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We recently reported that mold odor may be explained by chloroanisoles (CAs) formed by microbial biotransformation of chlorophenols (CPs) in legacy wood preservatives. Here we examine psychophysical aspects of CAs and trace their historic origins in buildings. Our exposure of healthy volunteers shows that 2,4,6-triCA is often perceived as unpleasant, characterized as musty or moldy and is detected at 13 ng/m3 or lower. Similar concentrations are reported in buildings with odor complaints. Scrutiny of written records reveal that new building construction methods were introduced in the 1950s, namely crawlspaces and concrete slabs on the ground. These constructions were prone to dampness and attack from wood decay fungi, prompting chemical companies and authorities to advocate preservatives against rot. Simultaneously, CPs became household chemicals used for example in indoor paints. When large-scale odor problems evolved, the authorities that once approved the preservatives attributed the odor to hidden mold, with no evidence that substantial microbial biomass was necessary for odor formation. Thereby the public remained unaware of problematic exposure to CPs and CAs. We conclude that the introduction of inappropriate designs of house foundations and CP-based preservatives once ignited and still provide impetus for indoor air research on "dampness and mold".

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Perceptions that arise from stimulation of olfactory and trigeminal receptors in the nasal cavity guide the evaluation of chemical environment in humans. Strong interindividual differences in these assessments may be attributed to nonsensory factors such as gender, anxiety, and chemical sensitivity. Knowledge regarding the influence of these factors originates mainly from basic odor research using short-term exposure scenarios. In situations with continuous chemical exposures-common in the working environment-their impact is less clear. To investigate their role during the exposure to workplace chemicals, 4-hour experimental exposure studies (total N = 105) using nine different airborne chemicals were summarized. In each study, subjects evaluated a single chemical in a controlled environment by rating five chemosensory perceptions, including odor intensity, disgust, annoyance, pungency, and burning, several times during occupational limit and low exposures. It was investigated whether the effects of trait-like modulators, such as anxiety and self-reported chemical sensitivity, depend on exposure-related factors and gender. Trait-like modulators markedly affected ratings by women, but not men. Highly anxious women reported more intense annoyance and disgust than less anxious women. Stronger self-reported chemical sensitivity was associated with increased ratings of pungency and burning in women exposed to occupational limit concentrations. This study demonstrates that a complex interplay of exposure-related factors, gender, and trait-like individual differences affects perceptual ratings during continuous chemical exposure. It seems necessary to incorporate the assessment of specific as well as general trait-like modulators into future experimental exposure studies.

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The anterior medial temporal lobe (TL), including the amygdala, has been implicated in olfactory processing, e.g., coding for intensity and valence, and seems also involved in memory. With this background, the present study evaluated whether anterior medial TL-resections in TL epilepsy affected intensity and valence ratings, as well as free and cued identification of odors. These aspects of odor perception were assessed in 31 patients with unilateral anterior medial TL-resections (17 left, 14 right) and 16 healthy controls. Results suggest that the anterior medial TL is in particular necessary for free, but also cued, odor identification. TL resection was also found to impair odor valence, but not intensity ratings. Left resected patients rated nominally pleasant and unpleasant odors as more neutral suggesting a special role for the left anterior TL in coding for emotional saliency in response to odors.

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Chemosensory active volatile organic compounds occur in the breathing air at many workplaces and it has been assumed that they are potent to impair workers' cognitive performance; however, the nature of this relationship is not understood. In the current study we investigated whether the combination of strong chemosensory potency and unpleasant odor valence is a sufficient predictor for the appearance of neurobehavioral impairment. Human volunteers were exposed to three workplace-relevant concentrations of the malodorant cyclohexylamine: 0.3 (odor control condition), 0-4 (varying condition), and 10 ppm (occupational exposure limit value, OEL, Sweden & Germany). The highest exposure evoked strong chemosensory sensations (annoyance), rather much olfactory related symptoms (bad air, stink), and increase in eye-blink frequency, which can be interpreted as indicator of trigeminal mediated adversity. Neurobehavioral performance measures (reaction times, accuracy) from three visual tasks requiring attention, motor inhibition and cognitive control did not show impairment in a consistent, dose-response related way and thus could not be related to cyclohexylamine exposure. Odorant characteristics of intensity and unpleasantness seem not sufficient to predict neurobehavioral impairment. Instead factors like participant selection bias, personality factors as well as effects related to the study design are discussed as contributing factors.

