Airborne Chemicals Research Articles

Sensory irritation and multiple chemical sensitivity.

Many of the symptoms described in Sick Building Syndrome (SBS) and multiple chemical sensitivity (MCS) resemble the symptoms known to be elicited by airborne irritant chemicals. Irritation of the eye, nose, and throat is common to SBS, MCS, and sensory irritation (SI). Difficulty of breathing is often seen with SBS, MCS, and pulmonary irritation (PI). We therefore asked the question: can indoor air pollutants cause SI and/or PI? In laboratory testing in which mice breathed the dilute volatile emissions of air fresheners, fabric softeners, colognes, and mattresses for 1 h, we measured various combinations of SI and PI as well as airflow decreases (analogous to asthma attacks). Air samples taken from sites associated with repeated human complaints of poor air quality also caused SI, PI, and airflow limitation (AFL) in the mice. In previous publications, we have documented numerous behavior changes in mice (which we formally studied with a functional observational battery) after exposure to product emissions or complaint site air; neurological complaints are a prominent part of SBS and MCS. All together, these data suggest that many symptoms of SBS and MCS can be described as SI, PI, AFL, and neurotoxicity. All these problems can be caused by airborne irritant chemicals such as those emitted by common commercial products and found in polluted indoor air. With some chemical mixtures (e.g., emissions of some fabric softeners, disposable diapers, and vinyl mattress covers) but not others (e.g., emissions of a solid air freshener), the SI response became larger (2- to 4-fold) when we administered a series of two or three 1-h exposures over a 24-h period. Since with each exposure the intensity of the stimulus was constant yet the magnitude of the response increased, we concluded that there was a change in the sensitivity of the mice to these chemicals. The response was not a generalized stress response because it occurred with only some mixtures of irritants and not others; it is a specific response to certain mixtures of airborne chemicals. This is one of the few times in MCS research that one can actually measure both the intensity of the stimulus and the magnitude of the response and thus be allowed to discuss sensitivity changes. The changing SI response of the mice might serve as a model of how people develop increasing sensitivity to environmental pollutants. Intensive study of this system should teach us much about how people respond to and change sensitivity to airborne irritant chemicals.

A theoretical approach to the Ferguson principle and its use with non-reactive and reactive airborne chemicals.

The Ferguson principle has been widely used in toxicology to separate or indicate possible mechanisms for acute toxic effects of chemicals. However, this principle has never been adequately tested because of the lack of a database containing a sufficient number of both types of chemicals, non-reactive and reactive, that the Ferguson principle purports to separate. Such a database is now available. In this report a theoretical framework for the Ferguson principle is presented, regarding one of the acute toxicological effects of volatile airborne chemicals: sensory irritation. Previously obtained results on series of non-reactive and reactive chemicals are then used to demonstrate that the Ferguson principle can be extended to reactive chemicals by adding chemical reactivity descriptors to the physicochemical descriptors required by the Ferguson principle. This approach can be successful, provided that specific chemical reactivity mechanisms can be identified for the reactive chemicals of concern. The findings suggest that it is possible to replace the empirical Ferguson principle by formal mechanistic equations which will provide a better foundation for the understanding of the mechanisms by which airborne sensory irritants exert their action.

Computer-based bioassay for evaluation of sensory irritation of airborne chemicals and its limit of detection.

We expanded a previously described rule-based computerized method to recognize the sensory irritating effect of airborne chemicals. Using 2-chlorobenzylchloride (CBC) as a sensory irritant, characteristic modifications of the normal breathing pattern of exposed mice were evaluated by measuring the duration of braking (TB) after inspiration and the resulting decrease in breathing frequency. From the measurement of TB, each breath was then classified as normal (N) or sensory irritation (S). Using increasing exposure concentrations, the classification S increased from < or = 2% (equivalent to sham-exposure) to 100% within a narrow exposure concentration range. The potency of CBC was then evaluated by calculating the concentration necessary to produce 50% of the breaths classified as S, i.e., S50. This approach is easier to use than obtaining RD50 (decrease in respiratory frequency by 50%) when high exposure concentrations are difficult to achieve. Detection limits were also established for this bioassay and experiments were conducted to obtain a level of response just around these limits, in order to delineate the practicality of using this bioassay at low exposure concentrations. Using this approach, sensory irritation was the only effect induced by CBC at low exposure concentrations. However, bronchoconstriction and pulmonary irritation were superimposed on this effect at higher exposure concentrations.

