PATTON BOGGSLlP 

ATTORNEYS AT LAW 

Honorable Lisa P. Jackson 

Administrator 

Environmental Protection Agency 

1200 Pennsylvania Avenue, NW 

Washington, DC 20460 

October 28, 2010 

2550 M Street, NW 

Washington, DC 20037-1350 

202-457-6000 

Facsimile 202-457-6315 

www.pattonboggs.com 

W. Caffey Nonnan 

202-457-5270 

cnonnan@ pattonboggs.com 

Re: Petition to Add n-Propyl Bromide to List of Hazardous Air Pollutants 

Regulated under § 112 of the Clean Air Act 

Dear Ms. Jackson: 

On behalf of the Halogenated Solvents Industry Alliance, Inc. ("HSIA"), an association 

of producers and users of chlorinated solvents, I submit the enclosed petition pursuant to Clean 

Air Act ("CAA'' or the "Act")§ 112(b)(3), 42 U.S.C. § 7412(b)(3). The petition seeks the 

addition of n-propyl bromide to the list of hazardous air pollutants codified at § 112(b )(1) of the 

Act, 42 U.S.C. § 7412(b)(1), on the basis that "emissions, ambient concentrations, 

bioaccumulation or deposition of the substance are known to cause or may reasonably be 

anticipated to cause adverse effects to human health or adverse environmental effects," CAA 

§ 112(b)(3)(B), 42 U.S.C. § 7412(b)(3)(B). 

The petition addresses uses of and exposure ton-propyl bromide. It then describes the 

scientific studies and other information that demonstrate that emissions of nPB are known to 

cause or may reasonably be anticipated to cause adverse effects to human health. We believe 

that the case for listing is strong and we urge you to grant the petition well in advance of the 18-

month statutory deadline for action. 

Please do not hesitate to have your staff contact me if we can provide further information 

that will assist in your review. 

Enclosure 

cc: Honorable Regina A. McCarthy 

C. Scott Fulton, Esq. 

Very ~ tly yours, 

tc_ · ~Vj~ W. Caffey orman 

Was hin gt on DC I North ern Virg ini a 1 New Jer se y 1 New York 1 Dal la s 1 De nver 1 Anchorag e 1 Doha 1 Abu Dha bi 
BEFORE THE ENVIRONMENTAL PROTECTION AGENCY 

Petition to Add n-Propyl Bromide to List of Hazardous Air Pollutants 

Regulated under § 112 of the Clean Air Act 

HALOGENATED SOLVENTS INDUSTRY ALLIANCE, INC. 

1530 Wilson Boulevard 

OF COUNSEL: 

W. Caffey Norman 

Patton Boggs LLP 

2550 M Street, NW 

Washington, DC 20037 

October 28, 2010 

Arlington, VA 22209 
Petition to Add n-Propyl Bromide to List of Hazardous Air Pollutants 

Regulated under § 112 of the Clean Air Act 

Introduction 

The Clean Air Act Amendments of 1990 established an initial list of hazardous air 

pollutants, now codified at§ 112(b)(1) of the Clean Air Act ("CAA'' or the "Act"), 42 U.S.C. 

§ 7412(b)(l), sources ofwhich are subject to regulation under CAA §§ 112 (d), (f), (k) and other 

subsections. CAA § 112(b)(3), 42 U.S.C. § 7412(b)(3), provides that any person may petition 

the Administrator to add or delete a substance to the list, and requires the Administrator to grant 

or deny the petition and to publish a written explanation of the reasons for her decision within 18 

months after receipt of the petition. The Halogenated Solvents Industry Alliance, Inc. ("HSIA") 

submits this petition pursuant to CAA § 112(b)(3), 42 U.S.C. § 7412(b)(3). HSIA is an 

association of producers and users of chlorinated solvents. 

By its terms, CAA § 112(b)(3)(A), 42 U.S.C. § 7412(b)(3)(A), requires a petition to add a 

substance to the list of hazardous air pollutants to include a showing that there is adequate data 

on the health or environmental effects of the pollutant in question to support the petition. 

Specifically, CAA § 112(b)(3)(B), 42 U.S.C. § 7412(b)(3)(B), provides that an air pollutant shall 

be added to the list if "emissions, ambient concentrations, bioaccumulation or deposition of the 

substance are known to cause or may reasonably be anticipated to cause adverse effects to 

human health or adverse environmental effects." This petition addresses the uses of and 

exposure ton-propyl bromide (also known as 1-bromopropane, and hereinafter as "nPB") (CAS 

No. 1 06-94-5). It then describes the scientific studies and other information that demonstrate 

that emissions of nPB are known to cause or may reasonably be anticipated to cause adverse 

effects to human health. 

Use and Production of nPB 

NPB is a brominated hydrocarbon with a strong odor. Its chemical formula is 

C3H7Br. NPB is used as a carrier solvent in aerosols and adhesives. Some brand names of 

products using nPB are: Abzol,® EnSolv,® and Solvon® cleaners; Pow-R-Wash® NR Contact 

Cleaner, Superkleen Flux Remover 2311, and LPS No Flash NU Electro Contact Cleaner 

aerosols; and Whisper Spray and Fire Retardant Soft Seam 6460 adhesives. It also is used to 
remove wax, oil, and grease from electronics, metal, and other materials. 1 Specific applications 

include:2 

Aerosol Solvents. NPB is used as an aerosol solvent in lubricants, 

coatings, or cleaning fluids for electrical or electronic equipment; lubricants, 

coatings, or cleaning fluids for aircraft maintenance; and spinnerrette lubricants 

and cleaning sprays used in the production of synthetic fibers. 

Adhesives. NPB is used in adhesives for laminates, flexible foam, 

hardwood floors, tire patches, and metal to rubber adhesives. Of these 

applications, nPB-based adhesives have been used most widely in spray adhesives 

used in manufacture of foam cushions, and to a lesser degree in laminate 

adhesives. 

Electronics, Metal, and Precision Cleaning. NPB is used in open vapor 

degreasing applications to remove processing lubricants such as oils, greases, and 

waxes which have been applied to aid manufacture but need to be removed before 

further processing of the manufactured substance. 

Originally, nPB was used as a chemical intermediate in closed processes. It was 

nominated to the National Toxicology Program (NTP) for testing as a result of its introduction 

into the emissive applications described above: 

"In the early to mid 1990s, 1-bromopropane was used primarily as an 

intermediate in the production of pesticides, quaternary ammonium compounds, 

flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, 

closed processes. In the mid to late 1990s, it was introduced as a less toxic 

replacement for methylene chloride in emissive applications such as vapor and 

immersion degreasing operations and critical cleaning of electronics and metals. 

1-Bromopropane was also introduced as a nonflammable, nontoxic, fast-drying, 

and inexpensive solvent for adhesive resins, and has been marketed as a 

replacement for ozone depleting refrigerants. 1-Bromopropane was nominated for 

study by the Occupational Safety and Health Administration based on the 

potential for widespread occupational and environmental exposure and a lack of 

toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1 mice 

were exposed to 1-bromopropane (99% or greater pure) by inhalation for 2 weeks, 

3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella 

typhimurium and Escherichia coli and mouse peripheral blood."3 

1

72 Fed. Reg. 30168,30171 (May 30, 2007). 

3 NTP Technical Report 564 (Board Draft), copy enclosed. 

2 
As a result of the growing emissive use, global production ofnPB was estimated to be 

20,000-30,000 metric tonnes in 2007. 4 It is assumed to be produced in China, France, India, 

Israel, Japan, Jordan, and the United States. China is estimated to have produced around 20,000 

metric tonnes in 2008, of which approximately 40% were exported. Use as a solvent was 

reported to be growing at a rate of 15-20% per year in the United States (5,000 metric tonnes) 

and Asian countries other than China. Solvent use in Japan was 1,100- 1,200 metric tonnes in 

2009. No information was available to the United Nations Environment Programme (UNEP) for 

other regions. 5 

Exposure to nPB 

Attached is a summary of workplace exposure data for nPB collected by the EPA 

Significant New Alternatives Policy (SNAP) program from a variety of sources.

