Document ID: EPA-HQ-OAR-2002-0064-0276
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-05-16T04:00Z

Responses to Public Comments on the Environmental Protection Agency
(EPA)’s 

June 2003 Proposed Regulation of

n-Propyl Bromide (nPB)

May 15, 2007 

Final Version

Table of Contents

  TOC \o "1-4" \h \z \u    HYPERLINK \l "_Toc53201259"  Section I
EPA’s  Proposed Acceptability Determinations for Uses of nPB	  PAGEREF
_Toc53201259 \h  1  

  HYPERLINK \l "_Toc53201260"  I.A General Comments Concerning EPA’s
Proposed Acceptability Determination for nPB in Several End Uses	 
PAGEREF _Toc53201260 \h  1  

  HYPERLINK \l "_Toc53201261"  I.B Solvent Cleaning	  PAGEREF
_Toc53201261 \h  2  

  HYPERLINK \l "_Toc53201262"  I.C Aerosol Solvents	  PAGEREF
_Toc53201262 \h  3  

  HYPERLINK \l "_Toc53201263"  I.D Adhesives	  PAGEREF _Toc53201263 \h 
4  

  HYPERLINK \l "_Toc53201264"  I.E Coatings	  PAGEREF _Toc53201264 \h  5
 

  HYPERLINK \l "_Toc53201265"  Section II Toxicity of nPB	  PAGEREF
_Toc53201265 \h  6  

  HYPERLINK \l "_Toc53201266"  II.A Derivation of the Acceptable
Exposure Limit (AEL) for nPB	  PAGEREF _Toc53201266 \h  6  

  HYPERLINK \l "_Toc53201267"  II.A.1 General Methodology	  PAGEREF
_Toc53201267 \h  6  

  HYPERLINK \l "_Toc53201268"  II.A.2 Selected Endpoint	  PAGEREF
_Toc53201268 \h  8  

  HYPERLINK \l "_Toc53201269"  II.A.2.a Sperm Motility in F0 and F1
Generation Male Rats	  PAGEREF _Toc53201269 \h  8  

  HYPERLINK \l "_Toc53201270"  II.A.2.b Neurotoxic Effects	  PAGEREF
_Toc53201270 \h  10  

  HYPERLINK \l "_Toc53201271"  II.A.2.c Other endpoints	  PAGEREF
_Toc53201271 \h  11  

  HYPERLINK \l "_Toc53201272"  II.A.3 Studies Considered	  PAGEREF
_Toc53201272 \h  12  

  HYPERLINK \l "_Toc53201273"  II.A.4 Benchmark Dose (BMD) Modeling and
Benchmark Dose Lowerbound (BMDL)	  PAGEREF _Toc53201273 \h  14  

  HYPERLINK \l "_Toc53201274"  II.A.5 Risk Management	  PAGEREF
_Toc53201274 \h  16  

  HYPERLINK \l "_Toc53201275"  II.A.6 Uncertainty Factors	  PAGEREF
_Toc53201275 \h  17  

  HYPERLINK \l "_Toc53201276"  II.A.6.a Animal to Human Extrapolation	 
PAGEREF _Toc53201276 \h  17  

  HYPERLINK \l "_Toc53201277"  II.A.6.b Intraspecies Variability	 
PAGEREF _Toc53201277 \h  19  

  HYPERLINK \l "_Toc53201278"  II.A.6.c Other Uncertainty Factors	 
PAGEREF _Toc53201278 \h  20  

  HYPERLINK \l "_Toc53201279"  II.B Appropriateness of Degree of
Protection/Stringency of Derived AEL for nPB	  PAGEREF _Toc53201279 \h 
22  

  HYPERLINK \l "_Toc53201280"  II.C Isopropyl Bromide	  PAGEREF
_Toc53201280 \h  24  

  HYPERLINK \l "_Toc53201281"  II.C.1 Contamination Limit Value	 
PAGEREF _Toc53201281 \h  24  

  HYPERLINK \l "_Toc53201282"  II.C.2 Appropriateness of Requiring a Use
Condition	  PAGEREF _Toc53201282 \h  25  

  HYPERLINK \l "_Toc53201283"  II.C.3 Recordkeeping Requirements	 
PAGEREF _Toc53201283 \h  26  

  HYPERLINK \l "_Toc53201284"  II.D Skin Notation	  PAGEREF _Toc53201284
\h  27  

  HYPERLINK \l "_Toc53201285"  II.E Reference Concentration	  PAGEREF
_Toc53201285 \h  28  

  HYPERLINK \l "_Toc53201286"  Section III Flammability of nPB	  PAGEREF
_Toc53201286 \h  29  

  HYPERLINK \l "_Toc53201287"  III.A Absence of nPB Flash Point	 
PAGEREF _Toc53201287 \h  29  

  HYPERLINK \l "_Toc53201288"  III.B Applicable Standards and
Regulations	  PAGEREF _Toc53201288 \h  30  

  HYPERLINK \l "_Toc53201289"  III.C European Union (Brandes) Adapted
Flammability Test 	  PAGEREF _Toc53201289 \h  32  

  HYPERLINK \l "_Toc53201292"  Section IV Legal Issues	  PAGEREF
_Toc53201292 \h  33  

  HYPERLINK \l "_Toc53201293"  IV.A Occupational Safety and Health
Administration (OSHA) Authority vs. EPA Authority to Set a Workplace
Exposure Limit	  PAGEREF _Toc53201293 \h  33  

  HYPERLINK \l "_Toc53201294"  IV.B Defining and Regulating Flammability
  PAGEREF _Toc53201294 \h  34  

  HYPERLINK \l "_Toc53201295"  IV.C Recommending vs. Requiring an AEL	 
PAGEREF _Toc53201295 \h  35  

  HYPERLINK \l "_Toc53201296"  IV.D Other Legal Issues	  PAGEREF
_Toc53201296 \h  36  

  HYPERLINK \l "_Toc53201297"  Section V Relative Toxicity	  PAGEREF
_Toc53201297 \h  37  

  HYPERLINK \l "_Toc53201298"  Section VI Ozone Depletion Potential	 
PAGEREF _Toc53201298 \h  38  

  HYPERLINK \l "_Toc53201299"  VI.A Latitude Considerations	  PAGEREF
_Toc53201299 \h  38  

  HYPERLINK \l "_Toc53201300"  VI.B EPA’s Stated Ozone Depletion
Potential (ODP) for nPB	  PAGEREF _Toc53201300 \h  39  

  HYPERLINK \l "_Toc53201301"  VI.C Comparison of nPB’s ODP to Other
Ozone Depleting Substances	  PAGEREF _Toc53201301 \h  40  

  HYPERLINK \l "_Toc53201302"  VI.D Ozone Depletion	  PAGEREF
_Toc53201302 \h  42  

  HYPERLINK \l "_Toc53201303"  Section VII Other Environmental Concerns	
 PAGEREF _Toc53201303 \h  43  

  HYPERLINK \l "_Toc53201304"  Section VIII Other Health Concerns	 
PAGEREF _Toc53201304 \h  46  

  HYPERLINK \l "_Toc53201305"  Section IX Market for nPB	  PAGEREF
_Toc53201305 \h  48  

  HYPERLINK \l "_Toc53201306"  Section X Other	  PAGEREF _Toc53201306 \h
 50  

 

Section I EPA’s Proposed Acceptability Determinations for Uses of
nPB

I.A General Comments Concerning EPA’s Proposed Acceptability
Determination for nPB in Several End Uses

Name of Commenter	Organization	Document ID No

Tami Weiss Cohen	DSBG	0038, 0053

James F. Stahl, Gregory M. Adams	LA County Sanitation District	0051,
0061

Adam Krantz	AMSA	0052

Kurt T. Werner	3M Performance Materials	0058

Steven H. Bernhardt	Honeywell	0059

Craig H. Farr	Atofina Chemicals	0060

Six sets of comments were received regarding general thoughts on EPA’s
proposed acceptability determination for nPB concerning more than one
end use.

	Comment Summary:  Some commenters supported EPA’s proposal to find
nPB acceptable, subject to use conditions, in solvent cleaning, aerosol
solvents, and adhesives.  Some commenters raised concerns about the
ability to use nPB safely in specific end uses, particularly aerosols
and adhesives, suggesting that nPB should be unacceptable or acceptable
with use conditions for ventilation equipment and personal protective
equipment.  Others supported finding nPB acceptable in solvents cleaning
or adhesives, but not in all end uses.  Some commenters suggested that
either EPA should not move to approve nPB at this time until further
study is completed or that nPB is not appropriate in any of the end uses
proposed.  

	Response:  See section V.A of the preamble concerning EPA’s
acceptability determination.I.B Solvent Cleaning

Name of Commenter	Organization	Document ID No

R.L. Smith	Albemarle Corporation	0024, 0067

Richard G. Morford	Enviro Tech International	0030

John R. Stemniski	N/A	0035, 0057

Tami Weiss Cohen	DSBG	0038, 0053

Kurt T. Werner	3M Performance Materials	0058

Steven H. Bernhardt	Honeywell	0059

Six sets of comments were received regarding EPA’s proposed
acceptability determination for solvent cleaning end uses of nPB.

	Comment Summary:  Two manufacturers of nPB-based solvents agreed with
EPA’s proposed acceptability determination for nPB in metal cleaning,
electronics cleaning, and precision cleaning sectors.  Based on
available exposure data, one commenter believes that exposures can be
controlled to protective levels in these end uses.  Other commenters,
including an independent consultant in the solvents industry and
companies that manufactures solvents that do not contain nPB expressed
concerns over the approval of nPB as acceptable for use in solvent
cleaning.  These commenters raised concern about the sufficiency of
toxicity data to address long-term effects, exposure levels in these end
uses and particularly exceedances of EPA’s recommended short term
exposure limit (STEL), and the data on ozone depletion potential (ODP).

Response:  See section V.A of the preamble concerning EPA’s
acceptability determination for solvent cleaning.  See section V.B.8 of
the preamble concerning the short-term exposure limit (STEL) and why EPA
believes that exceeding the STEL is not sufficient cause for finding nPB
unacceptable in solvent cleaning.  

I.C Aerosol Solvents

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0030

Tami Weiss Cohen	DSBG	0038, 0053

Jason Linnell	Electronic Industries Alliance	0043, 0044

Stephen P. Risotto	HSIA	0050

Barbara F. Kanegsberg	BFK Solutions	0034/0041

Kurt T. Werner	3M Performance Materials	0058

Six sets of comments were received regarding EPA’s proposed
acceptability determination for the aerosol solvent end use.

	Comment Summary:  A number of commenters submitted comments on EPA’s
proposed acceptability determination for the aerosol solvent end use.

	Response:  EPA is not addressing the aerosol solvent end use in this
final rule.  We will respond to any comments regarding this end use at
the time we take final action for aerosols.  The final rule associated
with this document only addresses the solvent cleaning sector –
metals, electronics and precision cleaning. 

