SUPPLEMENTAL REPORT TO THE CITY OF PHILADELPHIA

DEPARTMENT OF PUBLIC HEALTH/ AIR MANAGEMENT SERVICE S



### INCREASED TOXICITY and CARCINOGENICITY OF

n- PROPYL BROMIDE (1-BROMOPROPANE)

RELATIVE TO PERCHLOROETHYLENE

Adam M. Finkel, Sc.D., CIH

JUNE 20102

1. INTRODUCTION:

The city of Philadelphia has proposed to accelerate the federal (EPA) phase-down of perchloroethylene (“Perc”) in dry cleaning, due to health concerns for the residents (especially children) and workers in establishments co-located with cleaners. Although some co-commercial cleaners will likely stay with P erc and control exposures in colocated workplaces to the performance standard esta blished in the new regulations (at or below 40 ppb), others will switch to different solv ents, and all cleaners with co-located residences or “sensitive” facilities (schools, day care centers, hospitals, etc.) will either have to switch to another solvent or change their s ervice to “drop mode” (for cleaning at another location). The Ad Hoc Subcommittee of the Air Pollution Control Board (APCB) was concerned about ensuring that alternativ e solvents whose use might increase on account of the regulations would be safer whenev er possible, and certainly not more toxic than Perc: as its February 16, 2010 memo to t he full APCB indicated, the Subcommittee wanted Air Management Services to “Pro mote switching to clearly safer substitutes and seek to prevent the use of other ha zardous toxic substances as a substitute” (for Perc). Of the various “drain and drop” and other alternatives to Perc, some are clearly safer (e.g., wet cleaning, supercr itical CO 2 ,) some are probably less toxic but may raise concerns about flammability, but some are clearly more toxic.

I was asked by AMS to summarize the current scienti fic information about the relative toxicity of Perc and one particular alternative— n- propyl bromide (“nPB,” also known as 1-bromopropane). This report also discusses more g enerally the risk management issues that arise when a regulatory agency is faced with t he likelihood that well-meaning controls on a particular substance will lead to a n et increase in harm (Finkel 2007).

Absent a more comprehensive regulatory structure, t he obvious risk-increasing response to controls on Perc in dry cleaning will be for som e cleaners to substitute nPB for Perc. nPB was relatively unknown in the U.S. 10 years ago , but since then has been aggressively marketed as an unregulated alternative first to methylene chloride (regulated by OSHA in 1997), and later to Perc following EPA’s announced phase-down in dry cleaning. For example, here is a very frank descri ption from an industry website:

http://www.textilecleaning.com/npropylb.htm

. DrySolv is a newer alternative solvent that is available for drycleane rs to get out from under perc and its related rules, regulations, taxes, con tinually rising cost and general bad publicity. (emphasis added)

One of the major remaining manufacturers of nPB des cribes its advantages thus:

http://www.envirotechint.com/products/dry-cleaning/ details/drysolv

. DrySolv is a patented dry cleaning solvent that is non-chl orinated, nonflammable, non-hazardous, and is vastly more enviro nmentally responsible than PERC. It is a direct replacement f or PERC and other cleaning chemicals in the dry cleaning industry tha t works in your existing PERC dry cleaning machine. Research has shown DrySolv to be superior3

to PERC in that it cleans better, and cleans faster . Because DrySolv is non-hazardous, costly issues such as environmental compliance and waste disposal of PERC are eliminated or significantly re duced.

As this report will summarize, in my expert opinion, far from being “non hazardous ,” nPB is a potent neurotoxin, and has recently been s hown to be a potent animal
carcinogen . To a reasonable degree of scientific certainty, equal exposures to nPB will harm more residents and workers than would exposure s to Perc: both are harmful substances, but nPB is the more harmful of the two.

