Exposure study to examine chemosensory effects of ɛ-caprolactam in healthy men and women.

CONTEXT: ε-Caprolactam is an important industrial chemical with a relatively low human toxicity; of importance is the irritations that occur after exposure to ε-caprolactam as aerosols or vapors. OBJECTIVE: The aim of this study was to examine symptoms and objective effects, which occur on the mucous membranes of the eyes and the upper respiratory tract. METHODS: A total of 52 healthy volunteers (26 women and 26 men, aged between 19 and 50 years) were exposed by random to different ε-caprolactam concentrations (0.05, 0.5 and 5.0 mg/m³) and the control condition (0.0 mg/m³) for 6 h on four consecutive days. Eye blinking frequency, tear film break-up time, eye redness, nasal flows and resistance, olfactory function as well as total protein and interleukin-8 in nasal lavage fluid were determined daily before, during and after exposure. Questionnaires were used to record both subjective symptoms and personality factors. RESULTS: There were no significant specific effects on the subjective and objective endpoints examined. Statistical analysis yielded no evidence of concentration-response relationships. Evaluation of olfactory symptoms showed that the duration of the stay in the chamber and not the ε-caprolactam concentration was decisive for the perception of "impure air". Personality factors had no significant influence on the reported symptoms. CONCLUSIONS: Exposure to ε-caprolactam concentrations of 5.0 mg/m³ at maximum for 6 h did not cause chemosensory effects on the upper respiratory tract or eyes of healthy volunteers. Therefore, the concentration of 5.0 mg/m³ corresponds to the No Observed Adverse Effect Level (NOAEL).

Sensory irritation as a basis for setting occupational exposure limits.

There is a need of guidance on how local irritancy data should be incorporated into risk assessment procedures, particularly with respect to the derivation of occupational exposure limits (OELs). Therefore, a board of experts from German committees in charge of the derivation of OELs discussed the major challenges of this particular end point for regulatory toxicology. As a result, this overview deals with the question of integrating results of local toxicity at the eyes and the upper respiratory tract (URT). Part 1 describes the morphology and physiology of the relevant target sites, i.e., the outer eye, nasal cavity, and larynx/pharynx in humans. Special emphasis is placed on sensory innervation, species differences between humans and rodents, and possible effects of obnoxious odor in humans. Based on this physiological basis, Part 2 describes a conceptual model for the causation of adverse health effects at these targets that is composed of two pathways. The first, "sensory irritation" pathway is initiated by the interaction of local irritants with receptors of the nervous system (e.g., trigeminal nerve endings) and a downstream cascade of reflexes and defense mechanisms (e.g., eyeblinks, coughing). While the first stages of this pathway are thought to be completely reversible, high or prolonged exposure can lead to neurogenic inflammation and subsequently tissue damage. The second, "tissue irritation" pathway starts with the interaction of the local irritant with the epithelial cell layers of the eyes and the URT. Adaptive changes are the first response on that pathway followed by inflammation and irreversible damages. Regardless of these initial steps, at high concentrations and prolonged exposures, the two pathways converge to the adverse effect of morphologically and biochemically ascertainable changes. Experimental exposure studies with human volunteers provide the empirical basis for effects along the sensory irritation pathway and thus, "sensory NOAEChuman" can be derived. In contrast, inhalation studies with rodents investigate the second pathway that yields an "irritative NOAECanimal." Usually the data for both pathways is not available and extrapolation across species is necessary. Part 3 comprises an empirical approach for the derivation of a default factor for interspecies differences. Therefore, from those substances under discussion in German scientific and regulatory bodies, 19 substances were identified known to be human irritants with available human and animal data. The evaluation started with three substances: ethyl acrylate, formaldehyde, and methyl methacrylate. For these substances, appropriate chronic animal and a controlled human exposure studies were available. The comparison of the sensory NOAEChuman with the irritative NOAECanimal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects. The adequacy of this iEF was confirmed by its application to additional substances with lower data density (acetaldehyde, ammonia, n-butyl acetate, hydrogen sulfide, and 2-ethylhexanol). Thus, extrapolating from animal studies, an iEF of 3 should be applied for local sensory irritants without reliable human data, unless individual data argue for a substance-specific approach.

