Time course of sensory eye irritation in humans exposed to N-butanol and 1-octene

In this study, we investigated the time course effect of sensory eye irritation in 16 subjects exposed (i.e., eye only) to n-butanol and 1-octene. Half the subjects were exposed to n-butanol, and the remaining subjects were exposed to 1-octene. Each subject was studied on 5 different days; during each day each subject was exposed in three runs (i.e., run 1, run 2, and run 3) to a constant concentration of either n-butanol or 1-octene. We performed run 1 and run 3, both of which lasted 15 min each, to evaluate persistence in "sensitization." We performed run 2, which lasted 60 min, to study the time course of sensory irritation. Ratings of ocular irritation intensity were obtained continuously during all three runs. The exposure concentrations for n-butanol were 0 mg/m3, 300 mg/m3, 900 mg/m3, and 3 000 mg/m3, and the exposure concentrations for 1-octene were 0 mg/m3, 6 000 mg/m3, 10 400 mg/m3, and 18 000 mg/m3. During run 2, we observed a slight increase in perceived eye irritation intensity for the lower concentrations of 1-octene and for all exposure concentrations of n-butanol. However, the threshold for irritation was clearly exceeded for only the 1-octene 10 400-mg/m3 and 18 000-mg/m3 exposures. During these two exposures, the response increased 10-fold following 20-40 min of exposure during run 2, after which the response remained constant. We investigated the existence of persistence in "sensitization" by comparing intensity of responses between run 1 and run 3. Persistence in "sensitization" was apparent for only the 1-octene exposure.     

Cytological changes and conjunctival hyperemia in relation to sensory eye irritation

In general, irritation is a physiological response to a chemical or physical stimulus involving objective changes (e.g., local redness and edema) and subjective sensations (e.g., pruritus and pain). The perception of an irritating stimulus in the eyes and the upper airways is called sensory irritation. Sensory irritation is a prevalent symptom in relation to complaints about indoor air quality. The intensity of perceived sensory irritation in humans has mainly been evaluated using psychophysical methods. However, perceived sensory irritation is dependent on the subject expressing the symptoms; that is, it is a subjective measure. This is a problem in assessment of irritation effects from air pollution or other factors, since the expression of the irritation symptoms may be biased by, for example, interaction with other people and odors. The subjectivity of the measures is an important complication in several studies dealing with problems regarding indoor air quality. The bias problems make it important to complement the psychophysical measurements of sensory irritation with objective assessments of irritation. In addition, only little is known about the association between sensory irritation and possible physiological/pathological changes in the mucosal membranes in relation to studies of indoor air. Two studies (study 1 and study 2) were conducted to investigate changes in conjunctival hyperemia and conjunctival fluid cytology for subjects exposed to volatile organic compounds (VOCs) in their eyes only. Eight subjects participated in study 1. Each subject was exposed to three different mixtures of VOCs. A total of 16 subjects participated in study 2. Half of the subjects were exposed to 1-octene and the other half, to n-butanol. In both studies, photographs of bulbar conjunctiva were taken and conjunctival fluid was sampled before and after exposure. Moreover, the perceived irritation intensities were registered continuously during exposure. Overall, perceived irritation intensity and conjunctival hyperemia increased with increasing exposure concentrations, whereas cytological changes in the conjunctival fluid samples did not seem to be related to exposure concentration, perceived irritation, or changes in conjunctival hyperemia. Received: 4 April 1997 / Accepted: 25 September 1997     

Perceived odor,irritation, and health symptoms following short-term exposure to acetone