6 Given its use 

across a variety of applications, some of which are uncontrolled, it is not surprising that there is a 

wide range of exposures in the workplace, from a few parts per million ("ppm") up to 150 ppm 

or more. 

A recently published study of exposure to nPB in New Jersey dry cleaning shops, 

attached, found exposures as high as 54 ppm. 7 The report states: 

"This study suggested that some green or organic alternative solvents in 

the dry cleaning industry intended to replace PERC may result in significant 

exposures above acceptable guidelines among some workers. One dry cleaning 

worker reported serious adverse health effects resulting in an emergency room 

visit. Careful consideration and study of potential exposures and health effects 

4 Montreal Protocol On Substances that Deplete the Ozone Layer, Report of the UNEP Technology and 

Economic Assessment Panel (Progress Report, Volume 2, May 2010), 59. 

http://www.unep.org/ozone/teap/Reports/TEAP Reports/. Because of its ozone depleting potential, the Parties to 

the Protocol have sought to limit nPB use to those situations where more economically feasible and environmentally 

friendly alternatives are not available (Decision XIII/7). 

5 /d. UNEP reports that "Obtaining more complete and accurate data on production and uses ofn-PB, as 

well as its emissions, continues to be difficult. No governmental records are available on emission or uses since nPB is not classified or registered as a controlled chemical substance like CFCs, and HCFCs (ODS class I and II) nor 

designated as a hazardous air pollutant in the Clean Air Act in the USA or reportable compound for pollution release 

(emission) and transfer (PRTR) in Europe and Japan." 

6 EPA-HQ-OAR-2002-0064-0015. 

7 Blando, et al., Preliminary Study ofPropyl Exposure among New Jersey Dry Cleaners as a Result of a 

Pending Ban on Perchloroethylene, J. Air & Waste Manage. Assoc. 60(9): 1049-56 (2010). 

3 
among workers using new chemicals or new processes must precede any 

regulatory attempt to facilitate substitution for environmental purposes." 

Health Effects of nPB 

1. Reproductive Toxicity 

In a proposed rule to list nPB as acceptable for certain applications and unacceptable for 

others under its SNAP program, EPA discussed the available reproductive toxicity data in some 

detail. 8 EPA based its analysis of occupational exposures on effects on sperm motility observed 

in a two-generation reproductive toxicity study employing a benchmark dose (BMD) 

calculation.9 Since that time, additional BMD calculations have been developed based on effects 

on estrus cycle in the same multigeneration study. Petitioner has reviewed the documents 

provided by EPA detailing the selection of endpoints, the choice of study, and the preferred 

calculations ofBMD and the lower 95% confidence limit on the BMD (BMDL). We agree that 

the BMDL values selected (169 ppm based on sperm motility, 162 ppm based on effects on 

estrus cycle) are appropriate and follow accepted methods and principles. These values were 

then adjusted to take into account the temporal differences between the exposure regime in the 

rat study (6 hours per day, 7 days per week) and occupational exposures of 8 hours per day, 5 

days per week. The resultant human equivalent concentrations (HECs) are 177 ppm and 170 

ppm for male and female reproductive toxicity, respectively. The HEC value can provide a point 

of departure (POD) for calculation of a recommended exposure limit (REL) for noncancer 

effects. EPA's approach to setting a limit for occupational exposure is similar to that for 

calculation of the reference concentration (RfC) which defines the inhalation concentration at 

which even sensitive members of the general population are unlikely to experience adverse 

effects. We have modified EPA's calculations to derive an RfC for the general population. 

Although potential reproductive effects remain of concern, more recent evidence of neurotoxicity 

in workers and carcinogenicity in rodents may now indicate effects of greater concern. 

8 72 Fed. Reg. 30168 (May 30, 2007). 

9 WIL, An Inhalation Two-Generation Reproductive Toxicity Study of 1-Bromopropane in Rats, sponsored 

by the Brominated Solvents Consortium (May 24, 2001). 

4 
EPA modified its normal procedure to calculate an RfC as a basis for determining a 

recommended exposure limit for workers. This calculation involves applying a sequence of 

uncertainty factors to the POD based on the extrapolation of animal data to human exposures, 

variability among the population, and the completeness of the database. 

The maximum uncertainty factor applied for the animal to human extrapolation is 10-fold 

(i.e., man is 10-fold more sensitive than the laboratory animal). This factor of 10 is considered 

to include a 3-fold safety factor for pharmacodynamic species differences (sensitivity at the site 

of action) and a 3-fold factor for pharmacokinetic differences (delivery of the active moiety to 

the site of action). For nPB, EPA adopted a 3-fold uncertainty factor for pharmacodynamic 

differences between rat and man, but elected to include no uncertainty factor (i.e., a factor of 1) 

for pharmacokinetic differences. 

EPA's judgment that no uncertainty factor is necessary for dose-response extrapolation 

from rat to man was based on a higher blood/air partition coefficient for nPB in rats than in man 

(11.7 versus 7.1). EPA concluded that, for a given external concentration, "the delivered dose of 

nPB into the bloodstream ofrats is slightly higher than in humans." This relatively small 

difference in blood/air partition coefficients is insufficient, however, to overcome the many 

remaining uncertainties. The partition coefficient itself is only an indication of relative solubility 

and the target tissues in rat and man may be similar in ability to dissolve nPB such that, if nPB is 

poorly metabolized/cleared, the level achieved in the target tissue may be the same in the two 

species at equilibrium. 

There are only certain situations in which the blood/air partition coefficient is the 

controlling factor in determining the level of the active moiety at the site of action. Without 

information on nPB metabolism in humans, this level cannot be predicted with physiologicallybased pharmacokinetic ("PBPK") modeling for humans. The factors that support the application 

of a full 3-fold uncertainty factor for pharmacokinetics are the following: 

• the active moiety or moieties for reproductive effects are not known, 

• the relationship between blood level and active moiety is unknown, 

• the nature and extent of nPB metabolism and general pharmacokinetics in man are 

not known, 

• the difference in blood/air partition coefficients is small, and 

5 
• the blood/air partition coefficient is only controlling under certain conditions that 

can only be defined through PBPK modeling for man. 

Taken together, these uncertainties are highly significant and support the application of a safety 

factor of 3 for pharmacokinetics for extrapolation from rat to man. 

Combined with the 3-fold safety factor for pharmacodynamics, Petitioner believes that 

the full10-fold uncertainty factor should be applied for the interspecies (rat to man) 

extrapolation. This is particularly important when one considers the greater human sensitivity to 

reproductive toxins relative to responses in the rat. The rat possesses huge overcapacity in 

reproductive capabilities whereas man is considered to be much closer to infertility as a species. 

This fact suggests that humans are fundamentally more susceptible to reprotoxins than the rat. 

Although this sensitivity is captured, to a limited extent, in the 3-fold uncertainty factor for 

pharmacodynamics, it may not be sufficient to account for the greater sensitivity of humans. 

Regarding human variability, the RfC methodology allows up to a 10-fold uncertainty 

factor to account for the variability in sensitivity within the general population. In some 

circumstances, Petitioner acknowledges that this factor can be reduced for a working population 

because ofthe general good health required for employment. We agree with EPA's conclusion 

that there may be sensitive individuals for reproduction in the workforce because poor 

reproductive health may exist in individuals generally fit enough to work. EPA considers that 

variability in the worker population may be less than in the general population and that an 

uncertainty factor of 1 0-fold is greater than necessary. This is also a reasonable assumption and 

Petitioner supports the use of an intraspecies uncertainty factor of 3-fold for variations in 

sensitivity in a worker population exposed to nPB. As indicated by EPA, the general population 

is usually considered to include sub-populations that are more sensitive than the relatively 

"healthy" workers. This would indicate that an uncertainty factor of 10 should be applied for 

human variability in the general population. 

At the time that EPA was deriving the occupational exposure limit, there was no 

information regarding effects of long-term exposures to nPB. This normally leads to inclusion of 

a "database uncertainty factor" ofup to 10-fold. The subsequent results ofNTP 2-year cancer 

bioassays in rats and mice (discussed below) show that such an uncertainty factor should have 

been included for workers and a full factor of 1 0 would have been appropriate for the general 

population. The composite uncertainty factor for the general population is therefore 1 000 and 

6 
this, applied to the HEC based on the BMDL, leads to an RfC of 0.17 ppm for male and female 

reproductive effects. 

