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Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Letters to the Editor Published online: 03 Aug 2010.
To cite this article: (1992) Letters to the Editor, Archives of Environmental Health: An International Journal, 47:5, 388-390, DOI: 10.1080/00039896.1992.9938380 To link to this article: http://dx.doi.org/10.1080/00039896.1992.9938380
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Letter to the Editor.-Review articles written across disciplinary and professional lines may elicit puzzling and unexpected responses. Seldom has this been better illustrated than by Drs. Ziem and Davidoff‘s rather wide-ran ing editorial critique’ of my review of environmental odor pollution! Controversy abounds regarding the role of odor perception in the pathogenesis of acute and reversible symptoms from indoor air pollution, ambient (industrial) air pollution, and idiopathic reactions to environmental stimuli (“multiple chemical sensitivities” or “MCS”). Matters are further complicated by the fact that a phenomenon closely related to odor perception (i.e., sensory irritation from airborne chemicals) is studied by two different groups-toxicologists and psychophysicists-who use very different methods and descriptive termin~logies.~,~ In this context, promoting communication among clinicians, scientists, and air pollution professionals requires careful attention, not only to technical detail, but also to differences in professional perspective and vocabulary. Some of the differences between my paper and Drs. Ziem and Davidoff‘s editorial are more apparent than real. For example, I share their concern that my exposition of the mechanisms whereby odors trigger somatic symptoms may be used to downplay the toxicological significance of chemical exposures. Careful history taking, exposure assessment, and dose-response evaluation are always indicated in the evaluation of health complaints imputed to toxicants. I also wholeheartedly agree that “there is no such thing as a chemical odor without a chemical; clean air doesn‘t smell like chemicals.” In fact, the odor pollution review was originally written to provide a resource to air pollution and public health officials who have been reluctant to undertake environmental odor abatement actions, using California’s relatively stringent nuisance laws. Finally, I concede that the value in indices such as Amoore’s “Odor Safety F a c t ~ I ”lies ~ not in comparing odor thresholds to specific exposure standards,6 but in the notion that-even after a rigorous review of available data on chemical hazards-chemicals will be found to vary in their odor-warning properties. Notwithstanding the above points of agreement, we differ in our estimation of the ability of odors-as odors-to produce symptoms. Most members of the lay public who experience an involuntary wave of nausea when smelling spoiled food or when passing by a rendering plant consider themselves to have been “repulsed” by the odor, rather than intoxicated. Most scientists would agree with that assessment. Numerous amines 2nd reduced sulfur compounds, all of which are extremely potent odorants, are produced by spoilage organisms and industrial processes, and they can clearly elicit acute symptoms at levels that existing toxicologic models would be hard-pressed to explain. If one is committed to understanding such phenomena, one has the choice of forcing these observations into the toxicologic paradigm or of borrowing tools from the discipline of psychophysics. The latter field, also known as “sensory science,” is concerned with the stimulus-response characteristics of the various sensory modalities. In the context of odor (and trigeminally mediated sensory irritation), psychophysicists have made important contributions to the understanding of human responses to low-level airborne contaminants (described below). Drs. Ziem and Davidoff, significantly, approach this question with the belief that pathophysiologic mechanisms that involve perception -particularly those mediated by odors per se-are somehow less valid or important than those for which a toxicologicallbiochemical mechanism can be found. As noted below, this assumption is not necessarily shared by those who work in the field of air pollution. Ziem and Davidoff argue by analogy: smog and environmental tobacco smoke (two former “nuisances”) have been shown to cause irreversible physiological impairment; therefore, all symptomatic responses to low-level airborne contaminants will one day be found to have a toxi-
388
