**NOTE: This TOC has been fixed to generate properly. To generate:**

**(1) Click in the TOC area to highlight it; (2) Hit F9 and select the
update page numbers only OPTION. Table should not have to be completely
regenerated unless headings have been changed or moved.**

**BEFORE THE**

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**PETITION OF THE**

**CHEMICAL MANUFACTURERS ASSOCIATION**

**KETONES PANEL TO REMOVE METHYL ISOBUTYL KETONE**

**FROM THE LIST OF HAZARDOUS AIR POLLUTANTS**

**UNDER SECTION 112(b) OF THE CLEAN AIR ACT**

Carol R. Stack David F. Zoll, Esq.

Acting Vice President Vice President and

CHEMSTAR General Counsel

Barbara O. Francis Peter G. McHugh, Esq.

Manager Counsel, CHEMSTAR

CMA Ketones Panel

Of Counsel:

William K. Rawson

Jeffrey R. Holmstead

Gregory S. Slater

Latham & Watkins

1001 Pennsylvania Avenue, N.W.

Suite 1300

Washington, D.C. 20004

April 22, 1997

CHEMICAL MANUFACTURERS ASSOCIATION

1300 Wilson Blvd.

Arlington, VA 22209

\(703\) 741-5000

**[EXECUTIVE SUMMARY]{.underline}**

Pursuant to Section 112(b)(3) of the Clean Air Act (the Act), the
Ketones Panel of the Chemical Manufacturers Association hereby petitions
the Administrator of the Environmental Protection Agency (EPA) to remove
methyl isobutyl ketone (MIBK) from the list of chemicals that are
regulated as hazardous air pollutants (HAPs) under the Act.

**[Background Information]{.underline}**

MIBK is widely used as a solvent and chemical intermediate. It is a
highly efficient solvent that can be used with a wide variety of resins
and is therefore particularly valuable in the formulation of high-solids
coatings. MIBK is manufactured via the aldol condensation of acetone
under reductive conditions in a totally enclosed, continuous process.

**[Delisting Criteria]{.underline}**

EPA is required to delist a substance from the HAP list if "there is
adequate data on the health and environmental effects of the substance
to determine that emissions, ambient concentrations, bioaccumulation or
deposition of the substance may not reasonably be anticipated to cause
any adverse effects to human health or adverse environmental effects."
Several key aspects of this standard, as well as related statutory
requirements, must be taken into account.

First, as EPA has recognized, the Act does not require absolute proof
that a substance will not cause any adverse effects. Rather, the Agency
should use a weight-of-the-evidence approach to determine whether it is
"reasonable" to anticipate that emissions of MIBK will cause adverse
health or environmental effects. Second, in making HAP delisting
decisions, the Agency is not to consider potential accidental releases,
which are regulated under Section 112(r). Rather, it must consider
whether, under normal operating conditions, emissions can reasonably be
anticipated to cause adverse health or environmental effects. Finally,
Section 112(b)(2) of the Act makes it clear that MIBK should not be
listed as a HAP solely because it is a volatile organic compound (VOC).

**[Data on Health and Environmental Effects]{.underline}**

[Acute Health Effects]{.underline}. MIBK is not acutely toxic at the low
concentration levels that are reasonably likely to exist beyond facility
boundaries. Studies in laboratory animals by the oral and inhalation
routes of administration show that the acute toxicity of MIBK is low.
Exposures of humans to above 100 ppm MIBK may cause mild eye and nose
irritation, but are without permanent effects. No significant acute
effects are expected at exposures below these levels. Results from air
dispersion modeling using EPA-approved techniques show that maximum
ambient concentrations beyond industrial site boundaries are well below
levels of concern.

[Chronic Health Effects]{.underline}. MIBK also may not reasonably be
anticipated to cause significant chronic health effects in humans.
Inhalation studies conducted with rats, mice, dogs and monkeys indicate
low subchronic toxicity. The results from many different mutagenicity
screening assays indicate that MIBK exhibits very little, if any,
mutagenic activity. Existing studies also indicate that MIBK is not
teratogenic and exhibits low developmental toxicity. MIBK may cause
transient anesthetic effects at high vapor concentrations, but this
effect is readily reversible and is not associated with any evidence of
neurotoxicity. MIBK has not been tested specifically for
carcinogenicity, because data on its structure and metabolism,
subchronic health effects and the genotoxicity studies indicate that
MIBK is not likely to have oncogenic properties. Thus, the weight of the
evidence shows that MIBK cannot reasonably be anticipated to cause
cancer or other chronic health effects in humans.

The IRIS database does not contain an inhalation reference concentration
(RfC) for MIBK. However, the Ketones Panel has calculated an RfC for
MIBK based on the NOAEL from the subchronic inhalation study used by EPA
to calculate the composite score for MIBK under Section 112(g) of the
Clean Air Act. Based on this study, and using EPA's 1994 guidance on
deriving RfCs, the RfC for MIBK is 2.4 mg/m^3^. This value represents a
conservative estimate of the concentration of MIBK in air to which an
individual could be exposed for a lifetime without adverse effects, and
far exceeds likely human exposure levels from industrial releases of
MIBK.

[Environmental Effects]{.underline}. MIBK also does not cause
significant adverse environmental effects. MIBK occurs naturally in many
plants and animals. It undergoes rapid degradation in the atmosphere and
is readily biodegradable. Based on modeling of industrial emissions and
available ambient concentration data, the levels of MIBK likely to be
found in the environment are well below the lowest toxicity thresholds
for micro-organisms and aquatic organisms.

**[Data on Emissions and Exposure]{.underline}**

[Emissions Data]{.underline}. The Toxics Release Inventory (TRI) shows
that over 1,000 facilities reported emissions of MIBK in 1994. Most of
these sources were very small, however, with over 90 percent of them
reporting emissions of less than 25 tons.

[Ambient Monitoring Data]{.underline}. MIBK has been reported in ambient
air at very low concentrations at a limited number of sites in rural and
urban locations. Monitored levels of MIBK \-- even in industrial areas
\-- typically are several orders of magnitude below the calculated RfC.

[Air Dispersion Modeling Data for Industrial Facilities]{.underline}.
The Panel funded a study by ENSR Corporation to model the maximum
off-site concentrations of MIBK at a wide variety of facilities,
including the largest sources of MIBK emissions in the country. As part
of this study, the Panel identified all facilities that reported MIBK
emissions of more than 150 tons in 1994. It contacted each of these
facilities (12 based on 1994 TRI data) to gather information that could
be used to model maximum off-site concentrations. Based on data provided
by these companies, as well as information available from public sources
such as permit applications, ENSR was able to conduct site-specific
dispersion modeling for 10 of these 12 facilities, including the top two
emitters. ENSR also developed a generalized modeling approach, based on
the methodology employed by EPA in its rulemaking under Section 112(g)
of the Clean Air Act, to evaluate smaller sources of MIBK emissions.
Based on its study of both large and small sources, ENSR concluded that
maximum airborne concentrations beyond facility boundaries are well
below levels of concern and cannot reasonably be anticipated to cause
adverse health or environmental effects. The Panel also analyzed the
potential that groups of sources might collectively result in levels of
concern, and found that there is no such grouping.

[Effect of Delisting on Emissions and Ambient
Concentrations]{.underline}. If MIBK is removed from the list of HAPs,
use of MIBK is likely to increase. For several reasons, however, MIBK
emissions are unlikely to increase substantially. MIBK will continue to
be regulated as a VOC and is often used in blends with other compounds
that will continue to be regulated as HAPs. In addition, MIBK is most
widely used in paint and coating applications, where performance
requirements impose inherent limits on the amount of MIBK that can be
used. Moreover, based on the available monitoring data and the
dispersion modeling analysis conducted by ENSR, any reasonably likely
increase in emissions would not be expected to result in ambient levels
of concern. Perhaps most importantly, removing MIBK from the HAP list is
likely to decrease total VOC emissions by encouraging the use of MIBK in
place of other less effective solvents.

**[Other Considerations that Weigh in Favor of Delisting]{.underline}**

[Delisting MIBK Would Help to Reduce VOC Emissions from Many Coating
Operations]{.underline}. Over the last several years, EPA and state
regulators have encouraged or required the use of high-solid coatings as
an effective way to reduce VOC emissions from coating operations. It is
well known that MIBK is especially valuable in the formulation of
high-solids coatings. MIBK effectively dissolves a wide variety of
resins and is a more efficient solvent than the available non-ketone
alternatives. Thus, the use of MIBK allows the formulation of coatings
with higher solids content and lower VOC emissions. In EPA's recent rule
on shipbuilding coatings, the Agency explicitly recognized that the use
of highly efficient solvents such as MIBK is the most effective approach
for reducing VOC emissions in some coating applications.
[See]{.underline} 59 Fed. Reg. 62681, 62688 (Dec. 6, 1994).

[EPA Has Recognized in Other Contexts that MIBK Has Relatively Low
Toxicity]{.underline}. In two recent rulemakings, EPA has evaluated the
health effects data on MIBK and concluded that MIBK has relatively low
toxicity. In the Agency's proposed rule under Section 112(g) of the
Clean Air Act, EPA developed a methodology for ranking the relative
hazards of the chemicals listed as hazardous air pollutants (HAPs) and
found that MIBK was among the least toxic of the listed chemicals
(approximately 187 out of 189). At the same time, EPA also proposed "[de
minimis]{.underline} values" for listed HAPs. These [de
minimis]{.underline} values were intended to represent the amount of a
chemical that a typical facility could emit without posing more than a
"trivial" health risk. Although the [de minimis]{.underline} values in
the proposed rule were "capped" at 10 tons per year for policy reasons,
the true "uncapped" [de minimis]{.underline} value for MIBK based on
EPA's methodology would have been 5,000 tons per year. This amount is
approximately an order of magnitude higher than the emissions of the
facility reporting the highest MIBK emissions in the country in 1994.
EPA also evaluated the toxicity of MIBK under its Significant New
Alternatives Policy (SNAP) program, and determined that it has
"comparatively low toxicity."

[MIBK's Inclusion on the HAP List Was Not Based on a Finding of
Toxicity]{.underline}. The initial HAP list was developed from the list
of chemicals that must be reported under Section 313 of the Emergency
Planning and Community Right-to-Know Act of 1986 (EPCRA). MIBK was
included on the Section 313 list solely because it had been included in
a "Survey List" of chemicals prepared by the State of Maryland.
Inclusion of MIBK in the Maryland Survey List was not based on a finding
of toxicity or adverse environmental effects. There is no evidence that
the inclusion of MIBK on the original HAP list was based on a
determination by Congress, EPA or anyone else that emissions of MIBK can
reasonably be anticipated to cause adverse health or environmental
effects.

For the foregoing reasons, and as set forth in greater detail in this
Petition, the Ketones Panel respectfully urges the Administrator to
remove MIBK from the list of chemicals that are regulated as HAPs under
the Clean Air Act.

[TABLE OF CONTENTS]{.underline}

EXECUTIVE SUMMARY

INTRODUCTION

I. BACKGROUND INFORMATION

A. Chemical and Physical Properties

B. Production and Use

C. Natural Sources of MIBK

II\. STATUTORY CRITERIA FOR DELISTING

A. Standard of Proof for Delisting

B. A Substance May Not Be Listed as a HAP Unless it Reasonably Can Be
Expected to Cause Adverse Effects Under Normal Conditions

C. MIBK's Status as a VOC Is Not Relevant to the Decision of Whether it
Should Be Listed as a HAP

III\. DATA ON HEALTH AND ENVIRONMENTAL EFFECTS

A. Inhalation Is the Only Significant Route of Human Exposure to MIBK
Emissions

B. MIBK Cannot Reasonably Be Anticipated to Cause Adverse Acute Health
Effects in Humans

C. MIBK Cannot Reasonably be Anticipated to Cause Adverse Chronic Health
Effects In Humans

1\. Subchronic Studies

2\. Mutagenicity

3\. Carcinogenicity

4\. Reproductive and Developmental Toxicity

5\. Neurotoxicity

6\. Other Effects

7\. Derivation of an Inhalation Reference Concentration (RfC) for MIBK

8\. Conclusions Regarding Potential Chronic Effects

D. MIBK Does Not Cause Significant Adverse Environmental Effects

1\. Biodegradation

2\. Potential For Bioaccumulation

3\. Effects On Microorganisms

4\. Effects on Aquatic Organisms

5\. Effects on Plants

IV\. DATA ON EMISSIONS AND EXPOSURE

A. Emissions Data

B. Ambient Monitoring Data

C. Air Dispersion Modeling Data for Industrial Facilities

1\. Air Dispersion Modeling of the Highest Emitters

2\. Air Dispersion Modeling of Smaller Sources

3\. Potential Impacts from Groups of Sources

D. Effect of Delisting on Emissions and Ambient Concentration

V. OTHER REASONS FOR DELISTING MIBK

A. Delisting MIBK Will Help to Reduce VOC Emissions from Many Coating
Operations

B. EPA Has Recognized in Other Contexts that MIBK Has Relatively Low
Toxicity

1\. Proposed Rule Under Section 112(g) of the Clean Air Act

2\. Final SNAP Rule

C. The Inclusion of MIBK on the Initial HAP List Was Not Based on a
Finding of Adverse Health or Environmental Effects

CONCLUSION

**[APPENDICES]{.underline}**

**[Volume I]{.underline}**

A. Table of References

B. RfC Calculation for MIBK

C. Table of Ambient Air Concentration Levels of MIBK (taken from a study
conducted by the State of New Jersey Department of Environmental
Protection in 1979)

D. Houston Regional Monitoring Report (excerpts)

E. Report on the ENSR Modeling Study

F. MIBK Emissions by Zip Code

> **[Volumes 2, 3 and 4]{.underline}**
>
> G. References

**[INTRODUCTION]{.underline}**

Pursuant to Section 112(b)(3) of the Clean Air Act (the Act), the
Ketones Panel of the Chemical Manufacturers Association (CMA) hereby
petitions the Administrator of the Environmental Protection Agency (EPA)
to remove methyl isobutyl ketone (MIBK) from the list of chemicals that
are regulated as "hazardous air pollutants" (HAPs) under Section 112 of
the Act. The Ketones Panel includes all domestic manufacturers of MIBK
as well as manufacturers of several other ketone solvents.[^1] MIBK is a
highly efficient solvent that is widely used in a variety of
applications, and is particularly valuable in the formulation of
high-solids paints and coatings.

Under Section 112(b)(3)(C) of the Act, EPA is required to remove a
substance from the list of HAPs upon a showing that "there is adequate
data on the health and environmental effects of the substance to
determine that emissions, ambient concentrations, bioaccumulation or
deposition of the substance may not reasonably be anticipated to cause
any adverse effects to human health or adverse environmental effects."
This petition reviews the considerable body of literature on the health
and environmental effects of MIBK, along with extensive data on releases
and ambient concentrations, to show that MIBK meets this standard.

In 1988, EPA reviewed the health and environmental effects data on MIBK
in connection with two petitions submitted by the Panel asking that MIBK
and methyl ethyl ketone (MEK) be removed from the list of chemicals that
are reportable under Section 313 of the Emergency Planning and Community
Right-to-Know Act of 1986 (EPCRA). At that time, EPA identified three
areas of concern with the EPCRA Section 313 petitions: developmental
toxicity, neurotoxicity and potential liver and kidney effects. As a
result, the petitions were withdrawn. EPA's concerns with the 1988 MEK
petition have now been resolved in the IRIS database. Although the IRIS
database for MIBK has not yet been updated, the Panel believes that
EPA's treatment of the MEK data in the IRIS database also addresses the
concerns raised about MIBK in 1988. Moreover, those concerns are not
supported by the extensive body of literature regarding the health and
environmental effects of MIBK. Based on EPA's current methodology for
deriving inhalation reference concentrations (RfCs), the RfC for MIBK is
2.4 mg/m^3^. This value is indicative of MIBK's low toxicity, and is
consistent with the Agency's recognition in other regulatory contexts
that MIBK has relatively low toxicity.