Quantitative Structure-Activity Relationships (QSARs) for Odor Thresholds of Volatile Organic Compounds (VOCs)

Abstract A theoretical model for correlating odor thresholds of volatile organic compounds (VOCs) with their simple physicochemical properties has been developed. The partition coefficient between octanol and water, and that between water and air were used to model the partition process of airborne chemicals into the biophase where the olfactory signal is transformed. Validation was performed by fitting data on odor thresholds and partition coefficients for acetates, alcohols, ketones and amines into the model. Quantitative structure-activity relationships (QSARs) for the four series were developed from the model. The results suggest that acetates, alcohols and ketones probably bind to a common receptor site located in the hydrophobic interior of the lipid bi-layer membrane of the olfactory cilia. Amines probably bind to a different receptor site located closer to the mucus layer. The results also suggest that odor thresholds of related VOCs which appear to share a common receptor site may be additive.

Toxicological screening of chemical emissions from municipal solid waste landfills. application of a predictive framework to a state‐of‐the‐art facility

A screening‐level risk assessment was used to identify chemicals of potential health concern emitted during the normal operation of an hypothetical state‐of‐the‐art municipal solid waste landfill. Data on the amount of contaminants (carcinogens, non‐carcinogenic systemic toxicants, odorous compounds, and particulate‐bound metals) were obtained from existing facilities and used to estimate ground‐level air concentrations of airborne chemicals at the point of maximum impact (property line) and at year 20 (year of maximum emissions from the landfill). Concentrations of leachate components present in the corresponding underlying aquifer were also estimated. Intakes of chemicals experienced by a series of human receptors were then computed using either single‐media or multi‐media algorithms. Carcinogens of concern were selected as those contributing to a lifetime excess cancer risk (LECR) greater than 10‐6; for non‐carcinogenic systemic toxicants and odorous volatiles an Exposure Ratio (ER=intake or concentration/RfD, RfC, odor threshold) greater than 0.1 was used as cut‐off. The results obtained identified a final set of air emission components (n = 25) constituted mainly of carcinogenic and odorous substances whereas 2 leachate components were retained. Additional analysis using more refined risk‐based approaches are necessary to verify the relevance of these projections.

Occupational Exposure Limits for Airborne Chemicals in Britain

Abstract Exposure limits in Britain have legal force as part of the COSHH Regulations, which require employers to assess risk from chemicals and to control it. Compliance with the limits is a definition of adequate control. There are two types of limit, Occupational Exposure Standards (OESs), which are set at a level believed to correspond to negligible risk of injury, and Maximum Exposure Limits Levels (MELs), which are set when an OES level cannot be identified or is not reasonably practicable to achieve. Documentation is produced by a government body (the Health and Safety Executive), but the primary decisions are made by expert committees representing employers, trades unions, and other interests, subject to public consultation and (for MELs) parliamentary scrutiny. The substance reviews are multi-purpose: exposure limits are just one output; others can include proposals for classification and labelling, or hazard and risk assessment under the European Union's Existing Substances review program. The reviews take account of the Union's own non-binding exposure limit program, and an internationally-agreed format and quality standard enables documentation produced elsewhere in the Union to be used to review national limits. A key issue is whether the use of exposure limits justifies the considerable resources necessary to generate them, and results of a survey to help examine this question will be published later this year.