2. Neurotoxicity 

Earlier reviews of the neurotoxicity ofnPB focused on animal studies in which hind-limb 

weakness and neurophysiological measurements indicated effects on the peripheral nervous 

system. More recently, there have been a number of reports of severe neurotoxicity in workers 

exposed to nPB. In particular, the human effects noted relate to lower limb peripheral nerve 

effects with adverse sensory responses. These effects are qualitatively similar to those seen in rat 

experiments-- limb weakness progressing in some cases to paralysis. Central nervous system 

effects also were reported in a proportion of human cases. 

The consistency of severe effects across multiple independent investigations is 

remarkable and, although the measurements of atmospheric levels have limitations, the similarity 

of exposure levels associated with effects is striking. Many of the case subjects needed 

hospitalization and the reversibility of the effects is still in question. A publication by Majersik 

et al. provides a complete clinical analysis of the effects and indications of the slow recovery, if 

any, observed in patient follow- up. 10 More recently, two cases were reported involving workers 

exposed to nPB (in vapor degreasing and dry cleaning, respectively) who were diagnosed with 

clinical manifestations of nPB. 11 

Petitioner believes that neurotoxicity in humans exposed to nPB is of substantial concern. 

A recently published study showing neurophysiological effects in workers exposed to a range of 

levels allows for derivation of a dose response relationship for female workers. 12 This wellconducted study allowed the authors to calculate the lowest dose level at which female workers 

would be likely to experience measurable adverse effects (neurological and red blood cell 

reduction in number). This exposure is 1.28 ppm (presumably an 8 hour time-weighted 

average). Li et al. also report various effects associated with exposure to nPB and provide a 

10 Majersik et al., Severe Neurotoxicity Associated with Exposure to the Solvent 1-Bromopropane (nPropyl Bromide), Clinical Toxicology45: 270-276 (2007). 

11 Perrone et al., Neurologic Illness Associated with Occupational Exposure to the Solvent 1-

Bromopropane- New Jersey and Pennsylvania, 2007-2008, Morbidity and Mortality Weekly Report 57(48): 

1300-1302 (2008). 

12 Li et al., Dose-Dependent Neurologic Abnormalities in Workers Exposed to 1-Bromopropane, J. Occup. 

Environ. Med 52: 769-777 (2010). 

7 
clear definition of a dose-response relationship indicated in an earlier study. 13 Taking the results 

of Li eta!. and translating them to an RfC value for the general population involves adjusting the 

1.28 ppm from an 8 hour, 5 days per week occupational exposure to a continuous exposure, 

which a lowest-observed-adverse-effect level (LOAEL) of0.3 ppm. Although this is based on 

effects observed in humans, EPA will still apply uncertainty factors in deriving an RfC. Thus, an 

uncertainty factor as high as 10-fold would be applied for a LOAEL in the absence of a noobserved-adverse-effect level (NOAEL). In this case, a factor of 3 is probably sufficient since 

the calculated number is presumed to reflect the lowest level of detection. As the LOAEL is 

based on responses of workers, a factor for sensitive sub-populations in the general population 

would be applied. A factor of 3 may be sufficient to cover this uncertainty. The composite 

uncertainty factor to apply is thus 1 0-fold and the resultant RfC would be 0.03 ppm. 

3. Carcinogenicity 

Perhaps the most significant recent information relevant to the health hazard on nPB are 

the results of 2-year carcinogenesis studies conducted and reviewed by NTP. The enclosed draft 

report, which was unanimously approved by the NTP Technical Reports Review Subcommittee, 

shows: 

• Clear evidence of carcinogenicity in female F344 rats (adenomas in large intestine 

and equivocal evidence for skin tumors) 

• Some evidence of carcinogenicity in male F344 rats (adenomas in large intestine, 

skin tumors, and equivocal findings for mesotheliomas and pancreatic adenomas) 

• Clear evidence of carcinogenicity in female B6C3Fl mice (lung tumors) 

• No evidence of carcinogenicity in male B6C3Fl mice 

At this time, there are no reasons to assume that the mode, or modes, of action by which 

tumors are induced by nPB are not relevant to man and thus a linear, no-threshold dose-response 

relationship should be assumed. Using standard methodology for the calculation of cancer 

potency and risk estimation (the linearized multistage model) applied to the incidence of mouse 

lung tumors yields a q1 *term. This value is the 95% confidence limit of the linear term resulting 

from the model. The cancer potency term for mouse lung tumors from the NTP bioassay is a 

13 Ichihara eta!., Neurological Abnormalities in Workers of a 1-Bromopropane Factory, Environmental 

Health Perspectives 112(13): 1319-1325 (2004). 

8 
risk of 1.95 x 1 o-3 per ppm (lifetime exposure). This potency value indicates that a lifetime risk 

of 1 in 1 million is potentially associated with an exposure of 0.5 ppb or 2.5 11g/m3

• 

Recommendations/Regulatory Measures of Other Authorities 

1. American Conference of Governmental Industrial Hygienists (ACGIH) 

Threshold Limit Values (TL V s®) 

TL V s® refer to airborne concentrations of chemical substances and represent conditions 

under which it is believed that nearly all workers may be repeatedly exposed, day after day, over 

a working lifetime, without adverse health effects. The TL y® for nPB is 10 ppm as an 8-hour 

time-weighted average (TWA). This limit was set without regard to the recently reported cancer 

bioassay results, and is likely to be lowered in the future. 

2. California Workplace Limit 

The California Occupational Safety and Health Standards Board establishes workplace 

standards for toxic materials that assure, to the extent feasible, that no employee will suffer 

material impairment of health or functional capacity if exposed for a working lifetime. The 

Board recently adopted a Permissible Exposure Limit (PEL) for nPB of 5 ppm as an 8-hour 

TWA. Its rationale was as follows: 

"A new Permissible Exposure Limit for 1-bromopropane is proposed as an 

8-hour time-weighted average of 5 ppm TWA (25 mg/M3). The PEL proposed 

differs from the TL V of 10 ppm adopted by the ACGIH in 2005. 1-

bromopropane is a potential substitute for solvents used to clean metals and 

electronics such as in specialized aircraft part degreasing operations and has been 

used as a solvent in adhesives. The documentation of the TL V for 1-

bromopropane indicates that it was adopted to provide protection against the 

potential for neurotoxicity, hepatotoxicity, and reproductive and developmental 

toxicity. The PEL proposed also differs from the recommendation of the 

Committee for a PEL of 1 ppm. The Committee at its meeting January 9, 2004 

considered two possible 8-hour TWA PEL recommendations presented by Julia 

Quint of Hazard Evaluation Systems and Information Service (HESIS): 1 ppm 

based on 2003 HE SIS and Office of Environmental Health Hazard Assessment 

(OEHHA) documents and 3.3 ppm based on an assessment by the National 

Toxicology Program's (NTP) Center for the Evaluation of Risks to Human 

Reproduction (CERHR). The OEHHA assessment, dated December 2, 2003, 

was conducted for the California Air Resources Board and was based on 

reproductive system effects in male rats reported by Ichihara et al. in 2000. The 

CERHR assessment, dated October 2003, was based on reproductive system 

effects in both male and female rats reported in a study by WIL Research 

Laboratories in 2001 sponsored by the Brominated Solvents Consortium. The 

9 
value of3.3 ppm is calculated from the No Observed Adverse Effect 

Concentration (NOAEC) of 100 ppm in test animals in the WIL Research study, 

application of an interspecies uncertainty factor of 3.16 (the square root of 1 0) and 

an intraspecies uncertainty factor of 10, and adjustment for an 8-hour workday 

and 5-day workweek. At the May 18, 2005 advisory meeting, representatives of 

manufacturers and vendors of 1-bromopropane products commented on the 

Committee's recommendation of a PEL of 1 ppm. Their comments included 

concerns that a PEL of 1 ppm would amount to a ban on the use of 1-

bromopropane in California and that there were flaws in the Ichihara study 

underlying the OEHHA Interim Reference Exposure Level. They also noted the 

importance of skin absorption and suggested that a PEL for 1-bromopropane 

should include a "skin" notation. In light of concerns with the Ichihara study 

expressed by these stakeholders and by the authors of the CERHR report, this 

rulemaking proposes a PEL of 5 ppm (8-hour TWA) for 1-bromopropane, along 

with a "skin" notation. The PEL of 5 ppm is a rounding up from the level of 3.3 

ppm to a more standardized PEL value." 14 

As in the case of the TL V® recommendation discussed above, this limit was set without 

regard to the recently reported cancer bioassay results, and is likely to be lowered in the future. 