Part I of this Petition provides general background information on MIBK.
Part II discusses the statutory criteria for delisting substances from
the list of HAPs. Part III reviews the data on the potential health and
environmental effects of exposure to MIBK, and also explains how the
Panel calculated the RfC for MIBK. Part IV reviews the data that the
Ketones Panel has developed on emissions and ambient concentrations of
MIBK, and shows that ambient MIBK levels \-- even maximum off-site
levels around the largest industrial sources of MIBK emissions \-- are
well below the RfC. Finally, Part V discusses several other
considerations that weigh in favor of removing MIBK from the HAP list.
Based on the information presented in the Petition, the Panel
respectfully requests that the Administrator remove MIBK from the list
of HAPs under Section 112 of the Clean Air Act.[^2]

# [BACKGROUND INFORMATION]{.underline}

## [Chemical and Physical Properties]{.underline}

MIBK is a clear colorless liquid with a sharp, sweet odor and a
molecular weight of 100. Zakhari [et]{.underline} [al]{.underline}.
(1977).[^3] It has moderate water solubility and a vapor pressure of 15
mm Hg at 20° C. The melting point and boiling point of MIBK are
approximately -85° C and 116° C, respectively. [Id]{.underline}. The log
of the octanol/water partition coefficient is 1.19 (HSDB 1996).

## [Production and Use]{.underline}

MIBK is manufactured via the aldol condensation of acetone under
reductive conditions wherein dehydration and hydrogenation immediately
follow the initial condensation to form MIBK. The process and equipment
are continuous and enclosed, and product is transferred to bulk storage
tanks through closed lines. The equipment and tanks customarily are
vented to water scrubbers or through conservation vents to prevent loss
to the atmosphere through evaporation. These practices help to minimize
releases of MIBK to the environment.

MIBK currently is produced in the United States by three companies:
Eastman Chemical, Shell Chemical and Union Carbide. Estimated total
domestic capacity in 1995 was approximately 220 million pounds (Chemical
Marketing Reporter, August 5, 1996).

MIBK is used both as a solvent and as a chemical intermediate. It is a
highly efficient solvent that dissolves a wide variety of resins and,
therefore, is widely used in surface coatings, adhesives, inks, and
traffic marking paint. As discussed in Section V.A below, it is
especially valuable in the formulation of high-solids coatings, which
increasingly are being used to reduce emissions of volatile organic
compounds (VOCs) from many types of coating operations. MIBK is also
used as a solvent in cleaning fluids and dewaxing agents, and as an
extraction medium for fats, oils, waxes and resins.

## [Natural Sources of MIBK]{.underline}

Methyl ketones, such as MIBK, occur naturally in plants and animals.
They can be found in the odorous secretions of insects and in dairy
products including milk, butter, and cheese (Dumont and Adda 1978;
Gordon and Morgan 1979). In mammals, MIBK follows well known
intermediary metabolism pathways including reduction and oxidation
reactions (DiVincenzo [et]{.underline} [al]{.underline}. 1976).

# [STATUTORY CRITERIA FOR DELISTING]{.underline}

When Congress adopted the 1990 Amendments to the Clean Air Act, it
placed 189 chemicals and chemical categories on the "initial list" of
substances to be regulated as HAPs. [See]{.underline} Section 112(b)(1).
Congress recognized, however, that this initial list was not necessarily
definitive, but should be reviewed and, if appropriate, revised based on
the best available science. Significantly, Congress authorized the
Agency not only to add to the list, but also to remove substances from
the original list. It thus acknowledged the possibility that some
substances on the initial list should not be regulated as HAPs.

Under Section 112(b)(3) of the Act, Congress established the criteria
that EPA must use in making decisions about adding or removing chemicals
from the list. Under Section 112(b)(3)(C), EPA is required to remove a
substance from the HAP list "upon a showing" that

> there is adequate data on the health and environmental effects of the
> substance to determine that emissions, ambient concentrations,
> bioaccumulation or deposition of the substance may not reasonably be
> anticipated to cause any adverse effects to human health or adverse
> environmental effects.

This is the basic standard under which EPA must decide whether to remove
MIBK from the HAP list. As discussed below, there are several key
aspects of this standard, as well as related statutory requirements,
that must be taken into account.

## [Standard of Proof for Delisting]{.underline}

The delisting standard requires that there be "adequate" data to show
that adverse effects "may not reasonably be anticipated." The Agency
itself has recognized that Section 112(b) does not require absolute
proof that a substance will not cause adverse effects:

> The EPA does not interpret section 112(b)(3)(C) to require absolute
> certainty that a pollutant will not cause adverse effects on human
> health or the environment before it may be deleted from the list. The
> use of the terms "adequate" and "reasonably" indicate that the Agency
> must weigh the potential uncertainties and their likely significance.

60 Fed. Reg. 48081, 48082 (Sep. 18, 1995) (proposal to remove
caprolactam from the HAP list). Thus, in evaluating both the exposure
data and the data on health and environmental effects, the Agency should
use a weight-of-the-evidence approach to determine whether it is
"reasonable" to anticipate that emissions of MIBK will cause adverse
health or environmental effects. The Panel believes that the data
presented below clearly show that "emissions, ambient concentrations,
bioaccumulation or deposition of \[MIBK\] may not reasonably be
anticipated to cause any adverse effects to human health or adverse
environmental effects."

## A Substance May Not Be Listed as a HAP Unless it Reasonably Can Be [Expected to Cause Adverse Effects Under Normal Conditions]{.underline} 

At high exposure levels, virtually all chemicals can cause adverse
health or environmental effects. Under Section 112(b)(3), however, a
substance is to be listed as a HAP only if "emissions, ambient
concentrations, bioaccumulation or deposition" of the substance can
"reasonably be anticipated" to result in levels that are high enough to
cause such effects. Thus, if emissions of a listed substance are not
reasonably expected to result in ambient levels, deposition, or
bioaccumulation that reasonably can be anticipated to cause adverse
health or environmental effects, then that substance meets the Section
112(b) standard for delisting. As discussed below, there is no
appreciable deposition or bioaccumulation of MIBK, and ambient
concentrations are far below levels that reasonably may be expected to
cause adverse effects.

In this regard, it is significant that accidental chemical releases are
addressed in another part of the Act, Section 112(r). Section 112(b)(2)
specifically states that accidental releases that are subject to
regulation under Section 112(r) are not to be considered in HAP listing
decisions. Thus, it is clear that listing and delisting decisions must
be made based on exposure levels that result from normal or routine
emissions, not from accidental releases.

## MIBK's Status as a VOC Is Not Relevant to the Decision of [Whether it Should Be Listed as a HAP]{.underline} 

Like most solvents, MIBK is a volatile organic compound (VOC). VOCs are
regulated as ozone precursors under Title I of the Act because they can
react photochemically with other pollutants to form ground-level ozone.
Congress made it clear, however, that a substance is not to be listed as
a HAP solely because it is a VOC. Section 112(b)(2) of the Act provides
that a substance which is a precursor to a pollutant (such as ozone)
that is listed under Section 108(a) of the Act may not be included on
the HAP list unless it "independently meets" the HAP listing criteria.
The listing criteria under Section 112 are focused on direct toxic
effects, not on secondary effects that may result from the formation of
ozone. Substances that meet the HAP listing criteria include those which
"are known to be, or may reasonably be anticipated to be, carcinogenic,
mutagenic, teratogenic, neurotoxic, which cause reproductive
dysfunction, or which are acutely or chronically toxic." 42 U.S.C.
§ 7412(b)(2). Thus, the fact that a substance may be an ozone precursor
is not relevant to the decision of whether it should be listed as a HAP.
The Agency implicitly recognized this fact by removing caprolactam,
which is a VOC, from the list of HAPs. [See]{.underline} 61 Fed. Reg.
30,816 (June 18, 1996).

As a practical matter, it is also unnecessary to use Section 112 of the
Clean Air Act to regulate VOC emissions. There are many other programs
under the Clean Air Act that are specifically designed to control
emissions of VOCs and other ozone precursors. Under Section 110 and Part
D of the Act, any state that does not meet the national ambient air
quality standard (NAAQS) for ozone must adopt a state implementation
plan to regulate VOC emissions from both new and existing sources. In
addition, VOC emissions are regulated under Section 111 (new source
performance standards) and Part C (prevention of significant
deterioration). In light of the other programs designed specifically to
control VOC emissions, it is not surprising that Congress decided that
VOCs should not be regulated as HAPs unless they "independently meet"
the listing criteria under Section 112.

# [DATA ON HEALTH AND ENVIRONMENTAL EFFECTS]{.underline}

As noted above, there is a substantial body of toxicological literature
on MIBK. This Section of the Petition first reviews the potential
exposure pathways and explains why inhalation is the only significant
route of human exposure resulting from MIBK emissions. The Petition then
reviews the literature on the health and environmental effects of MIBK,
and demonstrates that MIBK cannot reasonably be anticipated to cause
adverse health effects or adverse environmental effects. Finally, the
Petition explains how the Panel derived an RfC of 2.4 mg/m^3^ for MIBK
based on EPA's 1994 guidance for setting RfCs.

## Inhalation Is the Only Significant Route of Human Exposure [to MIBK Emissions]{.underline} 

Section 112(b)(2) indicates that, in making listing decisions, the
Agency should consider whether a substance may reasonably be anticipated
to cause adverse effects "through inhalation or other routes of
exposure." In light of the reasonably anticipated ambient concentrations
(described in Section IV of the Petition), humans would not be expected
to ingest any appreciable amounts of MIBK resulting from air emissions.
Further, because of MIBK's relatively rapid biodegradation and
volatilization in water (see Section III.D), it is highly unlikely that
humans will be exposed to significant amounts of MIBK in drinking water.
In addition, given its lack of persistence and low bioaccumulation
potential (also described in Section III.D), MIBK emitted to the air
would be unlikely to concentrate in food sources. Finally, dermal
absorption is likely to be insignificant compared to inhalation, both
because dermal absorption is a less efficient exposure route to humans
and because ambient concentrations of MIBK are not high enough to make
this route toxicologically relevant. Thus, it is clear that inhalation
is the only route of human exposure with potential significance.

## MIBK Cannot Reasonably Be Anticipated to Cause Adverse [Acute Health Effects in Humans]{.underline} 

The available data show that MIBK's acute toxicity is low. The
concentration levels of MIBK that are likely to exist beyond facility
boundaries are several orders of magnitude below levels that have been
shown to cause significant adverse acute health effects in animals or
humans. Thus, MIBK cannot reasonably be anticipate to cause acute health
effects in humans.

MIBK's acute toxicity in animals has been shown to be very low. Smyth
[et]{.underline} [al]{.underline}. (1951) reported that the lowest
lethal concentration for rats after four hours of exposure was 4,000 ppm
MIBK; the rats survived 4‑hr exposures to 2,000 ppm. In other studies
with rats, exposures of 21,000 ppm were lethal within 53 minutes, while
exposures of 4,000 ppm for 6 hours caused loss of coordina­tion and
prostration but not death (Topping [et]{.underline} [al]{.underline}.
1994).

In mice, exposures of 19,500 ppm MIBK resulted in anesthesia within 30
minutes and rapid recovery upon removal to fresh air. Concentrations of
20,000 ppm also resulted in anesthesia, but deaths occurred after 30
minutes of exposure (Topping [et]{.underline} [al]{.underline}. 1994).
McOmie and Anderson (1949) reported that no mortality was seen in mice
exposed to vapors of MIBK at concentrations of 24,000 ppm for 15
minutes, 15,000 ppm for 6 hours, or 10,500 ppm for 5 hours; mortality
was observed after exposures of 20,000 ppm for 30 minutes. Zakhari
[et]{.underline} [al]{.underline}. (1977) reported an LC~50~ of 74.2
g/m^3^ (18,105 ppm) for mice exposed to vapor for 45 minutes.

Specht (1938) and Specht [et]{.underline} [al]{.underline}. (1940)
exposed guinea pigs to concentrations of 1,000, 16,800, and 28,000 ppm
MIBK. Exposure to 1,000 ppm MIBK for 24 hours caused little or no
irritation of the nose or eyes. The guinea pigs showed a decreased
respiratory rate during the first 6 hours of exposure, which the authors
attributed to low grade narcosis. Exposure to 16,800 ppm caused
immediate ocular and nasal irritation followed by ataxia and death of 9
of 10 animals within 6 hours of exposure. Exposure to 28,000 ppm was
lethal to 50% of the guinea pigs within 45 minutes.

de Ceaurriz [et]{.underline} [al]{.underline}. (1981, 1984) examined the
effects of acute inhalation exposure of MIBK vapor on indicators of
sensory irritation and neurobehavioral properties in mice. In acute
inhalation studies in male Swiss OF1 mice using various industrial
airborne chemicals, de Ceaurriz [et]{.underline} [al]{.underline}.
(1981) measured decreases in respiratory rate as an index of sensory
irritation. For MIBK vapor, the concentration that induced a 50%
decrease in respiratory rate in the mice after 5 minutes of exposure was
3195 ppm. The interpretation of this finding, however, is complicated
since MIBK may also produce a decrease in respiratory rate secondary to
narcosis (Specht [et]{.underline} [al]{.underline}. 1940). Therefore, it
is unclear whether the reduction observed in this study was actually the
result of narcosis or sensory irritation.

In a second short-term inhalation study, de Ceaurriz [et]{.underline}
[al]{.underline}. (1984) exposed mice to aliphatic ketones and evaluated
neurobehavioral effects using a "behavioral despair" swimming test. This
study determined that exposure of mice to 803 ppm MIBK vapor for 4 hours
produced a decrease by 50% for the duration of immobility in the
3-minute forced swimming test. A 4 hour exposure to 662 ppm MIBK
decreased the duration of immobility by 25%. Interpretation of data from
this unconventional test designed to detect the efficacy of
antidepressant drugs is uncertain.

The acute toxicity of MIBK has been studied by routes other than
inhalation with similar results. The administration of MIBK to rodents
by the oral and dermal routes was appreciably lethal at only very high
dose levels. Smyth [et]{.underline} [al]{.underline}. (1951) found that
the oral LD~50~ of MIBK in rats was 2.08 g/kg when administered as a 20%
emulsion in an anionic surfactant. Batyrova (1973) showed that the oral
LD~50~ in rats and mice was 4.6 and 2.85 g/kg, respectively. (Topping
[et]{.underline} [al]{.underline}. 1994) reported that the oral LD~50~
of MIBK was between 1.6 and 3.2 g/kg for both rats and guinea pigs.
Union Carbide Corporation (1976) reported an oral LD~50~ in the rat of
3.73 ml/kg (2.98 g/kg) and a dermal LD~50~ in the rabbit of greater than
20 ml/kg (16 g/kg) for MIBK.

Human data also indicate low acute toxicity of MIBK. Silverman
[et]{.underline} [al]{.underline}. (1946) exposed 12 people to MIBK
vapors for 15 minute periods and found that 200 ppm had an objectionable
odor and caused eye irritation; 100 ppm was the highest concentration
considered acceptable for an 8 hour exposure.

Elkins (1959) reported that a group of workers exposed to approximately
100 ppm while water proofing boots developed headaches and nausea. A
second group exposed to approximately the same levels at a different
facility reported only respiratory tract irritation. A tolerance was
said to be acquired during the work week, but was lost over the weekend.
Most of the effects reported at 100 ppm were not noted when ventilation
reduced the MIBK exposure to 20 ppm MIBK. These reports are described in
a single paragraph in the Elkins reference. No details or documentation
are provided to describe the calculation or measurement of exposure
levels, duration of exposures, range of exposure levels, number of
people exposed, location of workers, or whether the reports are based on
clinical observations or merely reflecting subjective responses. These
reports appear to be personal observations by the author, rather than a
careful investigation of the effects of exposure to MIBK.

Wayne and Orcutt (1960) studied the eye irritancy potential of an
irradiated mixture of MIBK and nitrogen dioxide using human volunteers.
Subjects received a direct ocular exposure to the reaction products
formed when a mixture of either 5 or 20 ppm MIBK and 1 ppm nitrogen
dioxide was irradiated for 1 hour at 110° C using a 400 watt mercury
vapor lamp. Under these conditions, subjective reports of eye irritation
occurred on average within 23 to 28 seconds of initiating the exposure
with the photochemical reaction products in the mixture. When
non-irradiated control mixtures or sunlight irradiated mixtures were
used to conduct the exposures there were few reports of the irritation
within the 90 second exposure period. The latter sets of conditions were
judged to cause negligible or only a very slight degree of eye
irritation in the subjects. An increase in MIBK concentration in the
reaction mixture did not cause a statistically significant reduction in
the response time because of the large amount of inter-individual
variability in the response. Attempts by the authors to relate their
findings to smog-induced eye irritation in urban atmospheres was
criticized in an editorial comment published at the end of the article.
The basis for the criticism was the difference in temperature and
reaction conditions between the experimental conditions where positive
effects were observed and the ambient conditions that exist in most
urban environments.