Drosophila melanogaster NADPH–cytochrome P450 oxidoreductase: pronounced expression in antennae may be related to odorant clearance

Insects perceive a large number of airborne chemicals as olfactory components mainly through the antenna. It is thought that detection of the odorants by specific receptors is followed by a degradative pathway that clears the olfactory organ from accumulating chemicals. In Drosophila, a number of P450 monooxygenases are involved in the metabolism of foreign chemicals [ Dunkov et al. (1996)Cytochrome P450 gene cluster in Drosophila melanogaster, Mol. Gen. Genet. 251, 290–297]. NADPH–cytochrome P450 oxidoreductases serve to transfer reducing equivalents to P450 monooxygenases. We isolated cDNA and genomic clones coding for a Drosophila NADPH–cytochrome P450 oxidoreductase (CPR). The largest cDNA of 2471 nucleotides in length contained an open reading frame of 693 amino acids that includes the putative CPR sequence. CPR is a single copy gene as shown by genomic Southern hybridisation and maps to the cytogenetic map position 26C on the second chromosome. Comparison of genomic and cDNA CPR sequences revealed a gene structure that is split into at least six exons. The CPR protein sequence is almost identical with that of house fly and remarkably conserved when compared to vertebrates and yeast. RNA expression is high in embryos and antennae as compared to adult heads, adult bodies and larvae. High expression in antennae may reflect the putative function in olfactory clearance. © 1997 Elsevier Science B.V. All rights reserved.

Evolving concepts of chemical sensitivity.

Chemical sensitivity appears to be an elusive phenomenon. Studies on individual differences in susceptibility may provide glimpses into the range of sensitivity in a population, which can be used for further study. Preliminary evidence in laboratory animals suggests the range of sensitivity to manufactured chemicals may span orders of magnitude. Determining the reasons that underlie individual differences in sensitivity is a more difficult enterprise. Conditioning of adverse physiological effects of airborne chemicals may play a vital role in the etiology of chemical sensitivity, and it provides a rigorous laboratory model by which to investigate some aspects of this elusive phenomenon.

Agonistic sensory effects of airborne chemicals in mixtures: odor, nasal pungency, and eye irritation.

Thresholds responses of odor, nasal pungency (irritation), and eye irritation were measured for single chemicals (1-propanol, 1-hexanol, ethyl acetate, heptyl acetate, 2-pentanone, 2-heptanone, toluene, ethyl benzene, and propyl benzene) and mixtures of them (two three-component mixtures, two six-component mixtures, and one nine-component mixture). Nasal pungency was measured in subjects lacking a functional sense of smell (i.e., anosmics) to avoid interference from olfaction. Various degrees of stimulus agonism (additive effects) were observed for each of the three sensory channels when testing mixtures. As the number of components and the lipophilicity of such components in the mixtures decreased, so did the degree of agonism. Synergistic stimulus agonism characterized the eye-irritation response for the most complex (the nine-component) and the most lipophilic (one of the six-component) mixtures. Physicochemical properties play a large role in the determination of sensitivity to airborne chemicals, particularly to their ability to evoke irritation. While this has revealed itself previously with respect to single chemicals, it seems to have relevance to mixtures as well.

Chamber Challenges: The Necessity of Objective Observation

The specialty of Allergy–Immunology has used human challenge testing procedures to test theories of causal relationships for decades. This includes highly characterized airborne allergens and chemicals with allergic sensitization potential. The utility of such testing to establish allergic sensitivity is well accepted. The causal relationship of chemical exposure and myriad clinical syndromes is a very contentious issue. The completion of the challenge chamber facility at EPA's Human Exposure Research Facility presents a grand opportunity for government investigators to work harmoniously with other nongovernment investigators in an effort to bring the redeeming spotlight of scientific discipline to the testy considerations of multiple chemical sensitivity, chronic fatigue, and Gulf War illness phenomena.

