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Low-level chemical sensitivity: implications for research and social policy.

There is increasing evidence that human exposure to levels of chemicals once thought to be safe--or presenting insignificant risk--are, in fact, harmful. So-called low-level exposures are now known to be associated with adverse biological effects including cancer, endocrine disruption, and chemical sensitivity. This requires that we change both (1) the way we design research linking chemicals and health, and (2) the solutions we devise to address chemically caused injury. The new and emerging science of low-level exposure to chemicals requires appropriate social policy responses which include regulation of toxic substances, notification of those exposed, and compensation and reasonable accommodation to those affected. Research and social policy need to be focused towards two distinct groups: (1) those individuals who could become chemically intolerant as a result of an initiating exposure, and (2) those individuals who have already become chemically intolerant and are now sensitive to chemicals at low levels.

Dose-Response Relationship, Drug↗

Prevalence and nature of allergy and chemical sensitivity in a general population.

The objectives of this study were (a) to determine the self-reported prevalence of allergy and chemical sensitivity in a rural population of eastern North Carolina, (b) to determine the type and frequency of symptoms for each condition, and (c) to determine the demographic groups affected. A random general telephone survey was conducted during the period May 14, 1993, to September 10, 1993, and questions about allergy and chemical sensitivity were asked. Of the 1 446 households contacted, 1 027 (71%) individuals agreed to participate. Allergies were reported by 365 (35%) individuals. Thirty percent of allergic individuals reported that symptoms occurred once or more each week, whereas 61% reported that symptoms occurred, at most, once each month. Allergic symptoms that occurred daily were reported by 5.3% of the total population. Chemical sensitivity was reported by 336 (33%) individuals. Thirty-five per cent of chemically sensitive individuals reported symptoms at least once each week, whereas 53% reported that symptoms occurred once (or less) each month. Symptoms of chemical sensitivity that occurred daily were reported by 3.9% of the total population. Both allergy and chemical sensitivity were distributed widely across age, income, race, and educational groups. Simultaneous allergy and chemical sensitivity were reported by 16.9% of the population, allergy without chemical sensitivity by 16.0%, chemical sensitivity without allergy by 18.2%, and neither condition by 48.9%. If the prevalence of sensitivity to chemical irritants is, in fact, equivalent to that of allergy, as was found in this study, then support for the scientific investigation of chemical sensitivity is justified.

Adolescent↗

Empirical approaches for the investigation of toxicant-induced loss of tolerance.

It has been hypothesized that sensitivity to low-level chemical exposures develops in two steps: initiation by an acute or chronic chemical exposure, followed by triggering of symptoms by low levels of previously tolerated chemical inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of Tolerance has formulated a series of research questions to test this hypothesis: Do some individuals experience sensitivity to chemicals at levels of exposure unexplained by classical toxicological thresholds and dose-response relationships, and outside normally expected variation in the population? Do chemically sensitive subjects exhibit masking that may interfere with the reproducibility of their responses to chemical challenges? Does chemical sensitivity develop because of acute, intermittent, or continuous exposure to certain substances? If so, what substances are most likely to initiate this process? An experimental approach for testing directly the relationship between patients' reported symptoms and specific exposures was outlined in response to the first question, which was felt to be a key question. Double-blind, placebo-controlled challenges performed in an environmentally controlled hospital facility (environmental medical unit) coupled with rigorous documentation of both objective and subjective responses are necessary to answer this question and to help elucidate the nature and origins of chemical sensitivity.

Controlled Clinical Trials as Topic↗

The Chemical Odor Sensitivity Scale: reliability and validity of a screening instrument for idiopathic environmental intolerance.

OBJECTIVE: The objective of this study was to examine the psychometric qualities of a brief screening measure for idiopathic environmental intolerance (IEI), the Chemical Odor Sensitivity Scale (COSS). METHODOLOGY: The COSS was administered together with other measures of environmental sensitivity, IEI, and symptom scales in large samples (students, individuals with IEI, and individuals without IEI). RESULTS: The COSS achieved high internal consistency (.88 < or = Cronbach's alpha < or = .96) and good factorial, convergent, and discriminant validity across diverse samples. In a longitudinal sample, the COSS and other IEI features were stable across time. According to receiver operating characteristic analyses, the COSS performs adequately in screening individuals likely to meet case criteria for IEI. CONCLUSIONS: The favorable psychometric qualities of the COSS recommend the scale as a useful tool both for assessing self-reported chemical odor sensitivity as a vulnerability marker and for screening for IEI.

