Hendrik Veulemans

Media warnings about environmental pollution facilitate the acquisition of symptoms in response to chemical substances.

Objective Previous studies showed that somatic symptoms can be acquired in response to chemical substances using an associative learning paradigm, but only when the substance was foul smelling and not when it smelled pleasant. In this study, we investigated whether warnings about environmental pollution would facilitate acquiring symptoms, regardless of the pleasantness of the smell. Method One group received prior information framing the study in the context of the rapidly increasing chemical pollution of our environment. Another group received no prior information. Conditional odor stimuli (CS) were diluted ammonia (foul-smelling) and niaouli (neutral-positive smelling); the unconditional stimulus (UCS) was 10% CO2-enriched air. Each subject breathed one odor mixed with CO2 and a control odor mixed with air in 80-sec breathing trials. The type of odor mixed with CO2 was counterbalanced across participants. Next, the same breathing trials were administered without CO2. Breathing behavior was measured during each trial; subjective symptoms were assessed after each trial. Results Only participants who had been given warnings about environmental pollution reported more symptoms to the odor that had previously been associated with CO2, compared with the control odor. This was so for both the foul- and the pleasant-smelling odor. Symptom learning did not occur in the group that did not receive warnings. The elevated symptom level could not be accounted for by altered respiratory behavior, nor by experimental demand effects. Conclusions Raising environmental awareness through warnings about chemical pollution facilitates learning of subjective health symptoms in response to chemical substances.

Generalization of acquired somatic symptoms in response to odors: a pavlovian perspective on multiple chemical sensitivity.

Objective Somatic symptoms that occur in response to odors can be acquired in a pavlovian conditioning paradigm. The present study investigated 1) whether learned symptoms can generalize to new odors, 2) whether the generalization gradient is linked to the affective or irritant quality of the new odors, and 3) whether the delay between acquisition and testing modulates generalization. Methods Conditional odor stimuli (CS) were (diluted) ammonia and niaouli. One odor was mixed with 7.4% CO2-enriched air (unconditional stimulus) during 2-minute breathing trials (CS+ trial), and the other odor was presented with air (CS− trial). Three CS+ and three CS− trials were conducted in a semirandomized order (acquisition phase). The test phase involved one CS+-only (CS+ without CO2) and one CS− test trial, followed by three trials using new odors (butyric acid, acetic acid, and citric aroma). Half of the subjects (N = 28) were tested immediately, and the other half were tested after 1 week. Ventilatory responses were measured during and somatic symptoms were measured after each trial. Results Participants had more symptoms in response to CS+-only exposures, but only when ammonia was used as the CS+. Also, generalization occurred: More symptoms were reported in response to butyric and acetic acid than to citric aroma and only in participants who had been conditioned. Both the selective conditioning and the generalization effect were mediated by negative affectivity of the participants. The delay between the acquisition and test phases had no effect. Conclusions Symptoms that occur in response to odorous substances can be learned and generalize to new substances, especially in persons with high negative affectivity. The findings further support the plausibility of a pavlovian perspective of multiple chemical sensitivity.

Exposure to ethylene glycol ethers and spermatogenic disorders in man: a case-control study.

A case-control study was conducted among first time patients at a clinic for reproductive disorders. The study group consisted of 1019 cases, defined as patients diagnosed infertile or subfertile on the basis of a spermiogram and 475 controls who were diagnosed as normally fertile by the same procedure. Possible exposure to ethylene glycol ethers was assessed by the presence of the urinary metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) respectively for 2-methoxyethanol and 2-ethoxyethanol or their acetates. In total, EAA was detected in 39 cases and six controls, with a highly significant odds ratio of 3.11 (p = 0.004). On the other hand, MAA was only found in one case and two controls. The presence of EAA in urine proved to be strongly associated with exposure to preparations containing solvents, especially paint products, and with some groups of occupations, the most important of which were also directly or possibly connected with paint products. The absence of a significant correlation between the concentration of urinary EAA and the various measures of sperm quality could be explained by the expected latent period between exposure and observed effects. Other temporal aspects of the relation between exposure as judged from the presence of urinary EAA and diagnosis are also discussed.

Acquisition and extinction of somatic symptoms in response to odours: a Pavlovian paradigm relevant to multiple chemical sensitivity.

