average exposure to lead over the last 3-4 months.

    ZPP is not sensitive enough for use as a lead screening test in children, as values do not rise until lead concentrations exceed the acceptable range. The maximum lead concentration considered safe in children has been set at a very low level by the Centers for Disease Control and Prevention (CDC). In this age group, tests that directly measure the blood lead concentration are done to detect exposure to lead.

    Iron deficiency anemia in children

    In children, the ZPP/heme ratio is sometimes ordered as an early indicator of iron deficiency. An increase in the ZPP/heme ratio is one of the first signs of insufficient iron stores and will be elevated in most young people before signs or symptoms of anemia are present. More specific tests of iron status are required to confirm iron deficiency.

  • When is it ordered?

    ZPP may be ordered along with a lead test when chronic exposure to lead is known or suspected in adults. Signs and symptoms of lead poisoning include:

    • High blood pressure
    • Numbness and/or tingling in the hands and feet
    • Memory loss, mood disorders
    • Weakness
    • Abdominal pain
    • Headache


    The test may be ordered when an employee is a participant in an occupational lead monitoring program or when someone has a hobby, such as working with stained glass, that brings the person into frequent contact with lead.

    The ZPP/heme ratio may be ordered as a screening test for iron deficiency in children and adolescents or when iron deficiency is suspected. Some symptoms of iron deficiency include:

    • Chronic fatigue, tiredness
    • Dizziness
    • Weakness
    • Headaches


    If the iron-deficiency anemia is severe, shortness of breath, dizziness, chest pain, headaches, and leg pains may occur. Children may develop learning (cognitive) disabilities. Besides the general symptoms of anemia, there are certain symptoms that are characteristic of iron deficiency. These include pica (cravings for specific substances, such as licorice, chalk, dirt, or clay), a burning sensation in the tongue or a smooth tongue, sores at the corners of the mouth, and spoon-shaped fingernails and toenails.

  • What does the test result mean?

    The ZPP concentration in blood is usually very low. An increase in ZPP indicates a disruption of normal heme production but is not specific as to its cause. The main reasons for increases in ZPP are iron deficiency and lead poisoning.

    It is important that ZPP levels be evaluated in the context of a person's history, clinical findings, and the results of other tests such as ferritin, lead, and a complete blood count (CBC). It is possible that the person may have both iron deficiency and lead poisoning.

    In cases of chronic lead exposure, ZPP reflects the average lead level over the previous 3-4 months. However, the amount of lead currently present in the blood and the amount in the organs and bones cannot be determined with a ZPP test. Values for ZPP rise more slowly than blood lead concentrations following exposure and take longer to drop after exposure to lead has ceased.

    An increase in the ZPP/heme ratio in a child is most often due to iron deficiency. A decreasing ZPP/heme ratio over time following iron supplementation likely indicates successful treatment.

  • Is there anything else I should know?

    ZPP may be elevated in inflammatory conditions, infections, and in people with anemia of chronic disease, but it is not generally used to monitor or diagnose these conditions. A very high ZPP level may be seen in two hereditary diseases: protoporphyria and congenital erythropoietic porphyria (see Porphyria). Both of these disorders are very rare and present with symptoms related to the skin (extreme sensitivity to sunlight). 

    Depending on the method used to test ZPP, high levels of other substances in the blood, such as bilirubin and riboflavin, can produce false-positive results. Falsely low values may occur if the sample is not protected from light before testing.

  • Besides ZPP and lead levels, what other tests might my doctor order to monitor exposure to lead?

    If you are in an occupational setting where you are frequently exposed to lead, your healthcare practitioner may order the following tests to evaluate your kidneys and red blood cell production:

  • If I have a hobby such as stained glass working but no symptoms, do I need to have a ZPP test done?

    Talk to your healthcare provider about this. If the hobby is a frequent activity, then it may be recommended that you have a ZPP test and a lead test to evaluate your lead exposure. You can have an increased ZPP level with few to no symptoms or you may have symptoms that have not yet been linked to lead exposure.

  • Should everyone have a ZPP test?

    No. This test will only be done for adults with suspected chronic exposure to lead, as a screening test to detect iron deficiency in children, or occasionally to test for a porphyria that affects the skin. 

View Sources

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