Proposal for a revised Reference Concentration (RfC) for manganese based on recent epidemiological studies

Regul Toxicol Pharmacol. 2009 Dec;55(3):330-9. doi: 10.1016/j.yrtph.2009.08.005. Epub 2009 Aug 15.


In 1993, based on observations of subclinical neurological effects in workers, the United States Environmental Protection Agency (US EPA) published a Reference Concentration (RfC) of 0.05 microg/m(3) for manganese (Mn). The geometric mean exposure concentration, 150 microg/m(3) respirable Mn, was considered the lowest observable adverse effect level (LOAEL), and uncertainty factors (UFs) were applied to account for sensitive populations, database limitations, a LOAEL, subchronic exposure, and potential differences in toxicity of different forms of Mn. Based on a review of more recent literature, we propose two alternate Mn RfCs. Of 12 more recent occupational studies of eight cohorts with chronic exposure durations, examining subclinical neurobehavioral effects, predominantly on the motor system, three were considered appropriate for development of an RfC. All three studies yielded no observable adverse effect levels (NOAELs) of approximately 60 microg/m(3) respirable Mn. Converting the occupational NOAEL to a human equivalent concentration (HEC) of 21microg/m(3) (for continuous exposure) and applying a UF of 10 to account for intraspecies variability yielded an RfC of 2microg/m(3). We also derived a similar RfC (7 microg/m(3)) using an Mn benchmark dose (BMD) as the point of departure. Overall confidence in both RfCs is medium.

MeSH terms

  • Air Pollutants, Occupational / chemistry
  • Air Pollutants, Occupational / toxicity*
  • Animals
  • Benchmarking
  • Environmental Monitoring / methods
  • Humans
  • Manganese / chemistry
  • Manganese / toxicity*
  • Neurotoxicity Syndromes / etiology*
  • No-Observed-Adverse-Effect Level
  • Occupational Exposure / analysis*
  • Reference Values
  • Risk Assessment
  • Species Specificity
  • United States
  • United States Environmental Protection Agency


  • Air Pollutants, Occupational
  • Manganese