Even worse than comparable levels of exposure to th e two solvents (in theory) would be the potential for much greater exposures to nPB than to Perc in actual practice. nPB is more volatile than Perc (its vapor pressure is appr oximately 111 mm Hg at 25 C, whereas the vapor pressure of Perc is about 18.5 mm Hg), an d so with equivalent equipment and controls, cleaners who use nPB would be expected to experience higher concentrations than if they used Perc. Indeed, data from a forthc oming journal article (Blando et al., 2010) shows that in four New Jersey dry cleaners wh o recently switched from Perc to nPB, air concentrations of nPB were as high as 54 p pm as an eight-hour time-weighted average—Perc concentrations using similar (“third-g eneration”) equipment as the shops in New Jersey use tend to be only in the range of 1 -5 ppm (OSHA 2006). Moreover, a regulation that only mentioned Perc would further t ilt the playing field towards greater exposures to substitute materials, because the actu al comparison would be of controlled exposures to Perc versus uncontrolled exposures to the substitute(s). Data from AMS (referenced in Section 5 of my January 2010 final r eport on Perc) shows that uncontrolled exposures to Perc in co-located facilities can appr oach 1 ppm (a reading of 864 ppb was documented with limited sampling); although interve ntions to control Perc emissions can reduce these concentrations to the 40 ppb performan ce standard or below, there would be no requirement or incentive for cleaners to underta ke control measures if they were permitted to switch to nPB without such restriction s. So although this report will summarize the risk-increasing problem of comparable exposures to nPB versus Perc, in reality the untoward consequences of a regulation t hat does not anticipate and address adverse substitution would be much greater.

2. SCIENTIFIC OVERVIEW:

As this report will summarize, Perc at high levels (approx. 100 ppm) can cause moderate neurologic symptoms in exposed humans; at low level s (1 ppm and below) it can cause

much less severe but still worrisome neurobehaviora l symptoms. On the other hand, at high levels (roughly 50 ppm), nPB can cause severe neurological damage, but there are as yet no studies of neurobehavioral effects (present or absent) of nPB at low levels. Absence of evidence is not necessarily evidence of absence: in other words, we can’t assume that nPB won’t cause the same (or worse) neu robehavioral effects as Perc does at low levels. But presence of evidence trumps absenc e: in other words, we can be fairly4

confident that there is not a “Perc syndrome” of irreversible neuropathy at ro ughly 50- 100 ppm, because we have tested Perc at these level s and found different (less severe)

human effects.

Moreover, we can now compare the carcinogenic poten cy of the two solvents directly. The National Toxicology Program has now finished a set of lifetime cancer bioassays of nPB (NTP, 2009) to complement its 1986 studies of P erc. nPB is clearly somewhat more potent a carcinogen than Perc (see Section 2-C belo w). Although absence of evidence is not definitive here, I note that there are various interesting (though, in my opinion, not currently fully developed) theories as to why some of the Perc cancer results may be partially or wholly irrelevant to humans (see pp. 12-17 of my January 2010 report)— there have been no such mechanistic attempts to exp lain away the variety of tumors found in the nPB bioassays. 1

Bitter experience with human diseases caused by low -molecular-weight brominated compounds (e.g., male sterility in Dow chemical pla nt workers caused by dibromochloropropane (“DBCP”), a compound closely r elated to nPB; neurological disease in workers exposed to the pesticide methyl bromide) suggests that brominated compounds are generally more toxic to humans than t heir chlorinated analogs. Several of these brominated compounds have since been banned n ationally and internationally. This pattern of toxicity is consistent with the fact tha t the carbon-bromine bond is weaker than the C-Cl bond, and thus a brominated compound may m ore readily form an electrophilic intermediate that reacts with DNA, as compared to i ts chlorinated analog. Table 1 shows four pairs of compounds that differ only with respe ct to whether they contain bromine or chlorine atoms, showing that the brominated analog is up to 33 times more potent 2 :

1 Note particularly that in the Perc bioassay, 22 pe rcent of the test animals developed the sentinel tu mor type (mononuclear cell leukemia) with NO exposure, whereas in the nPB bioassay the control rate (of lu ng tumors) was only 2 percent. Although I believe the MCL response for Perc is real and reliable (see my January 2010 report), the enormous increase in lung tumors above control rates with nPB is even more compelling.

2 Note that although Perc is, of course, a chlorinat ed hydrocarbon, it does not appear in this table be cause there is essentially no toxicological or use inform ation on “tetrabromoethylene,” which would be its d irect brominated analog.5

TABLE 1

DIRECT COMPARISON OF POTENCIES OF BROMINATED v.

