EPA/600/R-12/047F5 | December 2012 | www.epa.gov

Inhalation Health Effect Reference 

Values for Manganese 

(CASRN 7439-96-5 – Manganese) 

and Compounds (CASRN 1344-43-0; 

1317-35-7; and 1129-60-5)

CASRN 1344-43-0

CASRN 1129-60-5

CASRN 7439-96-5

CASRN 1317-35-7

 

 

National Center for Environmental Assessment

Office of Research and Development

U.S. Environmental Protection Agency

Research Triangle Park, NC
 

 

 

 

 

Manganese 

December 2012 

Inhalation Health Effect Reference Values for Manganese and Compounds 

(CASRN 7439-96-5 – Manganese) 

Overview 

The reader is strongly encouraged to read Section 1 of the following report for critical 

background information regarding the health effect reference values discussed in this summary: 

Graphical Arrays of Chemical-Specific Health Effect Reference Values for Inhalation Exposures 

[Final Report] (U.S. EPA, 2009a). This report is available on-line at 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=211003. 

This summary presents noncancer health effect reference values for inhalation exposures 

to manganese (Mn) across all durations for both the general public and workers. The physical 

size of Mn-containing particles has a bearing on the toxicity and some organizations have created 

different reference values based on size fraction, therefore some definitions of terms regarding 

particle size are provided below. 

A detailed description of the reference values compared in this summary and the 

categories of reference values can be found in Section 1 of the EPA report (U.S. EPA, 2009a). In 

general, inhalation health effect reference values have been included which have been developed 

and formally reviewed by an authoritative governing body (government agency or professional 

association) for use in assessments of risk to support regulatory decision-making. The main 

exception to this inclusion criteria are the Provisional Advisory Concentration (PAC) and 

Temporary Emergency Exposure Level (TEEL) values for emergency response, which are the 

only emergency response values available for manganese compounds. Another exception is the 

discussion of a proposed reference value developed by Bailey et al. (2009) and reviewed by a 

panel convened by Toxicology Excellence for Risk Assessment (TERA, 2011); this value was 

not developed or endorsed by an agency or professional association which typically develops 

such reference values. 

General Properties 

Manganese (Mn) occurs naturally in many types of rocks and soil, usually as a salt or 

other compound in combination with other elements such as oxygen, sulfur, and chlorine 

(ATSDR, 2012). The average concentration of manganese in urban air (as a component of PM10) 

is approximately 0.04 μg/m3

, ranging from < 0.01 μg/m3 for remote areas and up to 0.089 μg/m3 

in areas near industrial sources of manganese emissions (ATSDR, 2012). Manganese is a 

necessary trace nutrient, but is toxic at high levels of exposure. 

Production and Uses 

Manganese is used to improve hardness, stiffness, and strength in the production of 

various varieties of steel (carbon steel, stainless steel, high-temperature steel, and tool steel) 

(ATSDR, 2012). Manganese also occurs naturally in most foods and is often a component of 

nutritional supplements. Manganese is used in a wide variety of other products, including: 

fireworks; dry-cell batteries; fertilizer; paints; a medical imaging agent; in cosmetics; and as an 

octane boosting additive to gasoline. 

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Manganese 

December 2012 

Exposure Potential 

The Toxics Release Inventory for 2010 (U.S. EPA, 2010) reported 1,641,992 pounds of 

manganese were emitted to air from all industrial sources in the United States, with 111,391 

pounds emitted from point sources (stacks, vents, ducts, or pipes) and 1,530,600 pounds coming 

from fugitive sources (equipment leaks, losses from surface impoundments and spills, and 

releases from building ventilation systems). 

Potential Health Effects 

The adverse effect most commonly associated with inhalation exposure to Mn is 

neurological (ATSDR, 2012; U.S. EPA, 1993). Mn and compounds have not been associated 

with cancer. Developmental and reproductive effects have not been investigated adequately for 

characterizing those potential risks. 