3. California Proposition 65 

Effective December 7, 2004, nPB was listed as a chemical known to the state of 

California to cause reproductive toxicity for purposes of the Safe Drinking Water and Toxic 

Enforcement Act of 1986 ("Proposition 65"). The listing was based on a formal identification by 

an authoritative body that nPB15 

causes developmental and female and male reproductive 

toxicity. A "safe harbor" exposure level has not yet been adopted but is normally 1000-fold 

below the no observed effect level for reproductive toxicity, and thus is likely to be in the region 

of 1 -2 ppb. 

4. European Union Classification and Labelling 

The following "risk phrases" have been assigned to nPB: R 11 (highly flammable), 

R36/37/38 (irritant to eyes/skin/respiratory system), R 48/20 (danger of serious damage to health 

by prolonged exposure/harmful by inhalation), R 60 (may impair fertility), R 63 (possible risk of 

harm to the unborn child), R 67 (vapors may cause drowsiness and dizziness). The results of the 

14 California Occupational Safety and Health Standards Board, Initial Statement of Reasons, Airborne 

Contaminants (March 19, 2009); https://www.dir.ca.gov/oshsb/airborne_contaminants09 _ISOR.doc. 

15 National Toxicology Program Center for the Evaluation of Risks to Human Reproduction Expert Panel 

Report on the Reproductive and Developmental Toxicity of 1-Bromopropane (nPB) (March 2002). 

10 
NTP carcinogenicity bioassay are not reflected in this list but would be expected to add an 

additional risk phrase to be displayed on labels and safety data sheets. 

Conclusion 

Chlorinated solvents are listed as hazardous air pollutants and industrial sources of 

chlorinated solvent emissions are stringently regulated under CAA §§ 112(d) and (f). NPB is 

being aggressively marketed as an unregulated alternative to chlorinated solvents. 16 Indeed, 

sales literature for nPB emphasizes that it is essentially unregulated. Sales of nPB in adhesive 

and solvent cleaning uses are already substantial and appear poised for further growth. 

The results of the recently reported carcinogenicity bioassays show "clear evidence of 

carcinogenic activity" in female rats and female mice. An estimate of carcinogenic potency 

using standard methodology shows that the cancer potency is similar to or higher than that of the 

regulated materials nPB is being marketed to replace. Moreover, observations of toxic effects of 

nPB in animal experiments and workers exposed at various levels demonstrate that exposed 

populations may face other serious health risks, including reproductive effects (male and 

female), liver and kidney toxicity, immunotoxicity, and effects on red blood cells and 

hemoglobin. High levels of worker exposure have led to a number of documented cases of lower 

limb paralysis that has been slow to improve; the onset of adverse effects on peripheral nerves 

has been detectable in workers exposed at very low levels (estimated lowest-observed-effect 

level was 1.28 ppm). This translates to concern for the general population exposed to very low 

levels. 

16 E.g., http://www.envirotechint.com/products/dry-cleaning/: "Being "Green" has never been easier with 

DrySolv. The first environmentally responsible replacement solvent for your dry cleaning machine! 

• DrySolv is non-flammable, showing no flashpoint in multiple tests and test methods.(ASTM D-56 TCC, 

ASTM D-92 COC, ASTM D-93 TCC). 

• DrySolv is also non-chlorinated. 

• DrySolv is non-hazardous.(DOT, OSHA, NESHAP, RCRA, Clean Water Act) 

• DrySolv is not a hazardous air pollutant, is SNAP approved, and does not contribute to global warming. 

(NESHAP, Significant New Alternative Program-SNAP approved (Federal EPA), Not Title V) 

• The USEPA states that DrySolv's main ingredient is less persistent in the environment than many other 

solvents, is of low to moderate concern for movement in soil, does not warrant listing under the Toxics 

Release Inventory and is not prone to bioaccumulation. (US EPA - Federal Register May 30, 2007). 

• DrySolv does not have a hazardous decomposition or hazardous polymerization." 

11 
Clearly, nPB meets the statutory criteria for listing as a hazardous air pollutant under 

CAA § 112(b)(3)(B), 42 U.S.C. § 7412(b)(3)(B). We urge EPA forthwith to grant this petition. 

Attachments 

12 
7 

ABSTRACT 

1-BROMOPROPANE 

CAS No. I 06-94-5 

Molecular Weight: 122.99 

Synonyms: 1-BP; propyl bromide; n-BP; N-propyl bromide 

In the early to mid 1990s, 1-bromopropane was used primarily as an intermediate in the production of pesticides, 

quaternary ammonium compounds, flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, 

closed processes. In the mid to late 1990s, it was introduced as a less toxic replacement for methylene chloride in 

emissive applications such as vapor and immersion degreasing operations and critical cleaning of electronics and 

metals. 1-Bromopropane was also introduced as a nonflammable, nontoxic, fast-drying, and inexpensive solvent for 

adhesive resins, and has been marketed as a replacement for ozone depleting refrigerants. 1-Bromopropane was 

nominated for study by the Occupational Safety and Health Administration based on the potential for widespread 

occupational and environmental exposure and a lack of toxicity and carcinogenicity data. Male and female F344/N 

rats and B6C3Fl mice were exposed to 1-bromopropane (99% or greater pure) by inhalation for 2 weeks, 3 months, 

or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse 

peripheral blood. 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION 
8 1-Bromopropane, NTP TR 564 

2-WEEK STUDY IN RATS 

Groups of five male and five female rats were exposed to I-bromopropane vapor at concentrations ofO, I25, 250, 

500, I,OOO, or 2,000 ppm, 6 hours plus T90 (I2 minutes) per day, 5 days per week for I6 days. All rats survived to 

the end of the study except one 500 ppm male. Mean body weights of2,000 ppm rats were significantly less than 

those of the chamber controls. The absolute kidney weight of I ,000 ppm males, relative kidney weights of all 

exposed groups of males, and absolute and relative kidney weights of all exposed groups of females were 

significantly increased. The absolute and relative liver weights of I ,000 ppm males, relative liver weights of 500 

and 2,000 ppm males, and absolute and relative liver weights of 500 ppm or greater females were significantly 

increased. Nasal lesions included suppurative inflammation in males exposed to 500 ppm or greater, respiratory 

epithelial necrosis in I,OOO and 2,000 ppm males, and respiratory epithelial regeneration in I,OOO and 2,000 ppm 

females. 

2-WEEK STUDY IN MICE 

Groups of five male and five female mice were exposed to I-bromopropane vapor at concentrations ofO, I25, 250, 

500, 1 ,000, or 2,000 ppm, 6 hours plus T 90 (12 minutes) per day, 5 days per week for 17 days. All 2,000 ppm males, 

two 2,000 ppm females, four 500 ppm males, one I ,000 ppm male, and one I ,000 ppm female died early. The mean 

body weight gain of 1,000 ppm males was significantly less than that of the chamber controls. Abnormal breathing, 

lethargy, and eye discharge were observed primarily during week 1 in groups exposed to 500 ppm or greater. Liver 

weights of 1,000 ppm males and of females exposed to 500 ppm or greater were significantly increased. Kidney 

weights of 1,000 and 2,000 ppm females were significantly increased. Microscopic lesions related to 

1-bromopropane exposure occurred in the lung, liver, and nose of males and females and were primarily seen in 

mice exposed to 500 ppm or greater. 