The subjectivity of irritancy judgments can bias attempts to establish exposure guidelines that protect individuals from the sensory irritation produced by volatile chemicals. At low to moderate chemical concentrations, naive and occupationally exposed individuals often show considerable variation in the reported levels of perceived irritation. Such variation could result from differences in exposure history, differences in the perceived odor of a chemical, or differences in generalized response tendencies to report irritation, or response bias. Thus, experimental evaluation of sensory irritancy must dissociate sensory irritation from response bias. To this end, judgments of perceived irritation from 800 ppm acetone were obtained from acetone-exposed workers and age- and gender-matched naive controls. To assess the role of response bias during exposure to odorants, subjects were also exposed to phenylethyl alcohol (PEA), an odorant that does not produce sensory irritation. Following exposure, subjects completed a subjective symptom survey that included symptoms that have been associated with long-term solvent exposures and symptoms that have not. Acetone-exposed workers and naive controls reported large differences in the perceived intensity of odor and irritation from acetone, yet no differences in the perception of PEA. However, for both groups, the most significant factors mediating reported irritancy and health symptoms from acetone were the perceived intensity of its odor and an individual's bias to report irritation from PEA. The perception of odor intensity and degree of response bias will differ between and within groups of exposed and naive individuals; hence, an assessment of the influence of these factors in experimental and workplace studies of chemical irritancy is warranted. Am. J. Ind. Med. 31:558–569, 1997. © 1997 Wiley-Liss, Inc.     

The influence of cognitive bias on the perceived odor, irritation and health symptoms from chemical exposure

 Objective: Responses to volatile chemicals are often subjective and variable, both over time and across individuals. Although variability can derive from differences in individual olfactory sensitivity, the response to a chemical stimulus is also influenced by the complex environment surrounding the exposure, which can include the perceiver’s cognitive state. To explore the role of cognitive bias in chemical exposures, we evaluated whether information about the consequences of exposure to acetone could influence ratings of odor and irritation during exposure and/or the frequency or intensity of reported health symptoms following exposure. Methods: Ninety adults (mean age 33.7, range 25–64) with no history of occupational exposure to solvents, were exposed to 800 ppm acetone in a chamber for 20 min. To control for non-specific responses to the odor of acetone, the subjects were also exposed for 20 min to 200 ppm phenylethyl alcohol (PEA), a nonirritant volatile chemical that produces a distinct odor but does not elicit irritation in the vapor phase. Subjects were assigned to one of three groups (n=30/group); each group was given either a positive, negative or neutral bias towards the consequences of exposure to the chemicals in the study. During exposure, subjects rated the intensity of odor and irritation; following exposure, they completed symptom questionnaires. Results: During the 20-min exposure to acetone, the positive bias group exhibited the most adaptation to its odor and the lowest perceived irritation; following exposure they reported the fewest health symptoms. In contrast, the negative bias group rated higher levels of odor intensity and, on average, reported the most overall irritation; following exposure they reported significantly more health symptoms than the other groups. None of the demographic variables studied (e.g., age, gender, race, smoking status) were predictive of the response to odor or irritation. The perceived irritancy of acetone was well predicted by a linear combination of the perceived odor of acetone and the perceived irritation from PEA (the nonirritant), r ²=0.73. Conclusions: The results provide strong evidence that both the perceived odor and cognitive expectations about a chemical can significantly affect how individuals respond to it. Moreover, because naive control subjects appear to exhibit extreme variation in their cognitive evaluations of chemical effects, there may be limited value in using non-exposed controls to assess the irritancy of chemicals for worker populations. Received: 7 May 1996/Accepted: 20 September 1996     

Acute sensory irritation from exposure to isopropanol (2-propanol) at TLV in workers and controls: objective versus subjective effects

OBJECTIVES: Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and na?ve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using subjective health symptom reports and objective, physiological end-points; and (ii) differences in measured effects in relation to exposure history. METHODS: Before, during and after exposure subjects gave self-reports of health complaints. During exposure subjects rated the intensity of the odor, sensory irritation and annoyance. Objective end-points of ocular hyperemia, nasal congestion, nasal secretion and respiration were obtained at various times before, during and after exposure. Results were compared with exposure to phenylethyl alcohol (PEA), a negative control for irritation, and to clean air (CA), a negative control for odor and irritation, using a within-subjects design. RESULTS: Significantly higher intensity ratings of odor, irritation and annoyance were reported during the exposure to IPA, when compared with exposure to CA or PEA. Nevertheless, the overall level of reported sensory irritation to IPA was low and perceived as 'weak' on average. Health symptom ratings were not significantly elevated for IPA as compared with PEA or CA exposure. The only physiological end-point that showed a change exclusively in the IPA condition was respiration frequency: relative to baseline, respiration frequency increased in response to IPA in both groups. No differences were encountered between the occupationally exposed and the control groups. CONCLUSIONS: The increase in respiration frequency in response to IPA may reflect either a reflexive change due to sensory irritation (an autonomic event) or a voluntary change in breathing in response to perception of an unpleasant, solvent-like odor (a physiological event caused by cognitive mediation). Our findings on objective end-points, including nasal and ocular sensory irritation, did not confirm subjective irritation reports. Irritation reports and odor intensity decreased, rather than increased, over time, lending credence to the cognitive argument and suggesting that the elevated subjective responses to IPA may be mediated by responses to its odor.     