Most health effect reference values for inhalation exposure to manganese-containing 

compounds are based on the Mn concentration, with no distinction made based on the valence 

state of the Mn ion, with Mn(II), Mn(III), and Mn(IV) most commonly encountered. However, 

more soluble Mn salts have been associated with greater bioavailability. 

Cancer Potential 

The US EPA (U.S. EPA, 1993) has stated that manganese is “not classifiable as to human 

carcinogenicity.” This conclusion was based on the assessment that “existing studies are 

inadequate to assess the carcinogenicity of manganese.” 

Particle Size Definitions 

The location in the respiratory tract (extrathoracic, tracheobronchial, alveolar) where Mncontaining particles may be deposited is a determinant of toxicity. Many organizations refer to 

various particle size fractions (respirable, thoracic, and inhalable), with some slight variations in 

size cut-offs and in terminology, often with overlapping categories. The following definitions 

come from the Integrated Science Assessment for Particulate Matter (U.S. EPA, 2009b), and are 

generally applicable to the remainder of this discussion: 

•	 Particulate Matter (PM) - PM is the generic term for a broad class of chemically and 

physically diverse substances that exist as discrete particles (liquid droplets or solids) 

over a wide range of sizes. 

•	 Total Suspended Particulates (TSP) – Particulate matter up to a nominal size of 25-45 

micrometers (μm). 

•	 PM10 –Particulate matter with a nominal aerodynamic diameter1

 less than or equal to 

10 μm (50% cut point of the sampler). PM10delineates the subset of inhalable 

particles, referred to as thoracic particles, that are small enough to penetrate to the 

thoracic region (including the tracheobronchial and alveolar regions) of the 

respiratory tract. 

1 The more precise term is 50% cut point or 50% diameter (d50). This is the aerodynamic particle diameter for 

which the efficiency of particle collection is 50%. Larger particles are not excluded altogether, but are collected with 

decreasing efficiency which approaches zero for 20 μm particles. Smaller particles are collected with increasing 

efficiency (up to around 100% ) for less than 3 μm particles. 

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Manganese 

December 2012 

•	 PM2.5 – Particulate matter with a nominal aerodynamic diameter less than or equal to 

2.5 μm (50% cut point of the sampler), an indicator for fine particles. 

The ISA for PM (U.S. EPA, 2009b) also notes the following regarding particle size and 

dosimetry: 

“Particles of different sizes can penetrate different regions of the human respiratory 

tract. Thoracic particles refer to particles that travel past the larynx to reach the lung 

airways and the gas-exchange region of the lung, and respirable particles are those that 

reach the gas-exchange region. Respiratory tract dosimetry supports the choice of PM10 

as an index of thoracic particles. However, dosimetric considerations do not provide 

insight into the selection of a size cut to characterize a fine particle mode. American 

Conference of Governmental Industrial Hygienists (ACGIH, 2005), the International 

Standards Organization (ISO), and the European Standardization Committee (CEN) have 

adopted a 50% cut point of 4 μm as an indicator of respirable particles.” 

Airborne particles have been classified into different aerosol fractions based on the 

penetration of these particles in the various regions of the respiratory tract by the American 

Conference of Governmental Industrial Hygienists (ACGIH) and European Committee for 

Standardization (CEN). The definitions adopted from the European Committee for 

Standardization (CEN, 1993), are shown below: 

•	 Inhalable fraction – the mass fraction of total airborne particles which is inhaled 

through the nose and mouth. 

•	 Thoracic fraction – the mass fraction of inhaled particles penetrating beyond the 

larynx, which is inclusive of the trachea and bronchi. 

•	 Respirable fraction – the mass fraction of inhaled particles penetrating to the 

unciliated airways. More typically, the literature have defined this term in relation to 

the fraction of particles entering the gas-exchange region or the fraction penetrating 

through the tracheobronchial region, the ciliated airways, or conducting airways. 

The above definitions are stated in terms of a mass fraction. Relative to total airborne 

particles, the particle size having 50% penetration for the thoracic and respirable fractions are 10 

μm and 4.0 μm, respectively (ACGIH, 2005; CEN, 1993). 

