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, NCManganese
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 availab le 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 create d 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 in cluded 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 ar e 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 re ference 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 concent ration of manganese in urban air (as a component of PM 10 ) is approximately 0.04 μg/m 3 , ranging from < 0.01 μ g/m 3 for remote areas and up to 0.089 μ g/m 3
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 co smetics ; and as an octane boosting additive to gasoline.

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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 ( stack s, vents, ducts, or pipes) and 1,530,600 pounds coming
fr om 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 . D evelo pmental 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 disti nction 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 Mn

containing particles may be deposited is a determinant of toxicity. Many organizations refe r 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 remainde r 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) – P articulate matter up to a nominal size of 25-45
micrometers (μm)

.

• PM 10 –P articulate matter with a nominal aerodynamic diameter 1 less than or equal to 10 μm (50% cut point of the sampler). PM 10 delineate s 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. S maller particles are collected with increasing efficiency (u p to around 100% ) for less than 3 μm particles

.

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December 2012

• PM 2.5 – P articulate matter with a nominal aerodynamic diameter less than or equal t o 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 PM 10 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 t ract 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 fr action 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, respec tively ( 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

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December 2012

in the PAC values for manganese going from Revision 26 ( DOE, 2010 ) to Revision 27 ( DOE,
2012 ) ; a ll TEEL -0 values were dropped from the tables in the later version (including the value of 0.2 mg/m 3 for Mn) and the PAC-3 value increased from 500 mg/m 3 in Revision 26 up to 1,800 mg/m 3 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 valu e calculation 2 . T he 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 derivat ion 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 S afety and Health (NIOSH) and the American Conference of Governmental and Industrial Hygienists (ACGIH) have established

T ime -W eighted 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/m 3 ( NIOSH, 2007 ) and the ACGIH Threshold Limit Value (TLV ® ) is 0.2 mg/m 3 (200 μg/m 3 ) ( ACGIH, 1996 ). Additional assumptions of a healthy adult worker population are included in the derivation of the se occupational values. The Occupational Safety and Health Administration (OSHA) Ceiling value and NIO SH Short-T erm Exposure Level (STEL), for exposure durations of 15 minutes or less, have been established at 5 mg/m 3 and 3 mg/m 3 , 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/m 3 to a value of 0.02 mg/m 3 (20 μg/m 3 ) for the respirable fraction, and the addition of a separate value of 0.1 mg/m 3 (100 μg/m 3 ) for the larger
inhalable Mn

- containing particles (see particle size definitions above) . These proposed changes
indicate concerns raised by the studies of B ast

- Pettersen et al. (2004 ), Luc chini 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/m 3 , which is below the current TLV ® TWA of 0.2 mg/m 3 (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 particle s due in part to intestinal absorption subsequent to inhalation exposure (swallowing of mucus with entrained larg er particles) and possible absorption of soluble particles deposited in the nasopharynx , and due to the smaller particles (e.g., PM 5 ) 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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December 2012

General Public Values (Routine Non

- emergency Exposures)

IRIS RfC
The current R eference Concentration ( RfC ) on IRIS ( U.S. EPA, 1993 ) was derived using
the L owest O bserved A dverse E ffect Level (LOAEL) of 0.15 mg/m 3 (150 μg/m 3 ) 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/m 3 using a factor 2 to account for an assumption of 10 m 3 of air inhaled during active
work versus 20 m 3 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 app lication of a total U ncertainty F actor ( 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 a ccount 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 ). T he 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 Off ice 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 ( Roel s et al., 1992 ) to arrive at a BMCL 05 (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 betwee n 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 m 3 during the average 8-hour work day to an average 20 m 3 in
a 24 -hour day. The final chronic REL is 0.09 μg/m 3 and the final 8-hour REL value is
0.17 μg/m 3 . 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 ).