Exposure study to examine chemosensory effects of formaldehyde on hyposensitive and hypersensitive males.

OBJECTIVE: Main objective of this study was to examine the chemosensory effects of formaldehyde on hyposensitive and hypersensitive males at concentrations relevant to the workplace. Attention focused on objective effects on and subjective symptoms of the mucous membranes of the eyes, the nose, the upper respiratory tract and olfactory function. METHODS: Forty-one male volunteers were exposed for 5 days (4 h per day) in a randomised schedule to the control condition (0 ppm) and to formaldehyde concentrations of 0.5 and 0.7 ppm and to 0.3 ppm with peak exposures of 0.6 ppm, and to 0.4 ppm with peak exposures of 0.8 ppm, respectively. Peak exposures were carried out four times a day over a 15-min period of time. Subjective pain perception induced by nasal application of carbon dioxide served as indicator for sensitivity to sensory nasal irritation. The following parameters were examined before and after exposure: subjective rating of symptoms and complaints (Swedish Performance Evaluation System), conjunctival redness, eye-blinking frequency, self-reported tear film break-up time and nasal flow rates. In addition, the influence of personality factors on the volunteer's subjective scoring was examined (Positive And Negative Affect Schedule). RESULTS: Formaldehyde exposures to 0.7 ppm for 4 h and to 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min caused no significant sensory irritation of the measured conjunctival and nasal parameters. No differences between hypo- and hypersensitive subjects were seen. Nevertheless, statistically significant differences were noted for olfactory symptoms, especially for the 'perception of impure air'. These subjective complaints were more pronounced in hypersensitive subjects. CONCLUSIONS: Formaldehyde concentrations of 0.7 ppm for 4 h and of 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min did not cause adverse effects related to irritation, and no differences between hypo- and hypersensitive subjects were observed.

Is individual nasal sensitivity related to cellular metabolism of formaldehyde and susceptibility towards formaldehyde-induced genotoxicity?

Forty-one volunteers (male non-smokers, aged 32 ± 9.6yrs) were tested for susceptibility towards unspecific nasal irritation (sensitivity towards CO(2)) in order to define subgroups of hypersensitive and hyposensitive subjects. Blood samples were taken and the expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase gene (FDH, identical to alcohol dehydrogenase 5, ADH5; EC 1.2.1.46) was measured in leukocytes by quantitative real-time RT-PCR with TaqMan probes. FDH is the most important enzyme for the metabolic inactivation of FA. Blood samples were exposed to 150µM formaldehyde (FA) for 2h and the induction of DNA-protein crosslinks (DPX) in leukocytes was measured by means of a modification of the alkaline comet assay (i.e., by assessing the reduction of DNA migration induced by γ-radiation). Removal of DPX was determined by the abolition of FA-induced reduction in DNA migration within 4h after the end of the exposure. Furthermore, the induction of sister chromatid exchange (SCE) in cultured lymphocytes was studied after treatment of whole blood cultures with FA (150µM). A correlation analysis was performed for all parameters tested for the whole study group and for hypersensitive and hyposensitive subgroups. The results indicate that despite large differences in CO(2)-sensitivity, the susceptibility towards nasal irritation was not related to the induction of genotoxic effects (DPX, SCE) in peripheral blood or to the protection of blood cells against FA-induced effects (expression of FDH, repair capacity for FA-induced DPX). There was no correlation between CO(2)-sensitivity and the expression of FDH. There was also no close correlation between the various indicators of cellular sensitivity towards FA-induced genotoxic effects and no subgroups were identified with particular mutagen sensitivity towards FA.

Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions.

Forty-one volunteers (male non-smokers) were exposed to formaldehyde (FA) vapours for 4 h/day over a period of five working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 p.p.m. At concentrations of 0.3 and 0.4 p.p.m., four peaks of 0.6 or 0.8 p.p.m. for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (∼80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange test and the cytokinesis-block micronucleus test were performed with blood samples. The micronucleus test was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the glutathione (GSH)-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time reverse transcription-polymerase chain reaction with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA did also not cause alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.

Implications of latency period between benzene exposure and development of leukemia--a synopsis of literature.

From numerous epidemiological studies it is evidenced that risk after exposure to a carcinogen varies with time and there has been an increasing discussion about the temporal variation in case of smoking, ionizing radiation and various chemical carcinogens. The results of several independent epidemiologic studies of occupational cohorts with benzene exposure and the development of leukemia will be presented in order to find common aspects. In this context the data of 537 confirmed cases of leukemia as an occupational disease in Germany during the time period 1978-2007 will be presented. It is concluded that the epidemiologic findings are consistent and demonstrate a smaller or even absent risk of leukemia 10-15 years after exposure to benzene has been stopped. Temporal changes in relative risk highlights the importance of examining the relationship between follow-up time and risk estimates as part of the risk assessment process.

A field study to determine the effectiveness of several respiratory protection masks on the styrene exposure during lamination activities.

PURPOSE OF THE STUDY: The purpose of this study is to examine the effectiveness of several types of personal respiratory protection equipment at styrene exposed laminators under real work place conditions. SUBJECTS AND METHOD: 99 male styrene exposed workers were examined. During their lamination activities the average styrene concentrations in air ranged between 30 to 60 ppm (maximum: 205 ppm). The laminators were followed during an usual workweek from Monday to Thursday. The external styrene exposure was measured by means of passive active carbon badges. The excretion of mandelic acid (MA) and phenyl glyoxylic acid (PGA) in end-of-shift urine samples was used to quantify the internal styrene load. During the work shift some laminators did not use respiratory protection masks. The majority used either a half face mask with active carbon filter or an air purifying respirator. RESULTS: The respiratory masks were worn during an average between 31% and 72% of the work time. The styrene concentrations of the ambient air were -depending on the activity- in the range of 30 to 60 ppm. The end-of-shift concentrations of MA and PGA in urine samples varied considerably, their means range from 153 to 606 mg/g creatinine. The comparison shows that workers with air purifying respirators experience the lowest internal styrene body burden in spite of high external exposures. Their effectiveness during usual working condition was around 83% whereas the use of half face masks with active carbon filters reduce styrene exposure only of 26% as an average. CONCLUSIONS: The use of styrene-containing resins in boatbuilding can be associated with increased external styrene exposure of the laminators. During the use of different types of respiratory protection masks it is shown that only the application of air purifying respirators leads to a significant reduction of the internal styrene body burden of 83% when worn during 72% of the total work time. In this way it is possible to comply with or to stay clearly below the biological limit value of 600 mg MA + PGA/g creatinine (BAT-value).

Occupational styrene exposure, colour vision and contrast sensitivity: a cohort study with repeated measurements.

