N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort.

Cotinine is a proxy for secondhand smoke (SHS) exposure. Genetic variation along nicotine and cotinine metabolic pathways may alter the internal cotinine dose, leading to misinterpretations of exposure-health outcome associations. Caucasian children with available SHS exposure and hair cotinine data were genotyped for metabolism-related genes. SHS-exposed children had 2.4-fold higher hair cotinine (0.14±0.22 ng mg(-1)) than unexposed children (0.06±0.05 ng mg(-1), P<0.001). SHS-exposed children carrying the NAT1 minor allele had twofold higher hair cotinine (0.18 ng mg(-1) for heterozygotes and 0.17 ng mg(-1) for homozygotes) compared with major allele homozygotes (0.09 ng mg(-1), P=0.0009), even after adjustment for SHS dose. These findings support that NAT1 has a role in the metabolic pathway of nicotine/cotinine and/or their metabolites. The increased cotinine levels observed for those carrying the minor allele may lead to SHS exposure misclassification in studies utilizing cotinine as a biomarker. Additional studies are required to identify functional single-nucleotide polymorphism(s) (SNP(s)) in NAT1 and elucidate the biological consequences of the mutation(s).

Duration of day care attendance during infancy predicts asthma at the age of seven: the Cincinnati Childhood Allergy and Air Pollution Study.

BACKGROUND: Studies vary with respect to the reported effects of day care attendance on childhood asthma. OBJECTIVES: To evaluate the independent and combined effects of day care attendance and respiratory infections on the development of asthma at the age of seven in a prospective birth cohort. METHOD: At the age of seven, the study sample included 589 children with complete data of 762 enrolled at birth. Day care hours and number of respiratory infections were reported in follow-up questionnaires through age four. At 7 years of age, asthma was diagnosed in 95 children (16%), based on predefined symptoms criteria confirmed by either asthma FEV1 reversibility after bronchodilator or a positive methacholine test (PC20 ≤ 4 mg/mL). Logistic regression was used to investigate the relationships between asthma at the age of seven, cumulative hours of day care attendance and reported respiratory infections at ages 1-4. RESULTS: In the univariate analyses, day care attendance at 12 months was associated with an increased risk of asthma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.1-3.0]. Both upper and lower respiratory infections at 12 months also increased the likelihood of asthma [OR = 2.4 (1.4-4.1); OR = 2.3 (1.5-3.7), respectively]. In the final multivariate logistic model, cumulative hours of day care attendance and number of lower respiratory infections at 12 months were associated with asthma [OR = 1.2 (1.1-1.5); OR = 1.4 (1.2-1.7), respectively]. However, a threshold of greater than 37.5 hours per week of day care attendance was associated with a lower risk of asthma [OR = 0.6 (0.4-0.9)]. CONCLUSION: Depending on duration of attendance, day care during infancy can either increase or reduce risk of asthma at the age of seven.

Airway obstruction related to diacetyl exposure at microwave popcorn production facilities.

Obstructive lung diseases including bronchiolitis obliterans have been reported among microwave popcorn production employees. Butter flavourings including diacetyl have been associated with these findings. The present study was initiated at four microwave popcorn production plants to determine if exposure to diacetyl was associated with decrements in pulmonary function. Comprehensive diacetyl exposure assessment was undertaken for all job tasks. Spirometry was conducted for 765 full-time employees between 2005 and 2006. Outcomes included decrement in forced expiratory volume in one second (FEV(1)) % predicted, airway obstruction and persistent decline in FEV(1). Inclusion in the high-exposure group (mixers) prior to respirator use was associated with a significantly decreased FEV(1) % pred in non-Asian and Asian males at -6.1 and -11.8% pred, respectively, and an eight-fold increased risk for airway obstruction. Cumulative diacetyl exposure >or=0.8 ppm-yr caused similar results. No significant impact was seen in nonmixers or between current diacetyl exposure and persistent decline in FEV(1). Unprotected exposure as a mixer to butter flavouring including diacetyl resulted in decrements in FEV(1) (% pred) and increased airway obstruction. Control of employee exposure to butter flavouring additives is warranted in regard to both short-term peak and 8-h workday exposure.

An epidemiological appraisal instrument - a tool for evaluation of epidemiological studies.