3-MONTH STUDY IN RATS 

Groups of 10 male and 10 female rats were exposed to 1-bromopropane vapor at concentrations ofO, 62.5, I25, 250, 

500, or 1,000 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 14 weeks. Additional clinical 

pathology groups of 10 male and 10 female rats were exposed to the same concentrations for 23 days. All rats 

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft 
1-Bromopropane, NTP TR 564 9 

survived to the end of the study. Mean body weights of 1,000 ppm males were significantly less than those of the 

chamber controls. The increases in sorbitol dehydrogenase activities in 500 ppm males and 1,000 ppm males and 

females were consistent with the histopathologic evidence of mild hepatotoxicity caused by 1-bromopropane. Liver 

weights of males exposed to 250 ppm or greater and of females exposed to 125 ppm or greater were significantly 

increased. Spleen and kidney weights of 1,000 ppm females were significantly increased. Results of sperm count 

and vaginal cytology evaluations showed exposure concentration-related decreases in sperm motility and counts in 

male rats, reaching 28% and 37%, respectively, in the 1,000 ppm group. Female rats in all three exposure groups 

evaluated exhibited altered estrous cycles, spending significantly more time in extended estrus and less time in 

extended diestrus. The incidences of cytoplasmic vacuolization of the liver were significantly increased in males 

exposed to 250 ppm or greater and in females exposed to 500 ppm or greater. Hepatocyte degeneration was also 

observed in 1 ,000 ppm females. 

3-MONTH STUDY IN MICE 

Groups of 10 male and 10 female mice were exposed to 1-bromopropane vapor at concentrations ofO, 62.5, 125, 

250, or 500 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 14 weeks. One 250 ppm male and four 

males and five females in the 500 ppm groups died early. Mean body weights of exposed groups were similar to 

those of the chamber controls. Lethargy was observed in males and females exposed to 500 ppm, and abnormal 

breathing was observed in moribund mice. The kidney, liver, and lung weights of 500 ppm females were 

significantly greater than those of the chamber controls. The kidney weights of 500 ppm males were significantly 

decreased. Male mice in the 500 ppm group had decreased sperm counts that were 28% less than that in the 

chamber controls. Female mice exhibited altered estrous cycles, with females in the 500 ppm group spending 

significantly more time in extended diestrus and those in the 250 ppm group spending significantly more time in 

extended estrus compared to the chamber controls. Nonneoplastic lesions were observed in the nose, larynx, 

trachea, lung, and liver of 500 ppm males and females and in the adrenal cortex of 500 ppm females. 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION 
10 1-Bromopropane, NTP TR 564 

2-YEAR STUDY IN RATS 

Groups of 50 male and 50 female rats were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, or 

500 ppm, 6 hours plus T90 (10 minutes) per day, 5 days per week for 105 weeks. Survival of 500 ppm males was 

significantly less than that of the chamber control group. Mean body weights of exposed groups were similar to 

those of the chamber controls. 

Increased incidences of macroscopic, soft, pale-yellow to green, variably sized nodules were seen predominantly in 

the nose and skin of exposed rats. The number of animals with multiple masses was increased in the 500 ppm 

groups. In most cases, these lesions were microscopically shown to be suppurative inflammation, many with 

Splendore-Hoeppli material. 

The incidence of adenoma of the large intestine (colon or rectum) in 500 ppm females was significantly greater than 

that in the chamber control group. The incidence of adenoma of the large intestine in 250 ppm males exceeded the 

historical control ranges for inhalation studies and all routes. 

The incidences of keratoacanthoma, basal cell adenoma, basal cell carcinoma, or squamous cell carcinoma 

(combined) in all exposed groups of males were significantly greater than that in the chamber control group and 

exceeded the historical control range for inhalation studies. The incidences of keratoacanthoma and of 

keratoacanthoma or squamous cell carcinoma (combined) in 250 and 500 ppm males were also significantly 

increased and exceeded the historical control ranges for inhalation studies. In 500 ppm females, the incidence of 

squamous cell papilloma, keratoacanthoma, basal cell adenoma, or basal cell carcinoma (combined) exceeded the 

historical control range for inhalation studies. 

The incidence of malignant mesothelioma in 500 ppm males was significantly greater than that in the chamber 

control group. 

The incidences of pancreatic islet adenoma in all exposed groups of males and of pancreatic islet adenoma or 

carcinoma (combined) in 125 and 250 ppm males were significantly increased. 

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft 
1-Bromopropane, NTP TR 564 11 

Treatment-related nonneoplastic lesions were observed in the respiratory system of exposed male and female rats. 

In the nose, the incidences of suppurative chronic inflammation, chronic active inflammation, glandular hyperplasia, 

respiratory epithelial hyperplasia (females), and respiratory metaplasia of the olfactory epithelium (females) were 

increased in all exposed groups. In the larynx, the incidences of chronic active inflammation and squamous 

metaplasia (except 125 ppm females) were increased in all exposed groups, and the incidences of suppurative 

chronic inflammation were increased in the 500 ppm groups. In the trachea, there were increased incidences of 

chronic active inflammation in all exposed groups of females and 500 ppm males, and the incidence of epithelial 

hyperplasia was increased in 500 ppm females. 

2-YEAR STUDY IN MICE 

Groups of 50 male and 50 female mice were exposed to 1-bromopropane vapor at concentrations ofO, 62.5, 125, or 

250 ppm, 6 hours plus T 90 (1 0 minutes) per day, 5 days per week for 105 weeks. Survival of exposed groups was 

similar to that of the chamber controls. Mean body weights of all exposed groups were similar to those of the 

chamber controls throughout the study. 

In the females, there were increased incidences of alveolar/bronchiolar adenoma, alveolar/bronchiolar carcinoma, 

and alveolar/bronchiolar adenoma or carcinoma (combined); the incidences of alveolar/bronchiolar adenoma or 

carcinoma (combined) were significantly increased in all exposed groups of females. There were significantly 

increased incidences of cytoplasmic vacuolization of the bronchiolar epithelium in all exposed male groups and 

regeneration of the bronchiolar epithelium in all exposed groups of males and females. 

In the nose, there were significantly increased incidences of cytoplasmic vacuolization of the respiratory epithelium 

in all exposed groups of males and in 125 and 250 ppm females. There were significantly increased incidences of 

respiratory epithelial hyperplasia in all exposed female groups and in 62.5 and 250 ppm males. There were 

significantly increased incidences of respiratory metaplasia of olfactory epithelium in 62.5 and 125 ppm males and 

125 and 250 ppm females. 

Board Draft NOT FOR DISTRIBUTION OR ATTRIBUTION 
12 1-Bromopropane, NTP TR 564 

There were significantly increased incidences of cytoplasmic vacuolization of respiratory epithelium in the larynx 

and trachea of all exposed male groups and in the trachea of62.5 and 125 ppm females. 

GENETIC TOXICOLOGY 

1-Bromopropane was not mutagenic in either of two independent bacterial mutagenicity assays, each conducted with 

and without induced rat liver activation enzymes. Bacterial strains tested included S. typhimurium strains TA97, 

TA98, TA100, and TA1535, as well as E. coli strain WP2 uvrA/pKM101. In addition, no increases in the 

frequencies of micronucleated normochromatic erythrocytes were seen in male or female B6C3F1 mice exposed for 

3 months to 62.5 to 500 ppm 1-bromopropane via inhalation. 

CONCLUSIONS 

Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity* of 

1-bromopropane in male F344/N rats based on the occurrence of rare adenomas of the large intestine and increased 

incidences of neoplasms of the skin. Increased incidences of malignant mesothelioma and pancreatic islet adenoma 

may also have been related to 1-bromopropane exposure. There was clear evidence of carcinogenic activity of 

1-bromopropane in female F344/N rats based on increased incidences of adenoma of the large intestine. Increased 

incidences of neoplasms of the skin may also have been related to 1-bromopropane exposure. There was no 

evidence of carcinogenic activity of 1-bromopropane in male B6C3F1 mice exposed to concentrations of 62.5, 125, 

or 250 ppm 1-bromopropane. There was clear evidence of carcinogenic activity of 1-bromopropane in female 

B6C3F1 mice based on increased incidences of alveolar/bronchiolar neoplasms. 

Exposure to 1-bromopropane resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, 

the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lung of mice. 