Adolescent↗

Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol.

OBJECTIVES: The study examined acute neurobehavioral effects provoked by controlled exposure to 1-octanol and isopropanol among male volunteers. METHODS: In a 29-m3 exposure laboratory, 24 male students (mean age 25.8 years) were exposed to 1-octanol and isopropanol. Each substance was used in two concentrations (0.1 and 6.4 ppm for 1-octanol; 34.9 and 189.9 ppm for isopropanol:). In a crossover design, each subject was exposed for 4 hours to the conditions. Twelve subjects reported enhanced chemical sensitivity; the other 12 were age-matched controls. At the onset and end of the exposures neurobehavioral tests were administered and symptoms were rated. RESULTS: At the end of the high and low isopropanol exposures the tiredness ratings were elevated, but no dose-dependence could be confirmed. For both substances and concentrations, the annoyance ratings increased during the exposure, but only for isopropanol did the increase show a dose-response relation. The subjects reported olfactory symptoms during the exposure to the high isopropanol and both 1-octanol concentrations. Isopropanol provoked no sensory irritation, whereas high 1-octanol exposure slightly enhanced it. Only among the subjects with enhanced chemical sensitivity were both 1-octanol concentrations associated with a stronger increase in annoyance, and lower detection rates were observed in a divided attention task. CONCLUSIONS: Previous studies reporting no neurobehavioral effects for isopropanol (up to 400 ppm) were confirmed. The results obtained for 1-octanol lacked dose-dependency, and their evaluation, is difficult. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task.

2-Propanol↗

Treating the patient with multiple cosmetic product allergies. A problem-oriented approach to sensitive skin.

Treating patients with multiple allergies to cosmetic products is a difficult proposition. Many of these patients may simply be experiencing irritant contact dermatitis. Others may have defective barrier function caused by a dermatitis that requires treatment. And some patients with sensitive skin need to exercise care in choosing which products they use on their skin. For many of these patients, products with the fewest ingredients work best because they contain the least or no sensitizers, irritants, or cutaneous sensory stimulants.

Anti-Allergic Agents↗

Capsaicin inhalation test for identification of sensory hyperreactivity.

BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.

Administration, Inhalation↗

Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms.

BACKGROUND: A group of patients with asthma-like symptoms and sensitivity to chemical irritants, but without bronchial obstruction, has been found among subjects referred for suspected asthma. They have no well-defined diagnosis, and no objective diagnostic method has previously been available. These patients are more sensitive to inhaled capsaicin than are patients with asthma or healthy controls. The aim was to study cough and other capsaicin-induced symptoms and to test the effect of a drug (lidocaine) that inhibits nerve transmission in sensory nerves. METHODS: Twelve patients were provoked with three different concentrations of inhaled capsaicin solutions in a randomized, double-blind order. They all had asthma-like symptoms and were sensitive to chemical irritants, but had no IgE-mediated allergy or demonstrable bronchial obstruction. Before the provocations, the patients inhaled lidocaine or placebo (saline), also in a double-blind, randomized order. The results were expressed as the number of coughs and scores of various symptoms. RESULTS: The patients reacted in a dose-dependent way with cough, airway, and eye symptoms, which were significantly reduced after preinhalation of lidocaine. CONCLUSIONS: A drug that inhibits transmission in sensory nerves successfully blocked the number of coughs and other symptoms provoked by inhalation of capsaicin. This indicates that the mechanisms underlying chemical sensitivity in these patients may originate in the sensory nervous system, and we call this condition "sensory hyperreactivity".

Administration, Inhalation↗

Psychogenic chemical sensitivity: psychogenic pseudoseizures elicited by provocation challenges with fragrances.

A middle-aged woman with a 10-year history of disability attributed to chemical sensitivities complained that exposure to specific fragrances immediately elicited seizures. Video-EEG monitoring was performed in a hospital neurodiagnostic laboratory during provocative challenge studies employing fragrances identified by the patient as reliably inducing symptoms. The baseline clinical EEG was normal. Immediately after each provocation with air deodorant and perfume, she consistently showed both generalized tonic/clonic and multifocal myoclonic jerking, at times was nonresponsive, spoke with slurred speech, and complained of right-sided paralysis and lethargy. None of these events were associated with any EEG abnormalities. Psychological assessment (MMPI-2, MCMI-II) revealed personality traits that predisposed her to somatization and beliefs about environmental sensitivities. The convulsions were a manifestation of psychogenic pseudoseizures that had been iatrogenically reinforced.

