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PubMed2001

Effect of pulse frequency and interval on the toxicity of chlorpyrifos to Daphnia magna.

Due to the episodic nature in which organisms are exposed to non-point source pollutants, it is necessary to understand how they are affected by pulsed concentrations of contaminants. This is essential, as standard toxicity tests may not adequately simulate exposure scenarios for short-lived hydrophobic compounds, such as chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide. Studies were conducted with 7-day old Daphnia magna for 7 days to evaluate the effect of pulse frequency and interval among multiple CPF exposures. Daphnids were exposed to a total exposure of either 12 h at 0.5 microg/l or 6 h at 1.0 microg/l nominal CPF, respectively, in all studies. For interval studies, D. magna were exposed to two pulses of CPF at each concentration, with 0-96-h intervals between pulses. For frequency studies, D. magna were exposed to each CPF concentration altering the pulse scheme by decreasing the exposure duration but increasing the number of pulses, keeping the total exposure time the same. The pulse interval between multiple pulses in these experiments was 24 h. Our results suggest that D. magna can withstand an acutely lethal CPF exposure provided that there is adequate time for recovery between exposures.

Animals↗

PubMed1995

DNA repair capacity for ultraviolet light-induced damage is reduced in peripheral lymphocytes from patients with basal cell carcinoma.

Sunlight exposure and certain host factors such as red hair and fair skin are established risk factors for non-melanoma skin cancers. Because deficient DNA repair capacity has contributed to the development of skin cancers in a rare genetic disease, xeroderma pigmentosum, we explored this deficiency as an etiologic factor in a recent population study. We used a new DNA repair assay, the host-cell reactivation, in a clinic-based case-control study to test the hypothesis that reduced DNA repair is the underlying molecular mechanism for the development of sunlight-induced basal cell carcinoma. The peripheral lymphocytes from 88 patients with primary BCC and 135 cancer-free controls were tested for their capacity to repair ultraviolet light-induced DNA damage in a reporter gene, chloramphenicol acetyl transferase. All subjects were between the ages of 20 and 60 years and were frequency matched by age (+/- 5) and sex. Among those who reported frequent sunbathing, poor tanning ability, a history of multiple sunburns, exposure to chemicals, or multiple medical irradiations, the BCC patients had significantly lower DNA repair capacity than controls (p < 0.05). DNA repair capacity was also found substantially lower in the basal cell carcinoma patients who had red hair and light skin (type I). Compared to controls, basal cell carcinoma cases with selected risk factors had a relative decrease in DNA repair capacity of 10-28%. These findings provided evidence that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.

Adult↗

PubMed1999

Apparent cyclophosphamide (cytoxan) embryopathy: a distinct phenotype?

Cyclophosphamide (CP) is an alkylating agent widely used in treating cancer and autoimmune disease. CP is classified as a pregnancy risk factor D drug and is teratogenic in animals, but population studies have not conclusively demonstrated teratogenicity in humans. Six isolated reports of prenatally exposed infants with various congenital anomalies exist, but to date no specific phenotype has been delineated. The purpose of this report is to document a new case of in utero CP exposure with multiple congenital anomalies and to establish an apparent CP embryopathy phenotype. The mother had systemic lupus erythematosus and cyclophosphamide exposure in the first trimester. She also took nifedipine, atenolol, clonidine, prednisone, aspirin, and potassium chloride throughout pregnancy. The infant had growth retardation and multiple anomalies including microbrachycephaly, coronal craniosynostosis, hypotelorism, shallow orbits, proptosis, blepharophimosis, small, abnormal ears, unilateral preauricular pit, broad, flat nasal bridge, microstomia, high-arched palate, micrognathia, preaxial upper limb and postaxial lower limb defects consisting of hypoplastic thumbs, and bilateral absence of the 4th and 5th toes. Chromosomes were apparently normal. The reported cases of in utero exposure to cyclosposphamide shared the following manifestations with our patient: growth deficiency, developmental delay, craniosynostosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly. We conclude that (a) cyclophosphamide is a human teratogen, (b) a distinct phenotype exists, and (c) the safety of CP in pregnancy is in serious question.

Abnormalities, Multiple↗

PubMed1988

Potential for misleading associations between exposure and disease when reviewing multiple epidemiologic studies.