Many of the values developed for application to the general public assume exposure to 

the respirable fraction as being protective for exposure to larger particle fractions and are 

applicable to that fraction, unless specifically noted in the following text and table. 

Emergency Response Values 

No peer-reviewed emergency response values (Acute Exposure Guideline Levels – 

AEGLs, or Emergency Response Planning Guidelines – ERPGs) have been developed for Mn. 

The Provisional Advisory Concentrations (PACs) include an AEGL or ERPG value when 

available, and Temporary Emergency Exposure Levels (TEELs) values when they are not, using 

a methodology developed by the Department of Energy (DOE, 2008). Both the TEEL-1 and -2 

values for Mn draw largely from the occupational values (See Figure 1 and Table 1), in keeping 

with the DOE methodology, and were not independently developed. There were major changes 

3 
 

 

 

 

 

 

Manganese 

December 2012 

in the PAC values for manganese going from Revision 26 (DOE, 2010) to Revision 27 (DOE, 

2012); all TEEL-0 values were dropped from the tables in the later version (including the value 

of 0.2 mg/m3 for Mn) and the PAC-3 value increased from 500 mg/m3 in Revision 26 up to 1,800 

mg/m3 in Revision 27. The PAC-3 was equivalent to the NIOSH IDLH (see below) in Revision 

26. Although no documentation is currently available to the public documenting the basis for the 

revised PAC-3, it was based on a TEEL-3 value calculation2

. The TEEL-3 for manganese is 

based on a rat oral LD50 of 9 g/kg obtained from the Registry of the Toxic Effects of Chemical 

Substances (RTECS) database, and derived using the DOE TEEL methodology (DOE, 2008). 

Occupational Values 

Typically, there is less publically available information regarding the derivation of 

occupational values which are formulated based on a weight-of-evidence (WOE) approach and 

judgement by a panel of experts; therefore, fewer details are provided here on the derivation of 

occupational values. The National Institute for Occupational Safety and Health (NIOSH) and the 

American Conference of Governmental and Industrial Hygienists (ACGIH) have established 

Time-Weighted Average (TWA) values for exposure levels during the course of a working day, 

with assumptions of exposures repeated 5 days per week, for up to a 40-year career. See Figure 1 

and Table 1 for additional comparison of the occupational values described below. The NIOSH 

Recommended Exposure Level (REL) is 1 mg/m3 (NIOSH, 2007) and the ACGIH Threshold 

Limit Value (TLV®) is 0.2 mg/m3

 (200 μg/m3) (ACGIH, 1996). Additional assumptions of a 

healthy adult worker population are included in the derivation of these occupational values. The 

Occupational Safety and Health Administration (OSHA) Ceiling value and NIOSH Short-Term 

Exposure Level (STEL), for exposure durations of 15 minutes or less, have been established at 5 

mg/m3 and 3 mg/m3, respectively, to protect workers from spikes in exposure that may not be 

reflected on a TWA basis (NIOSH, 2007). All of these occupational values are for the respirable 

fraction with nominal particle aerodynamic diameter of 4 μm (see definitions above) and are 

based on neurological effects observed in studies on occupationally exposed adults. 

ACGIH has proposed changes (ACGIH, 2012) – Notice of Intended Change (NIC) – to 

the TLV® TWA from the current 0.2 mg/m3 to a value of 0.02 mg/m3 (20 μg/m3) for the 

respirable fraction, and the addition of a separate value of 0.1 mg/m3

 (100 μg/m3) for the larger 

inhalable Mn-containing particles (see particle size definitions above). These proposed changes 

indicate concerns raised by the studies of Bast-Pettersen et al. (2004), Lucchini et al. (1999), 

Mergler et al. (1994), and Roels et al. (1992), which indicated neurological effects in workers at 

levels between 0.03 and 0.04 mg/m3

, which is below the current TLV® TWA of 0.2 mg/m3 (i.e., 

the current value may not be protective enough). The inclusion of a separate value for the 

inhalable fraction is in recognition of the potential for toxicity from these larger sized particles 

due in part to intestinal absorption subsequent to inhalation exposure (swallowing of mucus with 

entrained larger particles) and possible absorption of soluble particles deposited in the 

nasopharynx, and due to the smaller particles (e.g., PM5) being included as a component of the 

larger particle definition (e.g., TSP). It should be emphasized that the ACGIH is an independent 

professional organization and not a governmental agency. 