Development of Pituitary Lesions in ND4 Swiss Webster Mice When Estimating the Sensory Irritancy of Airborne Chemicals Using ASTM Method E981-84

This study determined the origin of pituitary lesions found in male ND4 Swiss Webster mice following a single head-only exposure to inhaled test materials using ASTM E981-84, standard test method for estimating sensory irritancy of airborne chemicals. Necropsy and histopathology data were evaluated due to the occurrence of unexpected pituitary lesions in sham control and exposure groups. Groups of four mice were restrained in body plethysmographs and exposed for 30 min to increasing dust concentrations of one of three test chemicals to assess the ability to cause sensory irritation. Sham control and test material-exposed mice were sacrificed after a single exposure and subjected to a complete necropsy and microscopic evaluation of the pituitary gland. Control mice remained in the animal room and were not restrained in the plethysmograph. Gross observation at necropsy showed pituitary lesions in one of seven unrestrained control mice (revised to zero of seven after microscopic examination). Seven of seven sham control mice had pituitary lesions, suggesting that the lesions were not related to test material exposure. Each test material-exposed group also had pituitary lesions with high incidence (52/60 for all groups combined), which was not exposure concentration-dependent. Microscopic evaluation of the pituitary glands revealed that darkening of the gland was due to hemorrhage and confirmed that the lesions developed with 100% incidence (19/19) in plethysmograph-housed animals. The rubber neck seal used to restrict animal movement in the plethysmograph appears to have caused an increase in pressure in the blood vessels in the pituitary gland; vessels then ruptured and hemorrhaged. This finding should not adversely affect sensory irritation responses evaluated with this method.

Development of pituitary lesions in ND4 Swiss Webster mice when estimating the sensory irritancy of airborne chemicals using ASTM method E981-84.

This study determined the origin of pituitary lesions found in male ND4 Swiss Webster mice following a single head-only exposure to inhaled test materials using ASTM E981-84, standard test method for estimating sensory irritancy of airborne chemicals. Necropsy and histopathology data were evaluated due to the occurrence of unexpected pituitary lesions in sham control and exposure groups. Groups of four mice were restrained in body plethysmographs and exposed for 30 min to increasing dust concentrations of one of three test chemicals to assess the ability to cause sensory irritation. Sham control and test material-exposed mice were sacrificed after a single exposure and subjected to a complete necropsy and microscopic evaluation of the pituitary gland. Control mice remained in the animal room and were not restrained in the plethysmograph. Gross observation at necropsy showed pituitary lesions in one of seven unrestrained control mice (revised to zero of seven after microscopic examination). Seven of seven sham control mice had pituitary lesions, suggesting that the lesions were not related to test material exposure. Each test material-exposed group also had pituitary lesions with high incidence (52/60 for all groups combined), which was not exposure concentration-dependent. Microscopic evaluation of the pituitary glands revealed that darkening of the gland was due to hemorrhage and confirmed that the lesions developed with 100% incidence (19/19) in plethysmograph-housed animals. The rubber neck seal used to restrict animal movement in the plethysmograph appears to have caused an increase in pressure in the blood vessels in the pituitary gland; vessels then ruptured and hemorrhaged. This finding should not adversely affect sensory irritation responses evaluated with this method.

An attempt to define a just detectable effect for airborne chemicals on the respiratory tract in mice.

We have attempted to define a just detectable effect (JDE) for three different types of reactions along the respiratory tract: (a) sensory irritation of the upper airways (S), (b) airflow limitation along the conducting airways (A), and (c) pulmonary irritation at the alveolar level (P1 or P). Each type of reaction, S, A, P1 or P, was recognized by analyzing the breathing pattern of unanesthetized mice held in body plethysmographs. A rule-based computer program analyzed each breath during a period of 3.75 h and classified each breath as normal (N) or falling in any of the above categories (i.e., S, A, P1 or P). Eight groups of four mice were used for sham exposures: exposed to water vapor. These data sets were used, as sham exposure data, to define the variation which can occur with time in order to define an expected range of normal variation. Once this range was established, we defined JDE values for each type of effect and used such values to evaluate the results obtained in exposed animals. Eight groups of four mice were exposed to a mixture of airborne chemicals, machining fluid G (MFG), at concentrations from 0.17 to 55 mg/m3. Data sets for individual animals and for each group of animals exposed to MFG were analyzed to determine if and when a particular effect occurred. It was possible to recognize the effects of low exposure concentrations on groups of exposed animals or individual animals within each group. This procedure will be valuable when investigating the effect of airborne chemicals and when it is impossible to generate high exposure concentrations to define concentration-response relationships.