Irritation of the human eye mucous membrane caused by airborne pollutants

OBJECTIVES: The purpose of this study was to investigate the different irritative effects of carbon dioxide and n-butanol exposure on the ocular mucous membrane. MATERIAL AND METHODS: Provocation by the gases was at the same sensory level, which was 50% of maximum on a linear scale. The experiment was performed on nine healthy subjects with the aim of identifying the relationship between eye irritation and the human physiological response to this irritation. A goggle exposure system, invented at the Department of Occupational and Environmental Medicine, Aarhus University, was used for the experiment. The exposures lasted for 30 min each. RESULTS: There were no changes in tear film stability and conjunctival corrosion (lissamine staining) after carbon dioxide and n-butanol exposures leading to 50% sensory eye irritation. However, the study showed a delayed inflammatory response after carbon dioxide exposure when compared with clean air. The significant change was seen for tear fluid neutrophilic granulocytes 22 h after carbon dioxide (CO(2)) exposure only. CONCLUSIONS: It is concluded that the type of exposure made no difference to the elicited physiological responses and that tear film stability and epithelium damage were not affected by sensory irritation itself.     

Visual disturbances in man as a result of experimental and occupational exposure to dimethylethylamine.

Experimental exposure of four volunteers to 40-50 mg/m3 of dimethylethylamine (DMEA) for eight hours caused irritation of the mucous membrane of their eyes, subjective visual disturbances (haze), and slight oedema of the corneal epithelium. The thickness of the cornea showed a slight but consistent increase in all four subjects at these exposures and in two subjects exposed to 10 mg/m3. Concentrations of 80 and 160 mg/m3 for 15 minutes caused eye irritation but no visual disturbances or corneal oedema. Occupational exposure for eight hours to about 25 mg/m3 of DMEA (with peaks above 100 mg/m3) was also associated with eye irritation, haze, and corneal oedema. The divergence between our findings and other reports in which visual disturbances occurred at lower concentrations during occupational exposure may be due to peak concentrations.     

Visual disturbances in man as a result of experimental and occupational exposure to dimethylethylamine

Experimental exposure of four volunteers to 40-50 mg/m3 of dimethylethylamine (DMEA) for eight hours caused irritation of the mucous membrane of their eyes, subjective visual disturbances (haze), and slight oedema of the corneal epithelium. The thickness of the cornea showed a slight but consistent increase in all four subjects at these exposures and in two subjects exposed to 10 mg/m3. Concentrations of 80 and 160 mg/m3 for 15 minutes caused eye irritation but no visual disturbances or corneal oedema. Occupational exposure for eight hours to about 25 mg/m3 of DMEA (with peaks above 100 mg/m3) was also associated with eye irritation, haze, and corneal oedema. The divergence between our findings and other reports in which visual disturbances occurred at lower concentrations during occupational exposure may be due to peak concentrations.     

Prospective study of respiratory effects of formaldehyde among healthy and asthmatic medical students

We conducted a prospective evaluation of pulmonary function and respiratory symptoms among 103 medical students exposed to formaldehyde over a 7-month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 part per million (ppm) and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were no more likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential settings do not commonly cause significant bronchoconstriction, even among subjects with preexisting asthma.     

Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol

OBJECTIVES: The study examined acute neurobehavioral effects provoked by controlled exposure to 1-octanol and isopropanol among male volunteers. METHODS: In a 29-m3 exposure laboratory, 24 male students (mean age 25.8 years) were exposed to 1-octanol and isopropanol. Each substance was used in two concentrations (0.1 and 6.4 ppm for 1-octanol; 34.9 and 189.9 ppm for isopropanol:). In a crossover design, each subject was exposed for 4 hours to the conditions. Twelve subjects reported enhanced chemical sensitivity; the other 12 were age-matched controls. At the onset and end of the exposures neurobehavioral tests were administered and symptoms were rated. RESULTS: At the end of the high and low isopropanol exposures the tiredness ratings were elevated, but no dose-dependence could be confirmed. For both substances and concentrations, the annoyance ratings increased during the exposure, but only for isopropanol did the increase show a dose-response relation. The subjects reported olfactory symptoms during the exposure to the high isopropanol and both 1-octanol concentrations. Isopropanol provoked no sensory irritation, whereas high 1-octanol exposure slightly enhanced it. Only among the subjects with enhanced chemical sensitivity were both 1-octanol concentrations associated with a stronger increase in annoyance, and lower detection rates were observed in a divided attention task. CONCLUSIONS: Previous studies reporting no neurobehavioral effects for isopropanol (up to 400 ppm) were confirmed. The results obtained for 1-octanol lacked dose-dependency, and their evaluation, is difficult. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task.     

1998 equivalence of sensory responses to single and mixed volatile organic compounds at equimolar concentrations.

Exposure to low levels of chemicals indoors is often to a mixture of volatile organic compounds (VOCs). It is of interest to determine if the symptomatic and sensory responses can be attributed to a single chemical or to a mixture of chemicals. To determine if sensory or symptomatic responses differ with exposure to single or mixed VOCs, 100 female subjects participated in a 6-hr exposure study. Subjects were exposed to one of six equimolar concentrations equivalent to 24 mg/m3 toluene, control, m-xylene, n-butyl acetate, m-xylene plus n-butyl acetate, a mixture of 21 chemicals including n-butyl acetate and m-xylene, and to the same mixture of chemicals without n-butyl acetate and m-xylene (19 chemicals). The results indicated that there was no difference in reporting of symptoms or sensory responses between the exposures. When the control group was added, some variables, primarily odor intensity and nasal irritation, attained significance.     

Indoor air quality and personal factors related to the sick building syndrome

The "sick building syndrome" involves symptoms such as eye, skin and upper airway irritation, headache, and fatigue. A multifactorial study was performed among personnel in consecutive cases of sick buildings to investigate relationships between such symptoms, exposure to environmental factors, and personal factors. The total indoor hydrocarbon concentration was significantly related to symptoms. Other indoor exposures such as room temperature, air humidity, and formaldehyde or carbon dioxide concentration did not correlate with the symptoms. Personal factors such as reported hyperreactivity and sick leave due to airway diseases were strongly related to the sick building syndrome. Other factors associated with the sick building syndrome were smoking, psychosocial factors, and experience of static electricity at work. Neither atopy, age, sex, nor outdoor exposures correlated significantly with the number of symptoms. It was concluded that the sick building syndrome is of multifactorial origin and related to both indoor hydrocarbon exposure and individual factors.     

控制暴露人体实验--眼刺激感觉强度测量方法和评价基准的研究(续一)

引进和初步建立了“眼刺激感觉强度实验”和测量方法,并提出了三项“判断爱试样品为阳性的基准”：眼刺激感觉强度评分均值〉１５ｍｍ,即将１５ｍｍ作为眼刺激感觉的阈限值;对比试样品舱排除气与“０”空气的眼刺激感觉强度,判别有统计学意义;     

Perceived odor and irritation of isopropanol: a comparison between naïve controls and occupationally exposed workers