In reviewing evidence from multiple epidemiologic studies, a statistical artifact can leave an impression that a relationship exists between an exposure and a disease even if none exists. In this paper, two fundamental properties of probability were applied to hypothetical situations where results from independent studies were combined. It was evident that, even when a cause-effect relationship did not exist, several studies still appeared to confirm the relationship. This statistical artifact was related primarily to the total number of independent studies reviewed and to a lesser degree to the size of a given study. Thus, in examining evidence for a cause-effect relationship from multiple published articles, some studies are likely to show the association and some not, even if no association exists. If only the studies which show the association are considered, without regard to the total number of studies, the reviewer can be misled. This statistical effect is illustrated with an example from the rubber worker literature.

Environmental Exposure↗

PubMed1992

Risk factors for small bowel cancer in Crohn's disease.

Suspected risk factors for adenocarcinoma of the small bowel in Crohn's disease include surgically excluded small bowel loops, chronic fistulous disease, and male sex. Review of all seven University of Chicago cases failed to confirm any suspected risk factor. A case-control study was performed to identify possible alternatives. Each case was matched to four randomly selected controls from an inflammatory bowel disease registry matched for year of birth, sex, and confirmed small bowel Crohn's disease. Three factors were significantly associated with the development of cancer: (1) Four cancers developed in the jejunum, and jejunal Crohn's disease was associated with the development of cancer [odds ratio (OR) 8.0, 95% confidence interval (CI) 1.6-39.3]. (2) There was an association between the development of cancer and occupations known to be associated with an increased colorectal cancer risk (OR 20.3, CI 2.7-150.5). Three cases (a chemist with exposure to halogenated aromatic compounds and aliphatic amines, a pipefitter with exposure to asbestos, and a machinist with exposures to cutting oils, solvents, and abrasives) and one of 28 controls (a fireman with multiple hazardous exposures) had an occupational risk factor. (3) Among medications taken for at least six months, only 6-mercaptopurine use was associated with cancer (OR 10.8, CI 1.1-108.7). In conclusion, proximal small bowel disease, 6-mercaptopurine use, and hazardous occupations are associated with cancer of the small bowel in patients with Crohn's disease and can be added to the list of suspected risk factors.

Adenocarcinoma↗

PubMed2005

Typical GERD symptoms and esophageal pH monitoring are not enough to diagnose pharyngeal reflux.

BACKGROUND: Abnormal pharyngeal reflux of acid (PR) (as measured by pH monitoring) is associated with microaspiration, and is a good predictor of airway symptom response to medical and surgical anti-reflux therapy. However, in clinical practice the link between airway disease and Gastroesophageal reflux disease (GERD) is still based on the presence of typical symptoms (e.g., heartburn) and/or standard esophageal function testing (manometry and 24-pH monitoring). PR is rarely measured directly. We undertook this study to determine if typical symptoms and standard testing could reliably predict the presence of PR. METHODS: The study group consisted of 518 patients with suspected reflux induced airway disease evaluated from December 1998 through January 2002. Each patient completed a standardized symptom questionnaire, underwent esophageal manometry, and 24-h esophageal and pharyngeal pH monitoring. Patients were classified having abnormal pharyngeal reflux (PR+) if they had >1 episode of PR detected during pH monitoring. RESULTS: One hundred eighty-one patients were PR+ and 337 were PR-. The most common symptoms, namely cough (PR +73%, PR- 68%), hoarseness (PR +64%, PR- 66%), and dyspnea (PR +59%, PR- 59%) were present with similar incidence in PR+ and PR- patients. The incidence of heartburn was 54% in the PR+ and 52% in the PR- patients. Logistic regression analysis revealed that abnormal esophageal acid exposure was a predictor of PR+ (P < 0.001). Neither the presence of heartburn or specific respiratory symptoms, the pressure of the lower esophageal sphincter (LES) or upper esophageal sphincter (UES), or amplitude of esophageal contractions predicted PR+. There was substantial variability in esophageal length (UES to LES), thus the placement of the distal pH probe from the LES varied considerably (median = 13 cm, 2-20 cm). Using established normal values of acid exposure at multiple levels of the esophagus, 24% of PR+ patients had normal amounts of esophageal acid exposure. CONCLUSIONS: Typical GERD symptoms, such as heartburn, and typical symptoms of aspiration such as hoarseness, cough, or dyspnea are not enough to positively identify PR. While patients with abnormal esophageal acid exposure are three times more likely than those with normal values to have PR, abnormal esophageal acid exposure alone does not identify all patients with PR. Therefore, relying on symptoms and standard diagnostic testing may fail to identify patients with extraesophageal reflux. Pharyngeal pH monitoring should be considered for patients with suspected reflux-induced airway disease.