I.D Adhesives

Name of Commenter	Organization	Document ID No

R.L. Smith	Albemarle Corporation	0024, 0067

Tami Weiss Cohen	DSBG	0038, 0053

Stephen P. Risotto	HSIA	0050

Michael J. Ruckriegel	Poly Systems USA	0054

Barbara F. Kanegsberg	BFK Solutions	0034/0041

Mark Collatz	The Adhesive and Sealant Council (ASC)	0056

Six sets of comments were received regarding EPA’s proposed
acceptability determination for the adhesive end use.

	Comment Summary:  A number of commenters submitted comments on EPA’s
proposed acceptability determination for the adhesive end use.

	Response:  EPA is not addressing the adhesives end use in this final
rule.  We will respond to any comments regarding this end use at the
time we take final action for adhesives.  The final rule associated with
this document only addresses the solvent cleaning sector – metals,
electronics and precision cleaning. 

I.E Coatings

Name of Commenter	Organization	Document ID No

T.J. Herman	Alliant Techsystems	0029

One comment was received regarding EPA’s  acceptability determination
for the coatings end use.

	Comment Summary:  A military contractor for small caliber ammunition
provided EPA with a Significant New Alternatives Policy (SNAP)Program
application, requesting consideration of nPB as a substitute in the
coatings end use of the adhesives, coatings, and inks industrial sector.

	Response:  EPA is not addressing the coatings end use in this final
rule.  We will address this submission in a separate action.Section II
Toxicity of nPB

II.A Derivation of the Acceptable Exposure Limit (AEL) for nPB

II.A.1 General Methodology 

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0047

Dan Guth	Boeing	0065

Stephen P. Risotto	HSIA	0050

Three sets of comments were received on the subject of EPA’s
methodology in deriving the AEL for nPB.

	Comment Summary:  One manufacturer of nPB-based solvents asserted that
the methodology EPA used to derive the AEL is vastly different than that
used by the Occupation Safety and Health Administration (OSHA).  He
stated that EPA was imposing a new standard in the review of nPB.

	Response:  See section V.B.1 of the preamble.

	Comment Summary:  A manufacturer of nPB-based solvents objected to
EPA’s proposed methodology, saying that it has not been subjected to
any kind of notice or comment/review process. 

	Response:  See section V.F of the preamble.  EPA gave notice and took
comment on the particular methodology used for its derivation of an
acceptable exposure limit (AEL) for nPB by describing it in the June 3,
2003 proposal [68 Federal Register (FR) 33292-33295] and taking comment.
 

	The EPA risk assessment guidelines used to develop the proposed AEL
went through public notice and comment and peer review (e.g., October
31, 1996, 61 FR 56274; December 5, 1991, 56 FR 63798). 

	Comment Summary:  A manufacturer of nPB-based solvents requested that
EPA consider the American Conference of Governmental Industrial
Hygienists (ACGIH) approach used to determine Threshold Limit Values
(TLVs). (Exhibit A, pp. 6-9, 0047). [p.5, 0047]

	Response:  EPA thinks it is most appropriate to use EPA’s reference
concentration (RfC) guidelines because the guidelines have undergone
notice and comment and peer review, they provide transparent procedures
that allow the public to understand EPA’s decisions, and they provide
consistency with the approach EPA has used for evaluating other
chemicals under the SNAP program.  In addition, EPA believes that our
approach to deriving an AEL based on EPA reference concentration (RfC)
guidelines is substantially the same as the ACGIH’s approach outlined
in the paper submitted by the commenter.

		Comment Summary:  A representative from a potential end-user of nPB
agreed with EPA’s AEL of 25 parts per million (ppm) and general
approach to the derivation, though he noted that it would have been
simpler to divide a NOAEL of 250 ppm by 10 to reach 25 ppm. [p.1. 0065]

	Response:  EPA agrees that using a NOAEL would have been simpler. 
However, consistent with EPA guidance, we performed benchmark dose
modeling.  This has advantages over using the NOAEL, such as providing
for greater accuracy by considering the slope of the dose-response curve
and not just the threshold value.  Further, based on available
information, the appropriate NOAEL for nPB would be 100 ppm, rather than
250ppm (ICF, 2002a; ICF, 2006a; CERHR, 2002a; CERHR, 2004a) II.A.2
Selected Endpoint

II.A.2.a Sperm Motility in F0 and F1 Generation Male Rats 

Name of Commenter	Organization	Document ID No

Mark E. Stelljes	SLR International	0023

Tami Weiss Cohen	DSBG	0038, 0053

Richard G. Morford	Enviro Tech International	0047

Stephen P. Risotto	HSIA	0050

Michael J. Ruckriegel	Poly Systems USA	0055

Craig H. Farr	Atofina Chemicals	0060

Six sets of comments were received on the topic of sperm motility in F0
and F1 generation male rat.

	Comment Summary:  Some commenters stated that data from the F1
generation is inappropriate for calculating occupational exposure,
citing statements from some toxicologists that use of effects on adult
F1 generation animals is inappropriate.  They also stated that EPA has
not required this for other chemicals and that the resulting value is
more conservative than what is normal and appropriate for industrial
toxicology.    Others stated that sperm motility effects on the F1
generation are appropriate to consider, particularly because of the
potential for in utero effects and because of the consistent presence of
these reproductive effects in both generations and at multiple levels. 
A contractor for the nPB industry agreed with EPA’s proposed endpoint,
commenting that his company based the development of an OEL on the same
endpoint.  

Response:  See section V.B.1. of the preamble. 

	Comment Summary:  One commenter claims that because EPA’s review of
nPB differed from EPA’s review of other SNAP alternatives by using the
F1 offspring generation from a 2 generation reproductive study, the
process violates equal protection.

Response:  See section V.B.1 of the preamble.  EPA disagrees that that
we used a different standard for review of nPB than that for other
chemicals.  With all chemicals, we consider the entire database of
toxicological data available.  A workplace exposure limit is derived to
provide a guideline that would protect workers from against all known or
likely adverse effects.  

EPA also believes it is reasonable to target tests for different
compounds based on the information found in the existing set of
toxicological studies.  There are a large number of possible
toxicological tests, and it would be prohibitively expensive to require
every submitter to conduct every possible test.  Further, such extensive
testing requirements might discourage the development of new
alternatives, which would be counter to the purpose of the SNAP
program—to find safer alternatives to ozone depleting substances. 
Rather than requiring each submitter to perform a large number of tests,
most of which would probably be irrelevant to setting an AEL, we believe
it is more sensible to require a few basic tests for acute and
subchronic toxicity and to perform targeted additional testing for
health effects shown to be of concern.

Other governments and organizations use this same approach in developing
workplace exposure guidelines.  For example, in one document submitted
by the commenter, the Japanese Society for Occupational Health expressly
says that ”the quantity and quality of information used in setting
OELs is not always the same” and “OELs cannot be used simply as a
relative scale of toxicity.” (IV-D-24/EPA-HQ-OAR-2002-0064-0046)  The
ACGIH, in its Statement of Position for using its threshold limit values
(TLVs) and Biological Exposure Indices (BEIs), states that “ACGIH TLVs
and BEIs are established by committees that review existing published
and peer-reviewed literature in various scientific disciplines (e.g.,
industrial hygiene, toxicology, occupational medicine and epidemiology).
 Based on the available information [emphasis added], ACGIH formulates a
conclusion on the level of exposure that the typical worker can
experience without adverse health effects.” 

II.A.2.b Neurotoxic Effects

Name of Commenter	Organization	Document ID No

Jason Linnell	Electronic Industries Alliance	0043

Kurt T. Werner	3M Performance Materials	0058

George M. Rusch	Honeywell	0059

George M. Rusch	Honeywell	0068

Four sets of comments were received concerning neurotoxic effects as the
endpoint in deriving the AEL for nPB.

	Comment Summary:  A number of commenters on the June 2003 Notice of
Proposed Rulemaking (NPRM) suggested that EPA should consider
neurotoxicity as the endpoint in deriving the AEL for nPB.  In
particular, they requested that EPA consider the study conducted by Wang
et al. (2003) and epidemiological data on neurotoxic effects of nPB.  

Response:  See section V. B.1. of the preamble.

II.A.2.c Other endpoints 

Name of Commenter	Organization	Document ID No

Craig H. Farr	Atofina Chemicals	0060

One set of comments was received concerning other endpoints in deriving
the AEL for nPB.

	Comment Summary:  One commenter who markets nPB as a chemical
intermediate stated that his company sponsored several studies to
determine whether the alkylating potential of nPB could cause
genotoxicity, but concluded that genotoxicity does not appear to be the
critical effect of nPB. [pp. 1-3, 0060]

Response:  EPA agrees. The available short-term genotoxicity data for
nPB do not support the need for significant concerns regarding the
potential carcinogenicity/genetic toxicity of nPB.

Unpublished studies of in vivo micronucleus formation (Elf Atochem,
1995) indicate that nPB is not clastogenic.

A published dominant lethal assay with nPB was negative (Saito-Suzuki
et al., 1982).

Tests on bacteria (Ames test) were positive for genetic effects on two
of five strains of bacteria in one set of tests but this was not
reproduced in other tests (Barber et al., 1981; Barber and Donish, 1982,
Elf Atochem, 1996, Elf Atochem, 1994). 

A cell death bioassay using cultured human liver cells found no positive
responses reported at any concentration for tests that evaluated enzyme
function, DNA damage, or DNA damage and repair when tested at
concentrations up to 500 ppm. (SLR International, 2001a)

The compound did not induce forward mutations in mammalian cells in
culture and has been shown not to cause statistically significant DNA
strand breaks in peripheral leukocytes of nPB sprayers and other exposed
workers at two different facilities (Toraason et al., 2006).

	These data lead EPA to conclude that it is unlikely that nPB is
carcinogenic and if nPB is carcinogenic, it would be a weak carcinogen
that does not provide significantly greater risk than other acceptable
cleaning solvents.

II.A.3 Studies Considered 

Name of Commenter	Organization	Document ID No

Richard G. Morford	EnviroTech International	0002

Richard G. Morford	Enviro Tech International	0047

Stephen P. Risotto	HSIA	0050

Tami Weiss Cohen	DSBG	0038, 0053

George M. Rusch	Honeywell	0059

Craig H. Farr	Atofina Chemicals	0060

Six sets of comments were received regarding studies considered for the
derivation of the AEL for nPB.

	Comment Summary:  One commenter stated that documents by Drs. Doull,
Rozman, Stelljes, Murray, and Rodricks, criticizing ICF Consulting’s
derivation of an occupational exposure limit for nPB and use of F1
generational endpoints for the derivation of an AEL, and a report by the
KS Crump Group were not acknowledged.  Another commenter requested that
EPA take into account the scientific presentations presented by Drs.
Doull, Rozman and Stelljes and mentions a review by Dr. Rodricks.

	

Response:  See section V.B.4 of the preamble.  Below are a few
additional responses to the documents mentioned by the commenters that
are not found in the preamble:

Doull and Rozman’s critique of ICF’s AEL derivation (A-2001-07,
II-D-41b)-- 

EPA disagrees with Rozman and Doull’s critique of ICF Consulting’s
AEL derivation on several counts.  First, ICF Consulting was aware of
Rozman and Doull’s AEL derivation when deriving their own, but found
it faulty.  Since an AEL is a derivation from data in experimental or
case studies, it would have been unnecessary and even inappropriate to
include an analysis of other AELs in ICF’s derivation.