In recent years, ergonomics practices have increasingly relied upon the knowledge derived from epidemiological studies. In this regard, there is limited research devoted to the exclusive evaluation of the methodological qualities of ergonomics epidemiological studies. The aim of this study was to develop and test a general purpose 'epidemiological appraisal instrument' (EAI) for evaluating the methodological quality of existing or new ergonomic epidemiological studies using a critical appraisal system rooted in epidemiological principles. A pilot EAI version was developed and tested by a team of epidemiologists/physicians/biostatisticians, with the team leader being both epidemiologist and ergonomist. The pilot version was further tested with regard to other raters with/without a background in epidemiology, biostatistics and ergonomics. A revised version was evaluated for criterion validity and reliability. An assessor with a basic background in epidemiology and biostatistics would be able to correctly respond on four out of five questions, provided that subject matter expertise is obtained on specific items. This may improve with the article's quality. Training may have an effect upon assessors with virtually no background in epidemiology/biostatistics, but with a background in ergonomics. In this latter case, the inter-rater degree of agreement is largely above 90% and assessors can resolve their differences in a subsequent round. The EAI proved to be a valid and reliable appraisal instrument that may be used in various applications, such as systematic reviews and meta-analyses.

Electron microscopy study of refractory ceramic fibers.

In epidemiological studies designed to identify potential health risks of exposures to synthetic vitreous fibers, the characterization of airborne fiber dimensions may be essential for assessing mechanisms of fiber toxicity. Toward this end, air sampling was conducted as part of an industry-wide study of workers potentially exposed to airborne fibrous dusts during the manufacture of refractory ceramic fibers (RCF) and RCF products. Analyses of a subset of samples obtained on the sample filter as well as on the conductive sampling cowl were performed using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to characterize dimensions of airborne fibers. Comparison was made of bivariate fiber size distributions (length and diameter) from air samples analyzed by SEM and by TEM techniques. Results of the analyses indicate that RCF size distributions include fibers small enough in diameter (< 0.25 microm) to be unresolved by SEM. However, longer fibers (> 60 microm) may go undetected by TEM, as evidenced by the proportion of fibers in this category for TEM and SEM analyses (1% and 5%, respectively). Limitations of the microscopic techniques and differences in fiber-sizing rules for each method are believed to have contributed to the variation among fiber-sizing results. It was concluded from these data that further attempts to characterize RCF exposure in manufacturing and related operations should include analysis by TEM and SEM, since the smallest diameter fibers are not resolved with SEM and the fibers of longer length are not sized by TEM.

What is the potential measurement error in occupational exposure studies?

This paper demonstrates statistical methods that estimate measurement error from available industrial hygiene data. Errors in measuring a continuous exposure variable may arise when all individuals in a work area are assigned the same exposure. An example is when the mean of exposure measurements obtained on a sample of individuals is assigned to all workers with similar jobs. This may lead to inaccurate point and interval estimates in exposure-response modeling. A method of simulating the distribution of true (i.e., unobserved) individual exposures is described in order to estimate the mean and variance of measurement error. The minimum variance unbiased estimator approximates the mean of lognormally distributed exposure measurements. The distribution of true individual exposures is approximated by the distribution of simulated estimates of mean exposure. The methodology is illustrated by exposure data from work areas manufacturing refractory ceramic fiber (RCF) and RCF products. Results show that exposure is slightly underestimated in work areas with between 25 and 113 exposure measurements; measurement error variance averages about 1.3% of the total variance.

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied. Prioritized research needs include basic studies on the cellular-molecular and endocrine regulation of sexual differentiation and development; increased efforts regarding potential adverse effects on development in females, including breast development; expanded animal studies on different classes of chemicals, comparing responses during development (prenatal and postnatal) with responses in adults; and, more extensive explorations regarding the reproductive biology and toxicology of puberty in humans.

Weight change and lung function: implications for workplace surveillance studies.

This study evaluated the relationship between weight change and longitudinal measurement of lung function among 361 men providing at least five pulmonary function tests. The men in this study were participants in a workplace pulmonary surveillance program for subjects with exposure to refractory ceramic fibers (RCFs). Occupational and environmental studies are generally designed to evaluate factors suspected of causing excess decline in lung function. Failure to adequately account for all significant factors may lead to erroneous conclusions regarding change in lung function. This study utilized two different statistical models to evaluate longitudinal changes in a cohort of RCF workers. What was unique to this study was the modeling of longitudinally measured initial weight, weight change, and longitudinal exposure before and during the period of observation. Results showed a strong relationship between weight gain and longitudinal loss in lung function that approximated forced vital capacity declines of 16 mL for every kilogram of weight gain per year in both models. This value is comparable or greater in magnitude and significance to other factors known to be inversely related to lung function, such as age and pack-years smoking to time of initial testing. In conclusion, weight gain was found to have a significant impact on longitudinal change in lung function. Therefore, weight gain becomes a very important variable that requires consideration whenever longitudinal studies of pulmonary function are conducted.