Wigaeus-Hjelm [et al]{.underline}. (1990) exposed eight male volunteers
for 2 hours to 10, 100, and 200 mg/m^3^ (2.4, 24 and 48 ppm) of MIBK or
to a combination of 100 mg/m^3^ of MIBK and 150 mg/m^3^ of toluene on
four separate occasions. All participants in the study exercised lightly
(50 Watts) during the exposures. Two neurobehavioral tests (simple
reaction time and an arithmetic test) were conducted and both were
unaffected by the MIBK exposures. Using a self-administered subjective
symptom questionnaire up to a third of the participants in the study
reported symptoms of irritation to the nose or throat or headache and
vertigo. The simple nominal scale (symptom present/not present) used by
the authors to record the prevalence of each symptom is generally
regarded as the least valid approach for collecting and recording
subjective data of this type (Berglund and Lindvall 1992). Because
recent studies have shown that odorous volatile chemicals, such as MIBK,
are capable of causing false symptom reporting, it is essential for
studies that rely on subjective methods, such as symptom questionnaires,
to incorporate a non-irritating odorant control to account for the
non-specific responses arising from an unfamiliar smell. The
standardized human olfactory threshold for MIBK is 0.53 ppm (Devos [et
al]{.underline}. 1990).

In a follow-up study, Iregen [et al]{.underline}. (1993) exposed six
male and six female volunteers to 10 and 200 mg/m^3^ (2.4 and 48 ppm) of
MIBK for 2 hours. As in the previous study, simple reaction time and
arithmetic ability were not affected by the MIBK exposures. Likewise,
there were no effects on the participants heart rate or mood. A 17-item
subjective symptom questionnaire was used to assess irritancy and CNS
symptoms. The authors did not describe the individual questions that
were included in the survey or how the answers to the individual
questions were grouped for analysis. Based on a very cursory examination
with poorly described methods, the authors concluded that MIBK produced
symptoms of irritation and discomfort. The authors did not investigate
what role MIBK's odor had in evoking a positive response on the
questionnaire. Studies have shown that the odor from a chemical can be a
highly influential factor that can control the outcome of studies that
rely on the use of symptom questionnaires (Cavalini [et al]{.underline}.
1991; Knasko [et al]{.underline}. 1990).

Dick [et]{.underline} [al]{.underline}*.* (1992) tested subjects for
neurobehavioral performance during four-hour exposures to 100 ppm MIBK
in an environmental chamber. Subjects were recruited from local
universities. Neurobehavioral effects were measured using a series of
five psychomotor tests, one sensorimotor test, and a test of mood.
Additionally, subjects were asked to complete a questionnaire in which
"yes/no" responses were required to a series of questions addressing
perceived irritation. A total of seventeen subjects were exposed to MIBK
as part of a larger study in which additional subjects were exposed to
50 ppm MIBK together with 100 ppm MEK, 200 ppm MEK, or a placebo
atmosphere. Although sensory and irritant effects were noted during
exposure, no interpretable statistically significant performance effects
were identified which could be attributed to exposure to MIBK (or a
combination of MIBK and MEK or MEK alone). While 70% of the MIBK-exposed
subjects reported a strong odor during exposure, frank irritation
(throat irritation, headache, tearing, or nausea) was reported by only
approximately 20-30% of the subjects. Subsequent statistical analysis of
the subjective effects revealed a significant difference between
MIBK-exposed subjects and controls only with respect to the
identification of a strong odor. These results are consistent with the
study of Wigaeus-Hjelm [et al]{.underline}. (1990) and Iregen
[et]{.underline} [al]{.underline}*.* (1993), which also failed to detect
neurobehavioral effects in subjects exposed to MIBK.

Gagnon [et]{.underline} [al]{.underline}*.* (1994) exposed four healthy
subjects for 7 hours to 20 or 40 ppm of MIBK and examined perceived odor
intensity and the frequency of subjective symptom reporting during and
after the exposure. The subjects were shown to rapidly accommodate to
the odor of MIBK after entering the chamber with the perceived odor
intensity (subjective) decreasing and odor perception threshold
(objective) increasing as adaptation occurred. The odor perception
thresholds declined towards normal levels when measured 55-min and
95-min following the exposure. The authors failed to discuss the results
or findings from the subjective symptom questionnaire in any detail. It
is important to note that the adaptation observed in this study is a
well known sensory phenomenon that is relatively specific to each
chemical and seldom permanent (Cain 1970).

Linari [et]{.underline} [al]{.underline}. (1964) presented the results
from an occupational health survey involving 19 individuals who were
exposed to MIBK for 20 to 30 minutes a day for up to 1 year at
concentrations ranging from 80 to 500 ppm. In a companion study
performed 5 years after the original investigation, 14 out of 19
employees were reexamined for signs and symptoms of solvent overexposure
(Armeli [et]{.underline} [al]{.underline}. 1968). Both the original
study and the follow-up contain many serious procedural and technical
flaws that severely limit their usefulness and reliability. Although the
authors attribute many of their findings to MIBK, they acknowledge that
other chemicals were used in what appeared to be a chemical isolation
process, since it involved a final centrifugation step. Few details were
given, however, on the nature of the process, the other chemical
exposures involved, the monitoring methods for MIBK, or the extent of
alcohol consumption and cigarette smoking by the employees involved in
the study.[^4]

The American Conference of Governmental Industrial Hygienists (ACGIH)
has recommended a Threshold Limit Value (TLV) for MIBK of 50 ppm (8-hour
TWA). The current OSHA Permissible Exposure Limit (PEL) for MIBK is 100
ppm.

In summary, human exposure to high concentrations of MIBK in the range
of several thousand ppm may result in narcosis, which is readily
reversible on exposure to fresh air; exposures in the range of 100 to
several hundred ppm may be irritating to the eyes and nose; exposures
below 100 ppm appeared to be tolerated well, but are easily identified
by the characteristic odor of MIBK. Levels below 0.1 ppm are below the
odor detection level of the human nose (Verschueren 1977). As discussed
below, ambient air levels beyond industrial site boundaries as a result
of continuous or frequently recurring releases are well below levels
that would raise any concerns about acute human health effects.

## MIBK Cannot Reasonably be Anticipated to Cause Adverse[ Chronic Health Effects In Humans]{.underline} 

There is a considerable body of data which shows that MIBK does not
cause chronic health effects in humans at reasonably anticipated ambient
levels.

### Subchronic Studies

MacEwen [et]{.underline} [al]{.underline}. (1971) continuously exposed
rats, mice, dogs, and monkeys to 100 ppm MIBK for two weeks. Animals
were monitored for changes in body weight, organ to body weight ratios,
hematology, clinical chemistry, pathology, blood gases, blood pH,
spontaneous motor activity, and EEG (one monkey). No significant signs
of toxicity were observed during the exposures and no changes in EEG
activity were observed absolute and relative to body weight. Kidney
weights were statistically higher for the rats but not for any other
species, and rats showed a slight indication of reduced growth. The rat
kidneys showed histological changes in the proximal tubule epithelium.
The study was repeated at 200 ppm MIBK and the changes observed at 100
ppm were also observed at 200 ppm and, in addition, absolute and
relative liver weights were slightly elevated.

Based on these data, a 90‑day study was conducted exposing male rats,
dogs, and monkeys to 100 ppm MIBK continuously under reduced atmospheric
pressure which simulated space cabin conditions (MacEwen
[et]{.underline} [al]{.underline}. 1971). A group of rats was also used
to study recovery from MIBK effects. The only effects observed were in
male rats which showed increased liver and kidney weights and the
presence of hyalin droplets in proximal renal tubule epithelial cells.

Rats removed from MIBK exposure after two weeks showed a gradual return
to normal structure by 60 days post exposure, while those exposed for 90
days also exhibited recovery but at a slower rate. Hyalin droplets were
not associated with depressed growth or any indication of illness, and
dogs and monkeys showed no adverse effects related to MIBK exposures.
Based on the data, the authors concluded that (i) 100 ppm of MIBK should
be tolerable by man for 90 days and (ii) the 60 minute emergency limit
of 100 ppm and the 90- and 1,000-day provisional limit of 20 ppm
established by the Space Science Board, NAS/NRC, contained a wide margin
of safety.

As part of a testing program under Section 4 of the Toxic Substances
Control Act, the Ketones Panel conducted two‑ and 14-week inhalation
studies using Fisher-344 rats and B~6~C~3~F~1~ mice (Phillips
[et]{.underline} [al]{.underline}. 1987). In the two‑week study, rats
and mice (males and females) were exposed to 0, 100, 500 or 2,000 ppm
MIBK for 6 hours/day. Male rat livers were slightly heavier in the 2,000
ppm group and regenerative tubular epithelium and hyalin droplets were
observed in the kidneys of male rats from the 500 and 2,000 ppm groups.
A low incidence of lethargy and lacrimation was noted in both rats and
mice at the 2,000 ppm exposure concentrations.

The 14-week study was conducted at 0, 50, 250 and 1,000 ppm MIBK vapors
6 hours/day, 5 days per week. At 1,000 ppm, livers from male rats and
mice were slightly heavier than control livers. Liver weights were also
slightly heavier than controls for the 250 ppm male mice. Morphological
changes were not associated with the increase in liver weights. An
increased incidence and extent of hyalin droplets were seen
microscopically in the proximal renal tubule epithelium of male rats
exposed to 250 or 1,000 ppm MIBK. Control kidneys had similar droplets
but to a lesser degree. The increase in hyalin droplets was not
associated with changes in kidney function. The significance of renal
hyalin droplet formation in male rats is uncertain since it is not
observed in female rats, castrated male rats or males of other species.
Droplet formation occurs in normal male rats and appears to be related
to excretion of a rat‑specific protein 2‑microglobulin by the kidneys
(Alden [et]{.underline} [al]{.underline}. 1984). There is no evidence
that humans are susceptible to a chemically-induced protein droplet
nephropathy and subsequent renal disease similar to that which occurs in
male rats (Hard [et]{.underline} [al]{.underline}. 1993).

In 1985, EPA reviewed the Phillips study and concluded that there was
"an effect (increase in liver weights) but no conclusive toxicity under
the current condition" (Turner 1985 at p. 4). According to Turner, "no
gross or microscopic hepatic lesions related to MIBK exposure were seen.
There were no microscopic findings in any of the tissues examined which
could be related to MIBK exposures." [Id]{.underline}. at p. 1. Dr. I.
Baumel, Director of EPA's Health and Environmental Review Division
(HERD), concurred with Turner's analysis: "We agreed that there was no
significant toxicity seen at the concentrations tested" (Baumel
1985)[^5].

Liver and kidney effects were also observed following repeated oral
gavage exposure of rats to MIBK (Microbiological Associates, 1986 or
Levine [et]{.underline} [al]{.underline}. 1987). Sprague-Dawley rats
given 13 weeks of oral gavage administration of MIBK at dosages of 0,
50, 250 or 1,000 mg/kg daily were evaluated for effects on body weight,
feed consumption, organ weight, morbidity, clinical chemistry,
hematology and histopathology. Exposure to 1,000 mg/kg day produced a
reduction in body weight gain and evidence of lethargy following dosing.
Kidney weights were increased as were BUN (blood urea nitrogen
concentration), urinary protein and ketones, serum potassium levels, and
the incidence of nephrosis in male and female rats. Liver weights and
enzymes also were increased in both sexes, but in the absence of
corresponding histopathological lesions. Exposure to 250 mg/kg day
produced similar but less pronounced effects to the liver and kidney,
and exposure to 50 mg/kg day produced no effects to the rats.

Differences between the study results for the 90 day inhalation and the
oral gavage study could be related to differences in kinetics of oral
bolus dose versus continuous inhalation exposure or differences in the
strain of rat employed. The continuous inhalation exposure scenario is
considered more relevant to potential human chronic exposure.

Batyrova (1973) reported that 20 to 30 ppm of MIBK 4 hours/day for 4.5
months interfered with detoxification by the liver and increased the
eosinophil counts in rats. The reliability of this study, however, is
questionable. Subsequent repeated exposure studies (Phillips
[et]{.underline} [al]{.underline}. 1987; Microbiological Associates,
1986) have not reproduced any MIBK associated effects on hematological
parameters.

In summary, the principal health effects observed in the above
subchronic studies were an increase in liver and kidney weights and in
hyaline droplets in the kidneys of male rats. HERD has determined that
these effects do not indicate significant toxicity. No gross or
microscopic hepatic lesions related to MIBK exposure were seen at any
concentrations or in any species tested.

### Mutagenicity

In general, MIBK exposure has not been associated with genotoxicity
[in]{.underline} [vitro]{.underline} or [in]{.underline}
[vivo]{.underline}. The testing program under TSCA Section 4 also
involved a battery of genotoxicity tests, including the
Salmonella/mammalian microsome (Ames) assay, the L5178Y TK^+/‑^ mouse
lymphoma assay, the unscheduled DNA synthesis in rat primary hepatocyte
assay, the micronucleus cytogenetic assay in mice, and the BALB 3T3
mouse embryo cell transformation assay. The results of these assays
indicate that MIBK has very little, if any, mutagenic activity
(O\'Donoghue [et]{.underline} [al]{.underline}. 1988).

Brooks [et]{.underline} [al]{.underline}. 1988 also tested MIBK for
genotoxic activity in bacterial mutagenicity assays using *Salmonella
typhimuriumi* and *Escherichia coli* WP~2~ and WP~2~*uvr A*, a yeast
cell (*Saccharomyces cerevisiae* JD1) mitotic gene conversion assay, and
in *in vitro* assays for induction of chromosome damage in cultured rat
liver cells or in Chinese hamster ovary cells. The bacterial and yeast
assays were tested both in the presence and in the absence of rat liver
metabolic activation system (S9 fraction). MIBK gave a negative response
in all of these genotoxicity tests.

### Carcinogenicity

MIBK has not been tested specifically for carcinogenicity. Data on its
structure and metabolism, subchronic health effects, and the
genotoxicity studies reviewed above indicate that MIBK is not likely to
have carcinogenic properties.

MIBK neither belongs to a class of chemicals known to react with DNA nor
is metabolized to materials which are likely to react with DNA.
Materials which are oncogenic for mammals appear to cause cancer either
by interacting with the genetic material (DNA) (that is, they are
genotoxic and, therefore, are probably initiators of the carcinogenic
process), or they produce chronic toxic effects which result in
increased cell turnover and, therefore, produce effects by epigenetic
mechanisms and are probably promoters of the carcinogenic process. The
data available for MIBK indicate that this chemical substance is not
genotoxic and does not produce significant chronic toxicity.
Accordingly, MIBK is unlikely to be carcinogenic by either genetic or
epigenetic mechanisms, and is thus unlikely to be either an inducer or
promoter of carcinogenicity.

### Reproductive and Developmental Toxicity

Phillips [et]{.underline} [al]{.underline}. (1987) studied the effects
of exposures of 0, 50, 250, or 1,000 ppm MIBK vapor given 6 hours/day, 5
days/work for 14 weeks on the morphology of male and female reproductive
organs in mice and rats. No effects were found in testes weights or the
histology of the testes, epididymides, prostate gland, seminal vesicles,
ovaries, uterus, oviducts, vagina, cervix, and mammary glands.

The testing program sponsored by the Panel under TSCA Section 4 included
developmental toxicity studies in rats and mice (Tyl [et]{.underline}
[al]{.underline}. 1987). Timed-pregnant CD-1 mice and Fischer 344 rats
were exposed to MIBK vapors by inhalation on gestational days 6 through
15 at concentrations of 0, 300, 1,000 or 3,000 ppm. The animals were
sacrificed on gestational day 21 (rats) or 18 (mice), and live fetuses
were examined for external, visceral and skeletal alterations. In mice,
exposure to 3,000 ppm resulted in maternal toxicity (apparent
exposure-related increases in deaths (12.0%) and clinical signs),
increased absolute and relative liver weight, and fetotoxicity
(increased incidence of dead fetuses, reduced fetal body weight per
litter and reductions in skeletal ossification). No treatment-related
embryotoxicity was seen. No treatment-related increases in fetal
malformations were seen at any exposure concentration tested. There was
no evidence of treatment-related maternal, embryo, or fetal toxicity
(including malformations) at 300 or 1,000 ppm.