Concerning analysis of liver effects,  it is irrelevant to our
determination of acceptable levels of exposure and to our acceptability
determination because it would result in a higher exposure limit than
from reproductive effects and would result in the same acceptability
determination.

We find that the Benchmark Dose Lowerbound (BMDL) only accounts for
uncertainty in the fitting of data points to the dose-response curve. 
It does not account for variability in the animals’ response or
variability in human response.

As discussed in the preamble to the proposed (68 FR 33298) and final
rules, EPA finds that Rozman and Doull’s conclusions about the
relative sensitivity of humans and rats to reproductive effects of nPB
are insufficiently supported and inappropriate.

We agree that minors are not allowed to be employed in the workplace. 
However, we disagree that this means there is no need to protect for
differences in sensitivity between individual workers.  Also, because an
unborn child or a breast-feeding child may be exposed to chemicals in
the workplace through their mother’s blood or milk, we disagree that
no children would be exposed.

	Comment Summary  A commenter on the June 2003 NPRM requested that EPA
evaluate a study by Yamada et al (2003), a study published just prior to
the June 2003 NPRM.  

	Response:  See section V.B.1 of the preamble.

	Comment Summary:  A representative for the chlorinated solvents
industry remarked that EPA had down-played the results of the
well-conducted studies published by Ichihara and co-workers. [p. 2,
0050]

	Response:  Focus centered on the WIL (2001) study because of the
following strengths described in the June 2003 NPRM: (1) it was
conducted in accord with Good Laboratory Practice procedures and
standard test guidelines over multiple generations; (2) it underwent an
independent audit; (3) it contained a sufficiently large sample size;
and (4) the raw data were provided for detailed statistical analyses.

In contrast, the Ichihara studies had a smaller sample size, the raw
data were not available for further analysis, and the specific
laboratory procedures were not clear.  Thus, EPA gives greater weight to
the data from the WIL, 2001 study.  However, the data from these studies
result in similar conclusions about the reproductive toxicity of nPB.

	Comment Summary:  One commenter who markets nPB as a chemical
intermediate stated that the critical study for hazard assessment is the
rat 2-generation reproduction study. [p. 1-3, 0060]

Response:  See section V.B of the preamble.  

II.A.4 Benchmark Dose (BMD) Modeling and Benchmark Dose Lowerbound
(BMDL) 

Name of Commenter	Organization	Document ID No

Mark E. Stelljes	SLR International	0023

Stephen P. Risotto	HSIA	0050

Two sets of comments were received concerning BMD modeling for the
derivation of the AEL for nPB. 

	Comment Summary:  A representative from a consulting firm for the nPB
industry stated that the results of BMD modeling conducted by both EPA
and the commenter’s company yielded essentially the same BMDL. [p.3,
0023]  A representative for the chlorinated solvent industry asserted
that EPA’s methodology used to develop the proposed AEL is not
consistent with traditional approaches for establishing exposure limits,
such as the use of  a no observed effect level (NOEL) instead of the
benchmark dose approach EPA proposed.  In particular, this commenter
stated that, if it is assumed that human responsiveness is the same as
that of the rat, humans exposed at the BMD/BMDL would be expected to
display a 10% response, which is unacceptable to the commenter, if not
modified by uncertainty or safety factors. This commenter also asserted
that additional uncertainty factors should be used with a BMDL instead
of a NOAEL because the BMDL depends on statistical and mathematical
factors, whereas biological factors (e.g., species differences in
pharmacokinetics and dynamics, human inter-individual variability)
require separate consideration. [pp.2-3, 0050]

	Response:  	EPA agrees that both our consultant, ICF Consulting (ICF,
2002)  and SLR International found similar results when doing BMD
modeling, and that these values are relevant to risk assessment.

	EPA disagrees that a BMDL would automatically result in being less
protective than a NOAEL or that additional uncertainty factors should be
required when developing an AEL using a BMDL.  The traditional approach
to the development of exposure limits using the No observed adverse
effect level (NOAEL) or the Lowest observed adverse effect level (LOAEL)
was erroneously believed by many to be a system that used an exposure
concentration that did not result in any observable adverse effect in
the animal model studied (NOAEL).  However, in an empirical comparison
between NOAEL values and BMD responses, it was found that the NOAEL
identified were, on average, a factor of three higher than a BMDL with a
10% response rate (BMDL10)(Allen et al., 1994).  Thus, even though the
NOAEL for nPB happens to be lower than the BMDL10 for nPB for a number
of reproductive health effects, one cannot conclude that the use of a
BMDL results in greater uncertainty that justifies an additional
uncertainty factor.

	We believe that the uncertainty factors that EPA has selected will be
sufficient to account for biological factors such as species differences
in pharmacokinetics and dynamics, and variability between individual
humans, as discussed in section V.B.3 of the preamble.

II.A.5 Risk Management

Name of Commenter	Organization	Document ID No

Anonymous	Unknown	0003

Jason Linnell	Electronic Industries Alliance	0043

Stephen P. Risotto	HSIA	0050

Kurt T. Werner	3M Performance Materials	0058

Four sets of comments were received regarding the proposed adjustment to
 the AEL on the basis of risk management principles.

	Comment Summary:  Commenters stated that: 1) the SNAP program does not
create a presumption in favor of substances that are already available
on the market, especially where other alternatives exist; 2) EPA’s AEL
derivation of 18 ppm is not conservative enough and further adjustment
upward further reduces protection; 3) the data do not support adjusting
the AEL upward; 4) EPA should first use the same methodology in
establishing an AEL as for other chemicals to ensure that the
program’s guiding principle in comparing risks is not compromised; and
5) EPA should reconsider whether industrial exposures consistently occur
or can be controlled at 25 ppm.  No commenters specifically supported
adjusting the AEL upward. 

	Response:  See section V.B.2 of the preamble. As noted in the preamble,
EPA is not finalizing a specific AEL in this rule.

II.A.6 Uncertainty Factors

II.A.6.a Animal to Human Extrapolation

Name of Commenter	Organization	Document ID No

Mark E. Stelljes	SLR International	0023

Tami Weiss Cohen	DSBG	0038, 0053

Stephen P. Risotto	HSIA	0050

Kurt T. Werner	3M Performance Materials	0058

George M. Rusch	Honeywell	0059

Five comments were received regarding the uncertainty factor used in
animal to human extrapolation when deriving the AEL for nPB.

	Comment Summary:  A representative from a consulting firm for the nPB
industry disagreed with EPA’s statement that his company should have
applied uncertainty factors consistent with EPA’s RfC guidelines
because his company was developing an occupational exposure guideline
rather than a reference concentration.  The commenter also disagreed
with EPA’s use of uncertainty factors in deriving an AEL. [pp.1-2,
0023]

Response:  See section V.B.3 of the preamble.

	EPA finds that RfC guidelines do not need to be restricted to deriving
reference concentrations (RfCs).  They include a number of guidelines
useful in any risk assessment of inhaled substances, whether for the
workplace or for the general population.  For example, the RfC
guidelines discuss:

principles of dose-response assessment for non-cancer effects, 

selection of studies,

adequacy of data,

designation of effect levels,

respiratory anatomy and physiology, 

criteria for assessing epidemiological data,

adjusting exposure periods in an animal study to a human equivalent, and

characteristics for which an uncertainty factor may be necessary.

As discussed in the preamble to the proposed rule, EPA modifies the
guidelines for the workplace by accounting for a different exposure
period in the workplace and by using a smaller uncertainty factor for
variability within the exposed population, to account for less
variability in the working population than in the general population.

We believe that by using uncertainty factors of 1 (SLR International,
2001b; Stelljes & Wood, 2004), the commenter has calculated an
occupation exposure limit that likely will not sufficiently protect
workers.  The SLR International report (2001b) stated that “For nPB,
in vitro data on human cells correlate well with the BMDLs developed
from the animals tested.”  However, since the cited data are
specifically for liver cells, we conclude that this applies only to
liver effects.  There is no biological reason to expect that similarity
in liver cells would correspond to similarity in sperm motility in
different species, and there is considerable evidence that humans are
less efficient at reproduction and less prolific than animals.  The
commenter provided no data that humans are less sensitive to
reproductive effects than animals.  Because rats are a different species
with a somewhat different reproductive system and because they are far
more prolific than humans, it is not credible to assume that the human
reproductive system will be affected less or similarly by nPB exposure
without data.  The intent of an occupational exposure limit is to
protect against potential adverse effects, and failing to account for
biological differences between animals tested and human beings could
result in an exposure limit that is too lax to protect humans.

	Comment Summary:  Some commenters on the June 2003 NPRM stated that EPA
should use an uncertainty factor of 1 or 2 to extrapolate from animals
to humans, while others suggested uncertainty factors of 2 or 3 for
pharmacokinetics, or an overall uncertainty factor of 10 for rat to
human extrapolation because of a lack of information on the metabolism
and mode of action of nPB and because the rat is an insensitive model
for effects on male reproduction in humans.

Response:  See section V.B.3 of the preamble.

	EPA believes that the reproductive success of the human male is
particularly sensitive to chemical insult (US EPA, 1996).  For example,
EPA cites in its Guidelines for Reproductive Toxicity Risk Assessment
(US EPA, 1996),"compared with many other species, human males produce
fewer sperm relative to the number of sperm required for fertility
(Amann, 1981; Working, 1988).  As a result, many men are subfertile or
infertile (Amann, 1981)."  Because decreases in sperm motility will
negatively impact the number of sperm available to reach an egg, they
will negatively impact reproductive success.  Data indicate a tremendous
amount of variability in sperm parameters in the human male (US EPA,
1996), including men who work in factories and plants.  Human beings’
ability to reproduce clearly is sensitive to exposure to other toxic
chemicals, including some brominated compounds (Kumar, 2004; CERHR,
2004b), so it is reasonable to expect that exposure to nPB could impact
human reproduction.  Further, because the margin of excess sperm (sperm
numbers higher than those deemed minimally necessary to achieve
reproduction) is lower in human males than in rodent males, it is
appropriate to assume that human males may be more sensitive to the
adverse reproductive effects of nPB.  

II.A.6.b Intraspecies Variability

Name of Commenter	Organization	Document ID No

Mark E. Stelljes	SLR International	0023

Richard G. Morford	Enviro Tech International	0047

Tami Weiss Cohen	DSBG	0038, 0053

Michael J. Ruckriegel	Poly Systems USA	0055

Kurt T. Werner	3M Performance Materials	0058

Five sets of comments were received regarding the uncertainty factor
used for intraspecies variability when deriving the AEL for nPB:

Comment Summary:  Some commenters said that an uncertainty factor of 1
is appropriate for variability within the working population because
sensitive subpopulations will not be present in the working population. 
Other commenters stated that there will be very little difference in
variability between the worker population and the general population and
that it is unclear why EPA selected an uncertainty factor of 3 instead
of 10.  Commenters suggested uncertainty factors for variability in the
working population of 1, 2, and 5.  

	Response:  See section V.B.3 of the preamble.