OBJECTIVES: To assess sensory irritation levels from isopropanol (IPA) unconfounded by subjective evaluations of odor for comparison against the recommended exposure limits (400 ppm threshold limit value (TLV); American Conference of Governmental Industrial Hygienists). METHOD: The lateralization method was used to assess intra-nasal irritation thresholds for IPA, while odor detection thresholds were also measured. Thresholds for 1-butanol and phenyl ethyl alcohol (PEA) were obtained as positive and negative irritant controls. To compare potency and hedonic characteristics, subjects provided subjective ratings of odor, irritation and annoyance intensity for three concentrations of each chemical. Workers occupationally exposed to IPA ( n=26) were compared with previously unexposed controls ( n=26). RESULTS: The (geometric) mean odor detection threshold for IPA was slightly higher among exposed workers than controls (39 ppm vs. 11 ppm). Lateralization thresholds measuring intra-nasal irritation were elevated when compared with controls (6,083 ppm in exposed workers vs. 3,361 ppm in na?ve controls), with a significantly higher proportion of phlebotomists being unable to lateralize the maximum concentration regarded as safe, than controls. Calculations of the 6th percentile for lateralization thresholds revealed that 95% of the sample did not experience sensory irritation below 512 ppm. Thus, while odor detection thresholds were well below the current recommended exposure limits, the irritation thresholds were well above these values. The odor, irritation and annoyance from IPA was perceived, on average, as between weak and almost strong, from lowest to highest concentration. CONCLUSIONS: The results indicate that current exposure guidelines would be adequately protective of the acute adverse effect of nasal sensory irritation, as operationally defined by the intra-nasal lateralization threshold. Exposures to higher concentrations should perhaps be evaluated on the basis of existing knowledge about systemic, rather than local (e.g., irritation), toxic effects. IPA appears to be a weak sensory irritant and occupational exposure to IPA appears to elicit small changes in sensitivity that do not generalize to other odorants (e.g., PEA and 1-butanol) and are likely to be reversible.     

Changes in eye blink frequency as a measure of trigeminal stimulation by exposure to limonene oxidation products,isoprene oxidation products and nitrate radicals

Objectives To measure eye blink frequency as a measure of trigeminal stimulation of the eye. Human subjects were exposed to oxidation mixtures representative of reactive indoor pollutants and clean air, from which relative changes in blink frequencies were measured.Method Male subjects (n=8) were exposed for 20 min to limonene oxidation products (LOPs), isoprene oxidation products (IOPs), nitrate radicals (NO₃), their residual reactants, and clean air at 20% relative humidity. A baseline blink frequency was measured prior to and following each exposure (2×8 min). The subjects were exposed locally in the non-dominant eye and single blind in random order. Blinking was video-recorded and evaluated for full sessions of 36 min while the subjects viewed an educational film. The initial terpene concentrations were one to two orders of magnitude higher than mean indoor concentrations.Results The mean blink frequency increased significantly during subjects exposure to gas-phase oxidation products at lower part-per-billion (ppb) levels of LOPs, 42% (P<0.0001) and NO₃, 21% (P<0.022), compared with that at baseline. Neither the residual reactants nor clean air changed the blink frequency significantly. The findings coincided with qualitative reporting of weak eye irritation symptoms.Conclusions Changes in blink frequency appear to be a promising measure of trigeminal stimulation from exposure to eye irritants in ppb levels. Gaseous products of limonene and ozone, and reactive radicals may cause eye irritation indoors.     

Sensitivity of the eyes to airborne irritant stimuli: influence of individual characteristics.

The purpose of this study was to measure trigeminal sensitivity of the eyes to irritative exposures and to examine the influence of individual characteristics, e.g., gender, age, and smoking, on this sensitivity. During an experimental study, 158 of 2,025 randomly selected volunteers were examined for sensory irritation threshold in the eyes to carbon dioxide (CO2). Eyes were exposed to progressive concentrations of CO2 (10, 20, 40, 80, and 160 ml/l), until the subject claimed a distinct irritation. Each exposure level lasted 2 min. A special exposure mask system was used for eyes-only exposure. No significant dependence of gender or smoking was found, but subjects who were less than 40 y of age were more sensitive than were the elderly subjects. Subjects who reported frequent "sick building syndrome" irritation symptoms had lower thresholds (i.e., higher sensitivity). The CO2 threshold was related to skin irritation sensitivity, i.e., response to lactic acid smeared on the cheek, and there were indications that occupational stress was associated with low thresholds. Studies of irritation to n-decane indicate that the CO2 threshold may be an important factor in the prediction of individual sensitivity to irritation from airborne pollutants. The CO2 threshold of the eyes may be of value in the evaluation of hypersensitivity to indoor air pollution. Furthermore, the threshold may be used to assess important relationships between the different trigeminal innervated areas, e.g., skin and eyes. Finally, the method has the advantage of avoiding interference from olfactory stimulation.     