cologic basis. They attempt to bolster their case by lumping indoor air pollution, MCS, and environmental odor pollution together as “sub TLVIPEL” exposure problems, implying shared pathophysiology. However, in building their case regarding “subTLVlPEL” exposure problems, Ziem and Davidoff have considered only a limited spectrum of explanations for various published and unpublished findings. For example, after noting that MCS patients frequently experience dysosmias, whereas sick building subjects “focus[ed] on the odor of something that had made them ill previously,” the authors assert: “Observations of this type suggest that CNS dysfunction needs to be explored.” Whereas neurotoxic explanations are not totally implausible, other possibilities also exist. For example, there is a striking similarity between “focusing on the odor of something that made them ill previously” and”re-experiencing of a traumatic event” (cf. Schottenfeld and Cullen‘s “atypical post-traumatic stress d i ~ r d e r ” ) . ~ Also, in their explanation of the dysosmias experienced by MCS patients, the authors ignore the converse possibility, i.e., that individuals whose primary pathology is olfactory dysfunction (infectious, traumatic, inflammatory, or chemically may be labeled ”MCS” because of their anomalous response to odorant stimuli. Ironically, the very paper they cite to counter the thesis that odors precipitate asthma is entitled ”Effect of Odors in Asthma,” and it reports effects from such toxicologically innocuous incitants as body and cooking odors (as well as irritating cleaning products and cigarette smoke).” Mercifully, they did not cite Eriksson‘s “Flowers and Other Trigger Factors in Asthma and Rhinitis,” which documents odor-related responses even among ionatopic subjects.’* Drs. Ziem and Davidoff consider chemical exposure scenarios qualitatively, without reference to exposure levels or credible routes of exposure. They fault Bruvold‘s study of odor annoyance near wastewater treatment plants for not examining pulmonary f~nction;’~ exposure levels barely exceeded the odor threshold, very few respondents reported symptoms of any sort, and studies in more heavily H,S exposed cohorts have failed to demonstrate pulmonary function a b n~rmalities.’~ Drs. Ziem and Davidoff make much of the organophosphate (OP) activity of the mercaptan-releasing pesticides in the cotton d e f ~ l i a n t ’and ~ nernatocidel6 studies. Not mentioned was the weak OP potency of the cotton defoliant in question, the exceedingly low levels at which the cotton defoliant was documented in community air (average 2-6 parts-per-trillion among detectable samples), or the fact that the nematocide in question was incorporated directly into the soil in granular form, effectively precluding its dissemination in the environment. On the other hand, the odorous contaminants that off-gassed from soil or foliage in these cases (n-butyl and n-propyl mercaptans) were reported by community members to produce strong and offensive odors. Drs. Ziem and Davidoff imply that the terms nuisance and annoyance trivialize community health complaints. Part of the difficulty may arise from the very different meanings these terms have in everyday language, in clinical or industrial hygiene practice, and in air pollution control circles. In California, classification of an air pollution source as an ”odor nuisance” has anything but trivial consequences. Such an action opens the door not only to monetary penalties, but also to abatement orders; the latter can potentially lead to the closure of an industrial facility if control measures are not instituted timely. And far from denigrating toxicological issues, nuisance statutes are part of a two-pronged regulatory strategy in our state (the other involving airborne emissions inventories, exposure modeling, and sitespecific chemical risk assessment^).'^ If, in contrast to the editorial in question, one accepts the possibility that low-level chemical stimuli may exert adverse effects by mechanisms not normally addressed by toxicologists, one is then free to consider the contributions of psychophysics to our understanding of
Archives of Environmental Health
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low-level exposure phenomena. In the same issue of this journal in which the original odor pollution article appeared, several authors a p plied psychophysical techniques to the study of indoor air pollution. KjBergaard documented eye irritation to CO, using subjective endpoints;18 Hudnell similarly used subjective endpoints in documenting headaches, eye irritation, and throat irritation in response to a mixture of volatile organic compound^.'^ True to the predictions of psychophysics, odor waned, and irritation mounted over the course of exposure. Psychophysicists have been successful in explaining structure-activity and dose-response relationships for sensory irritation from airborne chemicals with moderate to weak chemical reactivity, which clearly exceeds the explanatory powers of current animal toxicologic models.20r21Sensory irritation, as documented b psychophysicists, in turn mutually interacts with odor perception?2,2J In my view, the two paradigms (toxicologic and psychophysical)are complementary, with odor perception and trigeminal stimulation potentially explaining those acute and reversible symptoms, which, at times, occur at exposure levels too low to be reasonably ascribed to toxicologic mechanisms, Drs. Ziem and Davidoff, however, maintain that psychophysical explanations are apparently “psychologic” (their word). Under the influence of such artificial parochial barriers, the discussion of low-level exposure phenomena will continue to generate more heat than light.