Male acceleration of ovarian development in Drosophila silvestris (Diptera, Drosophilidae): What is the stimulus?

In the fly Drosophila silvestris the onset of vitellogenesis is accelerated when sexually immature adult females are housed with mature males. We examined the proximate stimuli that could be responsible for this acceleration. This stimulus could be courtship, because mature males will court immature females. By housing females on the opposite side of a divided jar from males, we could isolate females from courtship stimuli, but allow them access to airborne and substrate chemicals. Females housed in that way did not show acceleration. However, when the females were housed on the opposite side of the jar from mature males, but the food dishes were moved daily, some acceleration occurred. When females were housed in undivided jars, with complete access to males, but with the food dishes being replaced by fresh food daily, no acceleration was found. This suggests that some aspect of food that has been exposed to mature males, perhaps a bacterium growing on its surface, is providing a nutritional supplement which allows acceleration of ovarian development.

Semiochemicals that Disrupt Foraging by the Argentine Ant (Hymenoptera: Formicidae): Laboratory Bioassays

Two different laboratory bioassays were developed to quantitatively determine the repellent activity of semiochemicals, such as famesol and methyl eugenol, against the Argentine ant. lridomymzex humilis (Mayr). One assay, based on the ability of ants to cross barriers of beeswax containing different concentrations of test chemicals, was not designed to discriminate between olfactory or gustatory modes of detection. The other was based on the ability of an ant to detect airborne chemicals and, therefore, measured only the olfactory response of ants to the chemicals. Both assays permitted construction nof dosage-response curves and determination of a Bl50, the concentration that provided 50% behavioral inhibition.

Millimeter-wave measurements of molecular spectra with application to environmental monitoring

This paper presents results of mm-wave spectral properties of chemicals in the 225-315 GHz frequency range at ambient atmospheric pressure. The effect of pressure broadening of the spectral lines is determined by both experiments and theoretical simulation. Subsequent to the laboratory measurements, the proof of the principle of the open-path monitoring of airborne chemicals was tested by using a monostatic swept-frequency radar system.

Characterization of the effects of an airborne mixture of chemicals on the respiratory tract and smoothing polynomial spline analysis of the data.

We expanded a previously published (Vijayaraghavan et al. 1994) computerized system to analyze the breathing pattern of unanesthetized mice in order better to recognize and quantify the effects of an airborne mixture of chemicals at three different levels of the respiratory tract. The airborne chemical mixture used was a machining fluid. Such fluids are widely used in industry and a large number of workers are exposed to these airborne mixtures. We found this mixture to be capable of inducing three types of effects on the respiratory tract: sensory irritation of the upper respiratory tract (S), airflow limitation along the conducting airways (A) and pulmonary irritation (P). Depending upon the exposure concentration, mainly S or P effects were obtained but an A effect was also identified. The three types of effects occurred at various times during the exposures and, furthermore, within a group of exposed animals some exhibited one type of effect while others exhibited another type. In order to analyze such complex data sets, two statistical methods for smoothing polynomial splines were utilized: the maximum likelihood (ML) method and generalized cross validation (GCV) method. The results indicated the previous methods used to characterize a single effect of airborne chemicals can now be extended to evaluate mixtures likely to induce multiple types of effects. However, statistical analysis methods, either the ML or GCV methods, or other appropriate methods are needed to evaluate the responses obtained due to the complex effects that a mixture can induce in comparison to single chemicals.