Adult↗

Approaches to testing for food and chemical sensitivities.

Testing for food and chemical sensitivities usually becomes necessary as part of the evaluation of otolaryngology patients who have chronic illness. The more complex the patient, and the more recalcitrant the problem is to treatment, the more likely it is that allergies, and especially food or chemical sensitivities, are involved in the pathogenesis of the illness. Failure to consider all major allergen contacts, including foods and chemicals, can lead to inadequate therapy. Similarly, failure to understand total allergic and oxidant load and the effects of chemical toxicity can lead to inappropriate or ineffective treatment. Clinically, food allergies occur in two different types: immediate, anaphylactic, fixed reactions and delayed, chronic, cyclic reactions. Different test methods have been developed for the two types. Fixed food allergies can be safely and efficiently detected by in vitro specific IgE or histamine release tests. Cyclic food allergies are best detected by either oral food challenges or by the IPDFT test. Choosing the best test for a particular patient requires a clear understanding of the two food allergy types and how their clinical presentations differ. Other tests for food allergies are compared and contrasted with these primary tests. Chemical sensitivity also occurs in two different clinical types: allergic, and toxic. True allergy to chemical haptens, either type I, IgE-mediated, or type IV, delayed hypersensitivity, occurs with significant frequency but is often unsuspected. Chemical toxicity can be caused by the aftereffects of an acute exposure or as a result of chronic, low-level exposure, but is even more frequently unsuspected and will not be diagnosed without a high index of suspicion. Both types of chemical sensitivity need to be addressed in any patients who have either a high allergen or chemical exposure load [105]. Either in vitro or in vivo tests can be used for chemical allergy detection; the advantages of each are outlined. Chemical toxicity screening tests are available and useful but do not detect all possible toxicants. Definitive toxic chemical tests usually require specialized laboratory facilities and expert consultation, for which possible sources are specified. The most important point in testing for food or chemical sensitivity is to be aware that food or chemical sensitivity can be contributing to a specific patient's clinical problems. Only then can appropriate investigations be undertaken to understand and then, perhaps, to intervene successfully in that illness.

Air Pollutants↗

Exacerbation of chemical sensitivity: a case study.

We report exacerbation of symptoms and chemical intolerances in three of four self-described chemically sensitive women following relocation to a newly constructed office building. Levels of total volatile organic compounds (TVOCs) in this building prior to occupancy were approximately 200 micrograms/m3 (toluene equivalent units) with a myriad of individual components present. By day 50 after occupancy, the concentration of TVOCs in the building dropped to approximately 50 micrograms/m3. Nevertheless, three women reported significant worsening of their symptoms with spreading of their sensitivities to previously tolerated chemical exposures. One woman relocated to another building, while the other two managed their symptoms by reducing time spent in the building or by using a room air cleaner. By day 600 following occupancy, although TVOCs had increased significantly (perhaps due to cleaning agents), there were fewer individual VOCs present in the air, and some of the women were able to tolerate the air in the building. We conclude that complex mixtures of VOCs at very low levels tolerated by the majority of building occupants may pose problems for persons who report pre-existing chemical sensitivities. TVOC measurements may not correlate with symptoms in these individuals. Reasonable accommodations by an employer can reduce problem exposures, making it possible for some affected individuals to continue productive employment.

Air Pollution, Indoor↗

Repeated low-level formaldehyde exposure produces cross-sensitization to cocaine: possible relevance to chemical sensitivity in humans.

Sensitivity to chemicals in humans has been proposed to be an acquired disorder in which individuals become increasingly sensitive to chemicals in the environment. A possible link between the manifestation of psychiatric symptoms in individuals claiming sensitivity to chemicals was investigated based on a leading hypothesis put forth by Bell and co-workers (1992) to explain the amplification of symptoms after chemical exposure. The hypothesis is that chemical sensitivities may be akin to sensitization observed in rodents after repeated psychostimulants. Repeated exposure to psychostimulants enhances behavioral activity and the underlying neurochemical responses in specific limbic pathways; a similar sensitization of limbic pathways has been proposed to occur in individuals who become sensitive to chemicals. To test this hypothesis, female Sprague-Dawley rats were exposed to either air or formaldehyde (Form) for 1 h/day for 7 days or 20 days (5 days/week x 4 weeks). Two to 4 days after the last exposure, rats were given a cocaine challenge (= early withdrawal) followed by an additional cocaine challenge 4-6 weeks later (= late withdrawal). No differences in cocaine-induced locomotor activity were noted between groups after 7 days of exposure. However, after 20 days of exposure to Form, vertical activity was significantly elevated at both early and late withdrawal times. These studies demonstrate that behavioral sensitization occurs after long-term, but not short-term, low-level exposure to Form, and lends support to the limbic system sensitization hypothesis of sensitivity to chemicals in humans.