Diagnostic Techniques, Digestive System↗

PubMed2003

Acinetobacter outbreaks, 1977-2000.

This review of Acinetobacter outbreaks summarizes factors related to the presence and recognition of organism transmission and describes the implementation of control and prevention measures directed at limiting spread. Exogenous transmission of Acinetobacter should be considered when infections are endemic and when case rates increase. Increasing or new antimicrobial resistances in a collection of isolates also suggest transmission, and transmission can be definitively confirmed when isolates are found to be indistinguishable from or related to one another by a discriminatory genotyping test. An investigation for a common source should be conducted. When a common source cannot be found and eliminated, or once an endemically transmitted organism is established, containment or prevention efforts may require aggressive interventions, complex interventions, or both. Colonization at multiple sites, the relative ease of induction of antibiotic resistance in the organism following patient exposure to multiple drugs, and long-term environmental survival provide enhanced opportunities for the transmission of Acinetobacter between and among patients. New approaches and interventional trials are needed to define effective measures for the prevention and control of Acinobacter infections.

Acinetobacter↗

PubMed1979

Controlled exposures of human volunteers to sulfate aerosols. Health effects and aerosol characterization.

Our laboratory has undertaken the study of possible acute adverse health effects of sulfate aerosols through controlled exposures of volunteer human subjects. Both healthy and asthmatic adult men were exposed for 2-hour periods (with intermittent exercise) to ammonium sulfate, ammonium bisulfate, and sulfuric acid of particle size distributions and concentrations intended to simulate "worst case" exposures during Los Angeles smog episodes. Lung function tests were performed by the subjects on entering and before exiting from a carefully controlled environmental chamber. Subject symptoms were evluated in a standardized manner. Aerosol concentrations and size distributions were determined by an on-line computer/aerometric monitoring system; gravimetric and chemical analyses were performed on impactor and total filter samples after test exposures. We found little or no evidence of adverse health effects from 2-hour multiple-day exposures to any of the compounds at "worst case" ambient concentrations.

Aerosols↗

PubMed2005

Aging and clinical pharmacology: implications for antidepressants.

The elderly frequently have changes in pharmacokinetics, sensitivity to medications, homeostatic reserve (ability to tolerate physiological challenges), exposure to multiple medications, and adherence. All of these age-associated factors can potentially influence total exposure to medication, adverse effects, and subsequent treatment outcome. Most clinical trials are performed with healthy, younger adults. Extrapolating the results of these trials to the elderly may be inappropriate, particularly for the antidepressant treatment of depression. The authors review these age-associated differences and discuss their implications for antidepressant use in older adults.

Adult↗

PubMed2005

Fundamental flaws of hormesis for public health decisions.

Hormesis (defined operationally as low-dose stimulation, high-dose inhibition) is often used to promote the notion that while high-level exposures to toxic chemicals could be detrimental to human health, low-level exposures would be beneficial. Some proponents claim hormesis is an adaptive, generalizable phenomenon and argue that the default assumption for risk assessments should be that toxic chemicals induce stimulatory (i.e., "beneficial") effects at low exposures. In many cases, nonmonotonic dose-response curves are called hormetic responses even in the absence of any mechanistic characterization of that response. Use of the term "hormesis," with its associated descriptors, distracts from the broader and more important questions regarding the frequency and interpretation of nonmonotonic dose responses in biological systems. A better understanding of the biological basis and consequences of nonmonotonic dose-response curves is warranted for evaluating human health risks. The assumption that hormesis is generally adaptive is an oversimplification of complex biological processes. Even if certain low-dose effects were sometimes considered beneficial, this should not influence regulatory decisions to allow increased environmental exposures to toxic and carcinogenic agents, given factors such as interindividual differences in susceptibility and multiplicity in exposures. In this commentary we evaluate the hormesis hypothesis and potential adverse consequences of incorporating low-dose beneficial effects into public health decisions. Key words: biphasic dose response, hormesis, individual susceptibility, low-dose exposures, nonmonotonic dose response, nonlinear dose response, public health, regulation, risk assessment.

Decision Making, Organizational↗

PubMed2003

Relationships between mercury body concentrations, standard metabolic rate, and body mass in eastern mosquitofish (Gambusia holbrooki) from three experimental populations.

