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Gas chromatographic retention data on 107 terpene hydrocarbons from the literature have been used to obtain a set of Abraham descriptors for these 107 compounds. For 88 aliphatic cyclic terpene hydrocarbons, a fragmentation scheme was constructed that allows key descriptors to be estimated just from structure. The total set of descriptors, including those estimated by the fragmentation schemes, were then used to predict water-octanol partition coefficients for the 88 compounds, there being good agreement with experiment. For a small number of terpene hydrocarbons, there was good agreement between predicted and experimental values of nasal pungency thresholds, and predicted and experimental gas-blood, gas-oil, and gas-water partition coefficients. It is suggested that the descriptors obtained for the 107 terpene hydrocarbons can be used to predict water-solvent partition coefficients, gas-solvent partition coefficients, and partition coefficients in a number of biological systems.

One hundred and ninety three odor detection thresholds, ODTs, obtained by Nagata using the Japanese triangular bag method can be correlated as log (1/ODT) by a linear equation with R2 = 0.748 and a standard deviation, SD, of 0.830 log units; the latter may be compared to our estimate of 0.66 log units for the self-consistency of Nagata’s data. Aldehydes, acids, unsaturated esters and mercaptans were included in the equation through indicator variables that took into account the higher potency of these compounds. The ODTs obtained by Cometto-Muñiz and Cain, by Cometto-Muñiz and Abraham, and by Hellman and Small could be put on the same scale as those of Nagata to yield a linear equation for 353 ODTs with R2 = 0.759 and SD = 0.819 log units. The compound descriptors are available for several thousand compounds, and can be calculated from structure, so that further ODT values on the Nagata scale can be predicted for a host of volatile or semivolatile compounds.

We present concentration-detection (i.e., psychometric) odor functions for 28 odorants tested on subgroups from a pool of 132 normosmic, nonsmoker participants (64 female), most of them between 18 and 40 years old (n=123), a few between 41 and 59 years old (n=9, 2 female). Odorants included n-alcohols (n=4), acetate esters (n=4), 2-ketones (n=4), alkylbenzenes (n=5), aldehydes (n=6), and carboxylic acids (n=5). Vapors were presented by dynamic olfactometry. We used a three-alternative forced-choice procedure against carbon-filtered air blanks, and an ascending concentration approach. During subject testing, gas chromatography (flame ionization detector) served to quantify delivered concentrations. The results from 12 subjects (8 female) tested on 10 or more odorants showed strong across-subject agreement regarding the least potent (highest odor detection thresholds) and the most potent (lowest thresholds) odorants. Odor functions from 6 subjects (3 female) tested on a common set of 6 odorants, agreed fully on which were the least and the most potent odorants, and agreed partially on the odorants of intermediate potency. Across these 6 subjects, the odor threshold range between the least and the most potent odorant covered 2 to 3 orders of magnitude. For each of the 6 odorants in common, the ratio between the least and the most sensitive of the 6 subjects was at or below 1 order of magnitude. All odorants had thresholds below 1 part per million by volume (ppm). Notably, carboxylic acids with 4 or more carbons in the chain length, and the aldehydes were the most potent olfactory stimuli with thresholds often below the part per billion (ppb) level.

1:1 Equilibrium constants, K, for the association of hydrogen bond bases and hydrogen bond acids have been determined using solvent octan-1-ol at 298 K for 30 acid-base combinations. The values of K are much smaller than those found for aprotic, rather non-polar solvents. It is shown that the log K values can satisfactorily be correlated against aH 2*bH 2, where aH 2 and bH 2are the 1:1 hydrogen bond acidities and basicities of solutes. The slope of the plot, 2.938, is much smaller than those for log K values in the non-polar organic solvents previously studied. An analysis of literature data on 1:1 hydrogen bonding in water yields a negative slope for a plot of log K against aH 2*bH 2, thus showing how the use of very strong hydrogen bond acids and bases                                                 does not lead to larger values of log K for 1:1 hydrogen bonding in water. It is suggested that for simple 1:1 association between mono-functional solutes in water, log K cannot be larger than about -0.1 log units. Descriptors have been obtained for the complex between 2,2,2-trifluoroethanol and propanone, and used to analyze solvent effects on the two reactants, the complex, and the complexation constant.