CHLORINATED ANALOGS

Note: when comparing RfCs, the more potent toxicant is the one that has the lower value (a lower concentration corresponding to the same “likely to be without app reciable risk” outcome); when comparing cancer pote ncy factors (“q 1 * ” values), the more potent carcinogen has the higher value (more tumorigenicity per unit of exposure).

Substance Brominated Analog Chlorinated Analog Ra tio Br:Cl toxicity

Ethylene di... X Ethylene dibromide:

q 1 * = 6x10 -4 (per ug/m 3 ) Ethylene dichloride:

q 1 * = 2.6x10 -5 (per ug/m 3 ) 23 : 1

Methyl X Methyl bromide:

RfC= 5x10 -3 mg/m 3 Methyl chloride:

RfC= 9x10 -2 mg/m 3 18 : 1

Vinyl X Vinyl bromide:

RfC=3x10 -3 mg/m 3 Vinyl chloride:

RfC=1x10 -1 mg/m 3 33 : 1

Chloro-di(X,X)

propane Dibromochloropropane

(“DBCP”):

RfC= 2x10 -4 1,2,3-trichloropropane:

RfC=3x10 -4 1.5 : 1

It is also important to note that various federal, state, and international expert bodies are gradually developing recommended or mandatory expos ure limits for nPB that are stricter than the corresponding ones for Perc (Tabl e 2). Each of these expert bodies develops recommended or binding exposure limits bas ed on a careful analysis of all available toxicologic and epidemiologic data, apply ing a coherent set of assumptions and rules for interpreting such data. Note in particul ar that these lower limits for nPB were

all set before the late 2009 release of the National Toxicology P rogram’s lifetime cancer bioassay on nPB, which if incorporated would tend t o drive the recommended limit lower

for nPB.

TABLE 2

NATIONAL AND INTERNATIONAL EXPOSURE LIMITS FOR

nPB and PERC

Type of Limit Limit for Perc Limit for nPB Ratio Perc : nPB

ACGIH Threshold

Limit Value® 25 ppm 10 ppm 2.5 : 1

California OSHA

PEL 25 ppm 5 ppm 5 : 1

Worksafe British

Columbia PEL 25 ppm 10 ppm 2.5 : 16

In addition to these decisions by expert bodies, in dividual companies have made decisions about nPB; in particular (Murphy 2001), a major multinational chemical company decided almost 10 years ago (long before th e case reports of neurotoxicity and the cancer bioassay were available) that it would c ease marketing nPB for solvent applications due to its toxicity. The document ann ouncing that decision said in relevant

part:

“nPB is a part of a toxicologically suspect family in which several compounds have toxic properties identified in animals and con firmed in humans. In 1995 and then in 1996, we learned that isopropyl bromide, th e structural isomer of nPB, had caused serious reproductive function problems in Ko rean and then in Chinese workers as well as blood effects following its use as a degreasing solvent... As

the effects observed in animals for iPB have also b een demonstrated in humans when used as solvent, the concerns expressed in 199 7 about the potential effects of nPB in solvent applications are reinforced.”

In addition, at least two other manufacturers have limited or eliminated the production of 1-BP for solvent applications. Great Lakes Chemical no longer sells 1-BP solvent blends. Albemarle Corp. has stated that use of 1-BP in adhe sive and other applications in which 1-BP exposure cannot be controlled should be restri cted or prohibited (NTP, 2003).

3. DETAILED TOXICOLOGICAL COMPARISION

The LC 50 (the airborne concentration that kills 1⁄2 of all tre ated animals) for nPB is approximately 7,100 mg/m 3 : the LC 50 for Perc is approximately 35,000 mg/m 3

, suggesting that nPB is roughly 5 times more acutely toxic than Perc. However, more relevant to regulatory policy are comparisons of ch ronic exposures to lower levels of the

two substances.

A. Neurotoxicity:

nPB, like Perc, can damage the central and peripher al nervous systems, but evidence to date strongly suggests that nPB is the more potent neurotoxin of the two. The severe effects of weakness and spasticity of the leg muscl es in humans correspond closely to effects seen in laboratory animals exposed to nPB:

• Ichihara et al. (2004) studied 27 female workers in an nPB production factory who were exposed to an average of 3 ppm (range 0.3 to 49 ppm). 15 of the workers showed diminution of the ability to sense v ibration in the fingers and toes, including one worker (who lost this ability c ompletely) whose exposure was 1.1 ppm.