II.A.6.c Other Uncertainty Factors

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0047

Kurt T. Werner	3M Performance Materials	0058

Two sets of comments were received regarding concerns about other
uncertainty factors:

	Comment Summary:  A manufacturer of nPB-based solvents contested Dr.
Brock’s peer review of ICF Consulting’s AEL derivation, in which he
stated “exposure limits that have historically been established are
generally, but not always, an order of magnitude below the NOEL” as
support for an overall uncertainty factor of 10. Based on a report by
the K.S. Crump Group on how the ACGIH has established TLVs, this
commenter concluded that an uncertainty factor of 10 is not
“generally” used to derive occupational exposure limits. [pp.2-3,
0047]

	Response:  We note that Dr. Daryl Dodd, another external reviewer,
concluded that a total uncertainty factor of 10 is “reasonable”
(Dodd, 2002)  EPA’s Office of Research and Development reviewed the
uncertainty factors and concluded that total uncertainty factors of 10
are reasonable (US EPA, 2002; USEPA, 2006). As discussed in section
V.B.4 of the preamble, it appears that ACGIH has set its TLV using an
overall uncertainty factor of 10.  Thus, we believe that EPA’s
approach to assigning uncertainty factors is consistent with ACGIH’s
approach for nPB, and this is more relevant than the general approach
referred to in the Crump Group’s Report.  Another independent group
evaluating the toxicity of nPB, Toxicological Excellence for Risk
Assessment (TERA), assigned total uncertainty factors of 10 (TERA,
2004).  

	Comment Summary:  A manufacturer of non-nPB-based solvents noted that
EPA has not assigned an uncertainty factor to account for the fact that
the data set is not yet complete or that subchronic studies are being
used to address chronic exposures.  Thus, this commenter concluded that
EPA should recognize the possible severity of the effects and account
for the uncertainty associated with carcinogenicity and neurotoxicity
with an uncertainty factor of 2. [pp.2-3, 0058]

	Response:  EPA agrees that we have not assigned an additional
uncertainty factor to account for using data from subchronic studies to
address chronic exposures.  We believe this is appropriate because
workplace exposures are not as extensive as chronic exposure of up to 24
hours a day for 50 weeks per year for up to 70 years.  In EPA risk
assessments, workers typically are assumed to spend 30 to 40 years in a
lifetime in the workplace for 40 hours a week, 50 weeks a year (US EPA,
1997, p. 74).  This is roughly 10 to 13 percent of the hours in one’s
lifetime.  Ten percent of the hours of a typical rat’s lifetime would
be comparable to the length of the two-generation reproductive study. 
Therefore, the available tests already provide data for a portion of a
lifetime comparable to that of a worker.  Thus, EPA believes that the
testing to date is sufficient to set an AEL for the workplace.

	We note that the database of toxicity tests for nPB is more complete
than that for most chemicals reviewed under the SNAP program.  Thus, we
do not believe an additional uncertainty factor for an incomplete data
set is necessary.

As discussed above, the data on mutagenicity, such as the equivocal
results of the Ames test and the results of testing for damage on human
cells, do not show a great likelihood that nPB is strongly carcinogenic.
 Further, cancer effects are typically not considered to have a
threshold, while in contrast, an AEL is set based on the assumption of a
threshold below which effects are not seen.  We think that a more
appropriate way to address carcinogenicity would be to inform the public
of the results of the current long term testing that is under way for
the National Toxicology Program.  It is unlikely that the results of
this testing would show a significant increase in risk that would result
in a different decision on the acceptability of nPB.  Depending on the
results of testing for cancer, it might be possible to determine a
cancer slope factor as a measure of risk. 

As discussed above, we do not think that neurotoxicity is a more
sensitive endpoint than reproductive toxicity.  Therefore, the AEL
derived based on reproductive toxicity would be protective also for
neurotoxic effects, and no further uncertainty factor would be
necessary.



II.B Appropriateness of Degree of Protection/Stringency of Derived AEL
for nPB

Name of Commenter	Organization	Document ID No

Anonymous	Unknown	0003

Mark E. Stelljes	SLR International	0023

R.L. Smith	Albemarle Corporation	0024, 0067

John R. Stemniski	N/A	0035, 0057

Tami Weiss Cohen	DSBG	0038, 0053

Anonymous	CA HESIS	0039

Barbara Kanegsberg	BFK Solution, LLC	0034/0041

Jason Linnell	Electronic Industries Alliance 	0043

Richard G. Morford	Enviro Tech International	0047

Stephen P. Risotto	HSIA	0050

Michael J. Ruckriegel	Poly Systems USA	0054

Michael J. Ruckriegel	Poly Systems USA	0055

Kurt T. Werner	3M Performance Materials	0058

Steven H. Bernhardt and George M. Rusch	Honeywell	0059

Craig H. Farr	Atofina Chemicals	0060

Dan Guth	Boeing	0065

Sixteen sets of comments were received regarding the degree of
protection or stringency of the AEL. 

Comment Summary:  Some commenters supported the proposed AEL of 25 ppm,
stating that it was derived using appropriate conservative and cautious
scientific processes.  Other commenters said that the proposed AEL of 25
ppm was too high, citing uncertainties in the data, the
inappropriateness of adjusting the AEL upward from 18 ppm, reports of
health effects on humans, and a need for higher uncertainty factors. 
Other commenters said that the proposed AEL of 25 ppm was too low,
citing higher AELs derived by Drs. Stelljes, Doull, Rozman, and
Rodricks, National Institute for Occupational Safety and Health (NIOSH)
studies, and a need for lower uncertainty factors.  Commenters suggested
alternate AEL values ranging from 1 ppm to 156 ppm.

	Response:  See section V.B.5 of the preamble.

	Comment Summary:  At an EPA stakeholders meeting, representatives from
a potential end user of nPB expressed concern that other offices of EPA
or OSHA might come out with a different and perhaps stricter AEL. [p.1,
0065]

	Response:  EPA’s Office of Air and Radiation consulted with other
offices of EPA, and this rule reflects the Agency’s current position. 
As with any decision made by the Agency, we may adjust our conclusions
based on additional analyses or new information.  If OSHA develops a
final standard, EPA would defer to their standard.

II.C Isopropyl Bromide

II.C.1 Contamination Limit Value

Name of Commenter	Organization	Document ID No

R.L. Smith	Albemarle Corporation	0024

Tami Weiss Cohen	DSBG	0038, 0053

Richard G. Morford	Enviro Tech International	0042

Three sets of comments were received concerning the contamination limit
value: 

	Comment Summary:  Two commenters from companies that manufacture nPB,
agreed with EPA that 0.05% isopropyl bromide (iPB) is an appropriate and
achievable limit. One manufacturer noted that industry test studies
showed that lower limits were neither toxicologically justified nor
economical. [p.2, 0024; p.1, 0038, 0053]  A manufacturer of nPB-based
solvents stated that EPA should defer to the 1 ppm limit on iPB set by
the government of Korea and the Japan Society for Occupational Health
(JSOH) and that EPA’s proposed regulation does not add any value to
existing standards. [pp. 3-5, 0042]

	Response: See section V. B. 6 of the preamble.

II.C.2 Appropriateness of Requiring a Use Condition

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0042

One set of comments was received regarding the appropriateness of the
proposed use condition that would require that iPB contamination in nPB
formulations be no greater than 0.05% by weight.

	Comment Summary:  A manufacturer of nPB-based solvents opposed the
implementation of the proposed use restriction on iPB contamination,
stating that it places an undue legal burden on end users, rather than
the manufacturers of raw materials, and would not benefit worker safety.
 

	Response: See section V. B. 6 of the preamble.

	Comment Summary:   A manufacturer of nPB-based solvents stated that
this is the only instance that SNAP has regulated residual contaminants,
and thus, this action would violate equal protection unless EPA intends
to adopt the same approach to other reviews.  [pp.1-2, p.4, 0042]

	Response:  EPA is not establishing a use condition in the final rule.

II.C.3 Recordkeeping Requirements

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0042

One set of comments was received concerning recordkeeping requirements
for iPB content: 

	Comment Summary:  A manufacturer of nPB-based solvents asserted that
keeping records such as those proposed by EPA is already customary
industry practice and, therefore, the proposal adds no benefit.  The
commenter suggested that it be the manufacturers of nPB that are
required to make the requested data available to EPA, customers, and end
users, since they have absolute control over iPB content, not the end
users. [pp.5-6, 0042]

	Response:  EPA is not establishing a use condition in the final rule.

II.D Skin Notation

Name of Commenter	Organization	Document ID No

R.L. Smith	Albemarle Corporation	0024

Tami Weiss Cohen	DSBG	0038, 0053

Anonymous	CA HESIS	0039

Kurt T. Werner	3M Performance Materials	0058

Four sets of comments were received concerning the listing of nPB as
acceptable with a skin notation. 

	Comment Summary:  Several commenters on the June 2003 proposal stated
that a skin notation for nPB is appropriate, while another commenter
agreed with EPA’s proposal that no skin notation is necessary (0024;
0039; 0058, 0038).  One commenter said that EPA should require
manufacturers, distributors, and marketers of nPB-containing products to
communicate such information on the Material Safety Data Sheets (MSDS)
and the product label.

	Response:  See section V. B. 6 of the preamble

II.E Reference Concentration

Name of Commenter	Organization	Document ID No

R.L. Smith	Albemarle Corporation	0024

Stephen P. Risotto	HSIA	0050

Washington State Department of Ecology	WDOE	0064

David Moore	Boeing Company	0065

Four sets of comments were received regarding the reference
concentration of nPB.

	Comment Summary:  Commenters noted that EPA followed standard Agency
practices for the derivation of reference concentration (RfC) values and
found that nPB exposure levels from use in adhesive applications fell
below a protective reference concentration.  At an EPA stakeholders
meeting, representatives from a state environmental agency asked if EPA
had derived a reference dose or a slope factor.  the commenter suggested
that it would be useful for EPA to formally develop an RfC by going
through the National Center for Environmental Assessment and putting it
in EPA’s Integrated Risk Information System (IRIS).  A representative
for potential end user of nPB asked if EPA planned to issue an official
RfC.

	Response:  We agree that we developed an RfC in accordance with
standard Agency practices for the derivation of RfC values to develop a
community exposure guideline.  Developing an official RfC to place into
IRIS is a complex process, is not necessary for making our determination
on the acceptability of nPB, and is beyond the scope of this rulemaking.

.  

	We did not determine a reference dose for ingestion, since we believe
that this is a far less common and less significant pathway for exposure
to nPB than inhalation.  We did not determine a slope factor for
carcinogenic effects, since there is not sufficient data available on
carcinogenic effects to warrant a slope factor or to derive one.  

	EPA is not taking final action on the adhesives end use in this final
rule.  EPA will address comments regarding adhesives in any future
action we take on this end use.

Section III Flammability of nPB

III.A Absence of nPB Flash Point

Name of Commenter	Organization	Document ID No

Ronald L. Shubkin, Richard DeGroot, Dov Shellef	Poly Systems USA	0025

Richard G. Morford	Enviro Tech International	0030, 0036

Barbara Kanegsberg	BFK Solution, LLC	0034

Tami Weiss Cohen	DSBG	0038, 0053

Joseph H. Miller	Albemarle Corporation	0040

Five sets of comments were received stating that data show that nPB does
not have a flashpoint.