Suppurative inflammatory lesions with Splendore-Hoeppli material were present primarily in the nose and skin of 

male and female rats exposed to 1-bromopropane. 

• Explanation of Levels of Evidence of Carcinogenic Activity is on page 14. 

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft 
1-Bromopropane, NTP TR 564 13 

Summar~ of the 2-Year Carcinogenesis and Genetic Toxicolog~ Studies of 1-BromoJ.!rOJ.!ane 

Concentrations in air 

Body weights 

Survival rates 

Nonneoplastic effects 

Neoplastic effects 

Equivocal findings 

Level of evidence of 

carcinogenic activity 

Genetic toxicology 

Bacterial gene mutations: 

Male 

F344/N Rats 

0, 125,250, or 500 ppm 

Exposed groups similar to 

the chamber control group 

23/50, 26/50, 18/50, 13/50 

Nose: inflammation, 

suppurative, chronic 

(0/50, I /48, 2/48, 7 /50); 

inflammation, chronic 

active (29/50, 33/48, 

34/48, 35/50); glands, 

hyperplasia (5/50, 14/48, 

14/48, 15/50) 

Larynx: inflammation, 

chronic active (21150, 

28/50, 31150, 26/50) 

Large intestine: adenoma 

(0/50, 0/50, 2/50, 1/50) 

Skin: keratoacanthoma 

(0/50, 3/50, 6/50, 6/50); 

keratoacanthoma or 

squamous cell carcinoma 

(1/50, 4/50, 6/50, 8/50); 

keratoacanthoma, basal 

cell adenoma, basal cell 

carcinoma, or squamous 

cell carcinoma (1/50, 

7/50, 9/50, 10/50) 

Malignant mesothelioma: 

(0/50, 2/50, 2/50, 4/50) 

Pancreatic islets: 

adenoma (0/50, 5/50, 

4/50, 5/50) 

Some evidence 

Micronucleated erythrocytes 

Mouse peripheral blood in vivo: 

Board Draft 

Female Male Female 

F344/N Rats B6C3Fl Mice B6C3Fl Mice 

0, 125,250, or 500 ppm 0, 62.5, 125, or 250 ppm 0, 62.5, 125, or 250 ppm 

Exposed groups similar to Exposed groups similar to Exposed groups similar to 

the chamber control group the chamber control group the chamber control group 

34/50, 33/50, 30/50, 24/50 37/50, 33/50, 32/50, 36/50 36/50, 40/50, 37/50, 42/50 

Nose: inflammation, Lung: bronchiole, Lung: bronchiole, 

suppurative, chronic vacuolization cytoplasmic regeneration (0/50, 45/50, 

(0/50, 1/50, 3/49, 7/50); (0/50, 18/50, 19/49, 43/50, 49/50) 

inflammation, chronic 17/49); bronchiole, 

active (24/50, 37/50, regeneration (1/50, 44/50, Nose: respiratory 

37/49, 36/50); glands, 38/49, 47/49) epithelium, vacuolization 

hyperplasia (6/50, 23/50, cytoplasmic (0/50, 3/50, 

28/49, 30/50); respiratory Nose: respiratory 5/50, 8/50); respiratory 

epithelium, hyperplasia epithelium, vacuolization epithelium, hyperplasia 

(5/50, 13/50, 9/49, 18/50); cytoplasmic (0/50, 12/50, (11/50, 25/50, 28/50, 

olfactory epithelium, 19/50, 20/50); respiratory 27/50); olfactory 

metaplasia, respiratory epithelium, hyperplasia epithelium, metaplasia, 

(3/50, 4/50, 6/49, 9/50) (16/50, 29/50, 23/50, respiratory (0/50, 4/50, 

26/50); olfactory 5/50, 14/50) 

Larynx: inflammation, epithelium, metaplasia, 

chronic active (18/50, respiratory (0/50, 7150, Trachea: vacuolization 

25/50, 30/50, 32/50); 6/50, 3/50) cytoplasmic (0/50, 8/49, 

metaplasia, squamous 7/50, 4/50) 

(3/50, 2/50, 6/50, 21 /50) Larynx: vacuolization 

cytoplasmic (0/48, 5/50, 

Trachea: inflammation, I 0/48, 11150) 

chronic active (0/50, 4/50, 

1/50, 6/50); epithelium, Trachea: vacuolization 

hyperplasia (0/50, 0/50, cytoplasmic (0/49, 15/50, 

0/50, 4/50) 24/47, 24/50) 

Large intestine: adenoma None Lung: 

(0/50, 1150, 2/50, 5/50) alveolar/bronchiolar 

adenoma (1/50, 6/50, 

4/50, I 0/50); 

alveolar/bronchiolar 

carcinoma (0/50, 7/50, 

5/50, 4/50); 

alveolar/bronchiolar 

adenoma or carcinoma 

(1150, 9/50, 8/50, 14/50) 

Skin: squamous cell None None 

papilloma, 

keratoacanthoma, basal 

cell adenoma, or basal 

cell carcinoma (1/50, 

1/50, 1/50, 4/50) 

Clear evidence No evidence Clear evidence 

Negative in Salmonella typhimurium strains TA97, TA98, TAIOO, and TA1535 with 

and without S9; and in Escherichia coli WP2 uvrA!pKMIOI with and without S9 

Negative 

NOT FOR DISTRIBUTION OR ATTRIBUTION 
14 1-Bromopropane, NTP TR 564 

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY 

The National Toxicology Program describes the results of individual experiments on a chemical agent and notes the strength of the evidence for 

conclusions regarding each study. Negative results, in which the study animals do not have a greater incidence of neoplasia than control animals, 

do not necessarily mean that a chemical is not a carcinogen, inasmuch as the experiments are conducted under a limited set of conditions. 

Positive results demonstrate that a chemical is carcinogenic for laboratory animals under the conditions of the study and indicate that exposure to 

the chemical has the potential for hazard to humans. Other organizations, such as the International Agency for Research on Cancer, assign a 

strength of evidence for conclusions based on an examination of all available evidence, including animal studies such as those conducted by the 

NTP, epidemiologic studies, and estimates of exposure. Thus, the actual determination of risk to humans from chemicals found to be 

carcinogenic in laborat01y animals requires a wider analysis that extends beyond the purview of these studies. 

Five categories of evidence of carcinogenic activity are used in the Technical Report series to summarize the strength of evidence observed in 

each experiment: two categories for positive results (clear evidence and some evidence); one category for uncertain findings (equivocal 

evidence); one category for no observable effects (no evidence); and one category for experiments that cannot be evaluated because of major 

flaws (inadequate study). These categories of interpretative conclusions were first adopted in June 1983 and then revised on March 1986 for use 

in the Technical Report series to incorporate more specifically the concept of actual weight of evidence of carcinogenic activity. For each 

separate experiment (male rats, female rats, male mice, female mice), one of the following five categories is selected to describe the findings. 

These categories refer to the strength of the experimental evidence and not to potency or mechanism. 

• Clear evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a dose-related (i) increase of 

malignant neoplasms, (ii) increase of a combination of malignant and benign neoplasms, or (iii) marked increase of benign neoplasms 

if there is an indication from this or other studies of the ability of such tumors to progress to malignancy. 

Some evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a chemical-related increased 

incidence of neoplasms (malignant, benign, or combined) in which the strength of the response is less than that required for clear 

evidence. 

• Equivocal evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a marginal increase of 

neoplasms that may be chemical related. 

No evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing no chemical-related increases in 

malignant or benign neoplasms 

Inadequate study of carcinogenic activity is demonstrated by studies that, because of major qualitative or quantitative limitations, 

cannot be interpreted as valid for showing either the presence or absence of carcinogenic activity. 

For studies showing multiple chemical-related neoplastic effects that if considered individually would be assigned to different levels of evidence 

categories, the following convention has been adopted to convey completely the study results. In a study with clear evidence of carcinogenic 

activity at some tissue sites, other responses that alone might be deemed some evidence are indicated as ''were also related" to chemical exposure. 

In studies with clear or some evidence of carcinogenic activity, other responses that alone might be termed equivocal evidence are indicated as 

"may have been" related to chemical exposure. 