Eastern mosquitofish (Gambusia holbrooki) were sampled from three experimental populations (two Hg-exposed populations and one reference population) to determine whether transgenerational exposure (lifelong exposure of multiple generations) to Hg adversely affects standard metabolic rate (SMR). Mosquitofish subjected to lifelong Hg exposure accumulated significant concentrations of Hg in their tissues compared to fish from the reference population (mean: 3.89-4.13 vs 0.08 microHg/g wet mass, respectively). Less than 10% of the variability in Hg tissue concentrations could be explained by fish body mass, likely because of the short life span and/or dietary habits of this species. Despite the high body burdens of Hg in exposed fish, we found no significant difference in SMR among individuals from Hg-exposed or reference populations. Our findings contrast recent laboratory work describing elevated SMR in mosquitofish exposed to 100 microg/L dissolved inorganic Hg for 48 h. To account for contrasting results between studies, we hypothesize that acute exposure to dissolved inorganic Hg damages gill epithelium, resulting in increased metabolic rate, but that lifelong Hg exposure via trophic uptake of methyl mercury does not affect fish respiratory structures. Alternative hypotheses include the possibility that G. holbrooki is a species that can tolerate high body burdens of Hg or that more than four years of genetic isolation during Hg exposure (8-12 generations) resulted in selection for Hg-tolerant or -resistant individuals.

Analysis of Variance↗

PubMedDate not supplied

Effects of daily fluoride exposures on fluoride release by glass ionomer-based restoratives.

It is well documented that glass ionomer cements absorb and release fluoride following single fluoride exposures. This study examined fluoride release among three glass ionomer-based restorative materials following multiple daily exposures to three topical fluoride regimens. Using a Delrin mold, 32 cylindrical specimens, each of a glass ionomer (Ketac-Fil), resin-modified glass ionomer (Photac-Fil) and polyacid-modified resin (Dyract AP) were created. Each specimen was subjected to one of four daily treatments (n = 8): (1) no fluoride treatment (control); (2) application of a fluoride dentifrice (1000 ppm) for one minute once daily; (3) application of the same dentifrice for one minute twice daily; (4) the same regimen as (3), plus immersion in a 0.05% sodium fluoride (NaF) mouth rinse (225 ppm) for one minute immediately following the second dentifrice application. Each specimen was suspended in a polyethylene test tube containing 1.0 ml demineralizing solution (pH 4.3) at 37 degrees C for six hours, then transferred to a new test tube containing 1.0 ml remineralizing solution (pH 7.0) at 37 degrees C for 18 hours. Fluoride treatments were completed at the time of transfer daily for seven days. Media solutions were buffered with equal volumes of TISAB II; fluoride levels were measured using a digital ion analyzer and fluoride electrode. Fluoride release decreased significantly from Day 1 to Day 3 for all materials regardless of fluoride treatment (Repeated Measures ANOVA, Tukey HSD, p < 0.05). All specimens released significantly more fluoride in demineralizing solution than in remineralizing solution. For Days 2-7, Treatment 4 produced greater fluoride release than both the control and Treatment 2 for all three materials (p < 0.05); For each material, the fluoride release produced by Treatments 3 and 4 was statistically similar on most days throughout the study. By Day 7, Photac-Fil demonstrated both the greatest total fluoride release and the greatest rechargability, followed by Ketac-Fil and Dyract AP. Although subsequent daily fluoride release never approached that of Day 1, increasing daily fluoride exposures enhanced fluoride release for all three restorative materials.

Absorption↗

PubMedDate not supplied

Sexual partnership patterns as a behavioral risk factor for sexually transmitted diseases.

