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INTRODUCTION Throughout this synthesis report there are numerous assess- ment statements, conclusions, discussion, and some identified needs for subsequent research. This chapter is a summary of key points and provides suggestions for logical steps to follow from this work. FINDINGS FROM THE LITERATURE REVIEW One of the primary goals of the synthesis was to identify and elaborate on published research regarding the many psycho- active chemical substances that drivers use. In particular, the synthesis team was in quest of information on psycho- active chemical compounds that might play a feasible role in sustaining driver alertness or promoting sleep, and therefore would assist in management of commercial driver fatigue. Although the literature review here does identify several chemical substances that may serve those purposes, this syn- thesis does not propose, nor prescribe specific usage protocols for any chemical substance described. Rather, it provides a reporting of the highlights of many research studies cited in the scientific literature, with a special focus on identifying those studies that purport to have measured the effects of chemicals on task performance related to roadway driving. Another goal was to cull through the scientific literature to identify and categorize the reported research on many other psychoactive substances having identifiable effects on the cognitive, psychomotor, and physiological performance of drivers. That is, one of the objectives was to assemble in one source document identification (at least a listing) of what has been published already, so as to ease the task of anyone desir- ing additional background information on these topics. Thus, in Appendix A, this synthesis presents a description of a vari- ety of chemical substances that drivers partake of, whether the evidence for psychoactive effects was strong or not. Addi- tionally, this synthesis presents in the References, not only a listing of citations used in the narrative text (Appendix D web-only), but also a supplemental bibliographic reading list of secondary source documents that pertain to the topics in this study (Appendix E web-only). In this synthesis, the coverage of the results of any indi- vidual study described within, by necessity, is brief. For more specific details, motivated readers are encouraged to acquire and consult the original journal articles. The literature review here is intended to provide important information to aid in the understanding of: 1. The state of scientific knowledge from published research findings regarding the health and performance effects of numerous chemical substances that sometimes are ingested by commercial drivers; 2. Findings and practices relating to which psychoactive chemicals offer promise to commercial drivers striving to sustain alertness and to manage driver drowsiness or fatigue during partial sleep deprivation, which is so often necessitated by extended freight delivery operations; and 3. What the literature and practice indicate to be acceptable sleep aids for use by commercial drivers in managing their sleep schedules during on-the-road operations, including at times of the day when it is not normally conducive to sleep. The comprehensive literature review reports numerous laboratory experimental studies of the performance of indi- viduals under the influence of many psychoactive chemical substances. Some of those chemicals (medications, drugs, etc.) have been safely used in various sustained work settings. Pre- dominately, these instances described have been in military operations wherein limited use of varying stimulant and sleep aid compounds has been permitted after a personâs experience with the particular compound is established first, voluntary consent for their use is obtained and then only under close medical supervision, with the constant scrutiny and control of safety officers charged to manage operational use of chemi- cals by their military teammates, partners, or âemployees.â Most of the experiments and the actual operational use of such chemicals documents examinations of âacuteâ applications, in which the chemicals or drugs were taken only on a short-term basis, usually lasting no more than several days duration. Only rarely did the reported studies measure drug effects in repeated applications over days and weeks as might be the need for commercial driver applications. This literature survey therefore reaffirmed that there are only a few viable psychoactive chemical substances that commercial drivers can legitimately and safely use as sleep aids (hypnotics) or as alertness enhancers (stimulants) during transportation operations. The circumstances involved in commercial driving in the United States are somewhat dif- ferent from those of U.S. military operations. Sanctioned pharmaceutical use in military operations requires controlled CHAPTER EIGHT SYNTHESIS CONCLUSIONS AND DISCUSSION 65