Personal carbon monoxide exposure levels: contribution of local sources to exposures and microenvironment concentrations in Milan

In the framework of the EXPOLIS study in Milan, Italy, 48-h carbon monoxide (CO) exposures of 50 office workers were monitored over a 1-year period. In this work, the exposures were assessed for different averaging times and were compared with simultaneous ambient fixed-site concentrations. The effect of gas cooking and smoking and different methods of commuting on the microenvironment and exposure levels of CO were investigated. During the sampling the subjects completed a time-microenvironment-activity diary differentiating 11 microenvironments and three exposure influencing activities: gas cooking, smoking and commuting. After sampling, all exposure and time allocation data were stored in a relational database that is used in data analyses. Ambient 48-h and maximum 8-h distributions were similar compared to the respective personal exposures. The maximum 1-h personal exposures were much higher than the maximum 8-h exposures. The maximum 1-h exposures were as well higher than the corresponding ambient distribution. These findings indicate that high short-term exposures were not reflected in ambient monitoring data nor by long-term exposures. When gas cooking or smoking was present, the indoor levels at "home-" and in "other indoor" microenvironments were higher than without their presence. Compared with ambient data, the latter source was the most affective to increase the indoor levels. Exposure during commuting was higher than in all other microenvironments; the highest daily exposure contribution was found during "car/taxi" driving. Most of the CO exposure is acquired in indoor microenvironments. For the indoor microenvironments, ambient CO was the weakest predictor for "home indoor" concentrations, where the subjects spent most of their time, and the strongest for "other indoor" concentrations, where the smallest fraction of the time was spent. Of the main indoor sources, gas cooking, on average, significantly raised the indoor exposure concentrations for 45 min and tobacco smoking for 30 min. The highest exposure levels were experienced in street commuting. Personal exposures were well predicted, but 1-h maximum personal exposures were poorly predicted, by respective ambient air quality data. By the use of time-activity diaries, ETS exposure at the workplaces were probably misclassified due to differences in awareness to tobacco smoke between smokers and nonsmokers.     

Chemical and microbial exposures in a school building: adverse health effects in children

In this cross-sectional study, the authors examined the relationship between an unusual combination of indoor air contaminants in a school and adverse health effects among the attending children. A leaking roof and damp floors, together with gaseous leaks from the sewage system, led to a combined exposure of hydrocarbons, 2-ethylhexanol from plastic floor coverings, and moisture-associated microbes. The health status of 274 children in the school was assessed via repeated symptom questionnaires. Statistical analysis revealed a relationship between the indoor air contaminants and adverse health outcomes such as respiratory irritation, asthmatic symptoms, eye and general symptoms, and increased occurrence of common viral respiratory infections. No association was found between the exposures and doctor-diagnosed asthma, other allergic diseases, or bacterial respiratory infections. Chemical contaminants from the sewer system and damp construction materials were identified as the source of the problem. Remediation of the school building improved the indoor air quality and the health status of the children.     

Irritation effects from experimental exposure to n-butyl acetate

The irritation produced by acute exposure to n-butyl acetate in human subjects without any history of occupational solvent exposure was studied in three experiments. Exposure levels tested in the different experiments were 350, 700, 1,050, and 1,400 mg/m³ in 20 min sessions, 70 and 1,400 mg/m³ in 20 min sessions, and 70 and 700 mg/m³ in 4 h sessions. Rating scales, various measures of eye irritation, and pulmonary functions were used to evaluate the irritation produced by the exposures in different parts of the study. The results indicate only very slight irritation from the exposures as revealed by categorical ratings, magnitude estimation, and some of the clinical measures of eye irritation and pulmonary functions, such as eye redness, lipid layer thickness, and bronchial responsiveness. These essentially negative results indicate the need to explore and develop the utility of new/different methods of quantifying irritative effects of exposure to various substances. © 1993 Wiley-Liss, Inc.