	Comment Summary:  Several manufacturers of nPB and nPB-based solvents
and an independent contractor stated that nPB has no flash point under a
number of accepted consensus standards for flash point.  In support of
these statements, the manufacturers of nPB and nPB-based solvents
provided flash point test data from a number of different test methods
(American Society for Testing and Materials [ASTM] D 92 open cup, ASTM
D56 Tag closed cup, and ASTM D93 Pensky-Martens closed cup).

	Response:  See section V.E of the preamble.

III.B Applicable Standards and Regulations

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0002

Ronald L. Shubkin, Richard DeGroot, Dov Shellef	Poly Systems USA	0025

Ronald L. Shubkin, Richard DeGroot, Dov Shellef	Poly Systems USA	0026

Richard G. Morford	Enviro Tech International	0030

Barbara Kanegsberg	BFK Solution, LLC	0034

Tami Weiss Cohen	DSBG	0038, 0053

Six sets of comments were received concerning the applicable standards
and regulations for flammability of nPB. 

	Comment Summary:  Representatives of manufacturers of nPB-based
solvents and an independent contractor stated that EPA should find nPB
non-flammable based on appropriate standards and regulations such as
those issued by the US Department of Transportation (DOT) and OSHA,
National Fire Protection Association (NFPA) 704, NFPA 30, the Hazard
Materials Identification System, American National Standards Institute
(ANSI)/Chemical Manufacturers Association (CMA) A129.1-1994, the United
Nations (Recommendations on the Transport of Dangerous Goods), the
International Maritime Organization, Canada (Transportation of Dangerous
Goods Regulations), the European Union (Road Transportation
Regulations), the International Air Tranport Association (IATA), and
ASTM.  The commenters said that, according to these standards or
definitions, nPB would be classified as nonflammable. 

A manufacturer of nPB-based solvents remarked that flammability limits
are not determinative of flammability and that EPA has categorized as
nonflammable other SNAP-approved compounds that exhibit upper and lower
flammability limits. 

Response: See section V.E of the preamble.

 

III.C European Union (Brandes) Adapted Flammability Test

Name of Commenter	Organization	Document ID No

Ronald L. Shubkin, Richard DeGroot, Dov Shellef	Poly Systems USA	0025

Richard G. Morford	Enviro Tech International	0030, 0031 (Exhibits)

Two sets of comments were received regarding the flashpoint tests
performed by Dr. Elisabeth Brandes of the German National Flammables
Laboratory: 

	Comment Summary:  Representatives of manufacturers of nPB-based
solvents said that EPA should not rely upon tests performed by Dr.
Brandes using the ISO 1523 standard with a Pensky-Martens apparatus
(closed cup), as described in ISO 2719 (1998). 

Response:  See section V. E of the preamble.  EPA has not seen data from
Dr. Brandes’ test method and did not consider it in preparing either
the June 3, 2003 proposal or the final rule.  Data from standard flash
point testing, such as ASTM D 92 open cup, ASTM D56   SEQ CHAPTER \h \r
1 Tag closed cup, and ASTM D93   SEQ CHAPTER \h \r 1 Pensky-Martens
closed cup, is available, and we have used those data in our
determination. 

Section IV Legal Issues

IV.A Occupational Safety and Health Administration (OSHA) Authority vs.
EPA Authority to Set a Workplace Exposure Limit

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0002

Mark E. Stelljes	SLR International	0023

Richard G. Morford	Enviro Tech International	0049

Three sets of comments were received concerning EPA’s authority to
recommend a workplace exposure limit.

	Comment Summary:  Two commenters stated that EPA has no jurisdiction to
develop any AEL designed to be applicable to a workplace environment,
and that this right belongs to OSHA.

	One commenter stated that EPA’s authority is section 615 of the Act,
that the Agency only has authority to consider public health risks, and
that EPA does not have authority to evaluate worker health risks.  

	Response:  See section V.F. of the preamble.



IV.B Defining and Regulating Flammability

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0030

One set of comments was received regarding EPA’s authority to define
and regulate flammability: 

	Comment Summary:  A manufacturer of nPB-based solvents stated that nPB
should not be restricted under SNAP on the basis of flammability
concerns because EPA has no authority under the Clean Air Act to
consider restrictions on chemical compounds due to flammability.

	Response:  Flammability is one of the factors that EPA considers in
determining whether a potential substitute may be used safely when
compared with other available or potentially available substitutes.  A
flammable substance can potentially cause risk to workers and to end
users and thus any consideration of the “overall risk to human
health” must consider this factor. Thus, we disagree with the
commenter that we cannot restrict the use of a substitute based on its
flammability.  However, we note that in today’s final rule, the use of
nPB in solvent cleaning is not so restricted.

IV.C Recommending vs. Requiring an AEL

Name of Commenter	Organization	Document ID No

Jason Linnell	Electronic Industries Alliance	0043

Stephen P. Risotto	HSIA	0050

James F. Stahl, Gregory M. Adams	LA County Sanitation District	0051,
0061

Adam Krantz	AMSA	0052

Four sets of comments were received on the topic of recommending vs.
requiring an AEL for nPB.

	Comment Summary:  A commenter stated that even if ventilation or other
measures could reduce exposures to below 25 ppm, there is nothing to
ensure that companies will take such measures.  This commenter also
stated that he is aware of nPB formulators that have already announced
they will not adhere to this voluntary standard.  Three commenters, all
representing local environmental regulators, stated that a
recommendation that worker exposure be limited to 25 ppm will not carry
the enforcement powers of an OSHA standard, and that this lack of
control will encourage the use of nPB in applications beyond those
envisioned by EPA.  Another commenter asserted that the proposed
exposure limits (both the AEL and the STEL) should be established as use
conditions, citing Section 612 as the basis for EPA’s authority to do
so.  This commenter stated that a precedent has already been set for EPA
to accept an alternative chemical subject to use conditions—including
that observance of workplace concentration limits—in the adhesives,
aerosols, and solvent cleaning sectors (e.g., hydrochlorofluorocarbon
(HCFC)-225 ca/cb, hydrofluorocarbon (HFC)-4310mee, monochlorotoluenes,
benzotrifluorides; 40 Code of Federal Regulations (CFR) part 82, subpart
G, appendices A, B, and D).

	Response:  See section V.F. of the preamble.

IV.D Other Legal Issues

Name of Commenter	Organization	Document ID No

Richard G. Morford	Enviro Tech International	0002

Jason Linnell	Electronic Industries Alliance	0043

Richard G. Morford	Enviro Tech International	0030

Richard G. Morford	Enviro Tech International	0042

Four sets of comments were received regarding other legal issues with
respect to nPB:

	Comment Summary:  A manufacturer of nPB-based solvents stated that EPA
has no authority to act unless Congress confers such power upon it.
[p.3, 0002]

	Response:  See section V.F. of the preamble. EPA has authority to
regulate use of nPB under section 612 of the Clean Air Act.

	Comment Summary:  A representative for a national trade association for
the electronics industry asserted that both the Clean Air Act and
EPA’s own rules require that EPA analyze the comparative health risks
of substitutes in the work place. [p.2, 0043] 

	Response:  EPA has analyzed the comparative health risks of substitutes
in the work place, as well as other health and environmental risks. 
These are discussed in the preamble of the June 2003 NPRM at 68 FR
33304.  However, a substance used below its acceptable exposure limit
should have minimal risk, and would not pose more risk than other
substitutes used consistent with their AELs.

	Comment Summary:  A manufacturer of nPB-based solvents stated that, by
citing Dr. Brandes’ study, EPA published unsupported and inaccurate
scientific information, in violation of the Data Quality Act. [pp.
12-14, 0030] 

	Response:  The commenter is mistaken that EPA has relied on Dr.
Brandes’s study.  EPA has not seen data from Dr. Brandes’s study and
has not cited it or relied upon it.  EPA cited a UNEP study that was
published in 1999 and prepared even earlier, while Dr. Brandes’s study
was published in 2002.  As to the UNEP study, we recognized in our
proposal that the data cited were not conclusive and requested further
data from the public.  We did this precisely because we were not relying
on those data

	Comment Summary:  A manufacturer of nPB-based solvents believes that
EPA is obligated under law pursuant to the National Technology Transfer
and Advancement Act (NTTAA) to use ASTM-D6368-00 as the basis for any
regulation regarding iPB levels. [pp.3-5, 0042]

	Response:  EPA is not establishing a limit on iPB in the final rule.

Section V Relative Toxicity

Name of Commenter	Organization	Document ID No

Kurt T. Werner	3M Performance Materials	0058

One comment was received discussing the toxicity of nPB relative to
other solvents:

Comment Summary:  A manufacturer of solvents that do not contain nPB
said that EPA’s approval of nPB would be more harmful than the
continued use of chlorinated solvents in the adhesive sector because of
nPB’s inherent toxicological properties and the fact that it will be
managed less through other regulations than other approved substitutes.
[p.4, 0058]

	Response:  EPA is not addressing the adhesives end use in this final
rule.  We will respond to any comments regarding this end use at the
time we take final action for adhesives.  The final rule associated with
this document only addresses the solvent cleaning sector – metals,
electronics and precision cleaning. 

Section VI Ozone Depletion Potential

VI.A Latitude Considerations

Name of Commenter	Organization	Document ID No

Robert G. Morford	EnviroTech International	0002

John R. Stemniski	N/A	0035, 0057

Jason Linnell	Electronic Industries Alliance	0043

Three sets of comments were received regarding the effects of latitude
on the ozone depleting potential (ODP) of nPB: 

	Comment Summary:  A commenter representing a manufacturer of nPB-based
solvents stated that further work has been done on the MOZART 3D model,
and it is expected that analyses using this revised model will result in
lower ODP values for nPB at all latitudes, including equatorial regions.

	Response:  EPA recognizes that Dr. Donald Wuebbles, the atmospheric
scientist performing the calculations, has stated that the ODP of nPB
may be lower based on further revisions to the MOZART 3D model. 
However, since we have concluded in this rulemaking that the ODP is not
sufficiently high enough to be a basis for finding nPB unacceptable,
further studies concluding the ODP is lower than we currently believe,
would not affect our acceptability determination.

	Comment Summary:  A commenter noted that, according to Dr. Donald
Wuebbles, even if the entire amount of nPB produced in 2002 was emitted
across North American, European and Asian latitudes, the resulting
effects on ozone depletion would be too small to measure. Also according
to Dr. Wuebbles, this commenter noted that the effects on ozone would
only be larger if all emissions were to occur in the equatorial region.
[pp. 2-3, 0002]

	Response:  See section V.C. of the preamble.

	

	 Comment Summary:  Comments on the June 2003 NPRM expressed concern
that other countries, particularly those in equatorial regions, might
assume that nPB does not pose a danger to the stratospheric ozone layer
if the U.S. EPA’s SNAP program finds nPB acceptable.

Response:  See section V.C. of the preamble.  