66 closed-loop medical and safety supervisory settings that stress safe use of psychoactive medications for measured short durations intended to achieve time-limited missions. Such use of medications would likely be very impractical as well as very costly to manage in a commercial driving setting. Sleep-promoting Compounds Available sleep-promoting compounds and hypnotics include classes of prescription anxiolytic agents, depressants, anti- insomnia medications, over-the-counter (OTC) sleeping pills, first-generation antihistamines that induce drowsiness, syn- thetically formulated hormones such as melatonin that promote sleep, and herbal and dietary supplements touted as relaxants. Research studies on each of those categories of sleep-inducers are described in the literature review in this report. Benzodiazepines The literature survey confirmed that the variety of benzodi- azepines used to induce sleep present a number of serious limitations for operational use in the transportation industry context. As the research results depicted in this survey con- vey, a large number of the hypnotics described in this report either have already been, or might in the future be, declared unsuitable for commercial driver use on the roadway. Nonbenzodiazepines The literature survey also points out that some of the newer prescription sleep-inducing drugs, nonbenzodiazepines with shorter half-lives, may be preferable to older drugs for use as anti-insomnia treatments, because the amount of sleep inertia or hangover effects rapidly dissipate as the drugs clear the bodyâs biological systems. Some of these newer nonbenzodiazepines (e.g., Zolpidem, Zopiclone, Zaleplon, Indiplon, Eszopiclone, Ramelteon, and Alterial) might feasibly be applied to induce short ânapsâ in sustained work scenarios, and therefore could be evaluated more closely by means of more scientific testing for their potential application as pre- scribed sleep-inducing compounds in the commercial driving community. Some of these hypnotics are already being pre- scribed by physicians to drivers, presumably at least to combat persistent insomnia. However, the FMCSA expert medical panel on psychiatric disorders and driver safety recommended âNoâ to nonbenzodiazepine hypnotics, and stated that a driver must wait seven half-lives if such drugs are used acutely, or seven half-lives plus one week, if under their chronic use (Expert Panel Aug. 2009, p. 7) (http://www.fmcsa.dot.gov/ rules-regulations/TOPICS/mep/report/Medical-Expert-Panel- Psychiatric-Psychiatric-MEP-Panel-Opin.pdf). Melatonin The popular and natural sleep hormone melatonin, produced synthetically and sold in health food stores, is identified as an available safe sleep-inducing compound that can be used without prescription. However, because it is classified as a âhealth food,â the manufacture and distribution of synthetic melatonin is not subject to FDA approval and, therefore, con- sumers cannot be sure of the quantity, purity, and quality of the product they purchase. More research on âgood qualityâ melatonin could be fostered with a goal of developing rec- ommended operational use protocols (recommended timing, dose levels, duration of use, etc.) for commercial drivers who might benefit from using this more natural sleep promoter. Proper use of synthetic melatonin might be especially beneficial after completing night driving and when daytime sleep oppor- tunities present themselves in over-the-road operations. Antihistamines as Sleep Aids It is known that many commercial drivers employ OTC first-generation antihistamines (e.g., those containing diphen- hydramine) to obtain relief from seasonal allergies; however, in some applications, drivers take them simply to assist in falling asleep. Several OTC sleeping pills also contain diphen- hydramine or similar compounds that induce drowsiness. Appropriate usage protocols (times of administration, dose levels, cautions, and so on) could be developed for use of such sleep-inducing compounds, specifically for application to the many work-rest schedules inherent in the commercial driving community. Additional research may be required to examine the combined use of melatonin and antihistamines as sleep aids. Additional research could be done to confirm whether or not the newer second- and third-generation antihistamines declared to be nondrowsy, are as efficacious for treatment of seasonal allergies as their advertisements claim. Then, protocols for their appropriate and safe use for treatment of allergies should be developed and promulgated for the com- mercial driving community. Alcohol to Induce Sleep As the literature review confirms, the use of alcohol to put one to sleep brings about risks that the sleep, and of REM dream- ing sleep as well so obtained may be disrupted in the later, deeper stages of sleep and therefore may not be as restful as intended. With larger amounts of alcohol there is always the risk of hangover upon awakening. Stimulants and Alertness Enhancing Compounds A large number of alertness-enhancing or wake-promoting compounds is available; however, it appears there is no solid scientific foundation for finding most of them suitable for use in commercial driving applications. Whereas caffeine, nicotine, and energy booster supplements are viewed as being acceptable for driving situations, almost all other effective (efficacious) stimulant drugs are not. Some stimulant com- pounds are illicit and illegal drugs (e.g., cocaine) and are deemed too deleterious to driving performance to permit their