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OBJECTIVES: Though sulfur dioxide (SO(2)) is used widely at workplaces, itseffects on humans are not known. Thresholds are reported without reference to gender or age and occupational exposure limits are basedon effects on lung functioning,although localized effects in the upper airways can be expected.This study's aim is to determine thresholds with respect to age and gender and suggests a new approach to risk assessment using breathing reflexes presumably triggered by trigeminal receptors in the upper airways. METHODS: Odor thresholds were determined by the ascending method of limits in groups stratified by age and gender.Subjects rated intensities of different olfactory and trigeminal perceptions at different concentrations of SO(2). During the presentation of the concentrations, breathing movements were measured by respiratory inductive plethysmography. RESULTS: Neither age nor gender effects were observed for odor threshold. Only ratings of nasal irritation were influenced bygender. A benchmark dose analysis on relative respiratory depth revealed a 10%-deviation from baseline at about 25.27 mg/m(3). CONCLUSION: The proposed new approach to risk assessment appearsto be sustainable. We discuss whether a 10%-deviation of breathingdepth is relevant.

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A variety of national occupational exposure limits for ethyl acetate exist based on different studies, mostly relying on subjective evaluations of ethyl acetate as an irritant. Only one study also used physiological methods with inconsistent results in subjective and objective data. The present study was designed to investigate ethyl acetate on three different dimensions: behavioral, physiological and psychological indicators of adverse chemosensory effects were investigated during acute exposures to different concentrations of ethyl acetate. Twenty-four subjects were challenged with ethyl acetate in three exposure patterns (2 ppm, 400 ppm, 400 ppm including peaks of 800 ppm). While the odor intensity is rated "strong", trigeminal perceptions were rated less than "moderate". The absence of substantial trigeminal ratings was supported by physiological data. There was neither an effect of concentration on blinking frequency nor on nasal resistance which both are indicators of irritation. Furthermore, there are no effects of ethyl acetate concentration on behavioral measures indicating no olfactory or trigeminally mediated disturbance of cognitive processing. In conclusion, the results of this multilevel approach revealed no adverse chemosensory effects at ethyl acetate concentrations as recommended by the German MAK-value.

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In low concentrations, environment pollutants like volatile organic compounds (VOCs) may be perceived via olfaction. Modulators of odor-mediated health effects include age, gender, or personality traits related to chemical sensitivity. Severe multi-organ symptoms in response to odors also characterize a syndrome referred to as idiopathic environmental intolerance (IEI). One prominent feature of IEI is self-reported odor hypersensitivity that is usually not accompanied by enhanced olfactory functioning. The impact of interindividual differences in olfactory functioning on chemosensory perceptions is sparsely investigated, and therefore this study addressed the influences of different types of modulators, including olfactory functioning. In a psychophysical scaling experiment, an age-stratified sample of 44 males and females was examined. After controlled application of nine concentrations of six chemicals by flow-olfactometry, the participants rated four olfactory and nine trigeminal perceptions. Weak effects were found for gender and age, as well as some modulating effects of self-reported chemical sensitivity and odor discrimination ability. For chemical sensitivity, the results were as expected: Subjects with higher sensitivity reported stronger perceptions. The individual odor threshold (n-butanol) exerted no influence on the subjects' ratings of olfactory and trigeminal perceptions. Surprisingly, above-average odor discrimination ability was associated with lower ratings of odor intensity and nausea. This particular aspect of olfactory functioning might be a reflection of a more objective odor evaluation model buffering emotional responses to environmental odors.

