Failure of chelator-provoked urine testing results to predict heavy metal toxicity in a prospective cohort of patients referred for medical toxicology evaluation

Clin Toxicol (Phila). 2022 Feb;60(2):191-196. doi: 10.1080/15563650.2021.1941626. Epub 2021 Jun 29.


Introduction: Provoked urine testing (PUT), involving chelating agent administration prior to measuring urine metal excretion levels, is used by some alternative health care practitioners to diagnose patients with heavy metal poisoning. Multiple medical societies have advised against this practice due to its presumed unreliability, expense, and lack of validation. However, no prospective study of the predictive value of PUT for heavy metal poisoning has been undertaken.

Methods: This study utilized the Toxicology Consortium's prospective case registry to evaluate the reliability of PUT for diagnosing heavy metal poisoning. Inclusion criteria were toxicology clinic patients with PUT results who were subsequently evaluated by a board-certified medical toxicologist and had a determination made regarding whether their signs and symptoms were likely related or unrelated to toxicologic exposures. The primary outcome was the positive predictive value of PUT for heavy metal toxicity as diagnosed by the evaluating medical toxicologist. Patients presenting to participating toxicology clinics without PUT served as a comparison group.

Results: 74 of 106 cases presenting with PUT results met inclusion criteria and were analyzed. 15 cases were determined by the examining toxicologist to be likely related to a toxicologic exposure. Only three cases were found to be related to heavy metal exposure, giving a positive predictive value of 4.3%. 20.2% of patients with PUT were found to have signs or symptoms related to any toxicologic exposure, compared to 14.3% of clinic patients without PUT. Demographics of toxicology clinic patients with and without PUT results were not significantly different except for age.

Discussion: Our results provide empiric support that PUT is an inaccurate predictor of a diagnosis of heavy metal poisoning by a board-certified medical toxicologist. Given the inability to properly interpret PUT results along with the increased cost burden and risk of false positives, PUT should not be performed.

Keywords: Provoked urine; ToxIC Registry; chelation challenge; metal testing; urine metals.

MeSH terms

  • Chelating Agents
  • Cohort Studies
  • Heavy Metal Poisoning / diagnosis
  • Humans
  • Metals, Heavy* / urine
  • Poisoning* / diagnosis
  • Poisoning* / urine
  • Reproducibility of Results
  • Toxicology*


  • Chelating Agents
  • Metals, Heavy