In rats, exposure to 3,000 ppm resulted in maternal toxicity (clinical
signs, decreased food consumption, and decreased body weight and body
weight gain), increased relative kidney weight and fetotoxicity (reduced
fetal body weight per litter and reductions in skeletal ossification).
No increase in fetal malformations was observed in any exposure group
relative to controls. At 300 and 1,000 ppm there was no maternal,
embryo, or fetal toxicity (including malformations). Reduced fetal body
weight was observed in rats at 300 ppm, but, as explained below, this
apparent finding was confounded by litter size and should not be
considered treatment-related.

The reduction in fetal body weights seen in the rat at 300 ppm is an
artifact resulting from the fact that the litters in the 300 ppm group
contained more fetuses than the controls. In 1985, the Agency evaluated
these data and reached the same conclusion. Specifically, the Agency
stated: "The data show that, in the rat and the mouse, MIBK causes
significant developmental effects (fetal death, reduced fetal weight,
delayed ossification) in the conceptus at the high dose tested only
(3,000 ppm). No effects were noted at lower doses (1,000, 300, 0
ppm)\.... The NOEL derived from the data is 1,000 ppm." (Letter of
Ottley to Kariya, 1/18/85).[^6]

In summary, the weight of the evidence indicates that MIBK does not
cause any significant reproductive or developmental toxicity in mice or
rats exposed to 1,000 ppm MIBK vapors by inhalation.

### Neurotoxicity

Numerous studies have been conducted to assess the neurotoxic potential
of MIBK. These studies show that MIBK, like many other solvents, causes
transient pharmacologic effects at high exposures. The studies do not
demonstrate that MIBK produces nervous system damage, even following
repeated exposure at relatively high concentrations.

Three neurobehavioral studies in humans following acute exposure at
levels ranging from 2 to 100 ppm have already been described (see
Section III.B, pp. 12-13). The investigators did not detect
neurobehavioral effects in the test subjects in any of the studies.

The study by Phillips [et]{.underline} [al]{.underline}. (1987),
described in Section III.C.1 (subchronic studies) found no evidence of
neurotoxicity in mice or rats exposed to 0, 50, 250 or l,000 ppm MIBK, 6
hours/day, 5 days/week for 14 weeks. No signs of neurotoxicity were
observed clinically and histologic examinations of the brain, spinal
cord, and peripheral nerves were normal.

The Ketones Panel recently sponsored a schedule-controlled operant
behavior (SCOB) study in rats under an enforceable consent agreement
under TSCA (Bernard and David 1996). The study consisted of two sets of
animals, male Sprague-Dawley (SD) rats restricted to 13-18 g of feed per
day and used for SCOB testing and male *ad libitum-*fed SD rats used to
evaluate systemic toxicity. Both sets of animals were exposed to vapor
concentrations of 0, 250, 750, or 1500 ppm of MIBK over a 13-week
period.

Animals were observed for signs of toxicity prior to exposure, once per
hour during exposure, and 30 minutes to one hour after exposure. Animals
exposed to 1500 ppm exhibited transient reduced activity of minimal to
minor severity during exposure for Weeks 1 to 10 only. The severity of
reduced activity during exposure decreased over the course of the study.
No signs of reduced activity were observed immediately after exposure.
Animals exposed to 750 ppm exhibited transient reduced activity of
minimal severity during the exposure period for Weeks 1 to 8 only. The
severity of reduced activity during exposure was unchanged over the
course of 8 weeks. No signs of reduced activity were observed
immediately after exposure. No reduction in activity was observed during
exposure for the control or 250 ppm animals.

The mean absolute liver and kidney weights of all *ad libitum*-fed, test
substance-exposed groups, and the relative (to body weight) liver and
kidney weights for the 750 and 1500 ppm *ad libitum*-fed groups were
statistically higher (p [\<]{.underline} 0.05) when compared to the *ad
libitum*-fed control group. Mean terminal body weights for the 1500 ppm
SCOB group were statistically higher (p [\<]{.underline} 0.05) than for
the SCOB control group. The mean absolute liver weights for the 750 and
1500 ppm SCOB groups, and the mean relative (to body weight) liver
weights for the 250 and 750 ppm groups were statistically higher (p
[\<]{.underline} 0.05) when compared to the SCOB control group. No other
terminal body weight or organ weight differences were observed for
either the *ad libitum*-fed or the SCOB animals.

SCOB testing occurred daily in feed-restricted male rats during Weeks
1-13 of exposure and Weeks 14 and 15 following the cessation of
exposure. Fixed-ratio (FR) running rate, FR pause duration,
fixed-interval (FI) response rate, and index of curvature values for
each animal were calculated as percent of baseline activity and the
percents from Weeks 4, 8, 13, and 15 were compared across groups. No
significant differences were seen in SCOB values at any test vapor
concentration, and there was no apparent change in activity after
cessation of exposure. No exposure-related changes were detected during
gross necropsy examinations of *ad libitum*-fed or SCOB male rats
exposed to the test substance. No tissues were processed for microscopic
examination.

Spencer [et]{.underline} [al]{.underline}. (1975) exposed rats to 1,300
ppm of methyl n‑butyl ketone (MnBK) for 4 months or 1,500 ppm MIBK for 5
months. While MnBK produced central‑peripheral distal axonopathy, only
minimal distal axonal changes were seen in rats exposed to MIBK. The
axonal pathology seen after MIBK exposure may have been due to the 3
percent MnBK which was contained in the MIBK or more likely was due to a
neuropathy induced by the wire mesh caging the rats were housed in.

Spencer and Schaumburg (1976) gave cats subcutaneous injections of 150
mg/kg MIBK or MIBK/methyl ethyl ketone (9/l) twice daily, five days/week
for up to 8.5 months. No nervous system damage was found following these
exposures. Dogs were similarly given subcutaneous injections of 150
mg/kg MIBK, twice a day for 11 months without producing
electromyographic changes or other evidence of neurotoxicity. (Topping
[et]{.underline} [al]{.underline}. 1994).

Rats were given intraperitoneal injections of MIBK or a mixture of
MIBK/methyl ethyl ketone (9/1) five times a week for 35 weeks. Dose
levels of 10, 30 or 100 mg/kg were increased to 20, 60 or 200 mg/kg
after two weeks of exposure. Except for body weight suppression after
3‑4 weeks of exposure, the only other effect noted was transient
anesthesia during the first month of treatment in the 200 mg/kg animals
(Topping [et]{.underline} [al]{.underline}. 1994).

Garcia [et]{.underline} [al]{.underline}. (1978) reported that 2 of 7
rats exposed to 25 ppm MIBK vapor exhibited increases in lever-pressing
response rates. The significance of this finding is unclear since
statistical analyses of the data were not conducted and the single rat
exposed to 50 ppm did not exhibit an increase in response rate.

Geller [et]{.underline} [al]{.underline}. (1979-a) describes operant
behavior studies conducted on an undetermined number of rats using the
same procedures as in Garcia [et]{.underline} [al]{.underline}. (1978).
Data are presented for one rat only, which was exposed to 25 ppm MIBK.
In this animal, the response rate increased to 58% over the control
level. Seven days post exposure, the response rate remained 16% above
the control level. The presentation of data for a single rat makes this
report very difficult to interpret.

Geller [et]{.underline} [al]{.underline}. (1979-a) also describes
operant behavior tests on four baboons exposed to MIBK at 25, 35, 50 and
75 ppm for 1 week. In the presence of 50 ppm MIBK, one baboon had an
increased response rate during the delay interval on all five days the
tests were conducted. The increased response rate, however, was not
observed uniformly throughout the 2-hour test session, and an increase
in the MIBK concentration to 75 ppm for an additional 48 hours did not
alter the response rate. The authors speculated that differences in
response rates were due to anxiety levels in the test animals. There is
no indication that the data were reproducible and in fact, the results
from the one baboon with an [increased]{.underline} response rate at 50
ppm actually contradict the results ([decreased]{.underline} response
rate) seen at 50 ppm in a subsequent study by Geller [et]{.underline}
[al]{.underline}. (1979-b) described below.

In a similar study also using four baboons, Geller [et al]{.underline}.
(1979-b) reported delayed behavioral response times in baboons exposed
to 50 ppm MIBK alone, but no alteration of response was seen when MIBK
was combined with 100 ppm methyl ethyl ketone. Variability in the
response of the baboons was high and the profiles of the responses over
time and among the test subjects were dissimilar. Furthermore, the
pattern of the response time measured between exposures demonstrated no
persistence of any effects. A variety of mechanisms, all speculative,
were proposed by Geller to account for these findings. It should be
noted that this study used only one concentration of each substance or
combination of substances, no statistics were conducted, and the effects
were fully reversible.

MacEwen [et]{.underline} [al]{.underline}. (1971) reported no EEG
changes in monkeys (two) exposed continuously to 100 or 200 ppm MIBK for
two weeks. Spontaneous activity measurements were also unaffected by
MIBK exposure, but details of the experimental procedure were not
provided.

In a short-term inhalation study, de Ceaurriz [et]{.underline}
[al]{.underline}*.* (1984) exposed mice to aliphatic ketones and
evaluated neurobehavioral effects using a "behavioral despair" swimming
test. This study determined that exposure of mice to 803 ppm MIBK vapor
for 4 hours produce a decrease by 50% for the duration of immobility in
the 3-minute forced swimming test. A 4 hour exposure to 662 ppm MIBK
decreased the duration of immobility by 25%. Interpretation of data from
this unconventional test, which is designed to detect the efficacy of
antidepressant drugs, is uncertain.

Abou‑Donia [et]{.underline} [al]{.underline}. (1985-a) studied the
effects of MIBK, n‑hexane, and combinations of the two solvents on
induction of neurotoxicity in hens. Continuous exposures to 1,000 ppm
MIBK for 90 days followed by a 30-day observation period resulted in leg
weakness with recovery but no evidence of axonal damage. Simultaneous
exposures to MIBK and n-hexane resulted in potentiation of n‑hexane
neurotoxicity apparently by induction of hepatic p‑450 enzymes.

Batyrova (1973) reported that 20 to 30 ppm of MIBK administered 4
hours/day for 4.5 months produced disturbances in the conditioned
reflexes of rats. The reliability of this report, however, is
questionable. In a limited-design drinking water study, MIBK
administered to female rats at a dosage of 1 g/kg day for 120 days did
not produce adverse effects on the nervous system (CMIR 1977).

Two [in]{.underline} [vitro]{.underline} studies have been conducted for
MIBK. Selkoe [et]{.underline} [al]{.underline}. (1978) studied the
effects of methyl [n]{.underline}‑butyl ketone, [n]{.underline}‑hexane,
25‑hexanedine, methyl ethyl ketone, and MIBK on an [in]{.underline}
[vitro]{.underline} model used to study neurotoxins which produce
neurofilamentous hyperplasia. The model system was a murine
neuroblastoma cell line which develops cytoplasmic filamentous
hyperplasia when exposed to aluminum ions. In this model, methyl
[n]{.underline}‑butyl ketone and [n]{.underline}‑hexane induced a highly
reproducible series of cytotoxic effects and adversely affected
extension or maintenance of neuritic processes. In contrast to these
effects, MIBK did not produce cytopathological changes analogous to
methyl [n]{.underline}‑butyl ketone or [n]{.underline}‑hexane and did
not produce morphologic changes in neuroblastoma cells at concentrations
which routinely produced widespread cytoplasmic and nuclear changes when
methyl [n]{.underline}‑butyl ketone was present in the culture medium.

Huang [et al]{.underline}. (1993) studied MIBK and other monoketones
(carbon chain length from 3 to 10) for their *in vitro* effects on
synaptosomal membrane proteins. Specifically evaluated were
Na^+^-K^+^‑adenosine triphosphatase (Na^+^-K^+^-ATPase), a well known
cell membrane integral enzyme often used as a membrane toxicity model,
and ^3^H-DHA-labeled beta-adrenergic receptor binding, a synaptic plasma
membrane function indicator. The study found that all the monoketones
tested produced dose-dependent inhibition of Na^+^-K^+^-ATPase activity
and ^3^H-DHA binding to mouse synaptosomes. Thus monoketones, like other
lipophilic solvents, exert their membrane effects by perturbation of the
membrane micro-environment surrounding membrane receptors.

The literature contains two case reports of men developing peripheral
neuropathy following abuse of spray paint or lacquer thinner purported
to contain MIBK (AuBuchon [et]{.underline} [al]{.underline}. 1979; Oh
and Kim 1976). In these cases, there were no confirmations of the
presence of MIBK in the abused products and, therefore, there is the
distinct possibility that the reports are erroneous in referring to MIBK
as the potential causative agent of peripheral neuropathy.[^7]

In conclusion, the available data indicate that MIBK may cause transient
pharmacologic effects at high vapor concentrations, but these effects
are readily reversible and are not associated with any evidence of
neurotoxicity. The available studies do not demonstrate that MIBK causes
damage to the nervous system, even following repeated exposure at high
concentrations. Accordingly, MIBK cannot reasonably be anticipated to
cause neurotoxic effects in humans under realistic exposure scenarios.

### Other Effects

Several studies have evaluated the neurotoxicity and chemical
interactions of MIBK with chemicals associated with neurologic
dysfunction. While MIBK administered alone did not produce the specific
neurotoxic effect, when administered simultaneously with known
neurotoxic chemicals, the subsequent neurotoxicity was enhanced. This
enhancement was the likely result of MIBK induction of cytochrome P-450
enzymes and subsequent increased metabolism of these chemicals to their
neurotoxic metabolites.

Abou-donia [et]{.underline} [al]{.underline}. (1985-a) studied the
effects of MIBK, n-hexane, and combinations of the two solvents on
induction of neurotoxicity in hens. Continuous exposures to 1,000 ppm
MIBK for 90 days followed by a 30-day observation period resulted in leg
weakness with recovery but no evidence of axonal damage. Lapadula
[et]{.underline} [al]{.underline}. (1991) examined the role of liver
microsomal cytochrome P-450 in the mechanism of the synergism of
*n-*hexane neurotoxicity by MIBK. The results of this study suggested
that MIBK selectively induces cytochrome P-450 isozymes leading to the
metabolic activation of the weak neurotoxicant *n-*hexane to the potent
neurotoxicant 2,5-hexanedione.

Hens simultaneously treated 5 days/week for 90 days with technical
methyl butyl ketone vapor (70% methyl *n-*butyl ketone and 30% methyl
isobutyl ketone) and dermally applied *O-*ethyl *O-*4-nitrophenol
phenylphosphonothioate (85%) (EPN) exhibited greatly enhanced
neurotoxicity compared to the neurotoxicity produced by either chemical
when applied alone (Abou-Donia [et]{.underline} [al]{.underline}.
1985-b). The authors attributed this enhancement in part to MIBK
induction of cytochrome P-450 and the resulting increase in the
formation of neurotoxic products from methyl *n-*butyl ketone and EPN.

In a subsequent study, Abou-donia [et]{.underline} [al]{.underline}.
(1991) examined the joint neurotoxic action of simultaneous exposure to
vapors of MIBK and *n-*hexane and dermally applied EPN in groups of
hens. As was noted in their previous studies, increased neurotoxicity
was found after the concurrent exposure. This finding was specifically
related to MIBK induction of phenobarbital-inducible cytochrome P-450
isozymes and the subsequent metabolic activation of EPN.

MIBK was examined for effects on the duration of ethanol-induced loss of
righting reflex and on ethanol elimination in mice (Cunningham [et
al]{.underline}. 1989). MIBK, at a dose of 5 mmol/kg dissolved in corn
oil and injected intraperitoneally 30 minutes before injection of 4 g/kg
ethanol, produced a significantly prolonged duration of ethanol-induced
loss of righting reflex. The concentration of ethanol in blood and brain
upon return of the righting reflex were similar in MIBK-treated and
control animals suggesting the interaction altered ethanol metabolism
rather than increased CNS sensitivity. MIBK was found to reduce the
activity of mouse liver alcohol dehydrogenase *in vitro*; however, this
effect was not confirmed *in vivo* by a reduction in the elimination
rate of ethanol.