Dennis Shustennan, MD, MPH California Environmental Protection Agency Office of Environmental Health Hazard Assessment Berkeley, California
References 1. Ziem GE,Davidoff LL. Illness from chemical ’odors‘: is the health significance understood?Arch Environ Health 1992; 4768-91. 2. Shusterman D. Critical review. The health significance of environmental odor pollution. Arch Environ Health 1992; 4 7 76-87. 3. Cain WS. Perceptual characteristics of nasal irritation. In: Green BC, Mason JR, Kare MR (Eds.) Chemical senses, Vol. 2, Irritation. New York, Marcel Dekker, 1990, pp. 43-58. 4. Cain WS. A functional index of human sensory irritation. In: Seifert 6, et al. (Eds.) Indoor Air ‘ 8 7 Proceedings of the 4th International Conference on Indoor Air Quality and Climate (Vol. 2). Institute for Water, Soil and Air Hygiene, Berlin, 1987. 5. Amoore JE, Hautala E. Odor as an aid to chemical safety: odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. J Appl Toxicol 1983; 3972-90. 6. Robinson JC, Paxman DG. The role of threshold limit values in U.S. air pollution policy. Am J Ind Med 1992; 21:383-96. 7. Schottenfeld RS, Cullen MR. Recognition of occupation-induced post-traumatic stress disorders. J &cup Med 1986; 28365-69. 8. Davidson T, Jalowayski A, Murphy C, Jacobs RD. Evaluation and treatment of smell dysfunction. West J Med 1987; 146:434-38. 9. Doty RL. A review of olfactory dysfunctions in man. Am J Otolaryngol 1979 1:57-79. 10. Cometto-Muniz JE, Cain WS. Influence of airborne contaminants on olfaction and the common chemical sense. In Getchell Tv, et al. (Eds.): Smell and taste in health and disease. New York Raven Press, 1991; pp. 765-785. 11. Shim C, Williams HM. Effect of odors in asthma. Am J Med 1986; mi8-22. 12. Eriksson NE, Lowhagen 0, Nilsson J-E, Norrlind K, Wihl J-A. Flowers and other trigger factors in asthma and rhinitis-an inquiry study. Allergy 1987; 42:374-81. 13. Bruvold WH, Rappaport SM, Wu TC, Bulmer BE, DeGrange CE, Kooler JM. Determination of nuisance odor in a community. J Water Pollut Control Fed 1983; 55229-33. 14. Dales RE, Spitzer WO, Suissa S, Schechter MT, Tousignant P, Steinmetz N. Respiratory health of a population living downwind from natural gas refineries. Am Rev Respir Dis 1989; 139: 595-600. 15. Scarborough ME, Ames RG, Lipsett MJ,Jackson RJ. Acute health effects of community exposure to cotton defoliants. Arch Environ Health 1989; 44:355-60.
September/Oaober 1992 [Vd. 47 (No. 5)]
16. Ames RG, Stratton JW. Acute health effects from community exposure to N-prop$ mercaptan from an Ethoprop (MocaP)treated potato field in Siskiyou County, California. Arch Environ Health 1991; 46:213-17. 17. State of California. Health and Safety Code: Sedions 3479 and 41700 (Nuisance Statutes); Section 44300 et seq. (Air Toxics “Hot Spots” Informationand Assessment Act). 18. Kjaergaard S, Pedersen OF, Molhave L. Sensitivity of the eyes to airborne irritant stimuli: influence of individual characteristics. Arch Environ Health 1992; 4745-50. 19. Hudnell HK, Otto DA, House DE, Molhave L. Exposure of humans to a volatile organic mixture. [I. Sensory. Arch Environ Health 1992; 4731-38. 20. Cometto-Muniz JE, Cain WS. Thresholds for odor and nasal pungency. Physiol Behav 1990; 48:719-25. 21. Cometto-Muniz JE, Cain WS. Nasal pungency, odor, and eye irritation thresholds for homologous acetates. Pharmacol Biochem Behav 1991; 39983-89. 22. Cain WS, Murphy CL. Interaction between chemoreceptive modalities of odour and irritation. Nature 1saO; 2W255-57. 23. Cain WS. Contribution of the trigeminal nerve to perceived odor magnitude. Ann NY Acad Sci 1974; 2372834.
Response. Dr. Shusterman, in his article’ and in his response to our editorial, moves toward an explanation of symptoms that arise in conjunction with indoor, industrial, and community sources of odorous pollutants and toward a conceptualization of the pathogenesis of such conditions as sick building syndrome (SBS) and multiple chemical sensitivities (MCS). Our disagreements with Dr. Shusterman go beyond parochial concerns, misunderstandings related to terminology, disputes about the interpretation of specific chemical exposure scenarios, etc. The central points of contention are Dr. Shusterman‘s primary assumptions and proposed research agenda for scientists. Throughout his writings, Dr. Shusterman characterizes conditions that arise in conjunction with chronic, relatively low exposures to odorous pollutants as comprising only “acute and reversible symp toms.” That assumption is untenable. Credible studies of the natural history of illness complaints after chronic community, industry, and indoor exposures are unknown to us., Nor is it known whether, as patients report and some observers speculate, there is an induction phase for conditions such as SBS, MCS, and MCSlike conditions (i.e., acquired intolerance to organic solventsZ or pesticides3 It is clear, however, that affected individuals often suffer daily during many years after becoming ill and that many perceive their first 30 years as very healthy ones. In a pilot study in progress, SBS subjects, on average, reported feeling ill more than 20 h/wk and had more than 10 symptomdwk; 30% reported the need for 12 h or more recuperation time, once they became sick after environmental exposures. Moreover, it was not unusual for SBS subjects to report permanent changes in susceptibility to exposures that they had once considered inconsequential. MCS is definitely a chronic condition In our pilot study, affected