A large amount of data on the biological and toxicological activity of gases and vapors has been collected from the literature. Processes include sensory irritation thresholds, the Alarie mouse test, inhalation anesthesia, etc. It is shown that a single equation using only five descriptors (properties of the gases and vapors) plus a set of indicator variables for the given processes can correlate 643 biological and non-lethal toxicological activities of ‘non-reactive’ compounds with a standard deviation of 0.36 log unit. The equation is scaled to sensory irritation thresholds obtained by the procedure of Cometto-Muñiz,and Cain, and provides a general equation for the prediction of sensory irritation thresholds in man. It is suggested that differences in biological/toxicological activity arise primarily from transport from the gas phase to a receptor phase or area, except for odor detection thresholds where interaction with a receptor(s) is important.

We have measured concentration-detection (i.e., psychometric) functions to determine the odor detectability of homologous aliphatic aldehydes (propanal, butanal, hexanal, octanal, and nonanal) and helional. Subjects (16≤n≤18) used a three-alternative forced-choice procedure against carbon-filtered air (blanks), under an ascending concentration approach. Generation, delivery, and control of each vapor were achieved via an 8-station vapor delivery device. Gas chromatography served to quantify the concentrations presented. Group and individual functions were modeled by a sigmoid (logistic) equation. Odor detection thresholds (ODTs) were defined as the concentration producing a detectability (P) half-way (P=0.5) between chance (P=0.0) and perfect detection (P=1.0). ODTs decreased with carbon chain length: 2.0, 0.46, 0.33, and 0.17 ppb, respectively, from propanal to octanal, but the threshold increased for nonanal (0.53 ppb), revealing maximum sensitivity for the 8-carbon member. The strong olfactory-receptor ligands octanal and helional (0.14 ppb) showed the lowest thresholds. ODTs fell at the lower end of previously reported values. Inter-individual variability (ODT ratios) amounted to a factor ranging from 10 to 50, lower than typically reported, and was highest for octanal and hexanal. The behavioral dose-response functions emerge at concentrations 2 to 5 orders of magnitude lower than those required for functions tracing the activation of specific human olfactory receptors by the same aldehydes in cell/molecular studies, after all functions were expressed as vapor concentrations.

The solvation descriptors for cyclohexanone oxime and acetone oxime have been obtained from measurements on water-solvent partitions, and gas-liquid chromatographic retention data. These yield values of 0.33 and 0.37 for the Abraham hydrogen bond acidity, A , in reasonable agreement with a value of 0.37 for cyclohexanone oxime obtained by our recent n.m.r. method. The other descriptors E, S , B, L and V have also been obtained for cyclohexanone oxime and acetone oxime, and have been estimated for a number of other oximes as well. The value for A, the overall or effective hydrogen bond acidity of the oximes is reasonably close to the 1:1 hydrogen bond acidity, α2 H = 0.39 to 0.46, that can be deduced from previous literature measurements on oximes, and to the 1:1 hydrogen bond acidity, α2 H = 0.43 for another NOH compound, N,N-dibenzylhydroxylamine, that again can be deduced from literature measurements.

Descriptors have been determined for four inorganic mercury(II) species and for seventeen organic mercury(II) species, using experimental literature data. These descriptors can then be used in equations that we have already set out in order to estimate a large number of physicochemical properties. These include the water to octanol partition coefficient and the gas to water partition coefficient. For the organic mercury(II) species, including dimethylmercury and the methylmercury(II) halides, the latter has been estimated over the temperature range 273-373K.