OBJECTIVE: Associations between occupational styrene exposures and impairment of visual functions were investigated with a view to answering three questions: (1) are the published findings for colour vision deficiencies and impaired contrast sensitivity to reproduce in a new study approach, (2) if such effects exist, are they related to current or chronic exposures and (3) if effects exist, are there reductions in the effects during an exposure-free period? METHODS: Workers from a boat building plant were examined in groups of current low [n = 97, mean mandelic acid (MA) + phenylglyoxylic acid (PGA) = 51 mg/g creatinine], medium (n = 115, mean = 229 mg/g creatinine) and high (n = 30, mean = 977 mg/g creatinine) level exposure to styrene. Job tenure was about 6 years. In addition, subgroups chronically exposed to low-short (n = 34, lifetime weighted mean 200 mg/g creatinine for 6 years) and high-long (n = 17, mean = 660 mg/g creatinine, 15 years) styrene levels were analysed. The examinations were carried out during normal working days and during the company holidays. Colour vision was investigated with the Lanthony desaturated panel D-15d using the colour confusion index (CCI) as a relevant variable. Contrast sensitivity was investigated with the Vistech charts VCTS 6500 using frequency-related results as well as total scores as variables. Co-variance analyses with repeated measurements and multiple linear regressions were used for statistical analysis. RESULTS: There was no evidence of significant associations between exposure parameters and CCI. This is true for the analyses with all participants as well as for those with the subgroups with high-long versus low-short exposure. Thus, no exposure related changes in the relevant variables were found during the exposure-free period. The analyses for contrast sensitivity show similar results. The largest portions of the variances in both tests were explained by age. German as mother tongue covered a considerable portion of the CCI variances. Education, long-term alcohol use and job tenure explain only partly significant portions of the test variances exhibited. CONCLUSION: Both acute styrene exposure levels of 40 ppm (range of standard deviation up to 54 ppm) and long term exposures to 27 ppm (range of standard deviation up to 44 ppm with higher exposure levels in the past) for a period of about 15 years were not identified as causing elevated risks for the investigated parameters of colour vision and contrast sensitivity. This statement contradicts the published results for styrene-related colour vision deficiencies but it seems to be compatible with published results for contrast sensitivity due to styrene exposure.

Occupational styrene exposure and neurobehavioural functions: a cohort study with repeated measurements.

OBJECTIVE: Associations between occupational styrene exposure and cognitive as well as psychomotor functions were investigated with a view to answering three questions: (1) are the published results for neurobehavioural impairment reproducible, (2) if such effects exist, are they related to current or to chronic exposure and (3) if effects exist, are there reductions in the effects during an exposure-free period. METHODS: Workers from a boat-building plant, some of whom were laminators, were investigated in groups of low (n = 83, mean mandelic acid MA + phenylglyoxylic acid PGA = 53 mg/g creatinine), medium (n = 101, 230 mg/g creat.) and high (n = 29, 928 mg/g creat.) levels of exposure to styrene. The mean job tenure was about 6 years. In addition, subgroups chronically exposed to low-short (n = 30, lifetime weighted average exposure mean 184 mg/g creat. for 6 years) and high-long (n = 16, 693 mg/g creat., 15 years) styrene levels were analyzed. The examinations were carried out during normal working days and during the company holidays. A symptom questionnaire and the tests Benton visual retention, symbol digit substitution and digit span for cognitive functions as well as choice reaction, aiming, peg board, tapping, and steadiness for psychomotor functions were administered. Co-variance analyzes with repeated measurements and linear regressions were used for statistical analysis. Co-factors were education, age, job tenure, long-term alcohol consumption, and German as mother tongue. In some cases also the activity as a laminator was considered. RESULTS: Symptoms were not related to exposure. The tests for cognitive functions generally revealed (all variance analyses) no exposure-related associations. Only the linear regressions of Benton test results showed significant correlation with parameters of chronic exposure which was still evident as a tendency in the work-free and exposure-free period. Most tests for psychomotor functions also revealed no relationships with exposure. However, the peg board test results showed significant correlations with chronic exposure which disappeared during holidays. The activity as a laminator--considered in addition to exposure parameters--was significant as a factor to explain the variability of psychomotor variables. CONCLUSION: Acute exposures to up to 40 ppm styrene and long-term exposures to about 27 ppm averaged over a period of 15 years were not identified as being associated with an elevated risk of developing impaired cognitive and psychomotor functions or increased symptom levels with the tests applied. This statement must be qualified by two exceptions: performances in the Benton test and in a finger dexterity test were associated with parameters of long-term exposure as a dose-response relationship, but not with current exposure.