individuals reported more than 60 hlwk of illness, accompanied by an average of 20 symptomdwk; 40% reported taking 1-3 d or longer to recuperate after exposures. It was rare for those with MCS to report returns to pre-exposure health status. Also implicit in Dr. Shusterman‘s writings is the assumption that the effects of chronic exposures to multiple pollutants at low levels in varied human populations have been investigated thoroughly and are well understood. That assumption is critical for labeling such pollutant exposures “odor pollution” and for asserting that “exposure assessment, history taking, and dose-response evaluation” clarify the pathogenesis of responses to such exposures. This assumption, in our opinion, is also in error. Research on physiologic responses to chronic exposures of mixed pollutants at relatively low levels in susceptible human populations is sparse. Although the jury is out, more than a handful of recent studies suggest that measurable physiologic responses can underlie health effects from chronic exposures to common chemicals at levels that were not previously suspected of inducing physiologic effects. In a chamber analogue study of SBS, for example, Koren et a1.4 found evidence of inflammatory responses in the u p per airways of healthy young male subjects, as determined by the number of polymorphonuclear neutrophils (PMN) present in nasal la-
389
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vage. Rodgers and Ellefson5found that acute oral administration of as little as 0.25 mglkg of purified malathion modulated leukocyte respiratory burst and phagocytic activity and caused mast cell degranulation in the peritoneal cavity in mice. Previous studies showed that it would take more than 715 mdkg of malathion to affect plasma cholinesterase.6 The authors suggested that some health effects reported by humans may have been due to the nonspecific release of mast cell products. Schwartz et al.’ found that exposure to solvents at levels considered safe was associated with evidence of neural damage, as reflected in olfactory dysfunction and deficits in learning in memory. Biologically plausible patterns of symptom reporting also occur in noncomplaining populations at exposures considered safe by current standards. During the investigation of symptoms of 1 OOO noncomplaining occupants of mobile homes in California, Liu et aL8 linked eye, skin, and upper respiratory irritation with exposures to formaldehyde just below the 0.1 ppm level, i.e., the level that the Environmental Protection Agency designates to be the threshold for irritation. Overall, individuals with allergies and chronic respiratory conditions experienced higher rates of symptoms. Whereas irritation is an inflammatory process, and inflamed passageways show increased susceptibility to bacteria and chemicals, irritation alone may lead to disease. Dr. Shusterman would channel investigations of the health effects of chronic, relatively low-dose exposures to odorous pollutants narrowly. He would have scientists investigate explanations that rely on odor perception/malodor, odor dysfunction, psychophysiological law, and psychopathology (e.g., atypical post-traumatic stress disorder). What is needed instead, we submit, is comprehensive health effects research. Before coming to any conclusions, it is imperative to study chronic, as well as acute, low-dose exposures to multiple pollutants; to target relevant psychologic and physiologic (including neurologic and immune) responses; and to focus on vulnerable populations (not simply healthy young adult males who are, by and large, not the ones becoming ill). It is also important to gather prospective data on cohorts of affected individuals and, in addition, to examine the natural history of these conditions. Modelbuilding that
390
focuses research in the psychologic/psychiatric/psychophysiologic arena i s premature; there are too many unknowns about “the health significance of environmental ’odor‘ pollution.”
Linda Lee Davidoff, Ph.D. Division of Occupational Health Johns Hopkins University Baltimore, Maryland
References 1 . Shusterman D. Critical review. The health significance of environmental odor pollution. Arch Environ Health 1992; 47:76-87. 2. Gyntelberg F, Vesterhauge S, Fog P, lsager H, Zillstorff K. Acquired intolerance to organic solvents and results of vestibular testing. Am j Ind Med 1986 9363-70. 3. Tabershaw IR, Cooper WC. Sequelae of acute organic phosphate poisoning. J Occup Med 1966; 8:5-20. 4. Koren HS, Graham DR, Devlin RB. Exposure of humans to a volatile organic mixture. 111. Inflammatory response. Arch Environ Health 1992; 47:39-44. 5. Rodgers K, Ellefson D. Mechanisms of modulation of murine peritoneal cell function and mast cell degranulation by low doses of malathion. Agents Actions 1992; 33:57-63. 6. Rodgers K, Leung N, Ware CF, Devens BH, lmamura T. Lack of immunosuppressive effects of acute and subacute administration of malathion on murine cellular and humoral immune responses. Pest Biochem Physiol 1986; 25:358-65. 7. Schwartz BS, Ford DP, Bolla KI, et al. Solvent-associated decrements in olfactory function in paint manufacturing workers. Am J Ind Med 1990; 18:697-706. 8. Liu K-S, Huang Fy, Hayward SB, Wesolowski J, Sexton K. Irritant effects of formaldehyde exposure in mobile homes. Environ Health Perspect 1991; 94:91-94.
Archives of Environmental Health
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Letters to the Editor Published online: 03 Aug 2010.