MIBK administered alone produces an increase in liver weight in
laboratory animals but no associated microscopic evidence of
hepatotoxicity. Alternatively, when MIBK is administered before various
hepatotoxicants, the resulting hepatic injury induced by the
hepatotoxicant is enhanced. This potentiation of hepatic injury has been
best documented for MIBK and haloalkanes. In addition to the potential
of liver effects, MIBK has also been demonstrated to enhance the
nephrotoxicity produced by select haloalkanes. The explanation for these
interactions is considered in part related to ketone induction of
monooxygenase and subsequent secondary formation of haloalkane reactive
metabolites.

In male Sprague-Dawley rats, a single oral dose of MIBK enhanced the
hepatotoxicity of a single intraperitoneal dose of chloroform given 24
hours later. The no-observed-effect and minimal-effect levels of MIBK
were 375 and 560 mg/kg body weight, respectively (Vezina [et
al]{.underline}. 1985).

Pilon [et al]{.underline}. (1988) demonstrated that the extent of
potentiation of carbon tetrachloride liver toxicity (as shown by an
increase in plasma alanine transaminease activity and bilirubin
concentration) was dependent on the concentration of both MIBK and
carbon tetrachloride in male rats. The minimum effective MIBK dose
decreased 10-fold when the carbon tetrachloride dose was increased from
0.01 mL/kg to 0.1 mL/kg. These findings suggest that liver injury is
determined by the product of MIBK and carbon tetrachloride doses.

In addition to necrosis, effects to bile flow are potentiated by ketone
solvents. MIBK and two metabolites, 4-methyl-2-pentanol and 4-hydroxy
methyl isobutyl ketone potentiated the cholestasis induced in rats by a
combination of manganese-bilirubin or manganese alone (Vezina and Plaa
1987, 1988). Pretreatment of rats with doses of 375 mg/kg MIBK for at
least three days enhanced the reduction of bile flow caused by acutely
toxic doses of chloroform, taurolithocholate, manganese (4.5 mg/kg I.V.)
or a manganese-bilirubin combination. By increasing the manganese dose
to 6 mg/kg, given intravenously, the minimally effective dose of MIBK
that further reduced bile flow could be lowered to 94 mg/kg. A single
dose of MIBK as high as 1500 mg/kg or multiple doses of 750 mg/kg for 3
days or 188 mg/kg for 7 days did not reduce bile flow in the absence of
one of these other agents. When the taurolithocholate dose was reduced
from 20 mg/kg (which was a cholestatic dose) to 10 mg/kg (which was not
a cholestatic dose), MIBK pretreatment did not alter bile flow.

Vezina [et al]{.underline}. (1990) assessed the ability of MIBK and its
two major metabolites to potentiate the liver injury induced by
chloroform in rats. MIBK and both metabolites significantly increased
the liver damage induced by chloroform. The minimally effective dosage
to potentiate the chloroform-induced hepatotoxicity was approximately 5
mmol/kg for the three compounds. The induction of hepatotoxicity was
demonstrated to be associated with MIBK's capacity to induce cytochrome
P-450.

In addition to the enhancement of haloalkane hepatotoxicity, MIBK has
also been demonstrated to enhance the hepatotoxicity of
1,2-dichlorobenzene. Brondeau [et al]{.underline}. (1989) examined the
ability of acetone, methyl ethyl ketone, MIBK and cyclohexanone vapors
to influence the hepatotoxicity of 1,2-dichlorobenzene in rats and mice.
Sprague-Dawley rats were exposed to MIBK vapor at concentrations of 0,
595, 1280, and 3020 ppm and OF1 mice were exposed to levels of 0, 664,
1477, and 3260 ppm MIBK for 4 hours followed 18 hours later by a 4-hour
exposure to 1,2-dichlorobenzene. Exposure to MIBK alone increased
hepatic glutathione-S-transferase activity (40 to 65 percent) and
cytochrome P450 levels but did not alter glutamate dehydrogenase
activity in rats or liver glucose-6-phosphatase activity in mice.
Following pretreatment with MIBK, 1,2-dichlorobenzene-induced increases
in glutamate dehydrogenase and glucose-6-phosphatase activities were
potentiated. MIBK was concluded to potentiate 1,2-dichlorobenzene liver
injury upon reaching a threshold value of liver cytochrome P-450.

MIBK potentiation of haloalkane-induced nephrotoxicity is described by
Raymond and Plaa (1995). Sprague-Dawley rats pretreated with MIBK,
methyl ethyl ketone or acetone (13.6 mmol/kg) exhibited a significant
increase in chloroform induced kidney toxicity. Of the three ketones
tested, MIBK demonstrated the lowest potency ranking for chloroform
nephrotoxicity.

The interaction effects between MIBK and the hepatic porphyrinogen,
hexachlorobenzene was examined by Krishnan [et al]{.underline}. (1992).
This study found that when the two chemicals were administered
simultaneously, MIBK reduced the severity of hexachlorobenzene-induced
porphyria, but when given sequentially after hexachlorobenzene
accumulation, MIBK enhanced the porphyrinogenic-response. These results
suggest that the effect of combined exposure to hexachlorobenzene and
MIBK on hepatic porphyria depends on the sequence of the administration
of both chemicals, and the mechanism involved in the interaction may
invoke both the induction and inhibition of specific hepatic isoenzymes
by MIBK.

Krishnan [et al]{.underline}. (1989) demonstrated that MIBK potentiated
the methemoglobinemia induced by *N,N*-dimenthylaniline. Groups of male
Sprague-Dawley rats were pretreated (orally) with 7.5 mmol/kg of MIBK
followed, 18 hours later, by the intraperitoneal administration of 0.8
or 2.4 mmol/kg of *N,N*-dimethylaniline. Pretreatment with MIBK enhanced
significantly the methemoglobinemia produced by *N,N*-dimethylaniline.
Similar enhancements of *N,N*-dimethylaniline methemoglobinemia were
observed with pretreatments of microsomal enzyme inducers, suggesting
that ketones act by the same mechanism as the enzyme inducers.

The common conclusion in all of these studies is that enhanced
bioactivation of the co-administered chemical caused by MIBK appears to
be mainly responsible for these interactions.

### Derivation of an Inhalation Reference Concentration (RfC) for MIBK 

The IRIS database does not contain an inhalation reference concentration
(RfC) for MIBK. However, the Ketones Panel has calculated an RfC for
MIBK based on EPA's 1994 guidance for deriving RfCs. [See]{.underline}
EPA Office of Research and Development, "Methods for Derivation of
Inhalation Reference Concentrations and Application of Inhalation
Dosimetry," EPA No. 600/8-90/066F (October 1994) (hereinafter the "RfC
Guidance"). The RfC is based on the 1983 subchronic inhalation studies
in rats and mice sponsored by the Ketones Panel as part of the testing
program under Section 4 of TSCA. This study, which is also referenced in
an April 1987 document prepared by EPA's Environmental Criteria and
Assessment Office, was subsequently published by Phillips
[et]{.underline} [al]{.underline}. (1987). Significantly, it also was
used by EPA to calculate the composite score for MIBK as part of the
relative hazard ranking for MIBK and other compounds under Section
112(g) of the Clean Air Act. Based on the Phillips study, the RfC for
MIBK is 2.4 mg/m^3^. This RfC represents a conservative estimate of the
concentration of MIBK in air to which an individual could be exposed for
a lifetime without adverse effect.[^8]

### Conclusions Regarding Potential Chronic Effects

In summary, the weight of the available evidence suggests that MIBK can
not reasonably be anticipated to cause chronic health effects in humans.
Inhalation studies conducted with various animals indicate low
subchronic toxicity. MIBK is not teratogenic, and it exhibits low
developmental toxicity and very little, if any, mutagenic activity.
Based on its structure and metabolism, MIBK is not likely to have
oncogenic properties. The Ketones Panel has calculated an RfC for MIBK
of 2.4mg/m^3^, which far exceeds likely human exposure levels from
industrial releases of MIBK.

## [MIBK Does Not Cause Significant Adverse Environmental Effects]{.underline}

Under Section 112(b)(3)(C) of the Act, EPA must also consider whether
emissions of a substance may reasonably be anticipated to cause "adverse
environmental effects." The term "adverse environmental effect" is
defined as:

> any significant and widespread adverse effect, which may reasonably be
> anticipated, to wildlife, aquatic life, or other natural resources,
> including adverse impacts on populations of endangered or threatened
> species or significant degradation of environmental quality over broad
> areas.

Section 112(a)(7). Thus, to qualify as an "adverse environmental effect"
for purposes of delisting decisions, the effect must be both
"significant and widespread." As discussed below, MIBK emissions clearly
do not cause significant or widespread adverse effects on the
environment.

### Biodegradation

MIBK is readily biodegradable. Bridié [et]{.underline} [al]{.underline}.
(1979) determined the biochemical and chemical oxygen demands (BOD and
COD) for MIBK. The BOD test was conducted for five days using a standard
dilution method and seeded with coarse filtered effluent from a
biological sanitary waste treatment plant. The COD tests were conducted
using the standard potassium dichromate method. The BOD~5~ was 76% of
the theoretical oxygen demand (ThOD) and the COD was 79% ThOD. Price
[et]{.underline} [al]{.underline}. (1974) reported a BOD~20~ of 69% ThOD
for MIBK using non-acclimated seed from settled domestic wastewater and
a BOD~20~ of 53% ThOD in synthetic seawater. An earlier study by Lamb
and Jenkins (1953), using settled sewage seed, reported a BOD~20~ of
56.6% ThOD for MIBK. Since the reported BOD values are approximately
equal to or greater than 60% ThOD within 28 days, MIBK is considered
readily biodegradable according to EPA environmental fate guidelines
(see 40 C.F.R. § 796.3200).

### Potential For Bioaccumulation

Because MIBK readily biodegrades (Bridié [et]{.underline}
[al]{.underline}. 1979; Price [et]{.underline} [al]{.underline}. 1974;
Lamb and Jenkins 1952) and enters the intermediary metabolism of mammals
(DiVincenzo [et]{.underline} [al]{.underline}. 1976), it would not be
expected to bioaccumulate. Thus, it is not surprising that the
calculated ecological magnification for fish was zero in Metcalf's Model
Aquatic Ecosystem (Lande [et]{.underline} [al]{.underline}. 1976).

The bioconcentration potential of MIBK is also related to its
octanol-water partition coefficient (K~ow~). The reported values of log
K~ow~ for MIBK ranged from 1.09 to 1.31 (Ginnings [et]{.underline}
[al]{.underline}. 1940; Hansch [et]{.underline} [al]{.underline}. 1968;
Sangster 1989). Bioconcentration factors (BCF) of 2-5 and a log BCF of
0.38 were estimated for MIBK using linear regression equations from
Lyman [et]{.underline} [al]{.underline}. (1982) based on a log Kow of
1.19 and a water solubility of 20400 mg/L at 20°C (HSDB 1996). Chemicals
with BCF \< 100 have a low potential to bioconcentrate based on EPA's
criteria (Zeeman 1995).

### Effects On Microorganisms

Egyud (1967) reported that a concentration of 1 x 10^-3^ M MIBK had only
mild transient inhibitory effects on the growth of *E coli*. Bringmann
and Kühn (1980) reported a 16-hour toxicity threshold of 275 mg/L for
*Pseudomonas putida*. Using the Microtox^®^ toxicity analyzer to conduct
bacterial bioluminescense bioassays, Curtis [et]{.underline}
[al]{.underline}. (1982) obtained a 5 min EC50 of 80 mg/L for
*Photobacterium phosphoreum*.

Protozoans are less susceptible than bacteria to the effects of MIBK, as
indicated by the cell multiplication inhibition test toxicity thresholds
shown in Table 1. The lowest toxicity threshold for growth inhibition of
protozoa was 450 mg/1 for *Entosiphon sulcatum*.

**[TABLE 1]{.underline}**

  ---------------------------- ---------------------- -----------------------
  **Acute Toxicity of MIBK to                         
  Protozoa:\                                          
  Cell Multiplication                                 
  Inhibition Test Toxicity                            
  Threshold**                                         

                                                      

  ***\                         ***\                   ***Duration of\
  Protozoa***                  mg/l***                Experiment***

                                                      

  Saprozoic flagellate         \>800                  48 hours
  *(Chilomosas paramaecium)*                          

  Bacteriovorous flagellate    450                    72 hours
  *(Entosiphon sulcatum)*                             

  Bacteriovorous ciliate       950                    20 hours
  *(Uronema parduczi)*                                
  ---------------------------- ---------------------- -----------------------

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

References: Bringmann and Kühn (1980, 1981).

### Effects on Aquatic Organisms

MIBK has a low acute and low chronic toxicity to aquatic organisms based
on EPA's criteria (Zeeman 1995) of \> 100 mg/L and \> 10 mg/L for low
acute and low chronic toxicity, respectively. The acute toxicity values
ranged from 460 to 890 mg/L for several species of freshwater fish and
from 240 to 4280 mg/L for two invertebrate species (Table 2a). The
chronic toxicity of MIBK was studied in an early life stage test with
fathead minnows (Call and Geiger 1992) and in a life cycle test with
*Daphnia magna* (Kühn [et]{.underline} [al]{.underline}. 1989). The
no-observed effect concentrations (NOEC) were 56 and 168 mg/L for fish
growth and survival, respectively, and 78 mg/L for daphnid reproduction
(Table 2b).

MIBK also has a low toxicity to algae. EC~50~ values reported for two
genera of green algae ranged from 400 to 2000 mg/L, and no-effect or
threshold concentrations of 136 and 725 mg/L were found for a blue-green
and green algae species (Table 3).