• Majersik et al. (2007) studied six workers who used a solvent containing 70% nPB to glue together foam pieces; their exposures r anged from 91 to 176 ppm,7

with durations of between 3 to 36 months. The work ers experienced weakness and spasticity of the legs, chronic pain, memory loss, urinary incontinence, and daily headache while working with nPB. Even two years after cessation of exposure, some of the workers su ffered from “markedly impaired cognitive function.”

• Raymond and Ford (2007) studied eight workers expos ed to nPB in glue used in a furniture factory in North Carolina. Average exposures were approximately 80 ppm. The workers developed unstea dy, spastic gaits, loss of balance, and other neuromuscular signs and symptoms —in at least two of them, adverse effects (albeit milder in severity) w ere persisting eight years after having changed employment and presumed cessat ion of exposure.

• The CDC (2008) reported on two workers with severe nPB neurotoxicity: (1) an electronics worker in Pennsylvania exposed to ro ughly 180 ppm developed ataxia (difficulty walking), which was persisting m ore than a year after cessation of exposure; and (2) a dry cleaner in New Jersey who used “DrySolv” (see above) developed tingling, numbness, muscular twitching, and visual disturbances—no information was presented as to whether these symptoms persisted after he began using a respirato r at work (obviously, colocated residents and workers would/should not have the option of using protective equipment...). CDC wrote that this case “ likely represents a sentinel case of neurologic toxicity in the dry cle aning industry, and additional cases could occur as dry cleaners switch from perchloroethylene

use to 1-BP .”

Although Perc clearly can cause dizziness and CNS d epression at very high levels (above 100 ppm), at levels comparable to those in these nP B case reports and studies, nothing like the “nPB syndrome” of gait disturbances and pa in has been seen with Perc , over many decades of use. For example, although some of the earlier studies EPA references (Lauwerys et al. 1983; Seeber 1989—see p. 4-54 of E PA 2008) document effects of Perc at roughly 20 ppm that are more severe than the neu robehavioral effects used to set the RfC (e.g., lightheadedness), these studies revealed “no fine motor function deficits”— whereas slightly higher levels of nPB have caused i rreversible effects on the gross motor function of exposed workers.

In summary, at comparable levels (roughly 50-100 pp m), Perc produces moderate neurotoxic effects (diminished sensitivity to vibra tion; reduced nerve conduction velocities), but nPB can produce severe and apparen tly irreversible neuropathy, affecting gait and cognition. The neurobehavioral effects of Perc at much lower levels (1 ppm and less), such as decreased reaction time and decrease d color vision sensitivity, have not been looked for (yet) with nPB—but whether or not t hey are shown to occur, the clear danger of nPB at higher exposures makes controlling nPB levels an important addition to the Philadelphia regulation governing the use of Pe rc in co-located dry cleaners.8

B. Reproductive Toxicity:

There is much more concern about nPB than about Per c along this dimension. In particular, most of the workforce (64 percent of th e females and 75 percent of the males) of an entire factory in Korea was sterilized due to exposure to roughly 12 ppm of 2-BP (isopropyl bromide). 3 2-BP is a different substance than nPB, but its v ery high toxicity is

relevant here because it is an inevitable contamina nt of the commercial manufacture of

nPB. 4 California has listed nPB as “known to cause devel opmental toxicity in both

females and males” since 2004—it does not list Perc as a developmental toxicant.

The NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) evaluated the potential for 1-bromopropane (nPB) to produce a dverse reproductive and developmental effects in humans (NTP, 2003). CERHR concluded that there was convincing evidence for reproductive and developmen tal toxicity in experimental animals. Evidence in humans was limited, but in the monograph, note was made of a new case that was not available to the expert panel ind icating positive findings in women (altered menstruation) occupationally exposed to 1- bromopropane. The overall NTP

conclusion was that “there is serious concern for r eproductive and developmental effects of 1-bromopropane at the upper end of the human occ upational exposure range (18 to 381 ppm).” “Serious concern” is the highest level of NTP concl usion regarding the possibilities that human development and reproducti on might be adversely affected.