To cite this article: (1992) Letters to the Editor, Archives of Environmental Health: An International Journal, 47:5, 388-390, DOI: 10.1080/00039896.1992.9938380 To link to this article: http://dx.doi.org/10.1080/00039896.1992.9938380
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Downloaded by [University of Montana] at 19:57 02 April 2015
Letter to the Editor.-Review articles written across disciplinary and professional lines may elicit puzzling and unexpected responses. Seldom has this been better illustrated than by Drs. Ziem and Davidoff‘s rather wide-ran ing editorial critique’ of my review of environmental odor pollution! Controversy abounds regarding the role of odor perception in the pathogenesis of acute and reversible symptoms from indoor air pollution, ambient (industrial) air pollution, and idiopathic reactions to environmental stimuli (“multiple chemical sensitivities” or “MCS”). Matters are further complicated by the fact that a phenomenon closely related to odor perception (i.e., sensory irritation from airborne chemicals) is studied by two different groups-toxicologists and psychophysicists-who use very different methods and descriptive termin~logies.~,~ In this context, promoting communication among clinicians, scientists, and air pollution professionals requires careful attention, not only to technical detail, but also to differences in professional perspective and vocabulary. Some of the differences between my paper and Drs. Ziem and Davidoff‘s editorial are more apparent than real. For example, I share their concern that my exposition of the mechanisms whereby odors trigger somatic symptoms may be used to downplay the toxicological significance of chemical exposures. Careful history taking, exposure assessment, and dose-response evaluation are always indicated in the evaluation of health complaints imputed to toxicants. I also wholeheartedly agree that “there is no such thing as a chemical odor without a chemical; clean air doesn‘t smell like chemicals.” In fact, the odor pollution review was originally written to provide a resource to air pollution and public health officials who have been reluctant to undertake environmental odor abatement actions, using California’s relatively stringent nuisance laws. Finally, I concede that the value in indices such as Amoore’s “Odor Safety F a c t ~ I ”lies ~ not in comparing odor thresholds to specific exposure standards,6 but in the notion that-even after a rigorous review of available data on chemical hazards-chemicals will be found to vary in their odor-warning properties. Notwithstanding the above points of agreement, we differ in our estimation of the ability of odors-as odors-to produce symptoms. Most members of the lay public who experience an involuntary wave of nausea when smelling spoiled food or when passing by a rendering plant consider themselves to have been “repulsed” by the odor, rather than intoxicated. Most scientists would agree with that assessment. Numerous amines 2nd reduced sulfur compounds, all of which are extremely potent odorants, are produced by spoilage organisms and industrial processes, and they can clearly elicit acute symptoms at levels that existing toxicologic models would be hard-pressed to explain. If one is committed to understanding such phenomena, one has the choice of forcing these observations into the toxicologic paradigm or of borrowing tools from the discipline of psychophysics. The latter field, also known as “sensory science,” is concerned with the stimulus-response characteristics of the various sensory modalities. In the context of odor (and trigeminally mediated sensory irritation), psychophysicists have made important contributions to the understanding of human responses to low-level airborne contaminants (described below). Drs. Ziem and Davidoff, significantly, approach this question with the belief that pathophysiologic mechanisms that involve perception -particularly those mediated by odors per se-are somehow less valid or important than those for which a toxicologicallbiochemical mechanism can be found. As noted below, this assumption is not necessarily shared by those who work in the field of air pollution. Ziem and Davidoff argue by analogy: smog and environmental tobacco smoke (two former “nuisances”) have been shown to cause irreversible physiological impairment; therefore, all symptomatic responses to low-level airborne contaminants will one day be found to have a toxi-
388