VI.B EPA’s Stated ODP for nPB

Name of Commenter	Organization	Document ID No

Robert G. Morford	EnviroTech International	0002

John R. Stemniski	N/A	0035, 0057

Jason Linnell	Electronic Industries Alliance	0043

Three sets of comments were received concerning EPA’s statement of the
ODP of nPB: 

	Comment Summary:  A representative of a manufacturer of nPB-based
solvents stated that since the MOZART 3D model used to compute the ODP
for nPB was incomplete at the time of testing, EPA’s stated ODPs are
likely too large. [p.2, 0002]  An independent contractor in the solvents
industry stated that the chemical nature of nPB does not lend itself to
an accurate ODP determination, and noted that, even if the ODP is
determined to be low, the high volume of nPB released will still cause
high levels of ozone depletion. [p.1, 0035, 0057]  A representative of
the electronics industry suggested that the uncertainties regarding
nPB’s ODP merit further consideration and that EPA should find nPB an
unacceptable alternative for aerosol solvent uses under the SNAP program
because of impacts on the ozone layer. [pp. 10-11, 0043]

	Response:  See section V.C. of the preamble.  According to the
information available to EPA, the total amount of nPB being used in 2000
was not sufficient to have a significant impact on the ozone layer
(Wuebbles et al., 2000; Wuebbles, 2002).  Although it is possible, and
even likely, that the amount of nPB emissions will increase, EPA
believes it is unlikely that they will increase to more than 30 million
pounds per year, because producers of HCFC-141b, a solvent with slightly
lower cost and similar solvency to nPB, never sold more than 36 million
pounds per year as a solvent, even at the height of its usage (AFEAS,
2006).  

EPA is not addressing the aerosol solvent end use in this final rule. 
We will respond to any comments regarding this end use at the time we
take final action for aerosols.  The final rule associated with this
document only addresses the solvent cleaning sector – metals,
electronics and precision cleaning. 

VI.C Comparison of nPB’s ODP to Other Ozone Depleting Substances

Name of Commenter	Organization	Document ID No

R.L. Smith	Albemarle Corporation	0024

Jason Linnell	Electronic Industries Alliance	0043

Two sets of comments were received concerning EPA’s statement of the
ODP of nPB. 

	Comment Summary:  A representative from a company that manufactures and
markets nPB as a solvent stated that an atmospheric modeling evaluation
found that the atmospheric effects of nPB are more favorable than the
continued use of methyl chloroform. [p.2, 0024]

	Response:  EPA agrees that the atmospheric effects of nPB are less than
would occur with the continued use of methyl chloroform when nPB is used
at the latitude of the continental U.S.  

Comment Summary: A commenter from a national trade association
representing the electronics industry remarked that nPB is similar to
chlorobromomethane (CBM) in that both chemicals have ODP values over 0.1
in tropical regions, yet EPA banned CBM on the basis that it was being
aggressively marketed as an alternative to ozone-depleting substances
(ODS) and that a significant future global market may develop in the
absence of regulation.  This rationale, the commenter wrote, parallels
UNEP’s finding that nPB is being “aggressively marketed” and, in
the absence of regulatory approval, significant markets may develop.
[p.10, 0043]

	Response:  See section V.C. of the preamble.  

	EPA believes that our decision on the use of nPB under the SNAP program
is not comparable to our decision on the production and import of
chlorobromomethane.  The latter decision was required by the Parties to
the Montreal Protocol under the Beijing Amendments to the Protocol.  The
Parties decided it was not sufficient to control the use of CBM under
the SNAP program because “these restrictions do not control CBM use
outside of the United States.”  (67 FR 65920)  In the case of the
EPA’s decision to find CBM unacceptable as a cleaning solvent, a
aerosol solvent, a carrier solvent in adhesives, coatings and inks, and
a fire suppressant (April 28, 1999, 64 FR 22982), EPA found the ODP of
CBM to be in the range of 0.07 to 0.15.  In our decision on the use of
CBM, we stated that, “Numerous other alternatives exist with either
zero or much lower ODP that do not pose a comparable risk.”  In the
latitude of the United States, nPB’s ODP is almost an order of
magnitude lower than that of CBM.  Thus, we find that the risk to the
ozone layer of using nPB in the areas where the regulation is effective
is far less than the risk of using CBM.  For these reasons, it is
appropriate to have a different acceptability decision for nPB than for
CBM.

	The issue of nPB use in the global marketplace is an issue that is
better addressed in an international forum, such as the Montreal
Protocol discussions.  To the extent the ODP of nPB in areas outside the
United States raises concern, we anticipate the parties to the Montreal
Protocol would make a decision similar to that made for
chlorobromomethane.

VI.D Ozone Depletion and Substitutes

Name of Commenter	Organization	Document ID No

P. Hopkinson	N/A	0004

Anonymous	N/A	0032

Anonymous	N/A	0033

Three sets of general comments were received concerning protection of
the ozone layer and use of alternatives to ozone-depleting chemicals.

	Comment Summary:  A commenter (whose affiliation was not stated)
believes that alternatives to ozone depleting chemicals can be found,
and urged EPA to limit harmful chemicals into our atmosphere. [p.1,
0004]  Another commenter (whose affiliation was not stated) voiced
support for any regulations that helps to protect stratospheric ozone.
[p.1, 0032]  A third commenter (whose affiliation was not stated) stated
that nPB is dangerous to the ozone layer and workers and urged EPA to
find a safe substitute. [p.1, 0033]

	Response:  EPA agrees that alternatives to ozone depleting chemicals
can be found.  The SNAP program has already listed numerous acceptable
alternatives to ozone-depleting substances.  Because of numerous efforts
by industry to transition to alternatives to ozone-depleting substances
that are no longer being produced, the World Meteorological Organization
predicts that the ozone layer should recover in the middle of this
century.

EPA believes that nPB is not excessively dangerous to the ozone layer
when it is used at the latitude of the U.S.  Further, when used
consistent with typical practices in the solvent cleaning industry,
worker safety will not be compromised.

Section VII Other Environmental Concerns

Name of Commenter	Organization	Document ID No

John R. Stemniski	N/A	0035, 0057

James F. Stahl, Gregory M. Adams	LA County Sanitation District	0051,
0061

Adam Krantz	AMSA	0052

Joe Miller, Mick Kassem	Albemarle Corporation	0064

Washington State Department of Ecology	WDOE	0064

Five sets of comments were received regarding other environmental
concerns about nPB.

	Comment Summary:  Commenters stated that, until the safety of nPB has
been demonstrated conclusively, more stringent controls are necessary to
protect the public and the environment.  In particular, these commenters
said that the potential for cross-media impacts was not given adequate
consideration in the proposed rule.  They also stated that EPA did not
address the potential for nPB to bioaccumulate in the environment or its
impact on sensitive species. One commenter said that he thought it was
appropriate to ensure that nPB be kept out of wastewater, and an
independent contractor also mentioned concerns about water pollution. 
Another commenter said that nPB hydrolyzes more quickly than the
chlorinated solvents, and so would have less impact on water quality.  

	Response:  See section V. D. of the preamble.

	Based on EPA’s PBT Profiler tool, the ODS that nPB will substitute
for, methyl chloroform, chlorofluorocarbon (CFC)-113, and HCFC-141b all
should have greater persistence and bioaccumulation than nPB (PBT
Profiler, 2007).  nPB is predicted to be less persistent and to have
less tendency to bioaccumulate compared to several other ODS
substitutes, including HCFC-225ca, HCFC-225cb,
parachlorobenzotrifluoride, perchloroethylene, and trichloroethylene
(PBT Profiler, 2007).  Based on this screening and the information found
in sections IV.C. and V.D of the preamble, we believe it is unlikely
that nPB would create a greater bioaccumulation hazard than the ODS it
replaces or other available alternatives.

We also considered whether nPB is significantly more toxic to fish than
other available ODS substitutes.  The lethal concentration of nPB for
50% (LC50) of fathead minnows over a 96-hour period is 67,300 micrograms
per liter.  For comparison, here are LC50 values for a number of other
solvents found acceptable under the SNAP program:



Solvent	Methylene chloride	Trichloro-ethylene	Acetone	n-Hexane
d-Limonene	Isopropyl alcohol

LC50-96 hour for fathead minnows (microgram/l)	140,800	31,400	5,490,000
2100	619	6,550,000

Source of data	1	1	2	3	3	2

 1: Toxicity of Perchloroethylene, Trichloroethylene,
1,1,1-Trichloroethane, and Methylene Chloride to Fathead Minnows;
Alexander, H.C., W.M. McCarty, and E.A. Bartlett, 1978;
Bull.Environ.Contam.Toxicol. 20(3):344-352

2: Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales
promelas), Vol 1; Brooke, L.T., D.J. Call, D.L. Geiger, and C.E.
Northcott, 1984; Center for Lake Superior Environmental Stud., Univ.of
Wisconsin-Superior, Superior, WI I:414

3: Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales
promelas), Vol. 5; Geiger, D.L., L.T. Brooke, and D.J. Call, 1990;
Center for Lake Superior Environmental Stud., Univ.of
Wisconsin-Superior, Superior, WI I:332

Further, nPB had the highest toxicity threshold for fish of the
chemicals examined in the PBT profiler analysis described above, showing
less toxicity (PBT Profiler, 2007).  Thus, it appears that nPB is less
toxic to aquatic life than some compounds acceptable under the SNAP
program, such as trichloroethylene, n-hexane, d-limonene, HCFC-225ca/cb,
and parachlorobenzotrifluoride.

EPA is required by the Clean Air Act to consider whether a replacement
for an ODS is more harmful, overall, to human health and the environment
than other available or potentially available substitutes.  Compared to
many other substitutes that EPA has already found acceptable, the
available information shows that nPB should not be more hazardous than
other solvents if it enters the water or soil. 

	Comment Summary:  A commenter that is a publicly-owned treatment works
(POTW) expressed concern about how POTWs will treat nPB.

	Response: The commenter has not provided data to indicate that nPB is
present in any significant amount in water that a POTW must treat.  The
estimated amount of nPB used in the U.S. in the solvent cleaning sector
is roughly 5 million pounds per year, which corresponds to 1% or less of
the organic solvent cleaning market (US EPA, 2007).  We believe that,
considering the relatively small amount of nPB being used in metals,
electronics and precision cleaning and the relatively rapid evaporation
and hydrolysis of nPB compared to a number of acceptable cleaning
solvents, it should not be a significant concern for water pollution. 

	Comment Summary:  Three commenters, all local environmental regulators,
stated that there is a lack of effective disposal controls on nPB, and
that this will encourage its use in applications beyond those envisioned
by EPA.  The commenters believe that users faced with the choice of
either using chlorinated solvents—which have expansive requirements
under the National Emission Standards for Hazardous Air Pollutants
(NESHAPs)—or nPB, will increasingly opt for the latter. Furthermore,
these commenters noted that, although nPB is a volatile organic compound
(VOC), companies are already petitioning to abandon this classification.
[p.2, 0051, 0061;p.2, 0052]

Response:  Our review under SNAP is limited to the end uses for which we
have been petitioned and to those industries that historically used
ozone-depleting substances. Our determination that nPB is acceptable for
use in the metals, electronics, and precision cleaning end uses should
not be considered a position on whether it may be used safely in other
applications.  Furthermore, our review of whether to find nPB acceptable
in the solvent cleaning sector took into consideration whether it could
be used safely when compared to chlorinated solvents, which we
recognized were subject to other regulations such as those mentioned by
the commenter.  We find that nPB in solvent cleaning is acceptable
because it does not significantly increase overall risks to human health
and the environment compared to other available or potentially available
alternative.  