C. Carcinogenicity:

The U.S. National Toxicology Program began testing nPB in roughly 2001, and released an extensive report (NTP 2009) in late 2009. As wi th other brominated alkanes of low molecular weight tested previously, nPB showed “cle ar evidence” (according to NTP) of carcinogenicity in multiple animal bioassays. NTP noted that nPB caused rare tumors of the large intestine in both male and female F344 ra ts, and tumors of the lung and

3 Note especially that the workers in the North Caro lina furniture factory (Raymond and Ford 2007) were found to have been exposed to 2-BP at levels up to 0.68 ppm—this is less than 1/10 the amount that cau sed severe reproductive toxicity in Korea, but it shows that commercial formulations containing nPB in the U.S. may well have significant trace amounts of 2-B P. It makes sense that 2-BP levels would be about 1/200 that of 1-BP in air, since (Shubkin and Liima tta 1998) one of the patent holders recommends that when producing nPB, “the isopropyl bromide content should be kept low—for example, within the range of from about 0.01 to 0.5 %.” The higher figure (0.5% ) corresponds to 1 part in 200.

4 Note that because of trade secret concerns, we als o don’t know much about the stabilizers added to nP B. Apparently, while commercial Perc formulations used in dry cleaning only require about 1% stabilizer content, nPB products require about 6-7%. Although depending on the identities of the stabilizers, th is may not be a public health issue, even with stabilizers added nPB is more corrosive to metal than Perc, an d thus may be harder on dry cleaning equipment (see, e.g., the IRTA 2009 article which interviews a dry clean er in California who claims that switching to nPB crea ted a cloud of acid that “ate a hole in his boiler, completely destroyed the PERC machine and also corr oded a laundry dryer in the facility beyond repair” ).9

bronchus of female mice—it also noted that tumors o f the skin, pleura (mesothelioma), and pancreas in rats may have been related to nPB e xposure.

EPA has not yet analyzed the nPB bioassay data to c alculate a cancer potency factor (CPF) that could be compared to the CPF for Perc. As described in detail in my January 2010 report, the EPA CPF for Perc underwent an exte nsive set of modifications to account for the different pharmacokinetics of absor ption, partition, and excretion in rodents versus humans—no such adjustment can be mad e for nPB because no PBPK model currently exists for that compound. Neverthe less, it is routine and instructive to compare the CPFs on an equal footing (that is, with no PBPK modifications). I estimated the dose-response curves for both substances using a computer program (“MSTAGE87,” courtesy Edmund Crouch, Ph.D.) that emulates EPA’s linearized multistage program, and then, following EPA practice, calculated the upper 95 th percentile confidence limit on the linear term of the dose-response function, which EP A terms “q 1 * ,” or the CPF.

The most sensitive sex/strain/site combination for Perc carcinogenesis appears to be the mononuclear cell leukemia response in male rats (se e January report). In that experiment, Perc caused 14 cancers at 50 ppm (all P erc and nPB results are out of 50 animals per dose group), 22 at 200 ppm, and 27 at 6 00 ppm—at no exposure (control group), 11 cases of MCL were noted. In the recent bioassay of nPB, there was 1 lung/bronchus tumor at no exposure, 9 at 62.5 ppm, 8 at 125 ppm, and 14 at 250 ppm. Note that nPB clearly caused many more excess tumor s at lower doses as compared to

Perc.

The dose-response software yielded a q 1 * value of 1.95x10 -3 (per ppm) for nPB, as compared to a value of 1.46x10 -3 for Perc. By this comparison (which, again, canno t take PBPK into account, which could result in higher or lower relative potency for nPB compared to Perc), nPB is roughly 34% more potent per unit of exposure a carcinogen

than Perc is. 5

The chart below shows the two bioassays (in the bla ck-and-white version of this document, the Perc data points are diamond-shaped a nd the nPB data points are squares; the upper-bound linear slope estimate is a thicker line for nPB and a thinner line for Perc). In both cases, the y-values represent the n umber of tumor-bearing animals above the number in the control group. Note that the upp er confidence limit on the low-dose slope is larger (steeper) for nPB than it is for Pe rc.