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Organic solvents are still essential in many industrial applications. To improve safety and health in the working environment lower occupational thresholds limits have been established and less toxic substitutes were introduced. N-Methyl-2-pyrrolidone (NMP) is a versatile solvent that is used as a substitute for dichloromethane in paint strippers. Due to conflicting results, there is a debate whether NMP causes irritations of the upper airways/eyes or not. In a human experimental study we examined the chemosensory effects of NMP under controlled conditions. Fifteen healthy males were investigated in a cross-over study. NMP vapor concentrations were 10, 40 and 80 mg/m(3) for 2 x 4h with an exposure-free lunch break of 30 min. To maximize chemosensory effects a peak exposure scenario (25mg/m(3) baseline, 160 mg/m(3) peaks 4 x 15 min, time-weighted average: 72 mg/m(3)) was tested. The four different conditions were conducted with and without moderate physical workload. Chemosensory effects were measured physiologically by anterior rhinomanometry, eye blink rate and breathing frequency. Subjectively, ratings of acute health symptoms and intensity of olfactory and trigeminal sensations were collected repeatedly throughout the exposures. All physiological variables were unaffected by the different NMP concentrations and even the peak exposures were non-effective on these measures. Olfactory mediated health symptoms increased dose-dependently. For these symptoms a strong adaptation was observable, especially during the first 4h of the exposures. Other acute symptoms were not significantly affected. Comparable to the symptoms, only olfactory sensations increased dose-dependently. Trigeminal sensations (e.g. eye and nose irritations) were evaluated as being barely detectable during the different exposures, only during 160 mg/m(3) exposure peak weak and transient eye irritation were reported. The results clearly suggest that NMP concentrations of up to 160 mg/m(3) caused no adverse sensory irritation or undue annoyance.

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BACKGROUND: The event-related brain response mismatch negativity (MMN) registers changes in auditory stimulation with temporal lobe sources reflecting short-term echoic memory and frontal sources a deviance-induced switch in processing. Impairment, controversially present at the onset of schizophrenia, develops rapidly and can remain independent of clinical improvement. We examined the characteristics of the scalp-recorded MMN and related these to tests of short-term memory and set-shifting. We assessed whether the equivalent dipole sources are affected already at illness-onset in adolescence and how these features differ after a 14-year course following an adolescent onset. The strength, latency, orientation and location of frontal and temporal lobe sources of MMN activity early and late in the course of adolescent-onset schizophrenia are analysed and illustrated. METHODS: MMN, a measure of auditory change-detection, was elicited by short deviant tones in a 3-tone oddball-presentation and recorded from 32 scalp electrodes. Four dipole sources were placed following hypothesis-led calculations using brain electrical source analysis on brain atlas and MR-images. A short neuropsychological test battery was administered. We compared 28 adolescent patients with a first episode of schizophrenia and 18 patients 14 years after diagnosis in adolescence with two age-matched control groups from the community (n = 22 and 18, respectively). RESULTS: MMN peaked earlier in the younger than the older subjects. The amplitude was reduced in patients, especially the younger group, and was here associated with negative symptoms and slow set-shifting. In first-episode patients the temporal lobe sources were more ventral than in controls, while the left cingular and right inferior-mid frontal sources were more caudal. In the older patients the left temporal locus remained ventral (developmental stasis), the right temporal locus extended more antero-laterally (illness progression), and the right frontal source moved antero-laterally (normalised). CONCLUSION: From the start of the illness there were differences in the dipole-model between healthy and patient groups. Separate characteristics of the sources of the activity differences showed an improvement, stasis or deterioration with illness-duration. The precise nature of the changes in the sources of MMN activity and their relationship to selective information processing and storage depend on the specific psychopathology and heterogeneous course of the illness.

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Mismatch negativity (MMN) is an event-related potential reflecting automatic attention-related information processing marking the detection of auditory change. The bilateral scalp distribution develops by 14 years of age, and is elicited with adult latencies by 17 years. But consistent with reports of continued brain maturation after adolescence, we show here that features of the temporal and frontal lobe dipole sources also continue to develop in the third decade of life. This has consequences for studies of the developmental course of MMN anomalies, from childhood into adulthood, in attention-deficit/hyperactivity disorder. Two groups of healthy subjects with mean ages of 17 and 30 years were presented with a 3-tone auditory oddball. The duration-deviant MMN was recorded during attention to a visual discrimination (auditory-passive condition) and an active auditory discrimination. MMN amplitudes were smaller in the older subjects and the MMN lasted longer over the right hemisphere. Latencies and moments of the four dipoles in the temporal and frontal lobes did not distinguish the two subject-groups. But both temporal lobe sources were located significantly more ventrally and further left in the young adult than in the adolescent subjects. The left cingular source moved posteriorly and the right inferior frontal source moved antero-medially in the older subjects. Brain development in the third decade may cause the two frontal sources to move apart on the rostro-caudal axis but the temporal lobe sources to move left on the lateral and down on the dorsoventral axes. Thus special care is necessary in interpreting putative dysfunctional neurobiological changes in developmental attention-deficit disorders where as-yet-unspecified sub-groups may show a late developmental lag, partial lag, or no lag at all, associated with other impairments.

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