Occupational styrene exposure and hearing loss: a cohort study with repeated measurements.

OBJECTIVE: Associations between occupational styrene exposure and impairment of hearing function were investigated, guided by three questions: are there hearing losses concerning high frequency and standard audiometric test? Are there dose-response relationships and measurable thresholds of effects? Are there signs of reversibility of possible effects if the workers are examined during times of improvement from their work? METHODS: A group of workers from a boat building plant, some of whom were laminators, were examined in subgroups of current low (n = 99, mean mandelic acid MA + phenylglyoxylic acid PGA = 51 mg/g creatinine), medium (n = 118, mean 229 mg/g creat.) and high (n = 31, mean 970 mg/g creat.) exposure to styrene. In addition, subgroups chronically exposed to high-long (n = 17) and low-short (n = 34) styrene levels were analysed. The examinations were carried out during normal work days and during the company holidays. Hearing thresholds and transient evoked otoacoustic emissions (TEOAE) were measured. Statistics included multiple co-variance analyses with repeated measures, linear regressions, and logistic regressions. RESULTS: The analyses of all participants demonstrated no clear exposure effects. Particularly no sufficient proof of dose-response relationship measured against parameters of current exposure (MA + PGA, styrene/blood) and of chronic exposure (cumulative and average life time exposure resp.) was found. The analyses of groups exposed to high levels show elevated thresholds at frequencies up to 1,500 Hz among the subgroup exposed to high styrene levels (e.g. 40-50 ppm as average) for a longer period of time (e.g. more than 10 years). These participants also demonstrated signs of "improvement" at frequencies above 2,000 Hz during work holidays, when they were not exposed to styrene. A significantly elevated odds ratio for cases of hearing loss (more than 25 dB (A) in one ear, 3,000-6,000 Hz) was found among the group exposed to high levels (above 30 ppm as average) for a longer period of time (more than 10-26 years). The measurements of TEOAE did not exhibit significant results related to exposure. CONCLUSION: This study found, that chronic and intensive styrene exposure increases the hearing thresholds. At levels of about 30-50 ppm as an average inhaled styrene per work day over a period of about 15 years with higher exposure levels above 50 ppm in the past, an elevated risk for impaired hearing thresholds can be expected. The formerly published results on ototoxic effects below 20 ppm could not be confirmed. With few exceptions (at frequencies of 1,000 and 1,500 Hz) no dose-response relationship between threshold and exposure data was found. Improvements of hearing thresholds during work- and exposure-free period are possible.

Association between genetic polymorphisms in styrene-metabolizing enzymes and biomarkers in styrene-exposed workers.

Single-nucleotide polymorphisms (SNP) in genes of styrene-metabolizing enzymes could modulate biomarker concentrations in blood or urine after exposure to styrene. Ten SNP were analyzed to study their influence on styrene-specific biomarkers in 89 workers of a fiber-reinforced plastic boat building factory. The internal styrene body burden was analyzed in post-shift blood and urine samples. External styrene exposure was measured by passive samplers. Spearman rank correlations between styrene exposure and biomarkers were calculated and distributions of biomarkers were checked for lognormality. Mixed linear models were applied to analyze the influence of genotypes and styrene exposure, on styrene in blood (Monday and Thursday post-shift) and on phenyglyoxylic acid (PGA; adjusted for day of measurement, Monday to Thursday) due to a lognormal distribution, smoking (current, not current), and use of respirators. Stratified analyzes for workers without and with different types of respirators were also performed. The models of both the subgroups revealed a significant influence dependent on the respirator type that workers used for inhalation protection. An influence of the external styrene concentration on the urinary PGA concentration was not observed. After implementation of the SNP into the model significant lower adjusted means of urinary PGA concentrations were found for GSTP1 105IleVal and CYP2E1 -71TT. For styrene levels in blood no significant effect was observed. A significant influence on styrene levels in blood was correlated with external styrene concentration only in workers without use of respirators. The effects of two SNP on urinary PGA decrease indicated a limited modulating SNP effect. The most effective prevention for styrene exposure was obtained with the wearing of respirators.