67 use during operations on the road. For those licit-prescribed Schedule II stimulants, an FMCSA expert panel has opined that there is inadequate evidence for or against their safe use in commercial driving, and recommended âcontinued monitoringâ of the medical literature (Hartenbaum et al. 2006). Modafinil Described as an eugregoric compound (and therefore not an amphetamine-like drug), a âwake-promoting substance,â modafinil offers much promise for use as a stimulant, with probable application to the commercial driving community. Modafinil has been shown to increase alertness, memory, and planning activities in healthy adults. As laboratory research described in the review indicates, modafinil provides many of the same stimulant benefits that caffeine and other stronger stimulants provide, but with slightly different physiological side effects, some of them less offensive, such as not being as threatening to blood pressure as caffeine. A very important and interesting observation about modafinil is that, unlike any other stimulant (including caffeine), while a person is taking modafinil, he or she can still decide to go to sleep; that is, to take a nap without interference from the âdrug.â That feature of modafinil could be explored in subsequent research programs. Although several U.S. military medical laboratories con- tinue to research modafinil, more research could be specifi- cally designed to answer questions regarding the potential wider application of modafinil (or armodafinil) to commercial driving scenarios. In particular, research could help develop a suitable âusage protocol,â including identification of recom- mended dose levels, the time of day of administration, the time of administration within a work shift or during adjustments to shift changes, any limitations for the duration of more long- term usage of modafinil or armodafinil (e.g., weeks/months), and determination of whether or not there are interactions with other chemical compounds drivers consume, especially caffeine and antihistamines. Financial affordability of these relatively expensive medications might also be an inhibitor to commercial driver use. Caffeine Caffeine, the ubiquitous stimulant compound, is the most widely consumed psychoactive substance available. The litera- ture demonstrates that caffeine offers a relatively safe and effec- tive means of maintaining or restoring cognitive performance even under conditions of operational stress (see numerous citations in text). Caffeine restores cognitive function during prolonged wakefulness, and it can enhance certain types of cognitive performance, most notably vigilance and reaction times, in rested individuals, regardless of whether or not they are regular caffeine users. The doses of caffeine most likely to be effective without causing undesirable mood effects are within the range of 100 to 600 mg, and this amount of caffeine can easily be obtained in many readily available sources, including by drinking caffeinated coffee. Even with the significant amounts of caffeine research cited in the literature review however there does not appear to be a conveniently available ârecommended caffeine use protocolâ for how much (dose) and when to take in caffeine during commercial driving operations. The paucity of actual highway driving studies examining effects of caffeine suggests that more research on this obvious fatigue countermeasure needs to be focused on delineating numerous usage protocol variables for commercial driver alertness and fatigue management programs. It would be helpful to have an information packet that provides basic information about protocols for the use of caffeine, pointing out at least that as with any stimulant, the body adjusts to large intakes of caffeine, necessitating larger doses to obtain the same effect; that it takes about 20 min after consuming caffeine for the stimulation effects to kick-in; and that depending on the time of consumption before attempting to sleep, caffeine will affect sleep latency, quality, and rest- fulness. The differences in caffeine formulation (e.g., coffee, soft drinks, chewing gum, mints, and energy bars and drinks) also could be delineated and a description of some of the physiological side effects of caffeine use (e.g., raises blood pressure and nervousness) could be provided as well. One aspect of the research on caffeine that may warrant further exploration is the potential value of combining slow- release caffeine and a short nap (30 min) a technique reported as being successful in counteracting driversâ sleepiness in a partial sleep deprivation study. Not much information was located regarding either slow-release caffeine or combining naps with such stimulants as fatigue countermeasures. Nicotine Although nicotine is classified as a stimulant, the scientific literature describing its effects with regard to cognitive perfor- mance is equivocal. Whereas some laboratory evidence pre- sented indicates that nicotine can produce the enhancement of certain aspects of attention and cognition, no studies report true enhancement of sensory abilities, selective attention, learning, and other cognitive abilities such as problem solving and reasoning. Furthermore, nicotine has been demonstrated not to be effective in restoring alertness and cognitive perfor- mance during laboratory testing of sustained performance in the face of full sleep deprivation (48 h). Accordingly, any informational packets prepared for the commercial driving community should clearly highlight known facts to dispel common myths held about nicotineâs positive utility. Too many drivers are under the misimpression that the nicotine in their cigarettes will help maintain their alertness, and research illustrates that it probably does not. Supplements: Nutritional, Dietary, and Other A very large number and a wide variety of supplements are available and are being consumed by a large cross section of Americans, no doubt including numerous commercial drivers. As the literature survey herein suggests, the synthesis team