2 Correspondence between George Woodall (US EPA) and David Freshwater (US DOE), August 23, 2012. 

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Manganese 

December 2012 

General Public Values (Routine Non-emergency Exposures) 

IRIS RfC 

The current Reference Concentration (RfC) on IRIS (U.S. EPA, 1993) was derived using 

the Lowest Observed Adverse Effect Level (LOAEL) of 0.15 mg/m3 (150 μg/m3) from a study 

of occupationally exposed workers (Roels et al., 1992) exhibiting neurological effects (visual 

reaction time, eye-hand coordination, and hand steadiness). The LOAEL was duration adjusted 

to 0.05 mg/m3 using a factor 2 to account for an assumption of 10 m3 of air inhaled during active 

work versus 20 m3 inhaled over the course of a full day, and a factor of 5/7 to adjust for work 

during 5-days/week. Following the duration adjustments, derivation of the final RfC 

(0.05 μg/m3) included application of a total Uncertainty Factor (UF) of 1000, with factors of 10 

for inter-individual variability, 10 for going from a LOAEL to a No Observed Adverse Effect 

Level (NOAEL), and 10 to account for database uncertainty (including the lack of data for 

developmental and reproductive effects, as well as potential but unquantified differences in the 

toxicity of different forms of Mn). The median cut point of 5 μm aerodynamic diameter for the 

respirable fraction in the study of Roels et al. (1992) was used in the derivation of the RfC (U.S. 

EPA, 1993). 

California REL 

The Office of Environmental Health and Hazard Assessment (OEHHA) of the State of 

California developed Mn Reference Exposure Level (REL) values for both the 8-hour and 

chronic durations (OEHHA, 2008) using their most up-to-date methodologies. The point of 

departure (POD) was derived using benchmark analysis (U.S. EPA, 2008) on data from the same 

study as used for the current RfC (Roels et al., 1992) to arrive at a BMCL05 (the 95% lower 

confidence limit of the benchmark concentration for a 5% effect level). REL values for both 

durations were based on the same study, health endpoint, POD, and total UF (300); the main 

difference between the two REL values was in the adjustments for duration, with the 8-hour 

value only adjusted from 5-days/week to 7-days/week and the chronic value also adjusted to 

account for a breathing rate of 10 m3 during the average 8-hour work day to an average 20 m3 in 

a 24-hour day. The final chronic REL is 0.09 μg/m3 and the final 8-hour REL value is 

0.17 μg/m3

. OEHHA based their REL on inhalable particles with an assumption of a 3-4-fold 

greater deposition of inhaled particulates in the 1-10 μm range in the lungs of neonates relative to 

adults exposed to similar particulate levels in ambient air (OEHHA, 2008). 

Chronic3 ATSDR MRL 

ATSDR posted a revision to the chronic Minimal Risk Level (MRL) for Mn (respirable 

fraction) in December 2012 (ATSDR, 2012) of 0.3 μg/m3. The MRL was derived using 

benchmark analysis giving a 10% effect (BMCL10) of data from the same study as used in the 

current EPA RfC (Roels et al., 1992). The BMCL10 of 142 μg/m3 was adjusted from an 

occupational to continuous exposure (5/7 days per week and 8/24 hours per day), resulting in an 

adjusted value of 33 μg/m3

. Application of a total UF of 100 (10 for human variability; and 10 

for database deficiencies and limitations) lead to the final MRL value of 0.3 μg/m3. The previous 

MRL included an additional factor of 5 to account for potentially increased susceptibility in 

children based on differential kinetics in the young (ATSDR, 2010). However, ATSDR (2012) 

cited recent toxicokinetic studies in lactating rats and their offspring exposed to manganese by 

3 ATSDR defines chronic durations as being for periods of one year or longer. 

5 
 

 

 

 

 

 

 

 

 

Manganese 

December 2012 

the oral or inhalation routes which suggest that the human variability factor of 10 provides 

sufficient protection for differential kinetics in children and adults. 