We have applied a quantitative structure-activity (QSAR) approach to analyse the chemical parameters that determine the relative sensitivity of olfaction and nasal chemesthesis to a common set of volatile organic compounds (VOCs). We used previously reported data on odor detection thresholds (ODTs) and nasal pungency thresholds (NPTs) from 64 VOCs belonging to seven chemical series (acetate esters, carboxylic acids, alcohols, aliphatic aldehydes, alkylbenzenes, ketones, and terpenes). The analysis tested whether NPTs could be used to separate out “selective” chemosensory effects (i.e., those resting on the transfer of VOCs from the gas phase to the receptor phase) from “specific” chemosensory effects in ODTs. Previous work showed that selective effects overwhelmingly dominate chemesthetic potency whereas both selective and specific effects control olfactory potency. We conclude that it is indeed possible to use NPTs to separate out selective from specific effects in ODTs. Among the series studied, aldehydes and acids, except for formic acid, show clear specific effects in their olfactory potency. Furthermore, for VOCs whose odor potency rests mainly on selective effects, we have developed a QSAR equation that can predict their ODTs based on their NPTs.

In Experiment 1, subjects sought to localize the nostril stimulated, left or right, in tests with nine esters (acetates, propionates, and butyrates) at concentrations meant to trigger chemesthesis (pungency, irritation). The task produced psychometric functions for chemesthetic detection unconfounded by olfactory sensations. The functions indicated a sharp transition from no detection to perfect detection, rather uniform across the esters, which themselves varied in potency by two log units. The correlation between the thresholds for the eight materials that yielded thresholds and predictions from a published linear free energy relationship (LFER) equaled 0.99. In Experiment 2, amplitude of the negative mucosal potential (NMP) was recorded from the septum. The resulting functions also increased with concentration sharply. Against a criterion amplitude of the NMP, thresholds measured in the first experiment (and predictions from the LFER) correlated 0.99. The NMP seems to offer an adequate objective measure of sensory irritation. The LFER, although effective predictively, could stand to have a parameter to anticipate that molecules beyond a certain size fail to trigger irritation. In the present case, a cut-off of chemesthetic potency occurred between butyl butyrate and hexyl butyrate for the group of subjects, with some variation of the boundary among individuals.

The investigation explored the olfactory detectability of two chemically and structurally similar esters, ethyl propanoate and ethyl heptanoate, presented singly and in mixtures. Initially, we measured concentration-detection (i.e., psychometric) functions for the odor of ethyl propanoate and ethyl heptanoate presented singly. Using this information, we prepared binary mixtures of the two chemicals in varying complementary proportions and, also, selected concentrations of the single compounds, such that, if a rule of response-addition (i.e., independence of detection) were to hold, the stimuli (mixed and single) should approximate equal detection. Next, we measured the actual detectability of these stimuli within the same experiment. The results were analyzed in terms of response-addition (or -additivity) and of dose-addition (or -additivity). The outcome revealed that at low levels of detectability the mixtures approximate response-addition, that is, independence of detection, whereas at high levels of detectability they approximate dose-addition. In the light of previous findings for the olfactory detection of the more dissimilar chemical pairs 1-butanol/2-heptanone and butyl acetate/toluene, we conclude that the described outcome generalizes across a variety of chemical pairs. (C) 2004 Elsevier B.V. All rights reserved.

Previous research showed a cut-off along homologous volatile organic compounds (VOCs) in their ability to produce acute human mucosal irritation. The present study sought to specify the particular cut-off homolog for sensory eye irritation in an acetate and n-alcohol series. A 1,900 ml glass vessel system and a three-alternative forced-choice procedure served to test nonyl, decyl, and dodecyl acetate, and 1-nonanol, 1-decanol, and 1-undecanol. Flowrate to the eye ranged from 2 to 8 L/min and time of exposure from 3 to 24 sec. Decyl acetate and 1-undecanol were the shortest homologs that failed to produce eye irritation under all conditions, producing a cut-off effect. Increasing the vapor concentration of decyl acetate and 1-undecanol by 3 and 8 times, respectively, via heating them to 37 °C made either or both VOCs detectable to only half of the 12 subjects tested, even though the higher vapor concentration was well above a predicted eye irritation threshold. When eye irritation thresholds for homologous acetates and n-alcohols were plotted as a function of the longest unfolded length of the molecule, the values for decyl acetate and 1-undecanol fell within a restricted range of 18 to 19 Å. The outcome suggests that the basis for the cut-off is biological, i.e., the molecule lacks a key size or structure to trigger transduction, rather than physical, i.e., the vapor concentration is too low to precipitate detection.