**[TABLE 2a]{.underline}**

+------------+-------------------+-----------+--------+--------------+
| **Acute    |                   |           |        |              |
| Toxicity   |                   |           |        |              |
| of MIBK to |                   |           |        |              |
| Aquatic    |                   |           |        |              |
| O          |                   |           |        |              |
| rganisms** |                   |           |        |              |
+------------+-------------------+-----------+--------+--------------+
| ***\       | ***\              | ***LC~50~ | ***Dur | ***\         |
| O          | Species***        | or        | ation\ | Reference*** |
| rganism*** |                   | EC~50~\   | of     |              |
|            |                   | (mg/L)*** | T      |              |
|            |                   |           | est*** |              |
+------------+-------------------+-----------+--------+--------------+
| **         | Golden orfe\      | 675-890   | 48 hrs | Juhnke and   |
| Freshwater | *(Leuciscus idus  |           |        | Lüedemann    |
| fish**     | melanotus)*       |           |        | 1978         |
+------------+-------------------+-----------+--------+--------------+
|            | Goldfish\         | 460       | 24 hrs | Bridié       |
|            | *(Carassius       |           |        | [et]         |
|            | auratus)*         |           |        | {.underline} |
|            |                   |           |        | [al]{        |
|            |                   |           |        | .underline}. |
|            |                   |           |        | 1979         |
+------------+-------------------+-----------+--------+--------------+
|            | Rainbow Trout\    | 600       | 96 hrs | Stephenson   |
|            | *(Salmo           |           |        | 1983         |
|            | gairdneri)*       |           |        |              |
+------------+-------------------+-----------+--------+--------------+
|            | Fathead minnow    | 505-540\  | 96     | Veith et al. |
|            |                   | 780       | hrs\   | 1983\        |
|            | *(Pimephales      |           | 24-48  | Brooke       |
|            | promelas)*        |           | hrs    | [et]         |
|            |                   |           |        | {.underline} |
|            |                   |           |        | [al]{        |
|            |                   |           |        | .underline}. |
|            |                   |           |        | 1984\        |
|            |                   |           |        | Waggy and    |
|            |                   |           |        | Payne 1974   |
+------------+-------------------+-----------+--------+--------------+
| **F        | Water flea\       | 240-4280  | 24 hrs | Bringmann &  |
| reshwater\ | *(Daphnia magna)* |           |        | Kühn 1977    |
| inve       |                   |           |        | and 1982\    |
| rtebrate** |                   |           |        | Kühn         |
|            |                   |           |        | [et]         |
|            |                   |           |        | {.underline} |
|            |                   |           |        | [al]{        |
|            |                   |           |        | .underline}. |
|            |                   |           |        | 1989         |
+------------+-------------------+-----------+--------+--------------+
| **Marine\  | Brine shrimp\     | 1230\*    | 24 hrs | Price        |
| inve       | *(Artemia         |           |        | [et]         |
| rtebrate** | salina)*          |           |        | {.underline} |
|            |                   |           |        | [al]{        |
|            |                   |           |        | .underline}. |
|            |                   |           |        | 1974         |
+------------+-------------------+-----------+--------+--------------+

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Median toxicity threshold (TL~m~)

**[TABLE 2b]{.underline}**

  ---------------- ------------------- -------------- -------------- -------------------
  **Chronic                                                          
  Toxicity of MIBK                                                   
  to Aquatic                                                         
  Organisms**                                                        

  ***\             ***\                ***NOEC\       ***Duration\   ***\
  Organism***      Species***          (mg/L)***      of Test***     Reference***

  **Freshwater     Fathead minnow*\    168\           33 days        Call and Geiger
  fish**           (Pimephales         survival                      1992
                   promelas)*                                        

                                       56.2\          33 days        Call and Geiger
                                       weight                        1992

                                       \<56.2\        33 days        Call and Geiger
                                       length                        1992

  **Freshwater\    Water flea\         78\            21 days        Kühn
  invertebrate**   *(Daphnia magna)*   reproduction                  [et]{.underline}
                                                                     [al]{.underline}.
                                                                     1989
  ---------------- ------------------- -------------- -------------- -------------------

**[TABLE 3]{.underline}**

  --------------------- --------------- -------------- --------------------
  **Acute Toxicity of                                  
  MIBK to Freshwater                                   
  Algae**                                              

  ***\                  ***EC~50~\      ***Duration\   ***\
  Species***            (mg/L)***       of Test***     Reference***

  Bluegreen algae\      136\*           8 days         Bringmann and Kühn
  *(Microcystis                                        1978
  aeruginosa)*                                         

  Green algae\          725\*\*         7 days         Bringmann and Kühn
  *(Scenedesmus                                        1980
  quadricauda)*                                        

  Green algae\          980\            48 hours       Kühn and Pattard
  *(Scenedesmus         biomass                        1990
  subspicatus)*                                        

                        2000\           48 hours       Kühn and Pattard
                        growth rate                    1990

  Green algae\          400             96 hours       Stephenson 1983
  *(Selenastrum                                        
  capricornutum)*                                      
  --------------------- --------------- -------------- --------------------

\* EC~O~

\*\* Cell multiplication inhibition test toxicity threshold (TT).

### Effects on Plants

As noted in Section I.C above, MIBK occurs naturally in plants. The
effects of MIBK on lower order plants have been discussed in the
preceding section. Toxicity to higher order plants due to MIBK exposure
has not been reported. Higher order plants are unlikely to be exposed to
deleterious levels of MIBK because MIBK is readily degraded in the
atmosphere and by biodegradation.

# [DATA ON EMISSIONS AND EXPOSURE]{.underline}

## [Emissions Data]{.underline}

Because MIBK emissions currently must be reported under Section 313 of
EPCRA, the Toxics Release Inventory (TRI) is a good source of
information about MIBK emissions from industrial facilities. Table 4
below summarizes reported emissions of MIBK based on 1994 TRI data, and
indicates the number of TRI reporting facilities with MIBK air emissions
in different reporting ranges.

**[TABLE 4]{.underline}**

+----+--------+-------+---+------------------------+----------------------+
| *  |        |       |   |                        |                      |
| *\ |        |       |   |                        |                      |
| MI |        |       |   |                        |                      |
| BK |        |       |   |                        |                      |
| A  |        |       |   |                        |                      |
| ir |        |       |   |                        |                      |
| Em |        |       |   |                        |                      |
| is |        |       |   |                        |                      |
| si |        |       |   |                        |                      |
| on |        |       |   |                        |                      |
| s\ |        |       |   |                        |                      |
| ** |        |       |   |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
|    |        |       |   |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| ** |        |       | * |                        | ***% Distribution*** |
| *N |        |       | * |                        |                      |
| o. |        |       | * |                        |                      |
| of |        |       | R |                        |                      |
| F  |        |       | e |                        |                      |
| ac |        |       | p |                        |                      |
| il |        |       | o |                        |                      |
| it |        |       | r |                        |                      |
| ie |        |       | t |                        |                      |
| s* |        |       | i |                        |                      |
| ** |        |       | n |                        |                      |
|    |        |       | g |                        |                      |
|    |        |       | R |                        |                      |
|    |        |       | a |                        |                      |
|    |        |       | n |                        |                      |
|    |        |       | g |                        |                      |
|    |        |       | e |                        |                      |
|    |        |       | ( |                        |                      |
|    |        |       | l |                        |                      |
|    |        |       | b |                        |                      |
|    |        |       | s |                        |                      |
|    |        |       | / |                        |                      |
|    |        |       | y |                        |                      |
|    |        |       | r |                        |                      |
|    |        |       | ) |                        |                      |
|    |        |       | * |                        |                      |
|    |        |       | * |                        |                      |
|    |        |       | * |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 0 |                        | 75.5                 |
|  7 |        |       |   |                        |                      |
| 78 |        |       | - |                        |                      |
|    |        |       | 2 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 2 |                        | 15.7                 |
|  1 |        |       | 0 |                        |                      |
| 62 |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       |   |                        |                      |
|    |        |       | - |                        |                      |
|    |        |       | 5 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 5 |                        | 4.5                  |
| 46 |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       |   |                        |                      |
|    |        |       | - |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 1 |                        | 2.1                  |
| 21 |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       |   |                        |                      |
|    |        |       | - |                        |                      |
|    |        |       | 2 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 2 |                        | 1.1                  |
| 11 |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       |   |                        |                      |
|    |        |       | - |                        |                      |
|    |        |       | 3 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 3 |                        | 0.5                  |
|  5 |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       |   |                        |                      |
|    |        |       | - |                        |                      |
|    |        |       | 4 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | 4 |                        | 0.4                  |
|  4 |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 1 |                        |                      |
|    |        |       |   |                        |                      |
|    |        |       | - |                        |                      |
|    |        |       | 7 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
| >  |        |       | a |                        | 0.4                  |
|  4 |        |       | b |                        |                      |
|    |        |       | o |                        |                      |
|    |        |       | v |                        |                      |
|    |        |       | e |                        |                      |
|    |        |       | 7 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | , |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
|    |        |       | 0 |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
|    | 1,031  |       |   |                        |                      |
+----+--------+-------+---+------------------------+----------------------+
|    |        |       |   |                        |                      |
+----+--------+-------+---+------------------------+----------------------+

Reference: 1994 TRI Data.

As discussed above in Section I.B, MIBK is widely used in many types of
solvent-based systems because of its effectiveness. Table 4 shows that,
although MIBK is used at a large number of facilities, the vast majority
of them have very low emissions of MIBK. Over 75 percent of the
facilities reporting MIBK emissions emitted less than 10 tons in 1994.
Over 90 percent of those facilities reported 1994 MIBK emissions of less
than 25 tons.

## [Ambient Monitoring Data]{.underline}

MIBK has been reported in ambient air at very low concentrations at a
limited number of sites in rural and urban locations. Data on ambient
air levels of MIBK are presented in Appendices C and D. The following is
a brief overview of the information presented in those appendices, as
well as additional information found in the published literature.

Appendix C includes a table taken from a study conducted by the State of
New Jersey Department of Environmental Protection in 1979 (Bozzelli
[et]{.underline} [al]{.underline}. 1980). MIBK was detected in only 4
out of 168 samples taken in 1979 during a study conducted by the Air
Pollution Research Laboratory of the New Jersey Institute of Technology.
The highest measured value of MIBK in the study was 1.00 ppb. The six
sample sites included densely populated areas where large chemical
complexes were located, including the Exxon Bayway facility which, at
the time, produced MIBK (Bozzelli and Kebbekus 1983). Thirty-six samples
were taken in Elizabeth, New Jersey, near the Exxon Bayway refinery,
which at the time was the largest MIBK producer in the United States.

An ambient air monitoring study that included MIBK has been conducted in
the industrial (ship channel) area of Houston, Texas since January,
1987. The results from the seven monitoring stations in the ship channel
during the period of January 1, 1987 to December 31, 1995 show 24-hour
average airborne concentrations of MIBK from below the level of
detection to a high of 5.77 ppb. The mean (long-term average) airborne
concentrations of MIBK at the seven monitoring sites during the same
eight-year period ranged from 0.13 ppb to 0.18 ppb. [See]{.underline}
Houston Regional Monitoring Report, included in Appendix D.

## [Air Dispersion Modeling Data for Industrial Facilities]{.underline}

Over the last two years, the Ketones Panel has undertaken a program to
gather data on the maximum airborne concentrations of MIBK to which the
public may be exposed. As part of this program, the Panel funded a study
by ENSR Corporation to model the maximum off-site concentrations of MIBK
at a wide variety of facilities emitting MIBK, including the largest
sources of MIBK emissions in the country. The findings of the ENSR
study, along with a detailed description of the methodology employed by
ENSR, are contained in the report attached at Appendix E (hereinafter
referred to as the ENSR Report). This study shows that, even at the
largest industrial emitters of MIBK, maximum airborne concentrations
beyond facility boundaries are well below levels of concern and do not
pose a risk to human health or the environment.

The ENSR study was divided into three parts. First, because airborne
concentrations are likely to be highest around facilities with the
highest emission rates, ENSR separately evaluated maximum off-site
concentrations of MIBK around each of the facilities reporting MIBK
emissions of 150 tons or more in 1994. Second, ENSR used a generic model
to make conservative estimates of maximum off-site concentrations around
smaller facilities that emit MIBK. Third, ENSR analyzed the possibility
that groups of facilities located in the same area might collectively
cause airborne levels of concern. The three parts of ENSR's analysis are
discussed below.

### Air Dispersion Modeling of the Highest Emitters

As the starting point for its modeling program, the Ketones Panel sought
to model the maximum off-site concentrations for all facilities
reporting MIBK emissions greater than 150 tons per year. The Panel
selected this threshold based on the methodology that EPA developed to
set [de minimis]{.underline} values for hazardous air pollutants under
Section 112(g) of the Clean Air Act. [See]{.underline} Documentation for
De Minimis Emission Rates for Proposed 40 CFR part 63, subpart B
(EPA-453/R-93-035). Under Section 112(g), the [de minimis]{.underline}
value for a chemical is the amount that an EPA model facility could emit
without posing more than a "trivial" risk to human health or the
environment. (The [de minimis]{.underline} value for MIBK is discussed
further in Section V.B of this Petition.) In the Section 112(g)
rulemaking, EPA proposed to "cap" [de minimis]{.underline} levels at 10
tons per year (tpy), but at the same time recognized that, for low
toxicity chemicals, emissions of more than 10 tpy would still pose only
a trivial risk. 59 Fed. Reg. 15,504, 15,527 (April 1, 1994).
Significantly, EPA's methodology may also be used to calculate true
"uncapped" [de minimis]{.underline} values for different compounds.

EPA's methodology requires the use of an RfC. At the commencement of its
modeling exercise, the Panel believed that the RfC for MIBK was 0.75
mg/m^3^ based on EPA's pre-1994 approach for setting RfCs. (As discussed
above at p. 35, however, the correct RfC for MIBK, based on EPA's 1994
RfC Guidance, is actually 2.4 mg/m^3^.) Using the lower RfC in EPA's
model for calculating [de minimis]{.underline} values, the Panel derived
a [de minimis]{.underline} value for MIBK of 1,500 tons per year. In
order to establish a meaningful cutoff point for its modeling exercise,
the Panel decided that it would seek to model all facilities with
reported emissions that were more than 10 percent of this amount. Thus,
it sought to model the maximum off-site concentrations for all
facilities reporting MIBK emissions greater than 150 tons (or 300,000
pounds) per year. Based on 1993 TRI data, the Panel identified 13 such
facilities.

The Panel also worked with ENSR to develop a detailed questionnaire to
gather the information that would be necessary to model the maximum
off-site concentrations at each facility. This questionnaire, along with
a cover letter explaining the Panel's modeling program, was sent to the
13 facilities, and representatives from the Panel also contacted each of
the facilities to encourage their participation. By the time the Panel
received the necessary data and ENSR began its modeling exercise, the
TRI data for 1994 had become available. Based on the 1994 data, two of
the original 13 facilities were below the 150 ton threshold, but two
additional facilities now exceeded the threshold. During the course of
its discussions with the individual facilities, the Panel also
discovered that one facility had incorrectly calculated its reported
MIBK emissions and, in fact, was well below the 150-ton threshold. As a
result, this facility was not included in the modeling study, and the
ENSR Report covers 12 rather than 13 individual facilities.

As described in the ENSR Report, either facility-specific data or
pre-existing modeling results were obtained from 9 of the 12
highest-emitting MIBK sources in the country.[^9] One of the remaining
facilities declined to participate in the ENSR study because it had
already committed to phasing out the use of MIBK. In order to conduct
modeling for the other two facilities identified as top emitters, the
Panel and ENSR attempted to obtain site-specific information from public
sources, including EPA's Aerometric Information Retrieval System (AIRS),
permit applications, and site plans on file with local zoning boards.
This effort generated sufficient data to allow ENSR to conduct
site-specific modeling for one of the two remaining facilities that did
not provide information directly to ENSR. Thus, the data necessary for
site-specific modeling was obtained \-- either from the facilities or
from public sources \-- for 10 of the 12 highest emitters of MIBK.[^10]

Using this data, ENSR performed air quality modeling analyses for each
facility using EPA's "Tiered Modeling Approach for Assessing Risks Due
to Sources of Hazardous Air Pollutants" (1992). This approach uses three
successively more rigorous modeling techniques. Tier 1 requires only
limited source information and an EPA look-up table, and provides the
most conservative predictions of maximum concentrations. Tier 2 requires
additional source information and an EPA screening level computer
program, and generates predictions that are somewhat more realistic than
Tier 1 predictions. Tier 3, which requires extensive data from the
source and uses EPA's most advanced dispersion modeling techniques,
provides the most realistic predicted concentrations. Tier 3 modeling
was performed for a facility if Tier 2 modeling predicted maximum annual
concentrations above 1.0 mg/m^3^ or maximum 24-hour concentrations above
5.0 mg/m^3^. The results of the ENSR modeling study of the highest
emitters are shown on Table 5 and 6. Table 5 shows maximum annual
off-site concentrations; Table 6 shows maximum 24-hour off-site
concentrations. In both tables, facilities are listed according to Tier
2 modeling results in descending order.

**[TABLE 5]{.underline}**

+---------------+----------------+----------------+-------------------+
| **\           |                |                |                   |
| Air           |                |                |                   |
| Dispersion    |                |                |                   |
| Modeling      |                |                |                   |
| Results for   |                |                |                   |
| Hig           |                |                |                   |
| hest-Emitting |                |                |                   |
| MIBK Sources\ |                |                |                   |
| **            |                |                |                   |
+---------------+----------------+----------------+-------------------+
| Maximum       |                |                |                   |
| Annual MIBK   |                |                |                   |
| C             |                |                |                   |
| oncentrations |                |                |                   |
| (mg/m^3^)     |                |                |                   |
| (RfC = 2.4    |                |                |                   |
| mg/m^3^)      |                |                |                   |
+---------------+----------------+----------------+-------------------+
| Site†         | Tier 1         | Tier 2         | Tier 3            |
+---------------+----------------+----------------+-------------------+
| > B10         | 14.75          | 6.58           | 0.35              |
+---------------+----------------+----------------+-------------------+
| > B8          | 9.88           | 2.81           | 0.13              |
+---------------+----------------+----------------+-------------------+
| > B15         | 8.04           | 2.07           | 0.22\*            |
+---------------+----------------+----------------+-------------------+
| > B2          | 5.85           | 1.18           | 0.41\*            |
+---------------+----------------+----------------+-------------------+
| > B6          | 4.1            | 0.73           | \--               |
+---------------+----------------+----------------+-------------------+
| > B13         | 1.21           | 0.60           | \--               |
+---------------+----------------+----------------+-------------------+
| > B17         | 2.54           | 0.57           | \--               |
+---------------+----------------+----------------+-------------------+
| > B11         | 3.39           | 0.38           | \--               |
+---------------+----------------+----------------+-------------------+
| > B9          | \--            | 0.008\*\*      | \--               |
+---------------+----------------+----------------+-------------------+
| > B4          | \--            | \--            | 0.004\*\*         |
+---------------+----------------+----------------+-------------------+

\* Simplified conservative Tier 3 modeling conducted assuming all
emissions from a single point source with the minimum distance to
property boundary in all directions.