68 located only a few reports of experimental studies on most of the chemical compounds identified as supplements in this document. Although some scientists searching for the âideal stimulantsâ quickly discount the variety of supplements widely sold in truck stops and convenience stores, it is clear that commercial drivers are purchasing them. It appears incumbent on this community of researchers involved with commercial drivers to systematically examine the efficacy of many âsupplements,â and then to recommend protocols for their safe use. Accordingly, any risks associated with using these supplements, alone or in combination, or owing to concerns about their source and their purity, should be identified and the findings promulgated. Guarana Guarana (a caffeine-like substance) is showing up in many food and drink supplements, often in combination with other ingredients, some of them also touted as being psychoactive substances (e.g., caffeine, taurine, and ginseng). Guaranaâs caffeine-like ingredients, and its somewhat similar positive effects on cognitive performance to those of caffeine itself, suggest that guarana, alone or in combination with other sub- stances, should be investigated further. Additional research on guarana is called for to identify its effects individually and synergistically with other psychoactive ingredients in food and drink supplements. Then educational materials could be developed to promulgate the findings in the commercial driver safety community. Herbal Relaxants Herbal remedies are promoted to relieve stress, and promote relaxation and sleep. Although a number of herbal relaxants (e.g., passion flower, lavender, kava, valerian, ginseng, and St. Johnâs Wart) are described in the literature review here (see chapter five and Appendix C), not many qualifying sci- entific studies were found attesting to their efficaciousness, nor their potential effects on performance. A study to identify the increased use of such substances in the commercial driving community could determine whether or not subsequent con- trolled experiments of them are warranted. Nutritional Food Supplements Nutritional food supplements, amino acids, additional carbo- hydrates, antioxidants, multi-vitamins, and a myriad of others are described briefly in the literature review (see also Appen- dix C). At first glance, it does not appear that much addi- tional research on these items is warranted, at least not by way of prioritization in comparison with the other supple- ments that should be investigated further, such as those listed in the previous paragraph. However, because drivers and their employers are inquisitive about what they see, hear, and read about, it is important to describe what is known about some of the more widely advertised nutritional food items and to incorporate that information in some âhand-outâ literature on the whole category of supplements outlined in the literature review in this synthesis. Functional Energy Drinks The active ingredients (caffeine plus others) in some functional energy drinks (FEDs) were found to impact (interrupt) some aspects of daytime sleep following a simulated night shift. These researchers concluded that whereas FEDs may be effective âpepper-uppersâ for a single night shift, additional investigatory research is warranted into the use of FEDs over successive night shifts; and also to investigate the effects of drinking multiple containers of FEDS on the same dayâ that is, daily dose determinations. The commercial advertising media has barraged the public with countless claims of the benefits of new energy drink products. The daily use of popu- larly sold energy drinks (e.g., Red Bullâ¢, Monster Hitmanâ¢ shots, and a dozen others containing psychoactive substances) is quite widespread. The synthesis team suggests that some good laboratory research on this category of supplements is warranted to set the record straight regarding their effica- ciousness, or lack thereof, and, if possible, to delineate any recommended use protocols and identification of risks or hazards in consuming such products. RESULTS AND DISCUSSION OF MEDICAL EXAMINERS SURVEYS Since at least the 1970s, the use by commercial drivers of supplements, drugs, and prescribed medications has been recognized as accident-associated features of transportation crashes, without clearly identifying specific casual inference (NTSB studies and reports). Medical providers and examiners are frequently faced with decisions to qualify (or not qualify) drivers who admit to taking medications and prescribed psychoactive chemical substances, many of which are not covered or not covered consistently in published guidance from the FMCSA (Graziano et al. 2011). The convenience survey of medical examiners in this synthesis study gave insights into some aspects of how they conduct their work in accomplishing Certification of Driver Medical Examinations (CDMEs). The survey highlighted some of their knowledge base and the voids, in terms of dealing with chemical sub- stances in their exams of commercial drivers, and it portrayed some differences in practice approach, part of which might be at least regionally based. Although the findings of the survey of 23 medical examiners are outlined in detail in chapter six, some of the more cogent points are reiterated here by way of summary and conclusions. â¢ Medical examiner variance. CDME examiners have varying knowledge, attitudes, and beliefs leading to actions anticipated in certification decisions with respect to drivers who admit to taking prescription,