cologic basis. They attempt to bolster their case by lumping indoor air pollution, MCS, and environmental odor pollution together as “sub TLVIPEL” exposure problems, implying shared pathophysiology. However, in building their case regarding “subTLVlPEL” exposure problems, Ziem and Davidoff have considered only a limited spectrum of explanations for various published and unpublished findings. For example, after noting that MCS patients frequently experience dysosmias, whereas sick building subjects “focus[ed] on the odor of something that had made them ill previously,” the authors assert: “Observations of this type suggest that CNS dysfunction needs to be explored.” Whereas neurotoxic explanations are not totally implausible, other possibilities also exist. For example, there is a striking similarity between “focusing on the odor of something that made them ill previously” and”re-experiencing of a traumatic event” (cf. Schottenfeld and Cullen‘s “atypical post-traumatic stress d i ~ r d e r ” ) . ~ Also, in their explanation of the dysosmias experienced by MCS patients, the authors ignore the converse possibility, i.e., that individuals whose primary pathology is olfactory dysfunction (infectious, traumatic, inflammatory, or chemically may be labeled ”MCS” because of their anomalous response to odorant stimuli. Ironically, the very paper they cite to counter the thesis that odors precipitate asthma is entitled ”Effect of Odors in Asthma,” and it reports effects from such toxicologically innocuous incitants as body and cooking odors (as well as irritating cleaning products and cigarette smoke).” Mercifully, they did not cite Eriksson‘s “Flowers and Other Trigger Factors in Asthma and Rhinitis,” which documents odor-related responses even among ionatopic subjects.’* Drs. Ziem and Davidoff consider chemical exposure scenarios qualitatively, without reference to exposure levels or credible routes of exposure. They fault Bruvold‘s study of odor annoyance near wastewater treatment plants for not examining pulmonary f~nction;’~ exposure levels barely exceeded the odor threshold, very few respondents reported symptoms of any sort, and studies in more heavily H,S exposed cohorts have failed to demonstrate pulmonary function a b n~rmalities.’~ Drs. Ziem and Davidoff make much of the organophosphate (OP) activity of the mercaptan-releasing pesticides in the cotton d e f ~ l i a n t ’and ~ nernatocidel6 studies. Not mentioned was the weak OP potency of the cotton defoliant in question, the exceedingly low levels at which the cotton defoliant was documented in community air (average 2-6 parts-per-trillion among detectable samples), or the fact that the nematocide in question was incorporated directly into the soil in granular form, effectively precluding its dissemination in the environment. On the other hand, the odorous contaminants that off-gassed from soil or foliage in these cases (n-butyl and n-propyl mercaptans) were reported by community members to produce strong and offensive odors. Drs. Ziem and Davidoff imply that the terms nuisance and annoyance trivialize community health complaints. Part of the difficulty may arise from the very different meanings these terms have in everyday language, in clinical or industrial hygiene practice, and in air pollution control circles. In California, classification of an air pollution source as an ”odor nuisance” has anything but trivial consequences. Such an action opens the door not only to monetary penalties, but also to abatement orders; the latter can potentially lead to the closure of an industrial facility if control measures are not instituted timely. And far from denigrating toxicological issues, nuisance statutes are part of a two-pronged regulatory strategy in our state (the other involving airborne emissions inventories, exposure modeling, and sitespecific chemical risk assessment^).'^ If, in contrast to the editorial in question, one accepts the possibility that low-level chemical stimuli may exert adverse effects by mechanisms not normally addressed by toxicologists, one is then free to consider the contributions of psychophysics to our understanding of
Archives of Environmental Health
Downloaded by [University of Montana] at 19:57 02 April 2015
low-level exposure phenomena. In the same issue of this journal in which the original odor pollution article appeared, several authors a p plied psychophysical techniques to the study of indoor air pollution. KjBergaard documented eye irritation to CO, using subjective endpoints;18 Hudnell similarly used subjective endpoints in documenting headaches, eye irritation, and throat irritation in response to a mixture of volatile organic compound^.'^ True to the predictions of psychophysics, odor waned, and irritation mounted over the course of exposure. Psychophysicists have been successful in explaining structure-activity and dose-response relationships for sensory irritation from airborne chemicals with moderate to weak chemical reactivity, which clearly exceeds the explanatory powers of current animal toxicologic models.20r21Sensory irritation, as documented b psychophysicists, in turn mutually interacts with odor perception?2,2J In my view, the two paradigms (toxicologic and psychophysical)are complementary, with odor perception and trigeminal stimulation potentially explaining those acute and reversible symptoms, which, at times, occur at exposure levels too low to be reasonably ascribed to toxicologic mechanisms, Drs. Ziem and Davidoff, however, maintain that psychophysical explanations are apparently “psychologic” (their word). Under the influence of such artificial parochial barriers, the discussion of low-level exposure phenomena will continue to generate more heat than light.