OBJECTIVES: Multiple chemical sensitivity is a poorly understood syndrome in which various symptoms are triggered by chemically unrelated, but often odorous substances, at doses below those known to be harmful. This study focuses on the process of pavlovian acquisition and extinction of somatic symptoms triggered by odours. METHODS: Diluted ammonia and butyric acid were odorous conditioned stimuli (CS). The unconditioned stimulus (US) was 7.4% CO2 enriched air. One odour (CS+) was presented together with the US for 2 minutes (CS+ trial), and the other odour (CS-) was presented with air (CS-trial). Three CS+ and three CS-exposures were run in a semi-randomised order; this as the acquisition (conditioning) phase. To test the effect of the conditioning, each subject then had one CS+ only--that is, CS+ without CO2--and one CS- test exposure. Next, half the subjects (n = 32) received five additional CS+ only exposures (extinction group), while the other half received five exposures to breathing air (wait group). Finally, all subjects got one CS+ only test exposure to test the effect of the extinction. Ventilatory responses were measured during and somatic symptoms after each exposure. RESULTS: More symptoms were reported upon exposure to CS+ only than to CS-odours, regardless of the odour type. Altered respiratory rate was only found when ammonia was CS+. Five extinction trials were sufficient to reduce the level of acquired symptoms. CONCLUSION: Subjects can acquire somatic symptoms and altered respiratory behaviour in response to harmless, but odorous chemical substances, if these odours have been associated with a physiological challenge that originally had caused these symptoms. The conditioned symptoms can subsequently be reduced in an extinction procedure. The study further supports the plausibility of a pavlovian conditioning hypothesis to explain the pathogenesis of MCS.

Experimental human exposure to ethylene glycol monomethyl ether

SummaryThe uptake of EGME and the urinary excretion of its major metabolite (MAA) was studied in seven male volunteers during experimental exposure to EGME at rest. The exposure concentration was set at 16 mg/m3, the present Threshold Limit Value. A high retention (0.76) remained unchanged during the 4-h exposure period. In combination with a constant pulmonary ventilation and a fixed exposure concentration this resulted in an uptake rate that showed no significant variation in time. The total amount of EGME inhaled corresponded to a dose of only 0.25 mg/kg. During and up to 120h after the start of the exposure, MAA was detected in the urine. The elimination half-life was on average 77.1 h. The total amount of MAA excreted was calculated by extrapolation and averaged 85.5% of the inhaled EGME. The pharmacokinetic data are compared with those obtained from other human exposure studies to ethylene glycol ethers (EGEE and EGBE).

Acquiring Symptoms in Response to Odors: A Learning Perspective on Multiple Chemical Sensitivity

Abstract: In this chapter, a learning account is discussed as a potential explanation for the symptoms in multiple chemical sensitivity. Clinical evidence is scarce and anecdotal. A laboratory model provides more convincing results. After a few breathing trials containing CO2‐enriched air as an unconditioned stimulus in a compound with harmless odor substances as conditioned stimuli, subjective symptoms are elicited and respiratory behavior is altered by the odors only. Also, mental images can become conditioned stimuli to trigger subjective symptoms. The learning effects cannot be explained by a response bias or by conditioned arousal, and they appear to involve basic associative processes that do not overlap with aware cognition of the relationship between the odors and the CO2 inhalation. Learned symptoms generalize to new odors and they can be eliminated in a Pavlovian extinction procedure. In accordance with clinical findings, neurotic subjects and psychiatric cases are more vulnerable to learning subjective symptoms in response to odors. Consistent with a learning account, cognitive‐behavioral treatment techniques appear to produce beneficial results in clinical cases. Several criticisms and unresolved questions regarding the potential role of learning mechanisms are discussed.

Experimental Human Exposure to Toluene II Toluene in Venous Blood During and After Exposure

SummaryThe application as biologic exposure parameter of the toluene concentration in venous blood during and after an exposure to this solvent was experimentally studied. Under carefully controlled conditions 6 healthy male subjects were exposed to various concentrations of toluene in inspired air (50, 100, 125, 150 and 200 ppm) at rest or under different levels of physical effort. Peripheral venous concentrations (Cv) were followed in relation to the individual toluene uptake.A relatively constant relation was found between uptake rate of toluene and Cv under steady state conditions. Empirically, for lung clearances at rest and for differing inspired concentrations (CI), this relation was given by: Cv (mg/l) = 0.303 CI (mg/1) x Lung clearance (1/min).Under constant CI (50 ppm) and lung clearances varying from rest values to values under a continuous exercise of 50 W, the regression equation became: Cv (mg/l) = 0.328 CI (mg/l) x Lung clearance (1/min).Under non-steady state conditions no simple relation existed between uptake rate and Cv, indicating that equally no simple connection could be made between Cv and the calculated mixed venous concentration, or, extrapolating, the expected toxic load of most inner organs.In relation to the individual dose, Cv always presented a much greater variability than the toluene uptake by itself. The observed differences, both intra-individually as between subjects, were mostly statistically significant. Apparently Cv was influenced by some host factors in another manner than the uptake rate. In this respect evidence was obtained that the local blood perfusion and the amount body fat were involved to a certain extent. For this reason Cv proved a somewhat less satisfactory individual dose-parameter.