69 self-administered medications or drugs, and chemical supplements. â¢ Regional differences. There was significant regional vari- ation in responses (Salt Lake City, Utah, versus Reno, Nevada) that can possibly be attributed to the experience and number of examinations performed by individual examiners. Medication Survey Medical Examiner Response Inconsistencies Surveyed medical examiner responses to particular drugs and medications were inconsistent, and for one medication (Methadone), inconsistent with published federal regulations. For example, in the synthesis survey 8 of 23 surveyed medical examiners indicated they would issue a conditional certificate to a commercial driver who admitted using methadone [for- bidden under 391.41(b)(12)]. Tramadol, on the other hand, was acceptable to slightly more than half of the 23 surveyed CDMEs (with detailed history provided in the clinic). Tra- madol was an accident associated factor (medication) in at least one NTSB investigated accident (A.J. Barberi, DCA04MM001, Oct. 15, 2003). Response to Stimulants Commercial drivers admitting to the use of stimulants pro- voked mixed and varied responses from medical examiners. More than half of the surveyed examiners (14 of the 23) anticipated providing medical certification to a driver who admitted taking amphetamine. This was most often condi- tioned on receiving a treating physicianâs written statement, but could also occur with only a detailed history in clinic (3 of 23). Examiners indicated that medical cards were gener- ally issued for drivers admitting use of prescription stimu- lants (d-amphetamine, methylphenidate, and modafinil) with or without an accompanying written statement from the pre- scribing physician and additional medical history in the clinic. Antidepressants are usually approved for drivers who admit to taking them, after obtaining a detailed history in the clinicâ with the exception of lithium (used for bi-polar disorder), for which a provider written statement would be required by more than half of the respondents. Responses from the majority of (but not all) examiners indicated that first-generation antihist- amines are frequently (but not always) associated with instruc- tions given to drivers not to take them within 8 h of driving. Second-generation antihistamines had fewer such warnings from the medical examiners. Neuroleptics and Hypnotics The broad class of neuroleptic medications queried drew mixed responses. Medications typically used for neuropathy (gabapentin and pregabalin) were conditionally approved for more than three-quarters of respondents, based on detailed medical history or prescribing physician written statements (or both). Drivers admitting use of dilantin, and particularly phenobarbital (typically used to prevent seizures or for neu- ropathy), were either never qualified or required a prescrib- ing physicians written statements in the majority (but not all) respondents. Sedatives and hypnotics were also generally widely accepted, with the examiners offering advice to the drivers regarding not taking the medication within 8 h or more before driving. Of particular note were the longer-acting seda- tives clonazepam and trazodone (an antidepressant frequently used off-label as a hypnotic). Other Medications Movement disorder medications appeared on the survey list of medications specifically owing to their use for Restless Legs Syndrome and product warnings for episodes of âsudden onset sleepinessâ that have been reported to cause motor vehicle accidents in private vehicles. There appeared to be little aware- ness of these factors in that only 2 of 23 the examiners sur- veyed answered âNever issueâ and slightly less than half would issue a certificate conditioned on driving no sooner than 8 h for drivers admitting use of pramipexole (MirapexÂ®) or ropinirole (RequipÂ®). Drivers who admitted use of selected cardiac medications would generally be approved with addi- tional history or a prescriberâs written note. Examiners sur- veyed seldom marked âNever approved.â One of the listed medications, dobutamine, is primarily used in ambulatory treatment of severe congestive heart failure. NTSB identified dobutamine as an accident-associated factor in one NTSB investigated crash. [NTSB HAR 01/01 (PB2001-96201)]. Similarly, when asked about anti-arrhythmic amiodarone, only 3 of 23 examiners answered that they would never issue a medical certificate, with the majority indicating that drivers would be required to submit a prescriberâs written statement. Other medications with a propensity to cause sedation or adverse drug reactions or interactions, as well as adverse psy- chological effects, were generally not uniformly handled with respect to certification decisions. This was particularly true regarding varenicline (ChantixÂ®), for which only 35% of sur- veyed examiners answered they would âNever issueâ a medical certification card, despite advisory information to that effect provided by the FMCSA, which had been posted on FMCSAâs website in FAQ and in a statement from the administrator. Driver Education and Employer Interactions â¢ Convey little education. Surveyed medical examiners reported that they generally provided little education or guidance on safe medication use to commercial drivers or their employers in the context of their CDME process. â¢ Principal employer communication. Interactions between medical examiner and driversâ employer, including verbal and making the âLong Formâ available to employers were