Dennis Shustennan, MD, MPH California Environmental Protection Agency Office of Environmental Health Hazard Assessment Berkeley, California
References 1. Ziem GE,Davidoff LL. Illness from chemical ’odors‘: is the health significance understood?Arch Environ Health 1992; 4768-91. 2. Shusterman D. Critical review. The health significance of environmental odor pollution. Arch Environ Health 1992; 4 7 76-87. 3. Cain WS. Perceptual characteristics of nasal irritation. In: Green BC, Mason JR, Kare MR (Eds.) Chemical senses, Vol. 2, Irritation. New York, Marcel Dekker, 1990, pp. 43-58. 4. Cain WS. A functional index of human sensory irritation. In: Seifert 6, et al. (Eds.) Indoor Air ‘ 8 7 Proceedings of the 4th International Conference on Indoor Air Quality and Climate (Vol. 2). Institute for Water, Soil and Air Hygiene, Berlin, 1987. 5. Amoore JE, Hautala E. Odor as an aid to chemical safety: odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. J Appl Toxicol 1983; 3972-90. 6. Robinson JC, Paxman DG. The role of threshold limit values in U.S. air pollution policy. Am J Ind Med 1992; 21:383-96. 7. Schottenfeld RS, Cullen MR. Recognition of occupation-induced post-traumatic stress disorders. J &cup Med 1986; 28365-69. 8. Davidson T, Jalowayski A, Murphy C, Jacobs RD. Evaluation and treatment of smell dysfunction. West J Med 1987; 146:434-38. 9. Doty RL. A review of olfactory dysfunctions in man. Am J Otolaryngol 1979 1:57-79. 10. Cometto-Muniz JE, Cain WS. Influence of airborne contaminants on olfaction and the common chemical sense. In Getchell Tv, et al. (Eds.): Smell and taste in health and disease. New York Raven Press, 1991; pp. 765-785. 11. Shim C, Williams HM. Effect of odors in asthma. Am J Med 1986; mi8-22. 12. Eriksson NE, Lowhagen 0, Nilsson J-E, Norrlind K, Wihl J-A. Flowers and other trigger factors in asthma and rhinitis-an inquiry study. Allergy 1987; 42:374-81. 13. Bruvold WH, Rappaport SM, Wu TC, Bulmer BE, DeGrange CE, Kooler JM. Determination of nuisance odor in a community. J Water Pollut Control Fed 1983; 55229-33. 14. Dales RE, Spitzer WO, Suissa S, Schechter MT, Tousignant P, Steinmetz N. Respiratory health of a population living downwind from natural gas refineries. Am Rev Respir Dis 1989; 139: 595-600. 15. Scarborough ME, Ames RG, Lipsett MJ,Jackson RJ. Acute health effects of community exposure to cotton defoliants. Arch Environ Health 1989; 44:355-60.
September/Oaober 1992 [Vd. 47 (No. 5)]
16. Ames RG, Stratton JW. Acute health effects from community exposure to N-prop$ mercaptan from an Ethoprop (MocaP)treated potato field in Siskiyou County, California. Arch Environ Health 1991; 46:213-17. 17. State of California. Health and Safety Code: Sedions 3479 and 41700 (Nuisance Statutes); Section 44300 et seq. (Air Toxics “Hot Spots” Informationand Assessment Act). 18. Kjaergaard S, Pedersen OF, Molhave L. Sensitivity of the eyes to airborne irritant stimuli: influence of individual characteristics. Arch Environ Health 1992; 4745-50. 19. Hudnell HK, Otto DA, House DE, Molhave L. Exposure of humans to a volatile organic mixture. [I. Sensory. Arch Environ Health 1992; 4731-38. 20. Cometto-Muniz JE, Cain WS. Thresholds for odor and nasal pungency. Physiol Behav 1990; 48:719-25. 21. Cometto-Muniz JE, Cain WS. Nasal pungency, odor, and eye irritation thresholds for homologous acetates. Pharmacol Biochem Behav 1991; 39983-89. 22. Cain WS, Murphy CL. Interaction between chemoreceptive modalities of odour and irritation. Nature 1saO; 2W255-57. 23. Cain WS. Contribution of the trigeminal nerve to perceived odor magnitude. Ann NY Acad Sci 1974; 2372834.
Response. Dr. Shusterman, in his article’ and in his response to our editorial, moves toward an explanation of symptoms that arise in conjunction with indoor, industrial, and community sources of odorous pollutants and toward a conceptualization of the pathogenesis of such conditions as sick building syndrome (SBS) and multiple chemical sensitivities (MCS). Our disagreements with Dr. Shusterman go beyond parochial concerns, misunderstandings related to terminology, disputes about the interpretation of specific chemical exposure scenarios, etc. The central points of contention are Dr. Shusterman‘s primary assumptions and proposed research agenda for scientists. Throughout his writings, Dr. Shusterman characterizes conditions that arise in conjunction with chronic, relatively low exposures to odorous pollutants as comprising only “acute and reversible symp toms.” That assumption is untenable. Credible studies of the natural history of illness complaints after chronic community, industry, and indoor exposures are unknown to us., Nor is it known whether, as patients report and some observers speculate, there is an induction phase for conditions such as SBS, MCS, and MCSlike conditions (i.e., acquired intolerance to organic solventsZ or pesticides3 It is clear, however, that affected individuals often suffer daily during many years after becoming ill and that many perceive their first 30 years as very healthy ones. In a pilot study in progress, SBS subjects, on average, reported feeling ill more than 20 h/wk and had more than 10 symptomdwk; 30% reported the need for 12 h or more recuperation time, once they became sick after environmental exposures. Moreover, it was not unusual for SBS subjects to report permanent changes in susceptibility to exposures that they had once considered inconsequential. MCS is definitely a chronic condition In our