As discussed in section IV.B. of the preamble to the final rule on
solvent cleaning, at this time, unless and until EPA issues a final
rulemaking exempting a compound from the definition of VOC and states
change their SIPs to exclude such a compound from regulation, that
compound is still regulated as a VOC.  To date, EPA has not taken any
action to exempt nPB from the definition of a VOC.

Section VIII Other Health Concerns

Name of Commenter	Organization	Document ID No

John R. Stemniski	N/A	0035, 0057

Anonymous	CA HESIS	0039

Barbara Kanegsberg	BFK Solution, LLC	0041

Three sets of comments were received regarding other health concerns for
nPB: 

	Comment Summary:  An independent contractor in the solvents industry
believes that the long-term exposure effects of nPB have not been
adequately considered. This commenter cautioned that, with the ease of
obtaining nPB once it is approved by EPA, nPB users will have little or
no idea of the workplace regulations and will indiscriminately use it
for practical applications. [p.1, 0035, 0057]

	Response:  EPA disagrees.  Long-term testing is typically conducted to
determine if a compound is carcinogenic; the National Toxicology Program
has begun long-term testing of nPB.  The short-term data do not point to
carcinogenicity as a major health effect of concern.  Further, nPB has
been tested for a longer period of time than many other chemicals
submitted to the SNAP program, because nPB has been tested in a 90-day
test and a 2-generation test.  These tests correspond to exposure for a
significant portion of an individual’s lifetime.  

	The available information on nPB use in the cleaning solvent sector
shows that most users are using nPB appropriately in equipment while
achieving acceptable exposure levels.  We note that nPB is already
readily available in the marketplace and we don’t believe that our
acceptability determination would expand access to nPB.

 

	Comment Summary:  A local environmental regulator submitted a hazard
alert pamphlet on nPB. This pamphlet stated that nPB can harm the
reproductive system and the nervous system, cause sterility in both male
and female test animals, and harm the developing fetus when tested in
pregnant animals. The commenter also stated that 1-bromopropane, which
will soon be tested for carcinogenicity, may harm the human nervous
system, irritate the eyes, nose, and throat, dissolve the natural
protective oils on human skin and cause dermatitis, and harm the liver.
The commenter recommended an exposure limit of 1 ppm and recommended a
skin notation to protect against adverse reproductive and nerve toxicity
effects of nPB.  This pamphlet suggests ways to reduce exposure to nPB,
including reducing or replacing nPB, installing good ventilation or
other engineering controls, and/or using respiratory and skin
protection. [pp.1-4, 0039]

	Response:  For the reasons stated elsewhere in the preamble and this
response to comments document, we do not fully agree with the scientific
conclusions stated in the pamphlet, in particular the recommended
exposure limit of 1 ppm and recommended skin notation.  However, we
believe that many of the suggestions on how to reduce exposure to nPB
are useful guidelines for the public.  

	Comment Summary:  An independent contractor asserted that EPA approval
of nPB and the recommended AEL of 25 ppm for nPB, coupled with the
production ban on HCFC-141b, will effectively increase companies’ use
of chemicals that have not undergone adequate toxicity testing and,
therefore, do not have appropriate inhalation limits. This commenter
said that EPA should recommend a blanket, conservatively low inhalation
limit of 25 ppm for all compounds as well as aqueous, semi-aqueous, and
solvent blends for which no limit has been set or recommended by OSHA,
ACGIH, the American Industrial Hygiene Association (AIHA), or other
appropriate body or agency. [pp.1-3, 0041]

	Response:  A recommendation applying to other chemicals is beyond the
scope of this rulemaking.  Under the SNAP program, we evaluate each
substitute independently and compare it with other substitutes that are
available or potentially available in the same end use. Until someone
petitions EPA to review such chemicals as substitutes under the SNAP
program, they can not be marketed for use as a substitute for a Class I
or Class II substance under any of the end uses addressed by SNAP.

 Section IX Market for nPB 

Name of Commenter	Organization	Document ID No

Anonymous	N/A	0005

Barbara Kanegsberg	BFK Solution, LLC	0037

Richard G. Morford	Enviro Tech International	0049

Stephen P. Risotto	HSIA	0050

Four sets of comments were received regarding the market for nPB: 

	Comment Summary:  One manufacturer of nPB-based solvents stated that a
recommendation of an AEL of 25 ppm would have a severe negative effect
on the marketplace and would destroy the viability of nPB-based
solvents. [p.3, 0049]  An independent consultant provided an overview of
the U.S. solvents market and stated that EPA should evaluate realistic
estimates of expected U.S. trends..

This commenter asserted that while the exposure limit does impact the
choice of solvent or process, additional factors such as process
efficiency, suitability to the process in question, anticipated product
changes, physical and chemical properties, solvent cost, process cost,
other regulatory constraints, odor, and acceptance by employees also
play a role in the decision-making process.  Given the modest growth of
the nPB market, expected continued market fragmentation, and
availability of multiple process options, the commenter believes there
is not an industry rush to adopt nPB. 

Response:  EPA agrees that the market for nPB is not likely to grow to
be as large as the market for chlorinated solvents or to be a
substantial portion of the market for ODS substitutes because there are
a variety of other substitutes already available and to which some users
have already transitioned.  We also agree that users consider a large
number of factors, and not just the workplace exposure limit, when
selecting a solvent.  

We note that a number of companies, including some small companies, have
been selling nPB-based products with a recommended exposure limit of 25
ppm for years with no apparent impact on the companies’ viability. 
Further, since EPA’s June 2003 NPRM, Chemtura, a major U.S.
manufacturer of brominated chemicals, has re-entered the market for nPB
after leaving the market in 2000 and recommends an exposure limit of 10
ppm (Stouder, 2001; Tattersall, 2004; Chemtura, 2006).  Regardless,
EPA’s evaluation under SNAP must focus on ensuring that any acceptable
substitute will not pose significantly greater risk to human health and
the environment than other available substitutes.  In doing so, we must
consider whether there is a level above which a potential substitute
cannot be used safely.  We cannot trade off human health and safety
simply to ensure that the market for a substitute will not be impaired. 

	Comment Summary:  One commenter, representing the chlorinated solvents
industry expressed concern that the Agency contradicts itself in its
discussion of the perceived advantage of nPB over the competing solvent,
methylene chloride, in adhesive formulations. Specifically, according to
the commenter, EPA asserts that a 25 ppm AEL for nPB would not result in
a significant competitive advantage over methylene chloride and other
traditional chlorinated solvents, but then expresses concern that the
absence of regulatory controls on the use of nPB will be viewed as a
distinct advantage (68 FR 33308). 

	Response:  EPA is not addressing the adhesives end use in this final
rule.  We will respond to any comments regarding this end use at the
time we take final action for adhesives.  The final rule associated with
this document only addresses the solvent cleaning sector – metals,
electronics and precision cleaning. Section X Other

Name of Commenter	Organization	Document ID No

John R. Stemniski	N/A	0035, 0057

Kurt T. Werner	3M Performance Materials	0058

Puget Sound Clean Air Agency	PSCAA	0063

Claude Williams	Puget Sound Clean Air Agency	0063

Five sets of comments were received regarding other issues concerning
nPB.

	Comment Summary:  An independent contractor commented that it is
confusing to state that nPB is acceptable subject to the concentration
limits of iPB, since there are other significant conditions that should
also be met. [p.1, 0035, 0057]

	Response: EPA is not setting a concentration limit for iPB in the final
rule for solvent cleaning.

	Comment Summary:  A manufacturer of solvents that do not contain nPB
asserted that any consideration for approval of nPB by SNAP should
address the need for consistent communication of all the hazards
associated with nPB and the appropriate precautions for safe handling.
This commenter believes that compliance with this regulation among nPB
stakeholders is not universal and, therefore, products containing nPB
should have standard warnings on the label and on MSDS to caution users
of its potential hazards, including: liver toxicity, male and female
reproductive toxicity, and toxicity to both the central and peripheral
nervous system. This commenter attached a compilation of MSDSs for
products that contain nPB as a principle solvent, and noted the lack of
consistency in the hazards communicated on the various documents.
[pp.6-7, 0058]

Response:  EPA agrees that it is good policy for companies selling
products containing nPB, or any solvent, to communicate potential
hazards to their customers in their Material Safety Data Sheets (MSDSs).
 OSHA, not EPA, however, establishes the requirements for what must be
specified in MSDS under its hazard communication standard at 29 Code of
Federal Regulations (CFR) 1910.1200.  

	

List of Acronyms and Abbreviations Used in This Document

 

8-hr—eight hour

ACGIH–American Conference of Governmental Industrial Hygienists

AEL–acceptable exposure limit

AIHA—American Industrial Hygiene Association

ANSI--American National Standards Institute

ASTM–American Society for Testing and Materials

BMD–benchmark dose

BMDL–benchmark dose lowerbound, the lower 95%-confidence level bound
on the dose/exposure associated with the benchmark response

CAS Reg. No–Chemical Abstracts Service Registry Identification Number

CERHR–Center for the Evaluation of Risks to Human Reproduction

CFC-113–the ozone-depleting chemical
1,1,2-trifluoro-1,2,2-trichloroethane, C2Cl3F3, CAS Reg. No. 76-13-1

CBM—the ozone-depleting chemical chlorobromomethane, also known as
bromochloromethane or halon 1011, CBrClH2, CAS Reg. No.74-97-5 

CFC–chlorofluorocarbon

CFR–Code of Federal Regulations

CMA-Chemical Manufacturer’s Association

DNA—deoxyribonucleic acid

DOT--the United States Department of Transportation

EPA–the United States Environmental Protection Agency

FR–Federal Register

HCFC-141b–the ozone-depleting chemical 1,1-dichloro-1-fluoroethane,
CAS Reg. No. 1717-00-6

HCFC-225ca/cb–the commercial mixture of the two ozone-depleting
chemicals 3,3-dichloro- 1,1,1,2,2-pentafluoropropane, CAS Reg. No.
422-56-0 and 1,3-dichloro-1,1,2,2,3-pentafluoropropane, CAS Reg. No.
507-55-1

HCFC–hydrochlorofluorocarbon

HFC-4310mee –the chemical 1,1,1,2,3,4,4,5,5,5-decafluoropentane, CAS
Reg. No. 138495-42-8 

HFC–hydrofluorocarbon

IATA—International Air Transport Association

ICF–ICF Consulting

iPB–isopropyl bromide, C3H7Br, CAS Reg. No. 75-26-3, an isomer of
n-propyl bromide; also called 2-bromopropane or 2-BP

IRIS—Integrated Risk Information System

JSOH--Japan Society for Occupational Health

LC50 –the concentration at which 50% of test animals die

LOAEL–Lowest Observed Adverse Effect Level

MSDS—Material Safety Data Sheet

NESHAP–National Emission Standard for Hazardous Air Pollutants

NFPA--National Fire Protection Association

NIOSH–National Institute for Occupational Safety and Health

NOAEL–No Observed Adverse Effect Level

NOEL–No Observed Effect Level

nPB–n-propyl bromide, C3H7Br, CAS Reg. No. 106-94-5; also called
1-bromopropane or 1-BP

NPRM–Notice of Proposed Rulemaking

NTTAA–National Technology Transfer and Advancement Act

ODP–ozone depletion potential

ODS–ozone-depleting substance

OSHA–the United States Occupational Safety and Health Administration

PEL–Permissible Exposure Limit

POTW—Publicly owned treatment works

ppm–parts per million

RfC–reference concentration

SNAP–Significant New Alternatives Policy 

STEL- Short term exposure limit

TERA–Toxicological Excellence for Risk Assessment

it Value™

VOC–volatile organic compound

References

AFEAS, 2006.  Alternative Fluorocarbons Environmental Acceptability
Study.  HCFC-141b Sales by End-Use Category.  November 14, 2006. 
Available online at   HYPERLINK
"http://www.afeas.org/2004/html/hcfc-141b.html" 
http://www.afeas.org/2004/html/hcfc-141b.html 

Alexander, H.C., W.M. McCarty, E.A. Bartlett, 1978.  Toxicity of
Perchloroethylene, Trichloroethylene, 1,1,1,-Trichloroethane, and
Methylene Chloride to Fathead Minnows.  Bull. Environ, Contam. Toxicol. 
20(3):344-352.  