Health Canada RfC 

The chronic reference value developed by Health Canada (2010a) used a study of Italian 

ferroalloy workers (Lucchini et al., 1999). Neurotoxic effects were noted and serum prolactin 

levels were also observed to be affected. The results from a benchmark concentration analysis 

for a BMCL05 were duration adjusted from the occupational exposure of 8-h/day and 

5-days/week, to 24-h/day and 7-days/week. Uncertainty factors of 10 for inter-individual 

variability in response and 10 to account for limitations to the database (potential for the general 

population to be exposed to more soluble forms of Mn; the lack of studies on prenatal effects; 

and the impact of Mn on serum prolactin). “[The]... Health Canada reference concentration for 

inhaled manganese is 0.05 μg/m3 in PM3.5. This value reflects the concentration to which the 

general population, including sensitive subgroups, can be exposed for a lifetime without 

appreciable harm (Health Canada, 2010b).” 

World Health Organization Health Guidelines 

The WHO (2000) developed a Health Guideline value of 0.15 μg/m3 as an annual 

average for exposure to Mn based on a BMCL05 from the data reported by Roels et al. (1992), 

with an adjustment factor of 4.2 to account for duration adjustments, and a total UF of 50 (10 for 

human variability and a modifying factor of 5 for the potential for increased susceptibility in 

children). 

Ontario Ministry of the Environment (MOE) Ambient Air Quality Criteria and Standard 

In 2011, the MOE updated their Ambient Air Quality Criteria (AAQC) and Standards for 

Mn-containing particulates from a single AAQC and Standard based on total suspended 

particulates (TSP) to one based on the smaller sized fraction of PM2.5 (MOE, 2011). The MOE 

developed the AAQC for PM2.5 in much the same way as an RfC or other similar reference value 

would be developed. Benchmark analysis was applied to the study data from Roels et al. (1992) 

to arrive at a POD (BMCL05) of 84 μg/m3. Duration adjustments were applied in the same 

manner as in the RfC and REL derivation arriving at an adjusted value of 30 μg/m3. Application 

of a total UF of 300 (10 for human variability, 3 for database limitations, 3 for vulnerability to 

the developing nervous system, and 3 for subchronic to chronic extrapolation) led to final 

derivation of an AAQC value of 0.1 μg/m3

. 

Health Canada (1998) noted from observations across multiple monitoring sites that, on 

average, approximately 50% of TSP consisted of PM10, and similarly 50% of PM10 consisted of 

PM2.5. Therefore, the MOE (2011) used the PM2.5 AAQC of 0.1 μg/m3 and the previously 

mentioned ratios as the basis for deriving AAQCs for PM10 (0.2 μg/m3) and TSP (0.4 μg/m3). 

The revised 24-hour standard for Mn and Mn-containing compounds in TSP was set to equal the 

Mn AAQC for TSP (0.4 μg/m3). An additional half-hour monitoring standard of 1.2 μg/m3 was 

also set for Mn and Mn-containing compounds in TSP. 