Formaldehyde and chemosensory irritation in humans: a controlled human exposure study.

OBJECTIVES: The objective of this study was to examine the possible occurrence of sensory irritation and subjective symptoms in human volunteers exposed to formaldehyde concentrations relevant to the workplace. The set up of the study included formaldehyde exposures with and without peaks, the presence and absence of a masking agent, and evaluation of the influence of personality factors. METHODS: Testing was conducted in 21 healthy volunteers (11 males and 10 females) over a 10-week period using a repeated measures design. Each subject was exposed for 4h to each of the 10 exposure conditions on 10 consecutive working days. The 2-week exposure sequences were randomized, and the exposure to formaldehyde and the effect measurements were conducted in a double-blind fashion. During 4 of the 10 exposure sessions, 12-16 ppm ethyl acetate (EA) was used as a 'masking agent' for formaldehyde exposure. Measurements consisted of conjunctival redness, blinking frequency, nasal flow and resistance, pulmonary function, and reaction times. Also subjective ratings of discomfort as well as the influence of personality factors on the subjective scoring were examined. These were carried out pre-, during and/or post-exposure, and were used to evaluate the possible irritating effects of formaldehyde at these concentrations. RESULTS: The results indicated no significant treatment effects on nasal flow and resistance, pulmonary function, and reaction times. Blinking frequency and conjunctival redness, ranging from slight to moderate, were significantly increased by short-term peak exposures of 1.0 ppm that occurred at a baseline exposure of 0.5 ppm formaldehyde. Results of the subjective ratings indicated eye and olfactory symptoms at concentrations as low as 0.3 ppm. Nasal irritation was reported at concentration levels of 0.5 ppm plus peaks of 1.0 ppm as well as at levels of 0.3 and 0.5 ppm with co-exposure to EA. However, exposure to EA only was also perceived as irritating. In addition, volunteers who rated their personality as 'anxious' tended to report complaints at a higher intensity. When 'negative affectivity' was used as covariate, the level of 0.3 ppm was no longer an effect level but 0.5 ppm with peaks of 1.0 ppm was. Increased symptom scores were reversed 16 h after the end of the exposures. CONCLUSIONS: The results of the present study indicated eye irritation as the most sensitive parameter. Minimal objective eye irritation was observed at a level of 0.5 ppm with peaks of 1 ppm. The subjective complaints of ocular and nasal irritation noted at lower levels were not paralleled by objective measurements of eye and nasal irritation and were strongly influenced by personality factors and smell. It was concluded that the no-observed-effect level for subjective and objective eye irritation due to formaldehyde exposure was 0.5 ppm in case of a constant exposure level and 0.3 ppm with peaks of 0.6 ppm in case of short-term peak exposures.

Evaluation of long-term occupational exposure to styrene vapor on olfactory function.