CONTEXT: Women's and men's number of sexual partners and protective practices such as condom use can have a direct effect on their risk of contracting sexually transmitted diseases (STDs), including HIV. METHODS: The 1988 and 1995 cycles of the National Survey of Family Growth and five rounds of the General Social Survey conducted from 1988 to 1996 are used to examine women's and men's numbers of recent sexual partners. Levels of direct risk for STDs (two or more partners in the past year) and the social and demographic correlates of multiple partnership are analyzed among women and men. In addition, women's indirect risk for STDs (their partners' involvement with other partners in the past year) is used to estimate their overall risk of STDs through multiple partnerships. RESULTS: At least three-quarters of sexually active U.S. women and men in the late 1980s and mid-1990s had had only one sexual partner in the preceding 12 months. Moreover, there is no indication that the proportion with more than one partner in the past year changed substantially over that period. Nevertheless, combining women's and men's partnership reports suggests that about 17 million women aged 15-44--34% of those sexually active in the past year--were at risk for STDs because of direct exposure to multiple partners (5.4 million), indirect exposure (6.3 million) or both direct and indirect exposure (5.5 million). In all, 21% of women were at direct risk and 23% were at indirect risk. In comparison, among men aged 18-44, 24% were at direct risk for STDs and an unknown proportion were at indirect risk. Multivariate analyses indicated that unmarried individuals, women younger than 40 and men aged 20-29, blacks and women in the South were all at elevated risk for STDs because of multiple partnership. Overall, in 1995, 19% of sexually active women aged 15-44 had used condoms to protect against STDs over the preceding year, and 19% of those sexually active in the three months before the survey were current condom users. Condom use specifically for STD prevention was more common among women reporting both direct and indirect risk for STDs (58%) and among those at direct risk (46%) than among other women; women whose partners put them at indirect risk only were less likely to be current or recent condom users than women who were not at risk or were only at direct risk. CONCLUSIONS: There is a continuing need to educate people regarding their risk for STDs, to increase the use of existing barrier methods and to develop new methods that protect against STD infection. In addition, if we are to develop a better understanding of the extent of STD risk through multiple partnership, the collection of information on number of partners and relationships between partners must be expanded and improved.

Adolescent↗

PubMed2004

Understanding sex differences in environmental health: a thought leaders' roundtable.

Under the auspices of the Society for Women's Health Research, a thought leaders' roundtable was convened at the National Institute of Environmental Health Sciences in October 2002 to discuss recent advances in environmental health research, particularly those findings that explain sex differences in response to environmental exposures. Researchers discussed the latest findings on the interaction between sex and environmental exposures on health. Participants concluded that a greater focus on interdisciplinary, hypothesis-driven research is essential to advancing the field. To understand fully the potential effect of chronic exposures, researchers need to develop models to explore not only physiologic sex differences but also behavioral responses to low-dose and multiple chemical exposures. Future research should examine sex differences from the cell line to behaviors and should track these differences across multiple generations. Federal agencies should support such research in their awards of investigator-initiated grants.

Carcinogens, Environmental↗

PubMed1994

The relationship between traumatic exposure, family dysfunction, and post-traumatic stress symptoms in male juvenile offenders.

This study examined some chronic, stressful conditions and some acute, traumatic events which may place youths at risk for specific types of psychopathology. Ninety one delinquent adolescents with histories of serious and repeated crimes were assessed for their exposure to 11 different types of trauma. The subjects were also tested using measures which assess family functioning, and frequency and intensity of Post-Traumatic Stress Disorder (PTSD) symptoms. Results indicated that 24% of the subjects tested met full DSM III-R criteria for PTSD. Both exposure to violence and family dysfunction were significantly associated with PTSD symptomatology. These findings suggest that juvenile offenders may constitute a high risk group for exposure to multiple types of trauma and the development of post-traumatic stress symptoms related to such exposure. This study provides a rationale for future cross-trauma research both within the juvenile offender population and between it and other identified trauma groups.

Adolescent↗

PubMed2006

Validity and reliability of adult recall of past sun exposure in a case-control study of multiple sclerosis.

BACKGROUND: Measurement of past sun exposure through recall by adults has the potential for measurement error. We aimed to investigate aspects of validity and reliability of self-reported past sun exposure. METHODS: A population-based case-control study was conducted in Tasmania on 136 cases with multiple sclerosis and 272 age- and sex-matched community controls. Repeat interviews on 52 cases and 52 controls were done on average 11 weeks after the initial interview. Sun exposure was assessed by questionnaire and lifetime calendar. Other measurements included serum 25-hydroxyvitamin D, actinic damage, and skin phenotype. RESULTS: There was an association between recent sun exposure and serum vitamin D (time in the sun: r = 0.22, P < 0.01; activities outside: r = 0.31, P < 0.01 for controls) and between lifetime sun exposure and actinic damage [correlation between 0.34 (P < 0.01) and 0.17 (P = 0.01) for controls]. The test-retest weighted kappa statistic of self-reported sun exposure ranged from 0.43 to 0.74. Recall of childhood/adolescent sun exposure by standardized questioning was no less reproducible than recall of recent adult sun exposure and no less reliable when made with the calendar method. Comparing the questionnaire and calendar method, the measures of childhood/adolescent sun exposure had a similar predictive validity for multiple sclerosis. CONCLUSIONS: The results of this study provide further evidence that adults are able to recall past sun exposure with shown validity and reliability and present information about the possible reasons for the good reliability of recalled sun exposure measures.