When a conclusion statement for a particular experiment is selected, consideration must be given to key factors that would extend the actual 

boundary of an individual category of evidence. Such consideration should allow for incorporation of scientific experience and current 

understanding of long-tenn carcinogenesis studies in laboratory animals, especially for those evaluations that may be on the borderline between 

two adjacent levels. These considerations should include: 

• adequacy of the experimental design and conduct; 

occunence of common versus uncommon neoplasia; 

progression (or lack thereof) from benign to malignant neoplasia as well as from preneoplastic to neoplastic lesions; 

some benign neoplasms have the capacity to regress but others (of the same morphologic type) progress. At present, it is impossible 

to identifY the difference. Therefore, where progression is known to be a possibility, the most prudent course is to assume that benign 

neoplasms of those types have the potential to become malignant; 

combining benign and malignant tumor incidence known or thought to represent stages of progression in the same organ or tissue; 

latency in tumor induction; 

multiplicity in site-specific neoplasia; 

metastases; 

supporting information from proliferative lesions (hyperplasia) in the same site of neoplasia or other experiments (same lesion in 

another sex or species); 

• presence or absence of dose relationships; 

statistical significance of the observed tumor increase; 

concunent control tumor incidence as well as the historical control rate and variability for a specific neoplasm; 

• survival-adjusted analyses and false positive or false negative concerns; 

structure-activity correlations; and 

in some cases, genetic toxicology. 

NOT FOR DISTRIBUTION OR ATTRIBUTION Board Draft 
Summary of Data on Workplace Exposure ton-Propyl Bromide 

The U.S. Environmental Protection Agency's (EPA) Significant New Alternatives Policy 

(SNAP) Program has received workplace exposure data for n-propyl bromide (nPB) from several 

different sources. The sources include: 

• 

• 

Data from organic vapor monitoring badges worn by workers using vapor degreasing 

equipment 

Data from charcoal tube samplers worn by workers using vapor degreasing equipment, 

cold batch cleaning equipment, aerosols, spray adhesives in foam fabrication, adhesives 

used for flooring, and manual cleaning 

Area samples taken using both organic vapor monitoring badges and charcoal tube 

samplers 

Data from three manufacturers or suppliers of products containing nPB 

Data from the National Institute for Occupational Safety and Health from four different 

facilities 

Data from spray adhesives, a highly emissive use, both before and after improvements to 

ventilation 

The Agency considered these data in determining whether it is feasible to meet the recommended 

workplace exposure limit for nPB using available, affordable control or ventilation equipment. 

Description of exposure data by sector 

Non-aerosol solvent cleaning 

Almost all samples for solvent cleaning were taken for vapor degreasing. 

• There are approximately 500 personal samples in all, roughly 90% taken using organic 

• 

badge monitors (3M or SKC). 

There are approximately 40 area samples, most taken with charcoal tube . 

Data sources for personal samples include exposure data from customers of two suppliers 

ofnPB-based solvents for vapor degreasing, 2003. 

For area samples, EPA also considered data from R.L. Smith, 1998a and 1998b. 

Approximately 75% of the personal samples were below 10 ppm on an 8 hour timeweighted average (TWA) 

>87% ofpersonal samples were below 25 ppm (8 hr TWA) 

In several situations where samples indicated workplace exposure greater than 25 ppm, 

the supplier and user worked to reduce emissions, and brought them below 25 ppm 

Earlier samples taken in 1997 had higher average concentrations than later samples. This may 

reflect that some manufacturers reduced their recommended workplace exposure limit in 2000, 

and therefore, users made greater efforts to attain lower emissions. 

There also was a Health Hazard Evaluation (HHE) by the National Institute for 

Occupational Safety and Health (NIOSH) for an air-tight "cold" batch cleaner with ventilation. 
Before use ofthe air-tight cleaning equipment, workers complained of adverse health effects such 

as headaches, nausea, vomiting, feeling faint, and irritation of the mucous membranes (NIOSH, 

2000c ). After installing the new equipment, NIOSH measured workplace exposure. NIOSH 

found that samples taken on 20 employees all read concentrations less than lppm ofnPB. These 

data from NIOSH are not included in the more than 500 personal samples mentioned above, 

which are all for vapor degreasing. 

Figure 1. Distribution of Exposure Data for Vapor Degreasing 

Distribution of nPB Exposure Data for Vapor 

Degreasing 

-C') 

co s:::: g ·c;; 35.0% 

~ m 30.0% 

C1) I.. 

c.. C') 25.0% 

'+- C1) 

0 c 20.0% 

C1) I.. 15.0% C')~ 

co In 10.0% c C1) 

C1) - 5.0% (.)c. 

s.. E o.o% 

C1) co 

C..tl) 

Concentration, 8 1-t TWA (ppm) 

• Percentage of Sarrples 

in Range 

EPA also examined data for two other "cold cleaning" applications that are not currently 

regulated under SNAP: flushing and hand wiping. At one site, personal exposure levels for 

manual flushing of coils ranged from 5 to 42 ppm, with three samples taken with charcoal tubes. 

EPA has data for three different sites for hand wiping. The personal samples were all greater than 

25 ppm. 

Table 1. Exposure Data from Hand Wiping Application 

Site #of Samples Avg Cone. Cone. Range (ppm) 

Hand Wipe Site #3 4 Not available 28 to 47 (6 to 10 min. exposure) 

Sources: Smith, R.L. 1998; November 16, 2001 Email from Mick Kassem, Albemarle Corporation. 

2 
Aerosol Solvents 

Ofthe three major applications that EPA evaluated, there was the least amount of 

exposure data for aerosol solvents. There are: 

Eight personal samples on an eight-hour TWA basis, most taken using organic badge 

monitors 

Four area samples, all taken with charcoal tube samplers 

Eight 15-minute samples, suitable for comparison with a short-term exposure limit (STEL) 

Sources of data include Kassem, 2001 and Aerosol data, 1998. 

• The eight personal samples on an eight-hour TWA basis ranged from 5 ppm to 30.2 ppm. 

Seven of the eight personal samples on an eight-hour TWA basis were below 25 ppm. 

The eight 15-minute samples ranged from 45.1 ppm to 254 ppm. 

Figure 2. Distribution of nPB Exposure Data for Aerosol Solvent Use (8 hr TWA) 

1/) 0.4 Q) 

Q. 

E 0. 3 5 n:l 

en 

'iii 0.3 1:: 

0 0.2 5 1/) 

.... 

Q) 

a. 0.2 0 

1/) 

0 

.... 0.1 5 Q) 

< 

.... 0. 1 0 

1:: 

0 0. 0 5 :;::; 

(.) 

n:l 0 .... 

u. 

Dis trib u tio n of n P 8 Exposure Data for Aero so I 

Solvent Use 

< 1 1 to 6 to 11 1 6 21 2 6 31 41 

5 1 0 to to to to to to 

15 20 25 30 40 50 

Concentration, 8 hr TWA (ppm) 

m~Fraction ofaerosol 

sam pies in range 

The 15 minute samples are useful for a comparison with a short-term exposure limit 

(STEL). The samples taken on a eight-hour time-weighted average are usefi.il for comparison 

with a workplace exposure limit. 

3 
Figure 3. Distribution of Short-Term nPB Exposure Data for Aerosol Solvent Use 

(15 Minute Exposures) 

Distribution of Short-Term nPB Exposure Data for 

Perosol Solvent Use 

ctJ 

r::: 

0 0.3 ~~~""'~ 

~ !I> 0.25 

c.. ~ 0.2 

o E" o.15 

r::: ctJ 0.1 

111 Fraction of samples in 

range 

0 en 0.05 ;; (.) 0 

ctJ 

.... 

u.. 1 to 51 101 151 201 251 

50 to to to to to 

1 00 150 200 250 300 

15-min Concentration, ppm 

Adhesives 

Almost all of the exposure data for adhesives were for spray adhesives using nPB as a carrier 

solvent in foam fabrication and construction of seat cushions. In addition, there were a few sites 

where nPB-based adhesives were applied for flooring. There are: 

Approximately 90 personal samples, all taken with charcoal tube samplers 

Five area samples, all taken with charcoal tube samplers 

Data sources include Smith, R.L. 1998, Kassem 2001, NIOSH 2000a, NIOSH 2000b, 

NIOSH 2001, NIOSH 2002a, and NIOSH 2002b. 