Chronic 3 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/m 3

. The MRL was derived using benchmark analysis giving a 10% effect (BMCL 10 ) of data from the same study as used in the

current EPA RfC ( Roels et al., 1992 ). The BMCL 10 of 142 μ g/m 3 was adjust ed from an
occupat ional to continuous exposure (5/7 days per week and 8/24 hours per day), resulting in an adjusted value of 33 μg/m 3 . 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/m 3 . 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 r ecent 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.

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the oral or inhalation routes which suggest that the human variability factor o f 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 ). N eurotoxic eff ects were noted and serum prolactin
levels were also observed to be affected. The results from a benchmark concentration analysis
for a BMCL 05 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 la ck 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 PM 3.5 . 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 BMCL 05 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 Standard s for

Mn

- containing particulates from a single AAQC and Standard based on total suspended particulates ( TSP ) to one based on the smaller siz ed fraction of PM 2.5 ( MOE, 2011 ). The MOE developed the AAQC for PM 2.5 in much the same way as an RfC or other similar reference value would be developed. Benchmark analysis was ap plied to the study data from Roels et al. ( 1992 ) to arrive at a POD (BMCL 05 ) of 84 μg/m 3 . Duration adjustments were applied in the same
manner as in the RfC and REL derivation arriving at an adjusted value of 30 μg/m 3 . 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/m 3

.

Health Canada ( 1998 ) noted from observations across multiple monitoring sites that , on
average, approximately 50% of TSP consisted of PM 10 , and similarly 50% of PM 10 consisted of

PM 2.5 . Therefore, the MOE ( 2011 ) used the PM 2.5 AAQC of 0.1 μg/m3 and the previously
mentioned ratios as the basis for deriving AAQCs for PM 10 (0.2 μg/m3 ) and TSP (0.4 μg/m3 ). The revised 24-hour standard for Mn and Mn-containing compounds in TSP wa s 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)

T he “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

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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
do se 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). ” Fo r 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 M inistry 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 th e table. Additionally, the Ontario MOE half-hour monitoring standard for Mn mentioned in the
text above was not included in the array or table. T he 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 BMCL 05 values based on the study of Roels et al. (1992 ) by OEHHA (0.072 mg/m 3 ) versus the value derived by MOE (0.084 mg/m 3 ). On the other hand, t he BMCL 10 value derived by ATSDR (0. 142 mg/m 3 ) is within the range of values described in Clewell et al. (2003 ) (0.09 – 0.27 mg/m 3 ). These apparent discrepancies are due in part to differences in application of the model s (e.g., model choice) and differences in policy and guidance between the organizations for performing BMD analysis and interpretation of the results. Th ese differences are noted here, but further analys is or commentary is beyond the scope of this document.

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### December 2012 

### Manganese: Comparison of Reference ValuesManganese 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 TSP24-Hours30-Days7-Years70-Years Acute Short Term Subchronic ChronicGeneral PublicEmergencyResponseOccupational

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

manganese

Reference

Value Na me Duration Reference
Value
Health Effect Point of Departure Qualifier Principal
S tudy Uncertainty

Factors 4 Notes on
Derivation Review
Status (mg/m 3 )EmergencyResponse 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

Rev ision 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 NAOccupational OSHA Ceiling < 15
minutes 5 Manganism; asthenia, insomnia, mental confusion;
metal fume fever: dry throat, cough, chest tightness, dyspnea, rales, flu

like fever; low

back 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 /m 3 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 (NIC 5 ) 8 hour
TWA 0.2 (0.02

– respirable; 0.1

- inhalable) CNS (manganism ) ; lung; reproduction 1 mg/m 3 LOEL ( Roels et al., 1992 ; 1987 ) NR WOE Approach Final ( ACGIH, 2001 )

(NIC is draft)

4 Uncertainty Factor (UF) component definitions: UF H – inter

- human variability; UF A – animal to human variability; UF L – LOAEL to NOAEL adjustment;

UF S – subchronic to chronic adjustment; UF DB – 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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Reference

Value Na me Duration Reference
Value
Health Effect Point of Departure Qualifier Principal
S tudy Uncertainty

