Related Experiment Video
Updated: Jun 20, 2026
Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry (CE-ICP-MS) for Quantification of Iron Redox Species (Fe(II), Fe(III))
Published on: May 4, 2020
Proposal for a revised Reference Concentration (RfC) for manganese based on recent epidemiological studies
Lisa A Bailey1, Julie E Goodman, Barbara D Beck
1Gradient Corporation, Cambridge, MA 02138, USA.
Abstract:
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.
Insights
New research proposes updated manganese (Mn) Reference Concentrations (RfCs) for air quality, suggesting lower safe exposure levels than the 1993 US EPA guideline. These updated RfCs aim to better protect public health from manganese neurotoxicity.
Area of Science:
- Environmental Health Sciences
- Toxicology
- Occupational Health
Background:
- The United States Environmental Protection Agency (US EPA) established a Reference Concentration (RfC) for manganese (Mn) in 1993 based on subclinical neurological effects in workers.
- The 1993 RfC of 0.05 microg/m(3) was derived using a lowest observable adverse effect level (LOAEL) of 150 microg/m(3) and applied uncertainty factors (UFs).
- Concerns exist regarding the adequacy of the 1993 RfC given new scientific literature on manganese neurotoxicity.
Purpose of the Study:
- To propose updated, scientifically-supported manganese (Mn) Reference Concentrations (RfCs) based on recent occupational exposure studies.
- To re-evaluate the safe inhalation exposure levels for manganese, considering chronic exposure durations and subclinical neurobehavioral effects.
- To provide more accurate risk assessment values for airborne manganese.
Main Methods:
- Reviewed 12 recent occupational studies of eight cohorts with chronic manganese exposure, focusing on subclinical neurobehavioral and motor system effects.
- Identified three studies suitable for RfC derivation, utilizing no observable adverse effect levels (NOAELs).
- Calculated human equivalent concentrations (HECs) from occupational NOAELs and applied uncertainty factors (UF) for intraspecies variability; also employed benchmark dose (BMD) modeling.
Main Results:
- Three recent occupational studies identified a NOAEL of approximately 60 microg/m(3) for respirable manganese.
- Conversion and UF application yielded a proposed RfC of 2 microg/m(3) for manganese.
- Benchmark dose modeling resulted in a similar proposed RfC of 7 microg/m(3) for manganese.
Conclusions:
- Recent scientific literature supports lower Reference Concentrations for airborne manganese than the current 1993 US EPA value.
- The proposed RfCs of 2 microg/m(3) and 7 microg/m(3) offer updated estimates for safe manganese inhalation exposure.
- Overall confidence in the proposed RfCs is medium, necessitating further research and consideration for regulatory updates.