Adolescent↗

PubMed2001

An overview of human exposure modeling activities at the USEPA's National Exposure Research Laboratory.

The computational modeling of human exposure to environmental pollutants is one of the primary activities of the US Environmental Protection Agency (USEPA)s National Exposure Research Laboratory (NERL). Assessment of human exposures is a critical part of the overall risk assessment paradigm. In exposure assessment, we analyze the source-to-dose sequence of processes, in which pollutants are released from sources into the environment, where they may move through multiple environmental media, and to human receptors via multiple pathways. Exposure occurs at the environment-human interface, where pollutants are contacted in the course of human activities. Exposure may result in a dose, by which chemicals enter the body through multiple portals of entry, primarily inhalation, ingestion, and dermal absorption. Within the body, absorbed pollutants are distributed to, metabolized within, and eliminated from various organs and tissues, where they may cause toxicologic responses or adverse health effects. The NERL's modeling efforts are directed at improving our understanding of this sequence of processes, by characterizing the various factors influencing exposures and dose, and their associated variabilities and uncertainties. Modeling at the NERL is one of three essential programmatic elements, along with measurements and methods development. These are pursued interactively to advance our understanding of exposure-related processes. Exposure models are developed and run using the best currently available measurement data to simulate and predict population exposure and dose distributions, and to identify the most important factors and their variabilities and uncertainties. This knowledge is then used to guide the development of improved methods and measurements needed to obtain better data to improve the assessment and reduce critical uncertainties. These models and measurement results are tools that can be used in risk assessments and in risk management decisions in order to reduce harmful exposures. Current areas of the NERL's exposure modeling emphasis include: Pollutant concentrations in ambient (outdoor) air using the Third Generation Air Quality Modeling System's Community Multiscale Air Quality model (Models-3/CMAQ); Air flow and pollutant concentrations at local and microenvironmental scales using computational fluid dynamics (CFD); Human inhalation exposure to airborne particulate matter, air toxics, and multipathway exposure to pesticides, using the Stochastic Human Exposure and Dose Simulation (SHEDS) model; Human and ecological exposure and risk assessments of hazardous waste sites using Framework for Risk Analysis in Multimedia Environmental Systems--Multimedia, Multipathway, Multireceptor Risk Assessment (FRAMES-3MRA), one of many software programs available from the NERL's Center for Exposure Assessment Modeling (CEAM); Physiologically based pharmacokinetic (PBPK) modeling of pesticides and volatile organic compounds (VOCs) in the Exposure-Related Dose-Estimating Model (ERDEM). A brief historical overview of the NERL's evolution of human exposure models is presented, with examples of the present state-of-the-science represented by SHEDS and FRAMES-3MRA.

Air Pollutants↗

PubMedDate not supplied

Neural sensitization model for multiple chemical sensitivity: overview of theory and empirical evidence.

This paper summarizes theory and evidence for a neural sensitization model of hyperresponsivity to low-level chemical exposures in multiple chemical sensitivity (MCS). MCS is a chronic polysymptomatic condition in which patients report illness from low levels of many different, structurally unrelated environmental chemicals (chemical intolerance, CI). Neural sensitization is the progressive host amplification of a response over time from repeated, intermittent exposures to a stimulus. Drugs, chemicals, endogenous mediators, and exogenous stressors can all initiate sensitization and can exhibit cross-sensitization between different classes of stimuli. The properties of sensitization overlap much of the clinical phenomenology of MCS. Animal studies have demonstrated sensitization to toluene, formaldehyde, and certain pesticides, as well as cross-sensitization, e.g., formaldehyde and cocaine. Controlled human studies in persons with self-reported CI have shown heightened sensitizability in the laboratory to nonspecific experimental factors and to specific chemical exposures. Useful outcome measures include spectral electroencephalography, blood pressure, heart rate, and plasma beta-endorphin. Findings implicate, in part, dopaminergic mesolimbic pathways and limbic structures. A convergence of evidence suggests that persons with MCS or with low-level CI may share some characteristics with individuals genetically vulnerable to substance abuse: (a) elevated family histories of alcohol or drug problems; (b) heightened capacity for sensitization of autonomic variables in the laboratory; (c) increased amounts of electroencephalographic alpha activity at rest and under challenge conditions over time. Sensitization is compatible with other models for MCS as well. The neural sensitization model provides a direction for further systematic human and animal research on the physiological bases of MCS and CI.

Autonomic Nervous System↗