Potential significance of airborne fiber dimensions measured in the U.S. refractory ceramic fiber manufacturing industry.

BACKGROUND: To determine dimensions of airborne fibers in the U.S. refractory ceramic fiber (RCF) manufacturing industry, fibers collected through personal air sampling for employees at RCF manufacturing and processing operations have been measured. METHODS: Data were derived from transmission electron microscopy analyses of 118 air samples collected over a 20-year period. RESULTS: Characteristics of sized fibers include: diameter measurements of <60; 0.19 to 1.0 micron, m of which 75% are less than 0.6 micron and length ranging from < 0.6 to > 20 micron, with 68% of fibers between 2.4 and 20 micron. CONCLUSIONS: Exposures in RCF manufacturing include airborne fibers with dimensions (diameter < 0.1-0.4 micron, length < 10 micron) historically associated with biological effects in pleural tissues. Air sampling data and a review of studies relating fiber size to pleural effects in animals and humans support the belief that information on fiber dimensions is essential for studies with synthetic vitreous fibers.

Male reproductive effects of solvent and fuel exposure during aircraft maintenance.

Few studies have addressed the effects of mixed, low-level exposures to complex mixtures on a man's reproductive potential. In this prospective study, each subject was evaluated before first exposure and at 15 and 30 weeks after exposures had begun. A total of 50 men working on aircraft maintenance at an Air Force installation were included in the study. In addition, eight unexposed men were concurrently sampled. Industrial hygiene (IH) sampling and expired breath samples were collected for jet fuel as measured by total napthas, benzene--a component of jet fuel, 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene, and methylene chloride. Sperm production, structure, and function (sperm concentration, sperm motion, viability, morphology, morphometrics, and stability of sperm chromatin) were evaluated. Exposures were low. All mean IH measures were below 6 ppm, which is less than 10% of the Occupational Safety and Health Administration standard for all chemicals except benzene. Sheet metal workers had the highest mean breath levels for both total solvents (24 ppb) and fuels (28.3 ppb). For most sperm measures, mean values remained in the normal range throughout the 30 weeks of exposure. When jobs were analyzed by exposure groups, some adverse changes were observed. The paint shop group had a significant decline in motility of 19.5% at 30 weeks. Internal dose measures, however, did not show a significant association with spermatogenic changes.

Comparison of internal dose measures of solvents in breath, blood and urine and genotoxic changes in aircraft maintenance personnel.

Solvents and fuels are in widespread use both in civilian and military populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone (MEK) and methylene chloride are found in a variety of compounds including degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and xylene are also found in fuels, which are complex mixtures of hundreds of agents. The purpose of this investigation was twofold. The first was to determine the optimum medium to measure internal dose of solvents comparing blood, urine and breath. The second was to determine if low level exposures were associated with genotoxic changes after a short-term exposure of fifteen or thirty weeks. To accomplish the first goal a pilot study was initiated involving eight volunteers who worked in aircraft maintenance including sheet metal, painting and assembly mechanic jobs. Industrial hygiene measurements were evaluated over 30 working days. Breath, blood and a 24-hour urine sample were collected twice to compare internal dose parameters. To achieve the second goal, 58 newly hired subjects were monitored prior to exposure and over 30 weeks to determine if there were genotoxic changes as a result of solvent and/or fuel exposure as measured by sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included workers involved in sheet metal (fuel cell) activities, painting, fueling operations and flight line. Results of the pilot study demonstrated that industrial hygiene air samples and internal breath measures taken on the same day were highly correlated for measuring TCA (r = 0.93) and toluene (r = 0.90) but was not as well correlated for the other compounds. Breath measures were more sensitive for measuring low level exposure than were either analytes in blood or 24-hour urine samples; these latter two measures were usually below the limit of detection. A small but statistically significant increase in the frequency of SCEs occurred after 30 weeks of exposure for sheet metal workers (p = 0.003) and for painters (p = 0.05). The MN frequency in the sheet metal workers initially showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance occurrence of exposures to other occupational or non-occupational agents can not be eliminated as a cause of the genotoxic results since between 58 and 93 total analytes could be found in the breath of some aircraft maintenance personnel.

An industry-wide pulmonary study of men and women manufacturing refractory ceramic fibers.