ITER “Proposed RfC” for Manganese Oxide (MnO) 

The “proposed RfC” for MnO was neither developed nor endorsed by an agency or 

professional association which typically develops reference values. This value was based on a 

paper from a peer-reviewed journal (Bailey et al., 2009) which was further reviewed by a panel 

6 
 

 

 

 

Manganese 

December 2012 

convened by TERA (2011), and placed on the International Toxicity Estimates for Risk 

Assessment (ITER) database managed by TERA. Values from ITER are also available through 

the National Library of Medicine TOXNET web site (http://toxnet.nlm.nih.gov). Although the 

ITER values (chronic values of 2 μg/m3 based on a NOAEL and 7 μg/m3 based on a benchmark 

dose analysis) have received a second level of review by TERA for methodological 

considerations, the level of review was not deemed to be comparable to the reviews provided by 

the other sources developing reference values. Additionally, no authoritative body (government 

agency or professional association) has endorsed the use of these values for the purposes of risk 

assessment; TERA states in their posting on ITER, “... the panel was not asked to explicitly 

endorse the value derived by Bailey et al. (2009).” For these reasons, the ITER values for 

manganese oxide are not included in the array shown in Figure 1 or described in detail in 

Table 1. 

Summary 

The graphical array of the available health effect reference values for inhalation exposure 

to manganese in Figure 1 includes all of the values described here and in Table 1, unless 

otherwise noted. The Ontario Ministry of the Environment (MOE) 24-hour Standard for Mn is 

equal to the TSP AAQC, therefore it was not included in the accompanying graphic or in the 

table. Additionally, the Ontario MOE half-hour monitoring standard for Mn mentioned in the 

text above was not included in the array or table. The Health Canada RfC (Health Canada, 

2010a, b) is identical to the EPA RfC (U.S. EPA, 1993) and may be difficult to discern on the 

graphic. 

Some variability in the results from application of BMD analyses between organizations 

using the same base study can be noted, for example when comparing the derivations of BMCL05 

values based on the study of Roels et al. (1992) by OEHHA (0.072 mg/m3

) versus the value 

derived by MOE (0.084 mg/m3

). On the other hand, the BMCL10 value derived by ATSDR 

(0.142 mg/m3

) is within the range of values described in Clewell et al. (2003) (0.09 – 0.27 

mg/m3). These apparent discrepancies are due in part to differences in application of the models 

(e.g., model choice) and differences in policy and guidance between the organizations for 

performing BMD analysis and interpretation of the results. These differences are noted here, but 

further analysis or commentary is beyond the scope of this document. 

7 
Manganese 

December 2012 

 

Manganese: Comparison of Reference Values
 December 2012 

Manganese Concentration (mg/m3) 

1.E+04 

1.E+03 

1.E+02 

1.E+01 

1.E+00 

1.E-01 

1.E-02 

1.E-03 

1.E-04 

1.E-05 

PAC-1 

PAC-2 

PAC-3 

NIOSH-IDLH* 

OSHA-Ceiling* 

NIOSH-STEL* NIOSH-REL (TWA)* 

ACGIH-TLV (TWA)* 

NIC: ACGIH-TLV (TWA)* 

CA-REL (8-hour) 

WHO Air Quality Guideline 

ATSDR-MRL (> 1yr) 

CA-REL (Chronic) 

US EPA RfC 

Ontario PM-2.5 

Ontario PM-10 

Ontario TSP 

PAC-1 

PAC-2 

PAC-3 

NIOSH-IDLH* 

OSHA-Ceiling* 

NIOSH-STEL* 

NIOSH-REL (TWA)* 

ACGIH-TLV (TWA)* 

CA-REL (8-hour) 

WHO Air Quality Guideline 

ATSDR-MRL (> 1yr) 

CA-REL (Chronic) 

US EPA RfC 

Health Canada RfC 

Ontario PM-2.5 

Ontario PM-10 

Ontario TSP 

24-Hours

30-Days

7-Years

70-Years 

Acute Short Term Subchronic Chronic 

General Public 

Emergency 

Response Occupational 

0 1 10 100 1,000 10,000 100,000 1,000,000 

Duration (hours) 

* Indicates an occupational value; expert judgment necessary prior to applying these values to the general public. 