\*\* Based on modeling results provided by the individual company.

† Companies submitted the information necessary to conduct the modeling
under conditions of confidentiality. For this reason, facilities are not
identified by name and modeling results cannot be presented side-by-side
with emissions data.

As shown on Table 5, airborne concentration levels of MIBK are clearly
below levels of concern. Based on the Tier 3 data, even the highest
predicted concentration is almost an order of magnitude below the RfC.
The data as a whole demonstrate that emissions of MIBK do not result in
ambient concentrations that may reasonably be anticipated to cause
chronic adverse health effects.

**[TABLE 6]{.underline}**

+---------------+----------------+----------------+------------------+
| **\           |                |                |                  |
| Air           |                |                |                  |
| Dispersion    |                |                |                  |
| Modeling      |                |                |                  |
| Results for   |                |                |                  |
| Hig           |                |                |                  |
| hest-Emitting |                |                |                  |
| MIBK Sources\ |                |                |                  |
| **            |                |                |                  |
+---------------+----------------+----------------+------------------+
| Maximum       |                |                |                  |
| 24-hour MIBK  |                |                |                  |
| C             |                |                |                  |
| oncentrations |                |                |                  |
| (mg/m^3^)     |                |                |                  |
| (Benchmark    |                |                |                  |
| =24 mg/m^3^)  |                |                |                  |
| †             |                |                |                  |
+---------------+----------------+----------------+------------------+
| Site††        | Tier 1         | Tier 2         | Tier 3           |
+---------------+----------------+----------------+------------------+
| > B10         | 59.2           | 32.9           | 2.73             |
+---------------+----------------+----------------+------------------+
| > B8          | 51.8           | 19.70          | 1.71             |
+---------------+----------------+----------------+------------------+
| > B15         | 44.9           | 14.46          | 2.56\*           |
+---------------+----------------+----------------+------------------+
| > B2          | 58.3           | 8.28           | 3.23\*           |
+---------------+----------------+----------------+------------------+
| > B13         | 6.8            | 4.23           | \--              |
+---------------+----------------+----------------+------------------+
| > B6          | 17.6           | 4.04           | \--              |
+---------------+----------------+----------------+------------------+
| > B17         | 14.2           | 3.97           | \--              |
+---------------+----------------+----------------+------------------+
| > B11         | 18.6           | 2.67           | \--              |
+---------------+----------------+----------------+------------------+
| > B9          | \--            | 0.04\*\*       | \--              |
+---------------+----------------+----------------+------------------+
| > B4          | \--            | \--            | 0.02\*\*         |
+---------------+----------------+----------------+------------------+

\* Simplified conservative Tier 3 modeling conducted assuming all
emissions from a single point source with the minimum distance to
property boundary in all directions.

\*\* Based on modeling results provided by the individual company.

† This health benchmark is based on the RfC of 2.4 mg/m^3^, modified
only to eliminate the uncertainty factor of 10 for extrapolating from
subchronic to chronic exposures.

†† Companies submitted the information necessary to conduct the modeling
under conditions of confidentiality. For this reason, facilities are not
identified by name and modeling results cannot be presented side-by-side
with emissions data.

Maximum 24-hour off-site MIBK concentrations were compared to a health
benchmark of 24 mg/m^3^ \-- the RfC modified to eliminate the
uncertainty factor of 10 that is used to extrapolate from subchronic to
chronic exposure. As shown on Table 6, the maximum 24-hour
concentrations were all well below this benchmark. Based on tier 3
values, the highest predicted 24-hour value was 3.23 mg/m^3^ \-- again
almost an order magnitude below the health benchmark. It should be noted
that the maximum predicted 24-hour concentrations are based on the
worst-case conditions occurring in any 24-hour period over the last 5
years, and are therefore very conservative.

It is also important to recognize that the methodology used by ENSR was
not intended to represent actual population exposure. Rather, it was
designed to identify the highest annual and 24-hour off-site
concentrations that might occur around each facility. In all cases, the
modeled maximum concentrations are near facility boundaries, and it is
unlikely that there is continuous exposure at any of these locations.
Further, because the methodology is designed to predict **maximum**
off-site concentrations, it incorporates a number of conservative
assumptions. Actual average concentrations are likely to be lower, and
could be lower by an order of magnitude or more. Thus, the results of
ENSR's air dispersion modeling analyses likely overpredict actual
exposures.

### Air Dispersion Modeling of Smaller Sources

The Panel also recognized that there could be relatively high off-site
exposures around smaller MIBK sources due to such things as unusual
dispersion climatology, lower emission release heights, and proximity of
nearby residents. Therefore, ENSR developed an approach for analyzing
maximum off-site concentrations around smaller facilities that emit
MIBK. All facilities that reported MIBK emissions of 10 tons or more on
the 1994 TRI were divided into source categories based on their
two-digit SIC codes. As discussed below, ENSR developed model facilities
for each source category in which no facility was individually modeled
under the first part of its analysis. It then used a generic EPA model
to predict maximum off-site concentrations for facilities in each source
category.

As described more fully in the ENSR Report, the air dispersion model
used to evaluate potential exposures around smaller sources was based on
the model developed by EPA as part of the Agency\'s rulemaking under
Section 112(g) of the Clean Air Act. This is a conservative model that
allows the prediction of maximum annual exposures based on two
parameters: emissions release height and distance to the nearest
receptor. The EPA model incorporates the following conservative
assumptions:

-   emissions all emanate from a single point;

-   emissions have negligible exit velocity (10 cm/second);

-   emissions are released at ambient temperature; and

-   emissions are subject to worst-case aerodynamic building downwash.

For purposes of the Section 112(g) rulemaking, the Agency applied the
model based on median dispersion climatology developed from 314 weather
stations located throughout the United States. To predict maximum annual
concentrations around smaller sources of MIBK, ENSR adjusted the model
to incorporate worst-case dispersion climatology.

ENSR then assigned each of the source categories identified with MIBK
sources to one of the following "dispersion categories" based on the
assumptions set forth below:

-   Heavy: Major facilities located in industrial areas on relatively
    large sites. (Stack height = 15 meters; distance to receptor = 200
    meters)

-   Medium: Moderate size facilities located in light industrial or
    commercial areas on smaller sites. (Stack height = 10 meters;
    distance to receptor = 150 meters)

-   Light: Smaller facilities located on relatively small sites in
    mixed-use areas, where emissions are likely to be released from roof
    vents in one-story buildings. (Stack height = 5 meters; distance to
    receptor = 100 meters)

The model was then used to predict maximum annual concentrations for
facilities representing each source category in which at least one
facility reported more than 10 tons of MIBK emissions in 1994. The
predicted maximum concentrations for each source category are based on
the emission rates reported by the facilities reporting the highest and
second highest emissions in each category. The results of this analysis
are presented in Table 7.

**[TABLE 7]{.underline}**

  ---------------- --------------- ------------- ----------- --------------- ---------- ---------------
  **Air Dispersion                                                                      
  Modeling Results                                                                      
  for Smaller MIBK                                                                      
  Sources\                                                                              
  **                                                                                    

  Maximum Annual                                                                        
  MIBK                                                                                  
  Concentrations                                                                        
  (mg/m^3^) (RfC=                                                                       
  2.4 mg/m^3^)                                                                          

  **\              **\             **\           **Highest   **Predicted     **2nd      **Predicted
  \                \               \             Emission    Concentration   Highest\   Concentration
  \                \               \             Rate\       from Highest    Emission   from 2nd
  SIC\             Source Category Dispersion\   in SIC      Rate\           Rate\      Highest Rate\
  Code**           Description**   Category**    Code\       (mg/m^3^)**     in SIC     (mg/m^3^)**
                                                 (lbs)**                     Code\      
                                                                             (lbs)**    

  23               Apparel         Light         127,930     0.525           28,514     0.117

  24               Lumber          Medium        180,000     0.164           58,160     0.053

  25               Furniture       Light         88,750      0.364           78,687     0.323

  26               Paper           Heavy         114,492     0.045           NA         NA

  27               Printing        Medium        24,885      0.023           NA         NA

  29               Refining        Heavy         236,000     0.092           112,470    0.044

  31               Leather         Medium        27,962      0.025           24,200     0.022

  32               Concrete        Medium        31,840      0.029           NA         NA

  34               Fab. Metal      Medium        207,502     0.189           83,336     0.076

  35               Ind. Machine    Heavy         93,523      0.036           46,700     0.018

  36               Electronic      Medium        56,000      0.051           48,700     0.044

  38               Measuring Inst. Medium        46,200      0.042           21,701     0.020

  39               Misc. Mfg.      Medium        43,450      0.040           32,900     0.030

  87               Engineering     Light         31,050      0.127           NA         NA

  97               Nat. Security   Heavy         20,610      0.008           NA         NA
  ---------------- --------------- ------------- ----------- --------------- ---------- ---------------

Based on this analysis, ENSR concluded that "\[g\]eneralized dispersion
modeling indicates that maximum annual off-site concentrations are below
1 mg/m^3^ in the vicinity of these lesser emitting facilities \[and\]
are well below 1 mg/m^3^ in most cases." ENSR Report, Executive Summary.
Thus, based on an assessment of a wide range of sources and source
categories, including both large and small sources, it appears that
maximum off-site concentrations of MIBK are well below levels of
concern.

### Potential Impacts from Groups of Sources

The ENSR study also evaluated the possibility that there might be groups
of facilities that collectively have significant health or environmental
impacts, even though no single facility reported emissions that would
raise concerns. ENSR began this part of its analysis by noting that,
based on the results of the modeling study for the highest emitters,
"for sources to contribute to off-site receptor concentrations above the
RfC, at least 3 major MIBK emitters would need to be side-by-side with a
receptor located between them." ENSR Report at p. 6-1. ENSR then pointed
out that no two of the top emitting facilities were even located in the
same geographic area. As a result, it concluded that it was "highly
improbable" that combined emissions from multiple facilities would
result in concentrations above the health benchmarks. [Id]{.underline}.

ENSR nevertheless conducted an evaluation to identify possible clusters
of MIBK sources. As a first step, it used the TRI database to identify
every facility in the country that reported MIBK emissions of more than
10 tons in 1994, including both point and fugitive emissions. For the
year 1994, there were 253 facilities above this threshold. Of this
number, 242 facilities are located in postal ZIP codes in which there
was no other facility reporting MIBK emissions greater than 10 tons in
1994. Each of the remaining 11 facilities are listed in Appendix F,
which is organized by ZIP code. Appendix F shows the reported emissions
for each facility, along with the total emissions for each ZIP code.

This analysis shows that there is no significant grouping of sources
that emit MIBK. The 11 facilities are distributed fairly evenly over 5
different ZIP codes. Only one of these ZIP codes contains more than 2
facilities, but total MIBK emissions from facilities in that ZIP code
were just over 40 tons in 1994. ENSR noted that, even if all the
facilities in any single zip code "were combined into one co-located
facility, both site specific and generalized modeling suggests that such
a facility would not cause ambient levels that would approach the health
benchmarks." [Id]{.underline}. Thus, ENSR concluded that "there is no
group of MIBK emitting facilities that collectively would result in
maximum off-site concentrations approaching the \[health\] benchmarks."
[Id.]{.underline} at p. 7-1.

## [Effect of Delisting on Emissions and Ambient Concentration]{.underline}

Because of MIBK's status as a HAP, companies currently are discouraged
from using it. In some cases, product formulators and users must comply
with regulatory limits on the HAP content of their products. In other
cases, companies are likely to reduce their use of HAPs in order to
avoid the need to install maximum available control technology (MACT)
under Section 112(d) of the Act. Even in the absence of regulatory
requirements, companies often try to avoid the use of chemicals that are
labeled as HAPs. Therefore, if MIBK is removed from the HAP list, usage
of MIBK is likely to increase.

For several reasons, however, MIBK emissions are unlikely to increase
substantially. First, MIBK is used primarily in paints and coatings and,
to a lesser extent, in inks and adhesives. In these and other solvent
applications, MIBK is rarely used by itself. Typically, MIBK is part of
a solvent blend that must be carefully formulated to achieve the proper
performance characteristics, including such things as evaporation rate,
surface tension, solvent balance, and flash point. Although there is
flexibility to increase the use of MIBK in many solvent blends, there
are inherent limits on the amount of MIBK (or any other single solvent)
that can be used in any formulation.

Second, because MIBK is used primarily in solvent blends, there will
often be other HAPs that are used in the same application. In many
cases, the facilities where such applications are used will be required
to meet "maximum available control technology" (MACT) standards and will
need to install control technology to reduce their HAP emissions. In
most cases, such technology will reduce all solvent emissions, including
emissions of MIBK. Therefore, although MIBK would no longer be listed as
a HAP, the implementation of MACT standards will control MIBK emissions
along with emissions of other chemicals.

Third, MIBK will continue to be regulated as a VOC. Many areas of the
country have not yet reached attainment with the national air quality
standard (NAAQS) for ozone and must reduce VOC emissions in order to
meet the NAAQS standard. Emissions of solvents, including MIBK, are
subject to increasingly stringent standards under both federal and state
programs designed to control ozone formation. Therefore, emissions of
MIBK will continue to be regulated even after it is removed from the HAP
list.

Significantly, the monitoring and modeling data discussed above show
that, even if MIBK emissions were to increase significantly, ambient
concentrations would be expected to remain well below levels of concern.
Actual monitoring data in a number of areas, including industrial areas,
indicate that ambient concentrations of MIBK are very low. The air
dispersion modeling study conducted by ENSR showed that, in most cases,
maximum annual off-site concentrations around facilities emitting MIBK
should be below the RfC by an order of magnitude or more. Even at the
worst-case off-site locations around the largest sources of MIBK,
ambient levels are below the RfC by a factor of 3 or more. Therefore,
even significant increases in MIBK emissions would not pose an
appreciable risk to human health or the environment.

Finally \-- and perhaps most importantly \-- any increase in MIBK
emissions is likely to be more than offset by decreases in emissions of
other solvents. As discussed in the next section of this Petition, MIBK
is a highly effective solvent. In many applications, relatively small
amounts of MIBK may be used to perform the same function served by
other, less efficient solvents. For this reason, it is widely used in
high-solids coatings, which offer the only feasible approach for
reducing VOC emissions from certain types of coating operations. Because
of MIBK's efficiency as a solvent, increases in MIBK emissions will in
many cases represent an overall decrease in VOC emissions.

# [OTHER REASONS FOR DELISTING MIBK]{.underline}

As discussed above, it is clear that MIBK meets the statutory delisting
criteria and should therefore be removed from the HAP list. EPA should
be aware, however, that there are additional considerations that weigh
in favor of removing MIBK from the HAP list. These additional
considerations are discussed below.

## Delisting MIBK Will Help to Reduce VOC Emissions from Many [Coating Operations]{.underline} 

As noted above, MIBK is especially valuable in the formulation of
high-solids coatings, which are increasingly used to reduce VOC
emissions from industrial and commercial coating operations. MIBK not
only dissolves a wide variety of resins, but is a more efficient solvent
than the available non-ketone alternatives. Thus, compared to the
alternatives, a smaller amount of MIBK may be used to perform the same
function. The use of MIBK therefore allows the formulation of coatings
with higher solids content and lower VOC emissions.

In addition to its solvent properties, MIBK has unique chemical
properties which are used in the manufacture of compliant high-solids
coatings. MIBK is a good polymerization solvent for low molecular weight
resins, which form the basic building blocks of high-solids (low VOC)
coatings. Key characteristics of MIBK \-- including its hydrophobicity,
good stability, low hydrogen-bonding attributes, low surface tension,
low viscosity, and low density \-- make it a leading choice for
high-solids polymer manufacturing. The resultant low viscosity,
high-solids polymers can then be used to produce low VOC coatings.