Allen BC, Kavlock RJ, Kimmel CA, and Faustman EM., 1994.  Dose-response
assessment for developmental toxicity.  II.  Comparison of generic
benchmark dose estimates with no observed adverse effect levels. 
Fundam. Appl. Toxicol. 23(4):487-495.

Amann RP., 1981.  A critical review of methods for spermatogenesis from
seminal characteristics.  J. Androl. 2:37-58.  (As cited in US EPA,
1996).

Barber E.D., Donish W., Mueller K., 1981.  A procedure for the
quantitative measurement of the mutagenicity of volatile liquids in the
Ames Salmonella/microsome assay.  Mutat Res 90:31-48.  (A-2001-07,
II-A-9)

Barber E.D., Donish W., 1982.  An exposure system for quantitative
measurements of the microbial mutagenicity of volatile liquids. 
(A-2001-07, II-A-29)

Brooke L.T., D.J. Call, D. L. Geiger, and C.E. Northcott.  1984.  Acute
Toxicities of Organic Chemicals to Fathead Minnows (Pimephales
promelas), Vol. 1.  Center for Lake Superior Environmental Stud., Univ.
of Wisconsin-Superior, Superior, WI I:414. 

CERHR, 2002a.  NTP- Center for the Evaluation of Risks to Human
Reproduction Expert Panel Report on the Reproductive and Developmental
Toxicity of 1-Bromopropane [nPB].  March 2002.  
(EPA-HQ-OAR-2002-0064-0096) 

CERHR, 2004a. NTP-CERHR Expert Panel report on the reproductive and
developmental toxicity of 1-bromopropane.  Center for the Evaluation of
Risks to Human Reproduction. Repro Toxicol. Vol.18, pp.157-188.  2004. 
(EPA-HQ-OAR-2002-0064-0096)

CERHR, 2004b.  NTP-CERHR Expert Panel report on the reproductive and
developmental toxicity of 2-bromopropane. Boekelheide, et al. Repro
Toxicol. Vol.18, pp.189-217.  2004.  (EPA-HQ-OAR-2002-0064-0098)

Chemtura, 2006.  Material Safety Data Sheet for n-propyl bromide. 
April, 2006. (EPA-HQ-OAR-2002-0064-0151)

Dodd, 2002.  July 17, 2002 Letter from Dr. Darol Dodd to J. Cohen re:
Review and Comment on ICF Report “Acceptable Industrial Exposure Limit
for N-Propyl Bromide” (A-2001-07, II-D-56)

Elf Atochem S.A., 1994. Ames test - reverse mutation assay on Salmonella
typhimurium.   n_Propyl Bromide.  HIS1005/1005A.  Study performed by
Sanofi Recherche, Service de Toxicologie.  (A-91-42, X-A-8)

Elf Atochem, 1995.  Micronucleus Test by Intraperitoneal Route in Mice. 
n-Propyl Bromide.  Study No. 12122 MAS.  Study Director, Brigitte
Molinier.  Study performed by Centre International de Toxoicologie,
Misery, France, September 6, 1995.  (A-91-42, X-A-9)

Elf Atochem S.A., 1996.  Amendment to Protocol.  n-Propyl Bromide. 
Study No. 13293 MLY.  Amendment No. 01. Study Director, Brigitte
Molinier.  January 29, 1996.  (A-91-42, X-A-12)

D. L. Geiger, Brooke L.T., and D.J. Call  1990.  Acute Toxicities of
Organic Chemicals to Fathead Minnows (Pimephales promelas), Vol. 5. 
Center for Lake Superior Environmental Stud., Univ. of
Wisconsin-Superior, Superior, WI I:332. 

ICF, 2002a.  Risk Screen for Use of N-Propyl Bromide.  ICF Consulting. 
Prepared for U.S. EPA, May, 2002. (EPA-HQ-OAR-2002-0064-0006 through
-0012)

ICF, 2006a.  ICF Consulting.  Risk Screen on Substitutes for
Ozone-Depleting Substances for Adhesive, Aerosol Solvent, and Solvent
Cleaning Applications.  Proposed Substitute:  n-Propyl Bromide.  April
18, 2006.  Attachments:  A, Determination of an AEL; B, Derivation of an
RfC; C, Evaluation of the Global Warming Potential; D, Occupational
Exposure Analysis for Adhesive Applications; E, Occupational Exposure
Analysis for Aerosol Solvent Applications; F, General Population
Exposure Assessment for n-Propyl Bromide

Kumar, 2004.  Sunil Kumar.  Occupational Exposure Associated with
Reproductive Dysfunction.  Journal of Occupational Health 46 (2004):
1-19  (EPA-HQ-OAR-2002-0064-0101)

PBT Profiler, 2007.  Results from the PBT Profiler Tool for methyl
chloroform, CFC-113, HCFC-141b, HCFC-225ca, HCFC-225cb, 1-bromopropane
(nPB), parachlorobenzo-trifluoride, perchloroethylene, and
trichloroethylene.  Downloaded on April 27, 2007 from   HYPERLINK
"http://www.pbtprofiler.net/default.asp" 
http://www.pbtprofiler.net/default.asp .    

Saito-Suzuki, R; Teramoto, S; Shirasu, Y.  1982.  Dominant lethal
studies in rats with 1,2-dibromo-3-chloropropane and its structurally
related compounds.  Mutation Research 101:321-327.  (A-91-42, X-A-55)

SLR International Corp, April 2, 2001a.  Human in vitro bioassays
conducted by EnviroMed Laboratories.  (A-2001-07, II-D-2)

SLR International, 2001b.  “Inhalation Occupational Exposure Limit for
n-Propyl Bromide.” Prepared for Enviro Tech International, Inc. 2001. 
(A-2001-07, II-D-15)

Stelljes and Wood, 2004.  Stelljes, M., Wood, R.  Development of an
occupational exposure limit for n-propylbromide using benchmark dose
methods.  Regulatory Toxicology and Pharmacology 40 (2004) 136–150 
(EPA-HQ-OAR-2002-0064-0087)

Stouder, 2001.  Letter from E. Stouder, Great Lakes Chemical
Corporation, 2/20/01.  (A-2001-07, II-D-80)

Tattersall, 2004.  Conversation between M. Sheppard, EPA, and Tom
Tattersall, MicroCare Corporation. (EPA-HQ-OAR-2002-0064-0171)

TERA, 2004.  Toxicological Excellence for Risk Assessment.  Scientific
Review of 1-Bromopropane Occupational Exposure Limit Derivations –
Preliminary Thoughts and Areas for Further Analysis.  2004. 
(EPA-HQ-OAR-2002-0064-0189)

Toraason, M., Lynch, D.W., DeBorda, D.G., Singh, N., Krieg, E., Butler,
M.A.,Toennis, C.A., Nemhauser, J.B., 2006. DNA damage in leukocytes of
workers occupationally exposed to 1-bromopropane.  Mutation Research 603
(2006) 1–14  (EPA-HQ-OAR-2002-0064-0130)

US EPA,1995.  SCREEN3 air dispersion model. (A-2001-07, II-A-53)

US EPA, 1996.  Guidelines for Reproductive Toxicity Risk Assessment.
Office of Research and Development. EPA/630/R-96/009. September, 1996. 
(EPA-HQ-OAR-2002-0064-0109)   

US EPA, 1997.  Exposure Factors Handbook.  EPA/Office of Research and
Development, National Center for Environmental Assessment.  August,
1997.  Available online at http://www.epa.gov/ncea/pdfs/efh/front.pdf

US EPA, 2002. Memorandum from Drs. Sally Darney and Gary Klinefelter to
Jeff Cohen re: Acceptable exposure limit for nPB.  (A-2001-07, II-C-1)

US EPA, 2006.  Memorandum from S. Darney and L. Pappas, EPA/Office of
Research and Development to J. Cohen re:    SEQ CHAPTER \h \r 1 Review
of documents on Acceptable Industrial Exposure Limit for N-Propyl
Bromide and associated peer review comments August 21, 2006.

US EPA, 2007.  US EPA, 2007.  Analysis of Economic Impacts of Final nPB
Rulemaking for Cleaning Solvent Sector.  2007.

Wang H, Ichihara G, Ito H, et al. 2003.  Biochemical changes in the
central nervous system of rats exposed to 1-bromopropane for seven days.
 Toxicological Sciences 67:114-120.  (EPA-HQ-OAR-2002-0064-0088)

WIL, 2001.  WIL Research Laboratories. “An inhalation two-generation
reproductive toxicity study of 1-bromopropane in rats.” Sponsored by
the Brominated Solvent Consortium.  May 24, 2001. (A-2001-07, II-D-10)

Yamada T. et al., 2003.  Exposure to 1-Bromopropane Causes Ovarian
Dysfunction in Rats. Toxicol Sci 71:96-103  (EPA-HQ-OAR-2002-0064-0097)

Working PK, 1988.  Male reproductive toxicity: comparison of the human
to animal models.  Environ. Health 77:37-44.  (As cited in US EPA,
1996).



Y

´

a

¾

$

$

$

$

$

$

$

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

&

8

G

H

M

U

s

ž

³

¿

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

ˆ

&

&

&

ᘌᅨ[㘀脈࡝ᘆᅨ[☀

&

@

&

@

 ociety, Boston, 2000  (A-2001-07, II-D-4)

Wuebbles, 2002.  “The Effect of Short Atmospheric Lifetimes on
Stratospheric Ozone” Donald J. Wuebbles Ph.D., University of Illinois,
Urbana.  Submitted by Envirotech Intl., 2/13/02 (A-2001-07, II-D-29)

		-   PAGE  56  -	

*** Final--  DATE  \@ "MMMM d, yyyy"  \* MERGEFORMAT  May 15, 2007  ***