The primary sensory neurons of the olfactory system are chronically exposed to the ambient environment and may therefore be susceptible to damage from occupational exposure to many volatile chemicals. To investigate whether occupational exposure to styrene was associated with olfactory impairment, we examined olfactory function in 2 groups: workers in a German reinforced-plastics boat-manufacturing facility having a minimum of 2 years of styrene exposure (15-25 ppm as calculated from urinary metabolite concentrations, with historical exposures up to 85 ppm) and a group of age-matched workers from the same facility with lower styrene exposures. The results were also compared with normative data previously collected from healthy, unexposed individuals. Multiple measures of olfactory function were evaluated using a standardized battery of clinical assessments from the Monell-Jefferson Chemosensory Clinical Research Center that included tests of threshold sensitivity for phenylethyl alcohol (PEA) and odor identification ability. Thresholds for styrene were also obtained as a measure of occupational olfactory adaptation. Styrene exposure history was calculated through the use of past biological monitoring results for urinary metabolites of styrene (mandelic acid [MA], phenylglyoxylic acid [PGA]); current exposure was determined for each individual using passive air sampling for styrene and biological monitoring for styrene urinary metabolites. Current mean effective styrene exposure during the day of olfactory testing for the group of workers who worked directly with styrene resins was 18 ppm styrene (standard deviation [SD] = 14), 371 g/g creatinine MA + PGA (SD = 289) and that of the group of workers with lower exposures was 4.8 ppm (SD = 5.2), 93 g/g creatinine MA+PGA (SD = 100). Historic annual average exposures for all workers were greater by a factor of up to 6x. No differences unequivocally attributable to exposure status were observed between the Exposed and Comparison groups or between performance of either group and normative population values on thresholds for PEA or odor identification. Although odor identification performance was lower among workers with higher ongoing exposures, performance on this test is not a pure measure of olfactory ability and is influenced by familiarity with the stimuli and their sources. Consistent with exposure-induced sensory adaptation, however, elevated styrene thresholds were significantly associated with higher occupational exposures to styrene. In summary, the present study found no evidence among a cross-section of reinforced-plastics workers that current or historical exposure to styrene was associated with a general impairment of olfactory function. When taken together with prior studies of styrene-exposed workers, these results suggest that styrene is not a significant olfactory toxicant in humans at current exposure levels.

Urinary pentachlorophenol in painters and bricklayers in a four-years time interval after the PCP prohibition ordinance in Germany.

Pentachlorophenol (PCP) was widely used as a wood preservative in Germany until 1989, when it was prohibited by law. Within a cross-sectional study we investigated the internal PCP exposure of painters and bricklayers between one year and four years after the ban. PCP was analysed in post-shift urine samples of 189 painters and 148 bricklayers by gas chromatography and electron capture detection (GC-ECD). The median PCP concentration in the urine of painters was 2.4 microg/g creatinine (range: 0.2-52 microg/g creatinine). For the bricklayers a range of 0.1-25 microg/g creatinine (median: 1.8 microg/g creatinine) was determined. The difference between both groups was statistically significant, pointing to a small additional uptake of PCP by the painters probably from an exposure to contaminated wood surfaces or residual PCP containing preservatives. The biomonitoring results for both groups coincided with background values of the general population at that time.

Assessment of local genotoxic effects of formaldehyde in humans measured by the micronucleus test with exfoliated buccal mucosa cells.

Volunteers (10 women, 11 men) were exposed to formaldehyde (FA) vapors for 4h per day over a period of 10 working days under strictly controlled conditions. Exposure varied randomly each day from constant 0.15 ppm up to 0.5 ppm with four peaks of 1.0 ppm for 15 min each (13.5 ppm h cumulative exposure over 10 working days). FA was masked on four days by co-exposure to ethyl acetate. During exposure, subjects had to perform bicycle exercises (about 80 W) three times for 15 min. Buccal smears were prepared 1 week before the start of the study (control 1), at the start of the study before the first exposure (control 2), at the end of the exposure period of 10 days and 7, 14 and 21 days thereafter. Two thousand cells per data point were analyzed for the presence of micronuclei (MN) and the frequency of MN per 1000 cells was determined on slides coded by an independent quality-assurance unit. No significant increase in the frequency of MN was measured at any time point after the end of the exposure. Twenty-one days after the end of the exposure MN frequencies were significantly lower in comparison with control 1. This study, which was performed under GLP-like conditions, clearly indicates that FA does not induce MN in buccal mucosa cells after peak exposures up to 1 ppm and a cumulative exposure of 13.5 ppm h over 2 weeks.

Field study to explore possible effects of styrene on auditory function in exposed workers.