Accurate assessment of upper respiratory tract and ocular irritation is critical for identifying and remedying problems related to overexposure to volatile chemicals, as well as for establishing parameters of irritation useful for regulatory purposes. This paper (a) describes the basic anatomy and physiology of the human upper respiratory tract and ocular mucosa, (b) discusses how airborne chemicals induce irritative sensations, and (c) reviews practical means employed for assessing such phenomena, including psychophysical (e.g., threshold and suprathreshold perceptual measures), physiological (e.g., cytology), electrophysiological (e.g., event-related potentials), and imaging (e.g., magnetic resonance imaging) techniques. Although traditionally animal models have been used as the first step in assessing such irritation, they are not addressed here since (a) there are numerous reviews available on this topic and (b) many rodents and rabbits are obligate nose breathers whose nasal passages differ considerably from those of humans, potentially limiting generalization of animal-based data to humans. A major goal of this compendium is to inform the reader of procedures for assessing irritation in humans and to provide information of value in the continued interpretation and development of empirical databases upon which future reasoned regulatory health decisions can be made.

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.

We have measured complete concentration-detection (i.e., psychometric or detectability) functions to study the olfactory and ocular/nasal chemesthetic (a term that includes sensory irritation) impact of VOCs presented singly and in various binary mixtures. Such functions provide considerably more information than that provided by measuring only a "threshold". The outcome for single VOCs confirmed the much higher absolute sensitivity of olfaction compared to chemesthesis, but also demonstrated that the detection of ocular and nasal sensory irritation increases as a function of vapor concentration at a much higher rate than that for the detection of odor. The outcome for the binary mixtures revealed that, for both olfaction and chemesthesis, complete additivity of detection of individual components held at relatively low levels of detectability but broke down at higher levels. The breakdown for odor detection, compared to that for sensory irritation detection, was, first, more extensive, and, second, dependent to a larger extent on the degree of structural and chemical similarity/dissimilarity between the mixed VOCs.

A series of experiments probed into the degree of chemosensory detection additivity exhibited by mixtures of ethyl propanoate and heptanoate in terms of their trigeminal detectability via nasal pungency (i.e., irritation) and eye irritation. Nasal pungency was tested in subjects lacking a functional sense of smell (i.e., anosmics) to avoid olfactory biases. First, we built concentration-detection functions for each chemical and sensory endpoint. Second, we used the data from the functions to prepare mixtures of the two compounds in complementary proportions, and suitable single-chemical standards, all of which should be equally detectable under a rule of complete additivity, i.e., independence of detection. Third, we compared the experimentally obtained detectability with that expected under such rule. The outcome revealed that, at a low detectability level (but still above chance), the mixtures showed complete additivity for both trigeminal endpoints. At a high detectability level (but below perfect detection), the mixtures showed complete additivity for nasal pungency but less than complete additivity for eye irritation. In the context of previous studies, the results consolidate a picture of higher degree of detection additivity at perithreshold levels in trigeminal than in olfactory chemoreception. The outcome presents another line of evidence suggesting broader chemical tuning in chemesthesis compared to olfaction.

Draize rabbit eye test scores, as modified maximum average score, MMAS, for 68 pure bulk liquids were adjusted by the liquid saturated vapor pressure Po. These 68 adjusted scores, as log (MMAS/ Po), were shown to be completely equivalent to eye irritation thresholds, EIT expressed as log (1/EIT), for 23 compounds in humans. Thus for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/ Po) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD =0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus the 91 compound equation can now be used to predict further EIT values to around 0.4 log units.        It is suggested that the mechanism of action in the Draize test and in the human eye irritation thresholds involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.