An industry-wide pulmonary morbidity study was undertaken to evaluate the respiratory health of employees manufacturing refractory ceramic fibers at five US sites between 1987 and 1989. Refractory ceramic fibers are man-made vitreous fibers used for high temperature insulation. Of the 753 eligible current employees, 742 provided occupational histories and also completed the American Thoracic Society respiratory symptom questionnaire; 736 also performed pulmonary function tests. Exposure to refractory ceramic fibers was characterized by classifying workers as production or nonproduction employees and calculating the duration of time spent in production employment. The risk of working in the production of refractory ceramic fibers and having one or more respiratory symptoms was estimated by adjusted odds ratios and found to be 2.9 (95 percent confidence interval 1.4-6.2) for men and 2.4 (95 percent confidence interval 1.1-5.3) for women. The effect of exposure to refractory ceramic fibers on forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), the ratio of the two (FEV1/FVC), and forced expiratory flow (liters/second) between 25 percent and 75 percent of the FVC curve (FEF(25-75)) was evaluated by multiple regression analysis using transformed values adjusted for height, by dividing by the square of each individual's height. For men, there was a significant decline in FVC for current and past smokers of 165.4 ml (p < 0.01) and 155.5 ml (p = 0.04), respectively, per 10 years of work in the production of refractory ceramic fibers. For FEV1, the decline was significant (p < 0.01) only for current smokers at 134.9 ml. For women, the decline was greater and significant for FVC among nonsmokers, who showed a decrease of 350.3 ml (p = 0.05) per 10 years of employment in the production of refractory ceramic fibers. These findings indicate that there may be important sex differences in response to occupational and/or environmental exposure.

Prevalence of work related musculoskeletal disorders in active union carpenters.

OBJECTIVES: To determine the prevalence and risk factors for work related musculoskeletal disorders among union carpenters. METHODS: A detailed questionnaire on musculoskeletal symptoms and work history was administered to 522 carpenters. The symptom questions assessed if carpenters experienced pain, numbness, or tingling in a particular body region. A subset of this group then received a physical examination of the upper extremities and knees. RESULTS: The study group was primarily white (94.9%) and male (97.8%) with a mean age of 42.3 years. The highest prevalence of work related musculoskeletal disorders cases by carpentry specialty ranged from 20%-24% for those doing drywall or ceiling, finishing or framing, and the building of concrete forms. Generally, as duration of employment increased, the prevalence of symptoms increased. An adjusted logistic regression analysis showed that the group with the longest (> or = 20 years) duration of employment in carpentry was significantly associated with work related musculoskeletal disorders of the shoulders (odds ratio (OR) 3.2, 95% confidence interval (95% CI) 1.1 to 8.9), hands or wrists (OR 3.1, 95% CI 1.1 to 8.4), and knees (OR 3.5, 95% CI 1.3 to 9.2). Also, analyses showed that carpenters who reported that they had little or no influence over their work schedule had significant increases of work related musculoskeletal disorders of the shoulders, hips, and knees with ORs of 1.9 (95% CI 1.1 to 3.2), 2.9 (95% CI 1.1 to 7.2), and 2.3 (95% CI 1.2 to 4.1), respectively. Feeling exhausted at the end of day was also a significant risk factor for work related musculoskeletal disorders of the knee (OR 1.8, 95% CI 1.1 to 3.1). Upper extremity disorders were the most prevalent work related musculoskeletal disorders reported among all carpenters. Drywall or ceiling activities involve a considerable amount of repetitive motion and awkward postures often with arms raised holding heavy dry walls in place, whereas form work is notable for extensive lumbar flexion and had the two highest rates of work related musculoskeletal disorders. The psychosocial element of job control was associated with both upper and lower extremity disorders. These union carpenters, who were relatively young, already were experiencing considerable work related physical problems. CONCLUSION: This study supports the need for vigilant ergonomic intervention at job sites and early ergonomic education as an integral part of apprenticeship school training to ensure that carpenters remain fit and healthy throughout their working lifetime.

Longitudinal estimates of pulmonary function in refractory ceramic fiber manufacturing workers.

Refractory ceramic fibers (RCF) are man-made vitreous fibers (MMVF) used in high-temperature industrial applications. Between 1987 and 1994, a prospective study evaluated pulmonary function of 361 male workers currently employed in RCF manufacturing and related operations for plausibility of a causal relationship between RCF exposure and pulmonary function changes. Workers included in the analysis provided at least five pulmonary function tests. The exposure-response relationship was modeled with two exposure variables: years in a production job, and cumulative fiber exposure (fiber-mo/cc). Comparison groups were nonproduction workers and workers with up to 15 fiber-mo/cc cumulative exposure. A statistically significant decrease in FVC was demonstrated among workers employed in production jobs more than 7 yr prior to initial test. A similar but nonstatistically significant result was demonstrated for FVC in workers with greater than 60 fiber-mo/cc cumulative exposure prior to initial pulmonary function test. Similar but nonstatistically significant results were obtained for FEV1. These findings, which primarily reflect workers employed before 1980, did not persist with analysis of follow-up production years and accumulated RCF exposure from initial pulmonary function test. Since longitudinal analyses are sensitive to influences that continue to affect annual decline during the study period, lower RCF exposure levels since the 1980s may be responsible for eliminating any further effect on pulmonary function.