5 Note that the recent National Academy of Sciences committee (NAS 2010) that looked carefully at the carcinogenicity data for Perc was divided about the confidence with which we should rely on the rat leukemia response, because of a possible species-sp ecific mechanism of action. Although I agree with those on the NAS committee who regard the leukemia data as relevant, if one did compute Perc’s cancer potency based on the kidney tumor data, the q 1 * value would instead be 3.8x10 -4 , which would make nPB

more than five times more potent a carcinogen than Perc.10

0 5 10 15 20 25 30

0 50 100 150 200 250

dose (ppm)# tumors above control response

observed perc tumor data

observed nPB tumor data

low-dose slope of Perc

low-dose slope of nPB

4. POLICY OVERVIEW:

Risk-risk tradeoffs are real and compelling—althoug h sometimes there is too much uncertainty about the eventual behavioral response to regulation (Finkel 2007) for government to regard a purported tradeoff as legiti mate, there clearly are cases where as one substance is more tightly controlled, a more to xic substitute will almost certainly replace it, causing a net increase rather than a de crease in risk. This reflects lack of good planning by government; the “regulatory czars” unde r both the Bush and Obama administrations (Sunstein, 1996; Graham and Wiener 1995) have each written extensively about the need for statutory change so that agencies will be forced to consider the risk-increasing consequences of their regulatio ns.

There are three basic responses to a valid concern that regulating X will cause substance Y to be used, with net risk-increasing results: (1) regulate X and ignore the consequences; (2) forego regulating X entirely; or (3) regulate b oth X and Y. The first response is dereliction of duty, and the second is cringing in the face of a more complicated problem; the third course of action generally makes the most sense.

Examples already exist of federal and state agencie s causing increased net risk by regulating particular solvents without considering that users will seek unregulated substitutes, especially whenever one solvent can be “dropped in” to replace another with little or no retrofitting. For example, Californiacracked down on Perc use as a brakecleaning solvent in auto repair shops in the late 1 990s; since then, case reports have arisen (CDC 2001) connecting serious neurological d amage in auto repair workers whose shops switched to n- hexane.

The momentum is clear that regulatory agencies shou ld and will think more seriously

about risk-risk tradeoffs. It is of course best to do so before it is too late. After the11

“genie is out of the bottle,” irreversible harm to human health or the environment may have occurred, but it is also important to emphasiz e that irreversible expense may also have been incurred: dry cleaners deserve the regula tory agency’s best current judgment about which substance(s) should not be used as subs titutes before they are led to make investments that later prove unwise. Sometimes the risks of current materials and their substitutes confront society with a true dilemma—bu t this is not such a case—there are ways to clean clothes safely without using a solven t that is even more toxic than Perc.

5. CONCLUSIONS

nPB is a potent neurotoxin, and has recently been s hown to be a potent animal carcinogen. As a result of my scientific analysis, I recommend that Philadelphia add a provision to its draft regulation forbidding dry cl eaners to substitute the more toxic alternative nPB for perchloroethylene (“Perc”). Th is is a laudable and forward-thinking improvement to the federal (EPA) dry cleaning rule, which will, in my opinion, increase risks to workers and nearby residents by encouragin g the substitution of the (federally) unregulated nPB for Perc in locales other than Phil adelphia. 6 To a reasonable degree of scientific certainty, exposures to nPB will harm mo re residents and workers than would exposures to Perc: both are harmful substances, wit h nPB the more harmful of the two. In addition to its plans to provide outreach and ed ucation to dry cleaners about ways to meet or go beyond the 40 ppb performance standard i n co-commercial facilities that wish to continue to use Perc, I applaud the City’s inten tion to provide informational materials

about the benefits of less toxic substitutes for Pe rc in dry cleaning.

6 Note that in the substitution of hexane for Perc, one could reasonably argue that while both substanc es are neurotoxic, only Perc is a probable carcinogen, and so the tradeoff was not necessarily an unfavorable one for workers. As this report will summarize, howeve r, both Perc and nPB are animal carcinogens, and so no such “silver lining” can be invoked in this case. Switching to nPB is likely to increase both cancer and

non-cancer risks.12

6. REFERENCES

Blando, James, D., Donald P. Schill, Mary P. De La Cruz, Lin Zhang, and Junfeng Zhang (2010). “Preliminary Study of Propyl Bromide Expos ure among New Jersey Dry Cleaners as a Result of a Pending Ban on Perchloroe thylene.” Journal of the Air and Waste Management Association, forthcoming August 2010 (Vol. 60, No. 8), 8 pp.