Physicochemical Properties of Nonreactive Volatile Organic Chemicals to Estimate RD50: Alternatives to Animal Studies

This article presents the correlations obtained between the results on the potency of nonreactive airborne chemicals as sensory irritants and several of their physicochemical properties. The potency of airborne sensory irritants obtained from a reflexively induced decrease in respiratory frequency has been measured in the past using mice. Typically, their potency has been expressed as the exposure concentration necessary to decrease respiratory frequency by 50% (RD50). A large database of RD50 values is now available and such values are highly correlated with occupational exposure guidelines such as threshold limit values (TLVs). We used the nonreactive volatile organic chemicals from this database, for which relevant physicochemical variables are available or can be calculated. These variables were vapor pressure (P) or Ostwald gas-liquid partition coefficients (L). The liquids used for L values were n-hexadecane, octanol, N-formylmorpholine, tri-(2-ethyl-hexyl)phosphate, and olive oil. Excellent correlations were found between log RD50 and log P, as well as between log RD50 and log L16, log L(Oct), log L(NFM), log L(EHP), or log L(Oil). It follows that as an alternative to the bioassay, these physicochemical variables can be used to estimate RD50 of nonreactive volatile organic chemicals. Appropriate exceptions to general estimation of RD50 values from physicochemical variables are also presented, as well as the most appropriate estimates which can be obtained within homologous series.

Design and field operation of an in-situ environmental enclosure for tree branches

In order to examine the effects of airborne chemicals and other atmospheric components on mature trees in natural ecosystems, branch-sized environmental chambers were developed. These were designed to withstand the rigors of season-long exposure in montane environments while effectively controlling the conditions within. Field testing of the chambers demonstrated a reasonable, although not exact semblance of ambient conditions. Solar heating effects were difficult to control, although a configuration was developed that allowed the chambers to operate within standard specifications for similar devices. Overall, performance was good, and it is felt that this technique is a valuable tool for the evaluation of the effects of atmospheric chemicals on trees, as long as attention is paid to the environmental alterations caused by the chambers, and comparisons are made against control chambers.

Air Pollution and Forest Ecosystems: A Regional to Global Perspective

Changes in the atmospheric concentrations of a number of air pollutants over the last century are hallmarks of the magnitude and extent of human impact on the environment. Some of these changes are important to ecologists because many pollutants, acting singly or in combination, affect ecological systems in general and forests in particular. The greatest concern lies with chronic levels of tropospheric ozone, cumulative deposition of hydrogen ion, nitrogen, and sulfur via wet and dry processes, a select number of airborne chemicals (e.g., mercury) that tend to bioaccumulate in continental landscapes, and ultraviolet—B radiation through the loss of stratospheric ozone. Because the atmospheric residence time of most pollutants of concern to ecologists is measured on time frames extending from a few weeks to decades, pollutant distribution and effects are regional to global in dimension. We present evidence that ambient levels of some air pollutants in North America are affecting managed and unmanaged forests, and that the two most important pollutants are tropospheric ozone and chronic nitrogen loading. Further evidence indicates that while concentrations of some air pollutants have been declining over the last decade in North America, others are expected to remain unchanged or increase, including tropospheric ozone. We conclude that air pollution is affecting many North American forests and some remote forests around the globe. In the immediate future, the concern for air pollution effects on forests and associated natural resources will broaden to include interactions with changes in climate and pollution effects in the world's developing countries. There has been a rapid evolution in air pollution studies in ecology, shifting away from the agricultural paradigm of single—factor experimentation toward new methodologies that are ecologically and multidisciplinarily based. This shift has been promoted by the recognition that air pollution is one of several factors influencing forest productivity, community dynamics, and biogeochemistry, and that effects arise through long—term exposures. This evolution in methodologies will become even more marked in the future as new ecological approaches are adopted and an understanding is developed of how air pollution interacts with changes in climate. One of the most promising methodologies is process level modeling, which utilizes the large base of data in tree physiology and forest ecology, watershed chemistry, and atmosphere— forest canopy meteorology to develop models of tree physiology and growth and to subsequently scale these investigations to the levels of forest stands and landscapes.