reported to vary by region, for factors that are unclear from the survey. Medical examiner comments indicated that those who did communicate information about the driver exams to the employers mostly were required to explain only if a driver did not âPass.â â¢ No lists of prohibited drugs were made available by the medical examiners to employers (motor carriers). Suggestions for Further Research The results of the survey of the medical examiners who con- duct CDM examinations prompted a number of suggestions for further research: â¢ To support development of an evidence-based list of approved medications and supplements. â The current testing required under Part 40 for ille- gal drugs of abuse does not fully address accident- associated medication questions for legally prescribed medications or supplements. Research could be under- taken to examine the potential for expanded drug test- ing of drivers to expand knowledge of actual med- ications taken (rather than only those admitted) in pre-employment, randomly, and in post-accident settings (similar to rotational testing for drugs of abuse performed by the U.S. military). Expanded post- accident testing for medications, as well as illegal drugs, has been called for in other settings (e.g., Expert Panel on Licit Schedule II drug use). â A methodology could be developed to address acci- dent causal inference that would cover the use of med- ications and other chemical substances (accident risk modeling, similar to fatigue risk modeling). â¢ To support more consistent practice among medical examiners of commercial drivers with respect to drugs, medications, and fatigue advising: â Specific medical examiner training materials could be developed that would focus on medications, sepa- rate from the underlying medical conditions, with a view to framing them in the context of previously investigated accidents where the medications have played a role as a causal associated factor. â Research could be undertaken toward compiling an anthology of accidents with medications as causal associated factors be published and analyzed from the point of view of the medical examiner. In particular, this treatise should cover those chemical substances identified in commercial driving settings. MOTOR CARRIER POLICIES REGARDING CHEMICAL SUBSTANCES With American Transportation Research Institute assistance, 31 company surveys were returned from safety and health officials and other company management personnel. Those that returned surveys (mostly truck carriers) consisted of 16 for-hire, 7 private, 7 truckload, 5 less-than-truckload, and 2 specialized companies. Representing more than 25,000 com- pany drivers, and more than 4,000 leased/owner-operator drivers, the range of the number of drivers was from a mini- mum of 10 drivers per company to a maximum of more than 6,200 drivers, with an average of 816 drivers per company. Although 29 of the 31 respondents in the survey indicated that their company had some form of policy regarding driver use of chemical substances, only 24 indicated that they had policies concerning prescription medications, 24 for alcohol, 23 for illegal drugs, and 12 for OTC medications. When asked if they had policies regarding other chemical substances, eight declared they had a policy concerning sleep aids, six for legal stimulants, and three for nutritional supplements. In answer to the more open-ended questions on the survey, a number of the companies expressed interest in obtaining more usable information, education, and guidance on the many chemical substances available to their drivers (employees). Some companies requested information on what chemical substances are acceptable for use by commercial drivers and which chemicals are not suitable. This in itself suggests that one outcome of this survey done for this synthesis study would be to develop more informative guidance information; âhand outâ materials on the most common forms of chemical substances used by commercial drivers. OVERALL CONCLUSIONS FROM THE SURVEY OF MEDICAL EXAMINERS AND MOTOR CARRIER MANAGERS â¢ Solid information packages are not available. All three elements of this synthesis on chemical substances (literature review, and surveys of carriers, employers, and medical examiners) point to the lack of detailed information about the numerous chemicals, drugs, sup- plements, popular energy enhancement products, and so on that might have an impact on commercial driversâ performance and health. Such information, presented in user-friendly packages, could be of benefit to three communities: (1) commercial drivers and their employ- ers; (2) medical providers who either treat commercial motor vehicle (CMV) drivers or who perform medical certification exams of drivers; and (3) representatives of the commercial driving safety community, researchers, and policy makers, who all must stay abreast of pharma- ceutical developments, nutritional supplement market- ing, and medical practices that involve the influence of psychoactive chemical substances with CMV driving and roadway safety issues. â¢ Additional research needed on some chemical sub- stances. As specified throughout the literature review, and highlighted in the conclusions, transportation researchers concerned with CMV safety issues can identify numer- ous areas where additional research may be called for regarding the chemical substances available to com- mercial drivers and that may impact driver performance and health. 70