pilot study, affected individuals reported more than 60 hlwk of illness, accompanied by an average of 20 symptomdwk; 40% reported taking 1-3 d or longer to recuperate after exposures. It was rare for those with MCS to report returns to pre-exposure health status. Also implicit in Dr. Shusterman‘s writings is the assumption that the effects of chronic exposures to multiple pollutants at low levels in varied human populations have been investigated thoroughly and are well understood. That assumption is critical for labeling such pollutant exposures “odor pollution” and for asserting that “exposure assessment, history taking, and dose-response evaluation” clarify the pathogenesis of responses to such exposures. This assumption, in our opinion, is also in error. Research on physiologic responses to chronic exposures of mixed pollutants at relatively low levels in susceptible human populations is sparse. Although the jury is out, more than a handful of recent studies suggest that measurable physiologic responses can underlie health effects from chronic exposures to common chemicals at levels that were not previously suspected of inducing physiologic effects. In a chamber analogue study of SBS, for example, Koren et a1.4 found evidence of inflammatory responses in the u p per airways of healthy young male subjects, as determined by the number of polymorphonuclear neutrophils (PMN) present in nasal la-
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vage. Rodgers and Ellefson5found that acute oral administration of as little as 0.25 mglkg of purified malathion modulated leukocyte respiratory burst and phagocytic activity and caused mast cell degranulation in the peritoneal cavity in mice. Previous studies showed that it would take more than 715 mdkg of malathion to affect plasma cholinesterase.6 The authors suggested that some health effects reported by humans may have been due to the nonspecific release of mast cell products. Schwartz et al.’ found that exposure to solvents at levels considered safe was associated with evidence of neural damage, as reflected in olfactory dysfunction and deficits in learning in memory. Biologically plausible patterns of symptom reporting also occur in noncomplaining populations at exposures considered safe by current standards. During the investigation of symptoms of 1 OOO noncomplaining occupants of mobile homes in California, Liu et aL8 linked eye, skin, and upper respiratory irritation with exposures to formaldehyde just below the 0.1 ppm level, i.e., the level that the Environmental Protection Agency designates to be the threshold for irritation. Overall, individuals with allergies and chronic respiratory conditions experienced higher rates of symptoms. Whereas irritation is an inflammatory process, and inflamed passageways show increased susceptibility to bacteria and chemicals, irritation alone may lead to disease. Dr. Shusterman would channel investigations of the health effects of chronic, relatively low-dose exposures to odorous pollutants narrowly. He would have scientists investigate explanations that rely on odor perception/malodor, odor dysfunction, psychophysiological law, and psychopathology (e.g., atypical post-traumatic stress disorder). What is needed instead, we submit, is comprehensive health effects research. Before coming to any conclusions, it is imperative to study chronic, as well as acute, low-dose exposures to multiple pollutants; to target relevant psychologic and physiologic (including neurologic and immune) responses; and to focus on vulnerable populations (not simply healthy young adult males who are, by and large, not the ones becoming ill). It is also important to gather prospective data on cohorts of affected individuals and, in addition, to examine the natural history of these conditions. Modelbuilding that
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focuses research in the psychologic/psychiatric/psychophysiologic arena i s premature; there are too many unknowns about “the health significance of environmental ’odor‘ pollution.”
Linda Lee Davidoff, Ph.D. Division of Occupational Health Johns Hopkins University Baltimore, Maryland
References 1 . Shusterman D. Critical review. The health significance of environmental odor pollution. Arch Environ Health 1992; 47:76-87. 2. Gyntelberg F, Vesterhauge S, Fog P, lsager H, Zillstorff K. Acquired intolerance to organic solvents and results of vestibular testing. Am j Ind Med 1986 9363-70. 3. Tabershaw IR, Cooper WC. Sequelae of acute organic phosphate poisoning. J Occup Med 1966; 8:5-20. 4. Koren HS, Graham DR, Devlin RB. Exposure of humans to a volatile organic mixture. 111. Inflammatory response. Arch Environ Health 1992; 47:39-44. 5. Rodgers K, Ellefson D. Mechanisms of modulation of murine peritoneal cell function and mast cell degranulation by low doses of malathion. Agents Actions 1992; 33:57-63. 6. Rodgers K, Leung N, Ware CF, Devens BH, lmamura T. Lack of immunosuppressive effects of acute and subacute administration of malathion on murine cellular and humoral immune responses. Pest Biochem Physiol 1986; 25:358-65. 7. Schwartz BS, Ford DP, Bolla KI, et al. Solvent-associated decrements in olfactory function in paint manufacturing workers. Am J Ind Med 1990; 18:697-706. 8. Liu K-S, Huang Fy, Hayward SB, Wesolowski J, Sexton K. Irritant effects of formaldehyde exposure in mobile homes. Environ Health Perspect 1991; 94:91-94.
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