There is a marked difference in the exposure data at two sites where NIOSH worked 

together with the facilities to improve their ventilation. 

Less than half of the personal samples were below 50 ppm on an 8 hour TWA before 

improving ventilation; 97% of the personal samples were below 50 ppm after improving 

ventilation. 

The mean concentration before improving ventilation was 141.7 ppm; the mean 

concentration after improving ventilation was 18.3 ppm. 

After improving ventilation, 78% percent of the samples were at 25 ppm or below. 

4 
1/) 

Q) 

c. 

E 

co 

(/) 

iii 

s:: 

0 

1/) 

... 

Q) 

c.. 

.... 

0 

Q) 

Cl 

co 

-s:: 

Q) 

(..) 

... 

Q) 

c.. 

Figure 4. Distribution of nPB Exposure Data for Adhesives 

Distribution ofnPB Exposure Data forAdhesives 

16.0% 

14.0% 

12.0% 

10.0% 

8.0% 

6.0% 

4.0% 

2.0% 

0.0% ~ 0 0 0 0 0 v ~ N (") 1.() 1'-

.8 .8 .8 .8 .8 c.o c.o c.o ~ N ~ 10 

Concentration, 8 

0 1.() 0) N 

.8 ~ 

00 .8 

0 

0 

~ 

Hr TWA 

1.() 0 1'- 1.() 

~ N 

.8 .8 

u; ;; ~ N 

(ppm) 

m~Percentage ofall 

sam pies. after ventilation 

1i111111Percentage of all 

samples, before 

vent i I at ion 

Figure 4 shows the distribution of personal samples taken in adhesives application both 

before and after making improvements to ventilation. Percentages are a percentage of all personal 

samples for adhesives for which we have data. Approximately 58% of the person samples are 

from after ventilation was improved and 42% are from before ventilation was improved. To see 

percentage of samples within each category, see Figure 5 below. 

Figure 4 does not include data from the Letter from Dept. of Health and Human Services 

(HHS) to Custom Products, Inc., December 1, 1999. The nPB exposure data at this plant were 

relatively high before NIOSH assisted Custom Products in improving ventilation. However, the 

individual measurements are not available, and thus they are not included in the distribution 

above. Table 2 summarizes the data from NIOSH's 1999 letter to Custom Products. 

Workplace exposure levels at Custom Products ranged from 60 ppm to 381.2 ppm during 

NIOSH's initial evaluation. The mean exposure level for the plant was 168.9 ppm. By 

comparison, after improving ventilation, the mean exposure level dropped almost tenfold to 18.9 

ppm, with a range from 1.2 to 58 ppm. 

5 
Table 2. Summary of nPB Exposure Data from Adhesives at Custom Products, 

Prior to Ventilation Im~rovements 

Exposure, ppm of nPB (8 Hour TWA) 

Job Title Department #of 

Samples Mean Minimum Maximum 

Assembly 36 169.8 60.0 250.7 

Sprayers Assembly 15 193.0 115.3 250.7 

Assemblers Assembly 20 154.7 60.0 234.9 

Sprayers Covers 21 197.0 117.3 381.2 

Saw Operator Saw 12 117.1 85.1 159.2 

All Exposure Data 69 168.9 60.0 381.2 

Conclusions 

Exposure levels to nPB in the workplace are much lower for vapor degreasing and for airtight cleaning equipment than for other applications. Most vapor degreasers are capable of 

containing nPB exposure levels to less than 10 ppm. 

There are limited nPB exposure data available for aerosol and cold cleaning applications. 

These data indicate that aerosol users are likely to attain workplace exposure levels below 20 

ppm. On the other hand, hand wiping appears to be a highly emissive application with exposure 

levels consistently above 25 ppm. 

Exposure levels are the highest for adhesives. It is possible to make improvements to 

ventilation when using adhesives that can reduce exposure levels below 20 ppm on average. 

Without proper ventilation, nPB exposure from spray adhesives can be extremely high, into the 

hundreds of parts per million. 

6 
Figure 5. Distribution of nPB Exposure Data by Use Category 

Distribution ofnPB Exposure Data by Use Category 

40.0% -.:~~-:--.-~.~. ~-.. ~-"":·· 

35.0% 

~ 

g, 30.0% 

.! 

m 

(.) 

.::: 

~ 25.0% 

a. 

E 

m 

(/) 

~ 20.0% 0 

!!! 

Q) 

c.. 

~ 15.0% Cl 

m 

"E 

Q) 

~ 

Q) 10.0% c.. 

5.0% 

0.0% 

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ,o 0 0 0 0 0 0 0 0 0 0 0 " " " " '"); '"); "j ~ " lo'"" "'"" lo'"" ""' fO"' "'"" ""' ""' "'"" """' ""' ,o ,o ,o ,o ,o ,o ,o ..., " " ~ '"); "j ~ ~ lo ~ ~ ~ ~ ~ ~ ~ ~ ~ >-.: ,__v " " '"); '"); 

Concentration, 8 Hr TWA (ppm) 

7 

IE! Vapor Degreasing 

IIIIIIAerosols 

DAdhesives (Before Ventilation) 

DAdhesives (After Ventilation) 
References 

Aerosol data, 1998. Airborne Exposure Assessment of 1-Bromopropane, 1998 (Docket 

A-2001-07, item II-D-89) 

Kassem, 2001. November 16, 2001 Email from Mick Kassem, Albemarle Corporation, 

concerning exposure levels using nPB in various applications. (Docket A-2001-07, item 

ll-A-19) 

NIOSH, 1999. Letter from Dept. of Health and Human Services to Custom Products, 

Inc., December 1, 1999. Re: results ofDec. 1998 survey ofworkplace exposure to nPB 

at Custom Products. (Docket A-2001-07, item ll-D-6) 

NIOSH, 2000a. Letter from Dept. of Health and Human Services to Marx Industries, 

Inc., February 1, 2000. Re: results ofnPB exposure assessment survey conducted Nov. 

16-17, 1999. (Docket A-2001-07, item ll-D-7) 

NIOSH, 2000b. Letter from Dept. of Health and Human Services to Custom Products, 

Inc., December 21, 2000. Re: results ofnPB exposure assessment survey conducted Nov. 

16, 2000. (Docket A-2001-07, item ll-D-8) 

NIOSH, 2000c. NIOSH Health Hazard Evaluation Report ofnPB exposure from cold 

vapor degreasers at Trilithic, Inc. (HHE Report 2000-0233-2845; Docket A-2001-07, 

item ll-D-11) 

NIOSH, 2001. Letter from Dept. of Health and Human Services to STN Cushion 

Company, March 7, 2001. Re: Results ofnPB exposure assessment survey conducted 

November 14, 2000. (Docket A-2001-07, item ll-D-9) 

NIOSH, 2002a. NIOSH Health Hazard Evaluation Report: HETA#2000-0410-2891, 

STN Cushion Company, Thomasville, NC, August 2002 (Docket A-2001-07, item Il-A31) 

NIOSH, 2002b. NIOSH Health Hazard Evaluation Report: HETA #98-0153-2883 

Custom Products, Inc. November 2002. (Docket A-2001-07, item ll-A-49) 

Smith, R.L. 1998a. Assessments of occupational exposure to nPB in adhesive spray and 

metal cleaning applications. Written communications from Robert Smith, Albemarle 

Corporation to EPA, March 19 through June 26, 1998. (a) 3/19/98; (b) 4/21198; (c) 

4/22/98; (d) 4/23/98; (e) 4/24/98; (f) 5/1198; (g) 5/29/98; (h) 6/3/98; (i) 6/26/98 (Docket 

A-91-42, item X-A-57) 

Smith, R.L. 1998b. Additional information from Robert Smith (Docket A-91-42, item VID-114) 

8 
Vapor degreasing data, 2003. Exposure data from customers of two suppliers ofnPBbased solvents for vapor degreasing, 2003 (see attached spread sheet and emails) 

9