OBJECTIVES: We conducted this study to examine, whether occupational styrene exposures are associated with reduced hearing ability. METHODS: The auditory function was investigated by pure tone audiometry and registration of transitory evoked otoacoustic emissions (TEOAE) in 32 workers of a fibre-reinforced plastic boat building factory. Sixteen subjects were laminators (mean age: 41 yr (SD: 8)) and therefore regularly exposed to styrene with mean duration of exposure to styrene of 7.5 yr (SD 5.0). The tests were applied to a reference group of 16 workers (mean age: 39 yr (SD: 8)) who were not directly exposed to styrene but had a similar noise exposure. RESULTS: A few and isolated correlations between the parameters of hearing acuity and exposure indices, such as current internal styrene exposures (sum of MA and PGA) and duration of styrene exposure, were statistically significant, but no consistent association was found. CONCLUSION: The results of this study do not support the assumption of an ototoxic effect of chronic styrene exposure in workers.

Examination of the influence of personal traits and habituation on the reporting of complaints at experimental exposure to ammonia.

OBJECTIVE: The aim of the study is to examine the impact of personal traits and habituation on the intensity of self reported health symptoms and complaints. METHODS: Forty-three healthy male volunteers were exposed to ammonia vapours in concentrations of 0, 10, 20, 20/40, and 50 ppm on five consecutive days. To explore a possible influence of habituation on the perception of symptoms, the study group was divided into 30 men who were not familiar with the smell of ammonia, and ten participants regularly exposed to ammonia at the workplace. The perceived acute health symptoms and self-reported changes of well-being were assessed by the German version of a questionnaire of the Swedish Performance Evaluation System (SPES). Personal traits were ascertained with the positive and negative affectivity schedule (PANAS) and the Freiburger Persönlichkeits Inventar (FPI). RESULTS: There are significant associations between personal traits and the amount of complaints. Subjects with high positive affectivity report less respiratory and irritative complaints, whereas persons with negative affectivity report significantly more olfactory and respiratory symptoms. In general, the strength of these correlations decreases with higher exposure levels. At ammonia concentration above 20 ppm, these associations were no more statistically significant. During the daily exposures, the score of symptoms did not vary significantly. The perceived intensity of health symptoms and annoyance increased with the concentration of ammonia, while the self-reported dimensions of well-being decreased. Workers familiar with the smell of ammonia vapours reported less symptoms compared to naïve subjects. CONCLUSIONS: Habituation to ammonia vapours as well as personal traits influence the reporting of complaints particularly at low exposure. Both factors should be considered in the examination of chemosensory irritative compounds.

Biological monitoring of experimental human exposure to hydrocarbon solvent mixtures.

The aim of the study was to develop and to validate a suitable analytical method in order to assess the internal exposure of persons to commercial products of hydrocarbon solvent mixtures (HSM). Twenty healthy volunteers were exposed to vapours of five commercial HSM for 8h at 200-1,000 mg/m(3) air. Aromatic-rich, aromatic-poor and aromatic-free HSM were used, as well as isohexane and technical hexane mixtures. A total of 300 exposures were carried out at rest or with an exercise period of 10 min/h at 50 and 75 W. Blood samples for the determination of the HSM were collected before and immediately after exposure. They were analyzed with a headspace analyzer by gas chromatography and mass spectrometry. The analytical method has detection limits of 2-50 microg HSM/L blood. With this method we obtained intra- and interassay variation coefficients of 3.7-15.1%, at concentrations of 53-1,500 microg HSM/L blood. The mean values of the HSM of the 20 volunteers after 8h range between 89 mug/L (technical hexane-mixture) and 1,369 microg/L blood (aromatic-free HSM) at rest. Physical exercises of 50 and 75 W, respectively, lead to a significant increase of the blood-concentrations by mean factors between 1.2 and 1.9 for the five HSM. In conclusion, our results demonstrate that physical activity should be considered in the setting of occupational exposure limits.