Factors 4 Notes on
Derivation Review
Status (mg/m 3 )General Public CA

- REL 8 hour 1.7 x 10 -4 (Respirable;

PM 5 ) Impaired
neurobehavior:
visual reaction time, eye

- hand coordination, hand
steadiness (Human) 0.051 mg/m 3

0.072 mg/m 3 BMCL 05- ADJ

BMCL 05 (5- d/wk,
mean of 5.3 yr) Roels et al. ( 1992 ) Total UF = 300

UF H-k = 10

UF H-d = 10

UF S = 3 Duration adjusted from
5- d/week to

7- d/week.

Final ( OEHHA, 2008 ) Chronic 9 x 10 -5 (Respirable;

PM 5 ) Impaired
neurobehavior:
visual reaction time, eye

- hand coordination, hand
steadiness (Human) 0.026 mg/m 3

0.072 mg/m 3 BMCL 05- ADJ

BMCL 05 (5- d/wk,
mean of 5.3 yr) Roels et al. ( 1992 ) Total UF = 300

UF H-k = 10

UF H-d = 10

UF S = 3 Duration adjusted 6

Chroni c ATSDR MRL Chronic (> 1 year) 3 x 10 -4 (Respirable;

PM 5 ) Abnormal performance in
tests of hand steadiness, eye

hand coordination,
or reaction time. (Human) 0.033

0. 142 mg/m 3

mg/m 3 BMCL 10- ADJ

BMCL 10 Roels et al. ( 1992 ) Total UF = 1 00

UF H = 10

UF DB = 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;

PM 5 ) Impairment of

neuro behavioral
function 0.05

0.15 mg/m 3

mg/m 3 LOAEL ADJ

LOAEL Roels et al. ( 1992 ) Total UF = 1000

UF H = 10

UF L = 10

UF DB = 10 Duration adjusted 6 Final ( U.S. EPA,
1993 )

Health
Canada RfC Chronic 5 x 10 -5
(PM 3.5 ) Neurobehavioral end points from a study of manganese alloy
workers 0.005 mg/m 3

0.019 mg/m 3 BMCL 05- ADJ

BMCL 05 Lucchini et
al. ( 1999 ) Total UF = 100

UF H = 10

UF DB = 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 m 3 of air inhaled for an 8

- hour work da y compared to 20 m 3 inhaled over a full day

.

10Manganese
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Reference

Value Na me Duration Reference
Value
Health Effect Point of Departure Qualifier Principal
S tudy Uncertainty

Factors 4 Notes on
Derivation Review
Status (mg/m 3 )

Ontario MOE
Ambient Air Quality
Criteria Chronic -
based on a
24 hour sampling period 1.0 x 10 -4
( PM 2.5 )

2. 0 x 10 -4

( PM 10 )

4. 0 x 10 -4

( TSP ) N eurological end

point from an occupational study

, 5.3 year average

exposure. 0.030 mg/m 3

0.084 mg/m 3 BMCL 05- ADJ

BMCL 05 Roels et al. ( 1992 ) Total UF = 3 00

UF H = 10

UF DB = 3

UF S = 3

MF 7 = 3 Duration adjusted 8

Values for larger size
fractions were
based on
effects seen
with PM 2.5 Final ( MOE, 2011 )

WHO Health
Guideline Chronic (Annual average) 1.5 x 10 -4
(PM 5 ) Neurotoxicity in
adult workers 0.007 mg/m 3

0.03 mg/m 3 BMCL 05- ADJ

BMCL 05 Roels et al. ( 1992 ) Total UF = 50

UF H = 10

MF 9 = 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 adjust ed from 5

- d/week to 7

- d/week, and for 10 m 3 of air inhaled for an 8

- hour work day compared to 20 m 3 inhaled over a full day

. 9 Modifying factor based on developmental effects in younger children “by analogy with lead where neurobehavioural effects were fou nd in younger children at

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

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References

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