Studies of olfaction and chemesthesis often rely on nominal, liquid-phase dilutions to quantify the chemicals tested, even though the associated vapor concentrations constitute the actual stimuli. For more than a decade now, our systematic studies of the olfactory and chemesthetic potency of members of homologous chemical series have routinely included quantification of vapors via gas chromatography. This article depicts the relationships between liquid- and vapor-phase concentrations for 60 volatile organic compounds (VOCs) and summarizes the theoretical and technical factors influencing these relationships. The data presented will allow other investigators working with these materials to express them as vapor concentrations even when lacking the resources to perform the analytical measurements. The paper represents a step toward creation of a practical archive for vapor quantification in chemosensory science.

In a series of experiments, we have explored the rules of olfactory detection agonism between the odorants butyl acetate and toluene. First, we obtained the concentration-detection function for the odor of the individual compounds. Second, we selected the concentrations of the two substances producing three levels of detectability (low, medium, and high) and, for each level, tested the comparative detectability of the two single chemicals and three mixtures of varying proportions. In each case, the mixtures were prepared in such way that, if a rule of complete dose addition were to hold, all five stimuli (two single, three mixtures) should be equally detected. The outcome revealed complete dose addition at relatively low detectability levels but fell short of dose addition at medium and high levels. A recent analogous study on trigeminal chemosensory detection via nasal pungency and eye irritation of these same stimuli have shown a similar trend but showed a less dramatic loss of dose additivity with increased detectability. These results on detection of mixtures suggest a more selective window of chemical tuning (i.e., less dose-addition) in olfaction than in trigeminal chemoreception.

Odor detection thresholds, that we have previously obtained, have been analysed by a general equation for selective transport. It is shown that such selective transport can account for some 77% of the total effect. The remainder is due to a specific size effect, that might involve odor-binding proteins, and a specific effect for aldehydes and carboxylic acids. Our analysis raises the question of whether selective transport is physically separable from the specific effects of receptor activation. The model predicts a chemical cut-off in odor detection along any homologous series.

A general equation set up for the study of transport properties has been applied to VOC nasal pungency and eye irritation thresholds, as log (1/NPT) and log (1/EIT). The equation accounts for 93-95 % of the total effect, thus suggesting that the main step is transport of the VOC from the gas phase to a receptor phase. In the case of odor thresholds, ODT, the general equation accounts for only 77% of the total effect. A modified equation incorporates a factor for aliphatic aldehydes and carboxylic acids, and a general size effect that depends on the VOC maximum length. The size effect is important in that it leads to a cut-off effect that greatly reduces the potency of higher homologues. The various equations can all be used to predict chemosensory thresholds for thousands of VOCs.

We have previously used two general solvation equations to correlate and to interpret a wide variety of physicochemical and biochemical properties of compounds (solutes). Application of these equations requires a knowledge of the relevant solute descriptors, viz. R 2, the excess molar refraction, p2 H , the solute dipolarity/polarizability, ∑aH 2 , ∑b2 H , the solute overall hydrogen bond acidity and basicity, and logL 16, where L 16 is the solute gas–hexadecane partition coefficient at 298 K. We have also shown that these solute descriptors can be obtained from partition coefficients of solutes in various water–solvent and gas–solvent systems. Here, we use this approach to calculate solute descriptors for a series of 18 organofluorocarbons, classed as refrigerants, including chlorofluorocarbons, hydrochlorofluorocarbons, hydrofluorocarbons and perfluorocarbons, using Henry’s law coefficients in water and five organic solvents that we have already measured. These data have been used to calculate Ostwald solubility coefficients, log L. Gas–water and gas–solvent partitions have been then combined to give log P for partition between water and solvent. A number of log P and L values have also been taken from the Medchem97 database. There are enough data to obtain the above descriptors for the 18 organofluorocarbons, and then to estimate log P and L values in a large number of other solvents. The chemosensory properties of the organofluorocarbons are also estimated.