SEQC Spanish Society of Laboratory Medicine

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• The adverse effects of exposure in children are reached with blood concentrations lower than those in adults and lead to intellectual deficit, as well as hyperactivity with attention deficit, aggressiveness, and antisocial behaviour 

• Experts highlight the importance of human biomonitoring of lead and other toxic substances in Spain to understand the current situation in the population, as well as to bring together the resources and determination necessary to prevent exposure

• Clinical laboratories face new challenges to accurately and precisely measure much lower concentrations of this substance, from the need to acquire new instrumentation to establishing new criteria for repeating the test

Lead is a toxic metal for which there is no known safe threshold for health and it can seriously affect any system and organ of the human body. Although there is no safe concentration, blood lead thresholds have been established over time, as recommended by the US Centers for Disease Control and Prevention (CDC), and are considered levels of concern, but have been wrongly interpreted as toxicity limits. Clinical Laboratory specialists have had to improve analysis methods to accurately and precisely measure much lower concentrations, in addition to facing new challenges, such as the need to acquire new instrumentation and take measures to eliminate lead contamination in reagents and laboratory processes.

Children are especially vulnerable to lead exposure due to their developmental stage, as well as because they have a greater absorption of this toxic metal at both respiratory and digestive levels. As explained by Dr. Montserrat González Estecha, a member of the Spanish Society of Laboratory Medicine (SEQC^ML) and voting member of the Subcommittee on Analytical Procedures for the Determination of Lead in Blood (Committee on Clinical Chemistry and Toxicology) of the Clinical and Laboratory Standards Institute (CLSI) of the USA, the adverse effects of exposure in children are reached with blood concentrations lower than those of adults and lead to intellectual deficit, hearing and language disorders, hyperactivity with attention deficit, aggression, and antisocial behavior. “In addition to neurological effects, they can produce adverse cardiovascular, immunological and endocrine effects,” says Dr. González.

Dr. González, co-author of the third edition of “Measurement procedures for the determination of lead in whole blood” published by the CLSI in April 2024, warns of the error of considering the blood lead thresholds recommended by the CDC as toxicity limits. “In particular, in 1991 the 'level of concern' of 10 µg/dL, which was a level of action and concern, was widely interpreted as the limit above which a blood lead concentration was toxic. This misinterpretation has also contributed to the CDC's change to a 'reference value', since there is no safe threshold and any concentration in the blood produces toxicity. However, it is common to read ‘the toxicity limit’ again in the interpretation of the CDC's reference value, set in 2021 at 3.5 µg/dL,” says the expert, who clarifies that this value is simply the 97.5 percentile of blood lead in American children aged 1 to 5 years obtained in the NHANES survey during the years 2015 to 2018, having decreased at present. For those countries where biomonitoring is not yet carried out, the World Health Organization (WHO) recommends using the value of 5 µg/dL to identify children who need monitoring or intervention.

Venous blood, the gold standard for determining lead

In the words of Dr. González Estecha, clinical laboratory specialists have had to improve analysis methos in order to accurately and precisely measure much lower concentrations, which produce toxicity especially in the child population. Among the different laboratory tests, the SEQC^ML member reports that venous blood is the gold standard or reference diagnostic test for determining lead, “as it presents less contamination and biological variability than other specimens.” In addition, in the latest version of the CLSI, “Measurement procedures for the determination of lead in whole blood,” urine has been eliminated for measuring lead due to its redundancy, and dried blood on filter paper is not recommended due to possible contamination, according to Dr. González Estecha.

According to the expert, the first measure to be taken in the event of an elevated blood lead result is to remove the source of exposure. “The blood lead concentration obtained in the analysis will first help to detect whether there is exposure and in many cases it will even help to identify the possible source, as well as the adverse effects expected according to the concentration obtained. It is also useful for monitoring and confirming that the exposure has been eliminated,” she explains.

The work of Laboratory Medicine, with the progressive decrease in blood lead levels in the population, together with the clear clinical symptoms of lead exposure, has become essential for its detection and subsequent management. As Dr. González Estecha emphasizes, a concentration such as the reference value established by the CDC creates new challenges and opportunities, so that some laboratories may need to acquire new instrumentation, optimize new analysis methods, improve detection limits and even request a new extraction. “Steps must also be taken to eliminate lead contamination in reagents and laboratory processes, and this could increase workloads due to additional repeat and confirmation tests.” In general terms, this new reference value could “toughen the acceptable criteria of external quality assurance programs and require the adoption of more restrictive criteria,” she points out. The new edition of the CLSI document establishes recommendations for laboratories to address these new challenges.

Another question raised by the expert is whether the units of lead in blood should be changed to µg/L when interpreting laboratory results, “given that a great benefit would be obtained in terms of perception and communication.” As the SEQC^ML member asserts, one of the problems that has arisen with the latest CDC “values ​​of concern” established at 10 µg/dL or the latest reference values ​​of 3.5 µg/dL is that they have been interpreted as a safe level of lead by doctors and especially by the general population. “If the latest reference value were expressed as 35 µg/L, this erroneous interpretation would be easier to counteract,” says Dr. González Estecha. 

The SEQC^ML member stresses the importance of human biomonitoring of lead and other toxic substances in Spain to know the current situation in the population, especially in the most vulnerable child population, and refers to the fact that an Interministerial Committee for Human Biomonitoring has recently been created in Spain. However, as Dr. González stresses, in 2024, more than 100 years after the introduction of lead in gasoline (the main cause of poisoning by this substance worldwide), children cannot continue to be used as “the canary in the mine” to identify the dangers of lead in the community. “Instead of waiting for children to reach an “arbitrary” threshold of this toxic metal in their blood, the necessary resources and determination must be brought together to prevent exposure before it occurs. The evidence from the last 40 years shows that children can be prevented from having high concentrations in their blood by controlling or eliminating the sources of lead in their surroundings and environment, thus carrying out primary prevention,” she concludes.