Figure 1. Graphic array of health effect reference values for inhalation exposure to manganese 

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Manganese 

December 2012 

Table 1. Summary information on the basis and derivation of the available reference values for inhalation exposure to 

manganese 

Reference 

Value Name Duration 

Reference 

Value 

Health Effect 

Point of 

Departure Qualifier 

Principal 

Study 

Uncertainty 

Factors4 

Notes on 

Derivation 

Review 

(mg/m Status 3) 

Emergency

Response 

PAC-3 1 hour 1800 

(Respirable) 

NA 9000 mg/kg Rat LD-50 

in RTECS 

(NIOSH, 

2009) 

Marhold 

(1972) 

NA PAC and 

TEEL values 

derived via an 

approach 

developed by 

the 

Department 

of Energy 

(DOE, 2008) 

Final 

Revision 27 

(DOE, 2012) 

PAC-2 1 hour 5 

(Respirable) 

NA OSHA 

Ceiling 

(see below) 

NA NA 

PAC-1 1 hour 3 

(Respirable) 

NA NIOSH 

STEL 

(see below) 

NA NA 

Occupational 

OSHA Ceiling < 15 

minutes 

5 Manganism; 

asthenia, insomnia, 

mental confusion; 

metal fume fever: 

dry throat, cough, 

chest tightness, 

dyspnea, rales, flulike fever; lowback pain; 

vomiting; malaise; 

lassitude; kidney 

damage 

NR NR NR NR Adoption of 

previous 

ACGIH TLV 

Final 

(2006) 

NIOSH STEL < 10 

minutes 

3 Various NA NA WOE 

Approach 

Final 

(NIOSH, 2007) 

NIOSH REL 

(TWA) 

10 hour 

TWA 

1 Various NA 

NIOSH IDLH 30 

minutes 

500 5,282 mg/m3 Adjusted 

from Oral 

Lethal Dose 

in mice 

Gupta et al. 

(1981) 

Total UF = 10 Total UF and 

adjusted POD 

from the IDLH 

Documentation 

(NIOSH, 1994) 

ACGIH 

TLV-TWA 

(NIC5

) 

8 hour 

TWA 

0.2 

(0.02 – 

respirable; 0.1 

- inhalable) 

CNS (manganism); 

lung; reproduction 

1 mg/m3 LOEL (Roels et 

al., 1992; 

1987) 

NR WOE 

Approach 

Final 

(ACGIH, 2001) 

(NIC is draft) 

4 Uncertainty Factor (UF) component definitions: UFH – inter-human variability; UFA – animal to human variability; UFL – LOAEL to NOAEL adjustment; 

UFS – subchronic to chronic adjustment; UFDB – database uncertainty 5 Notice of Intended Change – the values in parentheses are the proposed change in TLV-TWA, and include separate values for respirable and inhalable 

fractions. 

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Manganese 

December 2012 

Reference 

Value Name Duration 

Reference 

Value 

Health Effect 

Point of 

Departure Qualifier 

Principal 

Study 

Uncertainty 

Factors4 

Notes on 

Derivation 

Review 

(mg/m Status 3

) 

General Public 

CA-REL 

8 hour 1.7 x 10-4 

(Respirable; 

PM5) 

Impaired 

neurobehavior: 

visual reaction 

time, eye-hand 

coordination, hand 

steadiness 

(Human) 

0.051 mg/m3 

0.072 mg/m3 

BMCL05-ADJ 

BMCL05 

(5-d/wk, 

mean of 5.3 

yr) 

Roels et al. 

(1992) 

Total UF = 300 

UFH-k = 10 

UFH-d = 10 

UFS = 3 

Duration 

adjusted from 

5-d/week to 

7-d/week. 

Final 

Chronic 9 x 10 (OEHHA, 2008) -5 

(Respirable; 

PM5) 

Impaired 

neurobehavior: 

visual reaction 

time, eye-hand 

coordination, hand 

steadiness 

(Human) 

0.026 mg/m3 

0.072 mg/m3 

BMCL05-ADJ 

BMCL05 

(5-d/wk, 

mean of 5.3 

yr) 

Roels et al. 