CDC, Morbidity and Mortality Weekly Report (MMWR), November 16, 2001, (Vol. 50, No. 45), pp. 1011-3. “ n- Hexane-Related Peripheral Neuropathy Among Automoti ve Technicians—California, 1999-2000.”

CDC, Morbidity and Mortality Weekly Report (MMWR), Dec. 5, 2008, (Vol. 57, No. 48), pp. 1300-2. “Neurologic Illness Associated with Occ upational Exposure to the Solvent 1-Bromopropane —New Jersey and Pennsylvania , 2007-2008.”

Environmental Protection Agency (2008). Toxicological Review of Tetrachloroethylene, In Support of Summary Informat ion on the Integrated Risk Information System. Report No. EPA/635/R-08/011A, June 2008, 556 pp.

Finkel, A. M. (2007). “Distinguishing Legitimate R isk-Risk Tradeoffs from Straw Men.” Presentation at the Annual Meeting of the So ciety for Risk Analysis, San
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Graham, J.D. and Jonathan Wiener, eds, Risk Versus Risk: Tradeoffs in Protecting

Health and the Environment. Harvard Univ. Press, 1995.

Ichihara, Gaku, and 14 others (2004). “Neurologic Abnormalities in Workers of a 1- Bromopropane Factory.” Environmental Health Perspectives, 112(13): 1319-1325.

Institute for Research and Technical Assistance (IR TA) (2009). “n-Propyl Bromide Destroys Equipment in Dry Cleaning Plant,” The Alternative (IRTA Newsletter): 18(3): pp. 1, 6, 7, Summer 2009.

Koh, J.M., et al. (1997). “Primary Ovarian Failure Caused by a Solvent Containing 2- Bromopropane.” European Journal of Endocrinology, 138(5): 554-6.

Majersik, Jennifer J. et al. (2007). “Severe Neurot oxicity Associated with Exposure to the Solvent 1-Bromopropane (n-propyl bromide),” Clinical Toxicology, 45: 2 70-6.

Murphy, Sandi (2001). E-mail from ATOFINA (multin ational chemical company, now known as Total/Arkema) to Dr. Michael Shelby, D irector of the NIEHS Center for the Evaluation of Risks to Human Reproduction. Sent Sept. 27, 2001; 3 pp. including attachment; complete document available a t http://cerhr.niehs.nih.gov/chemicals/bromopropanes/ pubcomm/Atofina.pdf

.13

National Academy of Sciences (2010). Review of the Environmental Protection Agency’s Draft IRIS Assessment of Tetrachloroethyle ne , prepublication copy, 140 pp.

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Occupational Safety and Health Administration (2006 ). Reducing Worker Exposure to Perchloroethylene (PERC) in Dry Cleaning. Report No. OSHA 3253-05N, 28 pp.

Rascoff, Samuel and Richard Revesz (2002). “The Bia ses of Risk Tradeoff Analysis: Towards Parity in Environmental and Health-and-Safe ty Regulation.” Univ. of Chicago Law Review, 69: 1763-1836.

Raymond, Lawrence W. and Marsha D. Ford (2007). “Se vere Illness in Furniture Makers Using a New Glue: 1-Bromopropane Toxicity Co nfounded by Arsenic,” Journal of Occupational and Environmental Medicine, 49(9): 1009-1019.

Shubkin, Ronald L. and Eric W. Liimatta (1998). “N -propyl Bromide Based Cleaning

Solvent and Ionic Residue Removal Process.” U.S. P atent No. 5,792, 277, granted August 11, 1998.

Sunstein, Cass (1996). “Health-Health Tradeoffs,” Univ. of Chicago Law Review, 63:

1533-71.

Wiener, Jonathan (1998). “Managing the Iatrogenic R isks of Risk Management.” RISK: Health, Safety & Environment 9: 39-82.