Respiratory uptake and elimination of ethylene glycol monoethyl ether after experimental human exposure.

Ten male volunteers were exposed to ethylene glycol monoethyl ether (EGEE) under various conditions of exposure concentration and physical workload. Steady state levels of retention, atmospheric clearance, and rate of uptake were reached immediately after the start of the exposure period for all experimental conditions. Retention was high (64% in resting condition) and increased as physical exercise was performed during exposure. Atmospheric clearance increased as the pulmonary ventilation rate increased. The rate of uptake was higher as exposure concentration or pulmonary ventilation rate, or both, increased. Individual uptake appeared to be governed mainly by transport mechanisms (pulmonary ventilation or cardiac output or both) and not by anthropometric factors. Respiratory elimination of unchanged EGEE accounted for less than or equal to 0.4% of the total body uptake. Postexposure breath concentrations declined rapidly during the first minutes after cessation of exposure, after which a much slower decrease was observed. This slow decrease could be described by a regression equation containing two exponential terms indicating that at least two pharmacological compartments are concerned.

Gas chromatographic determination of methoxyacetic and ethoxyacetic acid in urine.

Methoxyacetic acid (MAA) and ethoxyacetic acid (EAA), the major metabolites of, respectively, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether and their acetates, are determined by gas chromatography after extraction from urine and methylation using 2-furoic acid (2-FA) as an internal standard. The mean recoveries (n = 30) from urine of MAA, EAA, and 2-FA are 31.4 +/- 7.0%, 62.5 +/- 13.4%, and 58.4 +/- 8.7%, respectively. The recoveries decreased (p less than 0.001), however, as the total amount of acids increased. Standard curves for MAA and EAA in urine are presented. The detection limits of MAA and EAA are 0.15 and 0.07 mg/l. Intra-assay variation for MAA and EAA was 6.0 +/- 2.5% and 6.4 +/- 2.8% and inter-assay variation was 6.2 +/- 2.2% and 8.9 +/- 2.4%. When volunteers were exposed to air containing ethylene glycol monoethyl ether (20 mg/m3), urinary concentration of EAA rose significantly one hour after the exposure period (2.39 +/- 1.03 v less than or equal to 0.07 mg/l, t = 5.2, p less than 0.005).

Survey of Ethylene Glycol Ether Exposures in Belgian Industries and Workshops

From 1983 onward, 2654 air samples from 336 different plants from the northern part of Belgium were analyzed for the presence of ethylene glycol ethers. One or more ethylene glycol ethers were detected in 262 air samples (9.9%) covering 78 plants or small establishments (23.2%) from a wide variety of industries. Ethylene glycol ethers were mainly present in establishments or operations where printing pastes, inks, paints and varnishes were used. About one third of the air samples covered various other industries. Car repair shops took a major part of this group. It was not always clear, however, in what precise operation the glycol ethers were involved. The ethylene glycol ethers most frequently identified were ethylene glycol monoethyl ether (EGEE) and its acetate (EGEE-Ac). Furthermore, ethylene glycol monomethyl ether (EGME), its acetate (EGME-Ac), and ethylene glycol monobutyl ether (EGBE) also were present in a large number of air samples. The glycol ethers were not distributed equally among the various groups of operations. Most exposure levels were far below the respective Threshold Limit Value (TLVs) (approximately less than 0.5 x TLV). About 25% of ethylene glycol concentrations, however, were higher than the current TLV. Most of the excursions were slight to moderate, although in selected cases extremely high concentrations were recorded. The majority of air samples revealed complex mixtures of ethylene glycol ethers with other solvents, the glycol ethers often being minor components. The possible implication of these other solvents on glycol ether toxicity and metabolism is discussed.