(1992) 

Total UF = 300 

UFH-k = 10 

UFH-d = 10 

UFS = 3 

Duration 

adjusted6 

Chronic 

ATSDR MRL 

Chronic 

(> 1 year) 

3 x 10-4 

(Respirable; 

PM5) 

Abnormal 

performance in 

tests of hand 

steadiness, eyehand coordination, 

or reaction time. 

(Human) 

0.033 

0.142 

mg/m3 

mg/m3 

BMCL10-ADJ 

BMCL10 

Roels et al. 

(1992) 

Total UF = 100 

UFH = 10 

UFDB = 10 

Duration 

adjusted from 

5-d/week, 

8-h/d to 

7-d/week, 

24-h/d 

Final 

(ATSDR, 2012) 

Chronic RfC 

(IRIS) 

Chronic 5 x 10-5 

(Respirable; 

PM5) 

Impairment of 

neurobehavioral 

function 

0.05 

0.15 

mg/m3 

mg/m3 

LOAELADJ 

LOAEL 

Roels et al. 

(1992) 

Total UF = 1000 

UFH = 10 

UFL = 10 

UFDB = 10 

Duration 

adjusted6 Final 

(U.S. EPA, 

1993) 

Health 

Canada RfC 

Chronic 5 x 10-5 

(PM3.5) 

Neurobehavioral 

end points from a 

study of 

manganese alloy 

workers 

0.005 mg/m3 

0.019 mg/m3 

BMCL05-ADJ 

BMCL05 

Lucchini et 

al. (1999) 

Total UF = 100 

UFH = 10 

UFDB = 10 

Duration 

adjusted from 

5-d/week, 

8-h/d to 

7-d/week, 

24-h/d 

Final 

(Health Canada, 

2010a, b) 

6 Duration adjusted from 5-d/week to 7-d/week, and for 10 m3 of air inhaled for an 8-hour work day compared to 20 m3 inhaled over a full day. 

10 
 

 

 

 

 

 

 

 

 

 

 

 

 

Manganese 

December 2012 

Reference 

Value Name Duration 

Reference 

Value 

Health Effect 

Point of 

Departure Qualifier 

Principal 

Study 

Uncertainty 

Factors4 

Notes on 

Derivation 

Review 

(mg/m Status 3

) 

Ontario MOE 

Ambient Air 

Quality 

Criteria 

Chronic - 

based on a 

24 hour 

sampling 

period 

1.0 x 10-4 

(PM2.5) 

2.0 x 10-4 

(PM10) 

4.0 x 10-4 

(TSP) 

Neurological endpoint from an 

occupational study, 

5.3 year average 

exposure. 

0.030 mg/m3 

0.084 mg/m3 

BMCL05-ADJ 

BMCL05 

Roels et al. 

(1992) 

Total UF = 300 

UFH = 10 

UFDB = 3 

UFS = 3 

MF7 = 3 

Duration 

adjusted8 

Values for 

larger size 

fractions were 

based on 

effects seen 

with PM2.5 

Final 

(MOE, 2011) 

WHO Health 

Guideline 

Chronic 

(Annual 

average) 

1.5 x 10-4 

(PM5) 

Neurotoxicity in 

adult workers 

0.007 mg/m3 

0.03 mg/m3 

BMCL05-ADJ 

BMCL05 

Roels et al. 

(1992) 

Total UF = 50 

UFH = 10 

MF9 = 5 

Factor of 4.2 

used to convert 

to continuous 

exposure. 

7 MOE termed this as an UF for “vulnerability of the Developing Nervous System;” it was termed a modifying factor in this document to be consistent with the 

application by other organizations. 8 Duration adjusted from 5-d/week to 7-d/week, and for 10 m3 of air inhaled for an 8-hour work day compared to 20 m3 inhaled over a full day. 9 Modifying factor based on developmental effects in younger children “by analogy with lead where neurobehavioural effects were found in younger children at 

blood lead levels five times lower than in adults and supported by evidence from studies of experimental animals.” 

11 
 

 

 

 

 

 

Manganese 

December 2012 

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