Anesthetics, Local↗

Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls.

Two hundred and twenty-five subjects, including normal volunteers and patients with previously documented seasonal affective disorder (SAD), chronic fatigue syndrome (CFS), Cushing's syndrome, Addison's disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported sensitivity to various chemical exposures. Patients with CFS, Addison's disease and SAD self-reported more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity than men. This report suggests that chemical sensitivity may be a relevant area to explore in certain medical and psychiatric populations. A possible relationship between reported chemical sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed.

Addison Disease↗

Episodic exposures to chemicals: what relevance to chemical intolerance?

Episodic exposures refer to intermittent acute exposures to chemicals that ordinarily have a rapid onset and short duration of effect. There has been a long tradition in preclinical behavioral pharmacology of using episodic-exposure paradigms in order to establish dose-response functions in individual organisms. In these experiments, stable baselines of behavior are first established and then followed by administering varying doses of a drug intermittently, for example, once or twice a week. The power of this approach is well established; the within-subjects design reduces error variance, allows exploration of the entire range of effective doses, and can be used to identify individual differences in drug sensitivity. Of course, the approach is only applicable to reversibly acting compounds, and checks need to be included to insure effects of one dose are not influenced by prior exposure to another dose. We have used baseline approaches to evaluate the effects of pesticides and solvents on the behavior of adult male rats and mice. Moreover, a novel probabilistic dose-tolerance analysis applied to the data suggests substantial individual differences in chemical sensitivity, often spanning orders of magnitude. These results suggest that individual differences in chemical sensitivity may be much greater than previously acknowledged.

Adolescent↗

The sensitive individual and the indoor environment: case study.

This case study describes an indoor environment investigation initiated in response to numerous health and comfort complaints suspected of being associated with a two-story office building. Conventional indoor environment investigation techniques were applied in an attempt to identify one or several contributing factors, such as inadequate outdoor air ventilation and the presence of a respiratory irritant. The air quality satisfaction percentage in the building was well above 80%; however, at least one individual was experiencing a fairly severe reaction only upon entering the subject building. Evaluating the building indoor conditions as acceptable without attempting to address all possible building-related causes and communicating findings to interested occupants would likely have resulted in more occupant complaints and increased the potential for hysteria conditions. This investigation necessarily addressed a sensitive individual and involved an occupational physician as a constructive participant in the investigation.

Air Pollutants↗

Contact and chemical sensitivities in the hospital environment.

As surgeons, otolaryngologists tend to most be interested in operative procedures and leave the hospital environment to the care of administrators and the nursing staff. Given the dangers that are present, it would seem prudent to spend some time considering the agents that used in patient care and in operating suites, to minimize the risk to patients and co-workers.

Adhesives↗

EEG beta 1 oscillation and sucrose sensitization in fibromyalgia with chemical intolerance.

Patients with fibromyalgia (FM) have diffuse musculoskeletal pain; half report concomitant intolerance for low levels of environmental chemicals (CI). Previous investigators have hypothesized that the chronic pain and chemical intolerance reflect sensitization of different central nervous system limbic and/or mesolimbic reward pathways. We evaluated electroencephalographic (EEG) beta activity and blood glucose responses of FM patients with and without CI and normals during three repeated sucrose ingestion sessions and during a final, water-only session (testing for conditioning). The FM with CI exhibited oscillation (reversal in direction of change from session to session) at rest and then sensitization (progressive amplification) of EEG beta 1 over time across the 3 sucrose sessions versus controls. FM with CI showed sensitization of blood glucose over the 3 sucrose sessions, which, like the EEG findings, reverted toward baseline in the final water-only session. The data suggest that the subset of FM patients with CI have increased susceptibility to oscillation and physiological sensitization without conditioning, perhaps contributing to fluctuations in their chronic course.

Adult↗