Over the last decade, EPA and many state agencies have sought to reduce
VOC emissions from coating operations and other commercial applications
that involve the use of organic solvents. In some cases \-- particularly
those involving large-scale coating operations \-- the most effective
approach for reducing VOC emissions is to install a solvent recovery
system or other type of control device. In other cases, companies have
reduced their VOC emissions by switching from solvent-based technologies
to alternative, non-solvent technologies. A number of coating
operations, for example, have switched from conventional solvent-based
coatings to waterborne or powder coatings.

In many cases, however, these options are simply not feasible. For
example, in many wood coating applications, water-based finishes cannot
be used because they are absorbed into the substrate and raise the grain
of the wood. Although a control device may be technically feasible for
some wood finishing operations, EPA has acknowledged that many such
operations are simply too small to justify the installation of a control
device. Where it is not practical to use a control device or a
non-solvent technology, EPA has recognized that the best alternative is
to use products that can accomplish a given task with the least possible
amount of solvent. For coating applications, this generally means a
switch from conventional coatings to \"high-solids\" coatings. In
several recent rulemakings, EPA has adopted standards that will
effectively require the use of such coatings in certain industries.
[See]{.underline}, [e.g.]{.underline}, 61 Fed. Reg. 19005 (April 30,
1996) (proposed rule; automobile refinishing coatings); 60 Fed. Reg.
62930 (Dec. 7, 1995) (final rule; wood furniture coating operations); 60
Fed. Reg. 64330 (Dec. 15, 1995) (final rule; shipbuilding coating
operations).

The amount of solids in a coating is limited by the ability of the
solvent to dissolve the resins and retain them in solution until the
coating is applied. After the coating is applied, the solvent evaporates
into the air, leaving behind a hard, uniform finish. Thus, the more
effective the solvent, the higher the proportion of solids and the lower
the emissions into the air.

EPA recognized this fact in its recent rule to reduce emissions from
shipbuilding operations. [See]{.underline} 60 Fed. Reg. at 64330. In
this rulemaking, EPA acknowledged that the use of highly efficient
solvents such as MIBK is the preferred environmental alternative in many
coating applications, even though such solvents may be listed as HAPs.
Although the primary purpose of the rule is to control HAP emissions,
EPA designed the rule to minimize VOC emissions as well. Thus, the
Agency adopted regulatory standards that effectively require the use of
higher-solids coatings in the shipbuilding industry.

MIBK and methyl ethyl ketone (MEK) \-- another ketone solvent with
similar solvency \-- are two of the most efficient solvents available to
coating formulators. Because they are currently listed as HAPs, a
formulator may need to increase the HAP content of a coating in order to
reduce its VOC content. The Agency explicitly recognized this tradeoff
in the preamble to the proposed rule. EPA noted that a coating
reformulated to reduce its HAP content may have \"higher VOC content
than the one it replaces,\" and went on to say that \"the HAP to VOC
ratio may even increase when a company develops a new reformulation with
lower VOC.\" 59 Fed. Reg. at 62688. The Agency also noted, however, that
even where the HAP to VOC ratio in the coating increases, \"the absolute
HAP [emissions]{.underline} are likely to go down,\" presumably because
higher solids coatings allow more coverage per gallon of coating.
[Id]{.underline}. (emphasis in original).

The Agency addressed this issue by setting identical limits for the VOC
and HAP content of the coatings covered by the shipbuilding rule. The
rule sets a limit on the amount of \"volatile organic hazardous air
pollutants\" (VOHAPs) that can be used in specified types of coatings.
Because VOHAPs are defined to include both HAPs and VOCs, a formulator
may use any solvent up to the VOHAP content limit for each coating. This
approach encourages the use of higher solids coatings and eliminates the
incentive for formulators to use less efficient solvents that must be
used in greater volumes. Thus, the rule recognizes that highly efficient
solvents such as MIBK are the preferred environmental approach for
reducing overall emissions from many coating applications.

Because MIBK is currently listed as a HAP, however, companies are
discouraged or even prevented from using it \-- even where it would
allow them to reduce their VOC emissions by switching to higher-solids
coatings. In some industries, such as the wood furniture industry,
facilities must comply with regulatory limits on the HAP content of
their coatings. In other industries, as already stated, companies are
likely to reduce their use of HAPs in order to avoid the need to install
maximum available control technology (MACT) under Section 112(d) of the
Act. Even in the absence of regulatory requirements, companies often try
to avoid the use of chemicals that are labeled as HAPs. For example, the
Ketones Panel is aware of a major manufacturing company that, as a
matter of corporate environmental policy, is seeking to eliminate the
use of MIBK and other listed chemicals from its manufacturing processes,
even though the company's toxicologists have recognized that MIBK does
not pose significant toxicity concerns. The simple fact that MIBK is
listed as a HAP discourages companies from using it \-- even in
applications where it would provide a clear environmental benefit.
Removing MIBK from the HAP list would eliminate this disincentive and
benefit the environment by facilitating the use of higher-solids
coatings.

## EPA Has Recognized in Other Contexts that MIBK Has Relatively [Low Toxicity]{.underline} 

In two recent rulemakings, EPA has reviewed the health effects of
exposure to MIBK. In both cases, EPA has recognized that MIBK has
relatively low toxicity.

### Proposed Rule Under Section 112(g) of the Clean Air Act

On April 1, 1994, the Agency published a proposed rule under Section
112(g) of the Act that included a detailed system for ranking and
setting "[de minimis]{.underline} values" for the various chemicals
listed under Section 112(b), including MIBK. 59 Fed. Reg. 15504. Under
the proposed hazard ranking system, the Agency developed a list of
\"threshold pollutants\" that were not considered "high concern"
pollutants, and were believed to pose the least risk of any of the
listed HAPs. Not surprisingly, MIBK was listed as a threshold pollutant.
For ranking the relative risk of the compounds on the threshold list,
the Agency assigned a \"composite score\" for each chemical based on the
severity of any health effect caused by the chemical in test animals and
the dose at which the effect is likely to occur. Under this system, a
chemical could receive a composite score from 1 - 100, although the
pollutants on the threshold list all had scores between 2 and 46.

Based on this proposed hazard ranking system, the Agency assigned a
composite score of 4 to MIBK, indicating that it is among the least
hazardous of the chemicals on the list (approximately 187 out of 189).
Only two compounds had a lower composite risk score than MIBK, and both
of them were scored at 3. Thus, under the hazard ranking proposed by
EPA, MIBK was one of the least hazardous chemicals on the HAPs list.

EPA also proposed a system for setting [de]{.underline}
[minimis]{.underline} values for the various chemicals listed as HAPs.
The [de minimis]{.underline} value was the amount of a chemical that,
based on an EPA model, a typical facility could emit without posing more
than a "trivial" risk to human health or the environment. For compounds
such as MIBK that are non-carcinogens, the values were designed to
ensure that public health was protected with an "ample margin of
safety." [Id]{.underline}. at 15, 525. The proposed [de
minimis]{.underline} values ranged from 0.0000006 tons per year to 10
tons per year. For policy reasons unrelated to risk, EPA \"capped\" [de
minimis]{.underline} levels at 10 tons per year, but at the same time
recognized that, for several low toxicity chemicals, emissions of more
than 10 tons a year would still pose only a trivial risk.
[Id]{.underline}. at 15,527. Not surprisingly, the proposed [de
minimis]{.underline} level for MIBK was set at the 10 ton cap.

Significantly, however, EPA's methodology may be used to calculate the
true "uncapped" [de minimis]{.underline} value for MIBK. This approach
is still conservative for at least two reasons. First, as noted above,
EPA's approach for setting [de minimis]{.underline} values was
specifically designed to allow an "ample margin of safety." Second,
although the EPA model used to calculate the [de minimis]{.underline}
values was not a "worst-case" model, the Agency recognized that it
incorporated a number of conservative assumptions. [Id]{.underline}. at
15,526. Therefore, based on this methodology, the uncapped [de
minimis]{.underline} level for MIBK derived from an RFC of 2.4 mg/m^3^
would have been 5,000 tons per year. Based on the most recent TRI data,
the facility with the highest MIBK emissions in the country emits only
about 10 percent of this amount.

### Final SNAP Rule

Under Section 612 of the Clean Air Act, EPA has developed a program \--
called the Significant New Alternatives Policy (SNAP) program \-- to
identify acceptable substitutes for chemicals that are being phased out
of production because they deplete the stratospheric ozone layer. 59
Fed. Reg. 13,044 (March 18, 1994). Under the SNAP program, the Agency
specifically evaluated the toxicity of MIBK and listed it as an
acceptable substitute in a number of applications. In the final SNAP
rule, EPA discussed concerns about possible risks posed by petroleum
hydrocarbons and concluded that these risks were relatively small and
were adequately addressed by existing regulations and work practices.
The Agency then discussed the use of oxygenated hydrocarbons and stated
that \"two of the typical oxygenated hydrocarbons examined in the
Agency\'s risk screen, methyl ethyl ketone and methyl isobutyl ketone,
also have comparatively low toxicity.\" 59 Fed. Reg. at 13,120. Thus,
EPA has recognized that MIBK has relatively low toxicity and that, under
some circumstances, the use of MIBK as a substitute actually helps to
protect the environment.

## The Inclusion of MIBK on the Initial HAP List Was Not Based [on a Finding of Adverse Health or Environmental Effects]{.underline} 

The inclusion of MIBK on the initial HAP list was not based on a finding
of adverse health or environmental effects. The initial HAP list was
developed from the list of chemicals that are reportable under Section
313 of EPCRA. The Section 313 list was a compendium of the New Jersey
\"Environmental Hazardous Substance List\" and a Maryland \"Survey
List.\" These two lists were combined in Committee Print No. 99-169 of
the Senate Committee on Environment and Public Works, entitled "Toxic
Chemicals Subject to Section 313 of the Emergency Planning and Community
Right-to-Know Act of 1986." The combined list constitutes the initial
list of chemicals subject to the reporting requirements of Section 313.
[See]{.underline} EPCRA Section 313(c).

At the time EPCRA was enacted, MIBK was not on the New Jersey list. When
New Jersey enacted the Worker and Community Right-to-Know Act (codified
at N.J.A.C. § 7:1G-1, et seq.), it compiled a list of 250 chemicals for
careful review based on three criteria: whether the chemical (1)
presented a public health hazard; (2) was an environmental contaminant;
or (3) was present in the State in quantities of 10,000 pounds or more.
New Jersey then gathered information about the production, use and
effects of these 250 chemicals from a number of sources and evaluated
each chemical for inclusion on its list based on two criteria: (1)
evidence of significant production in New Jersey and (2) evidence of
health or environment effects such as carcinogenicity, teratogenicity,
mutagenicity, acute toxicity, persistence and ability to bioaccumulate.
[See]{.underline} New Jersey Department of Environmental Protection,
\"Worker and Community Right-to-Know Basis and Background Document.\"
Notably, New Jersey did not include MIBK in its final Hazardous
Substance list.

MIBK was included in the Maryland Survey List, but its inclusion did not
reflect a finding of adverse health or environmental effects. The
Maryland Survey List was informally developed, based on a variety of
federal and state lists, for purposes of information gathering by the
State regarding chemical usage in Maryland. The Survey List eventually
was used to survey Maryland businesses to determine the production and
use levels in the State of Maryland for each chemical.

Therefore, the inclusion of MIBK on the initial HAP list does not
reflect a determination by Congress, EPA, the states of New Jersey or
Maryland, or anyone else that MIBK meets the listing criteria. Moreover,
the circumstances surrounding the creation of the initial list do not
create any presumption against delisting.

**[CONCLUSION]{.underline}**

The Ketones Panel respectfully submits that MIBK meets the delisting
criteria set forth in Section 112(b)(3)(C) of the Clean Air Act.
Accordingly, the Administrator should grant this Petition and remove
MIBK from the list of chemicals that are regulated as hazardous air
pollutants under the Clean Air Act.

\| DC_DOCS\\18399.1 \[W97\]\|\|

[^1]: The members of the Ketones Panel are: Eastman Chemical Company,
    Exxon Chemical Company, Hoechst Celanese Chemical Group, Inc., Shell
    Chemical Company and Union Carbide Corporation.

[^2]: The Panel has also submitted a separate petition asking that MIBK
    be delisted under Section 313 of EPCRA.

[^3]: The Table of References is found in Appendix A. Duplicate copies
    of all references denoted with an asterix in Appendix A have been
    submitted with this Petition. These references are contained in
    Appendix G.

[^4]: A wide range of clinical tests was performed with each of the
    employees in the study, including an electrocardiogram, a chest
    x-ray, liver function tests, urinalysis, serum protein
    electrophoresis, clinical chemistry, and hematology tests. Except
    for an occasional high or low reading, the authors did not find any
    consistent changes in their battery of objective tests that
    suggested any systemic toxicity. A variety of subjective health
    complaints were noted, however, when the employees were given a
    health questionnaire. The type of questionnaire used in study and
    the method of administration were not given. Subjective health
    complaints included gastrointestinal functional disorders,
    dizziness, headaches, sensory irritation, and muscle weakness. These
    findings are highly suspect, however, since the authors failed to
    include any control group in their study. In addition, the authors
    noted that respiratory protection was mandatory in the work area, so
    it is uncertain to what extent the employees were actually exposed
    to MIBK. It is essential that any study relying on the use of a
    subjective symptom questionnaire also include a reference group for
    comparative purposes, because many subjective complaints of the type
    observed in this study also frequently appear in unexposed control
    populations. The absence of a control group, the failure to consider
    lifestyle risk factors, and the acknowledged co-exposure to other
    unmentioned industrial chemicals are all serious problems.
    Therefore, the results of this study should not be used in any
    hazard, exposure, or risk determination for MIBK.

[^5]: In reviewing the same study in 1988, EPA found a NOAEL of 50 ppm
    based on increased liver weights in rats and mice. EPA's reviewer
    stated, "No alterations in liver weights were noted from female rats
    or mice. Gross and histopathological examination revealed no
    treatment-related lesions in either species. Based on the elevations
    in urinary glucose and protein, the NOAEL for this study appears to
    be 50 ppm\..." Griffin (1988) at p. 7. However, evidence of liver
    and kidney enlargement in an animal study, without any evidence of
    pathological damage, does not demonstrate an adverse effect in the
    animals, and is of no use in a human health hazard evaluation.

[^6]: In 1988, the Agency concluded that "it seems most prudent to \...
    use 300 ppm as the probable LOAEL for developmental toxicity." EPA
    Memorandum from M. Campbell to E. Dage, Chemical Review and
    Evaluation Branch (November 1, 1988) at p. 2. The Agency, however,
    did not state why it disagreed with its previous determination to
    disregard the effects seen in rats only at 300 ppm. The Panel
    believes the Agency's interpretation in 1985 was correct. The
    questionable finding in the rat at 300 ppm, which did not arise in
    the rat at 1,000 ppm or in the mouse at either dose, clearly is not
    sufficient to establish that MIBK can reasonably be anticipated to
    cause serious or irreversible developmental toxicity in humans.

[^7]: Further, the possibility of adverse effects following intentional
    abuse of a solvent product does not indicate a hazard from
    reasonably anticipated environmental releases.

[^8]: A further explanation of how the Panel calculated the RfC for MIBK
    is presented in Appendix B.

[^9]: Four facilities provided the full set of facility-specific data
    needed for modeling and two facilities provided results of
    dispersion modeling of MIBK emissions that had already been
    conducted independent of the ENSR study. In addition, three
    facilities provided limited information that was supplemented with
    publicly available data from the AIRS database and Title V permit
    applications.

[^10]: For the two remaining facilities, ENSR estimated maximum annual
    off-site concentrations using the generic approach developed to
    evaluate ambient concentrations around smaller sources. This
    approach is described fully in the ENSR Report and is discussed in
    Section IV.C.2 below. Even using conservative assumptions, the
    maximum predicted annual off-site concentrations at these 2
    facilities were less than 0.75 mg/m^3^. ENSR Report at pp. 4-3
    (Table 4-2) and 5-1.