Reliability of questionnaire information measuring musculoskeletal symptoms and work histories.

This study was designed to assess the test-retest reliability of a musculoskeletal symptom and work history (MSWH) questionnaire administered to 522 carpenters A 10% subgroup of carpenters completing the original interview was selected for the retest interview. The areas addressed included recall of work-related musculoskeletal symptoms, prior medical conditions, prior injuries, recall of work histories, and psychosocial items. The results show that for these sections of the MSWH questionnaire the observed agreements ranged from 75.5 to 97.0%, and the calculated kappa estimates ranged from 0.46 to 0.77. Injury to body regions, job specialty, and prior medical history had the highest kappa values of K = .70 or greater. Reliability of reporting frequency of job duties such as flooring and finishing was excellent, with kappa = 0.73 (95% confidence interval = 0.66, 0.80). Based on these results, the overall reliability of the MSWH questionnaire is very good.

A comparison of exposures to refractory ceramic fibres over multiple work shifts.

As part of an ongoing, industry-wide study in the manufacture of refractory ceramic fibres (RCF), time weighted average (TWA) exposures have been collected at five facilities according to a standardised protocol. Work activities were grouped into dust zones (DZs). Persons to be sampled were randomly selected according to a protocol designed to assure that at least one sample was collected annually from each DZ; each work shift is also sampled at least annually. TWA exposures calculated over a sampling period of at least 360 min were included in the data set. DZs were combined into one of three groups (DZGs): fibre production; vacuum processes; other. The data were analysed to identify any differences by DZG between airborne fibre exposures, by the shift worked at each facility, and across all facilities. There were no statistically significant shift-related differences detected between airborne fibre exposures across the five RCF facilities when analysed as a group. Within four of the facilities, no shift-related differences were detected between airborne fibre exposures; however, at one facility, first and third shift exposures were statistically different. No documentation related to job activities was found to account for the observation. The data generally support the use of a single exposure estimate for each DZG in each of these facilities, regardless of shift worked. Researchers reconstructing exposure and not able to determine the shift worked by study subjects may find these results useful, but are cautioned that substantial differences in exposure across shifts may exist in other types of manufacturing.

Genotoxic changes after low-level solvent and fuel exposure on aircraft maintenance personnel.

Individuals may be exposed to solvent mixtures and fuel either at work or home, through air, water and food contamination. Few studies have addressed the genotoxic effects of mixed, low-level exposure to fuel and solvent. This was an optimally designed study where each subject was sampled prior to exposure and after 15 and 30 weeks while exposed, in a repeated measures design with each subject serving as his own control. Fifty men aged between 18 and 50, working on aircraft equipment operation and maintenance at a military installation were included. Eight unexposed men were concurrently sampled. Sister-chromatid exchanges (SCE) and micronuclei (MN) frequency were measured in conjunction with air sampling and expired breath analysis for jet fuel (JP-4), 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene and methylene chloride. Exposure levels measured by industrial hygiene were very low (all means <6 p.p.m.), <10% of the OSHA standard. Expired breath levels were also low, <25 p.p.b. A small but statistically significant increase in the frequency of SCE occurred after 30 weeks of exposure for sheet metal workers (P = 0.003) and for painters (P = 0.05). The MN frequency in the sheet metal workers initially showed a statistically significant increase, but by 30 weeks had decreased. Cigarette smoking, alcohol and caffeine use were not associated with changes from baseline for either MN or SCE. Smokers, however, had significantly higher values of SCEs at baseline than did nonsmokers. In summary, these findings suggest that small increases in SCEs in particular, may serve as a sensitive biologic indicator of low level hydrocarbon exposure in as much as statistically significant changes occurred in the highest exposed groups but not in the low or no exposure groups. Chance occurrence or exposures to other occupational or non-occupational agents cannot be eliminated as a cause of the study findings.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. Birth defects and developmental disorders.

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. II. Female reproductive disorders.

Members of the workgroup on female reproductive disorders discussed methods to evaluate five principal functions: menstrual dysfunction, infertility, pregnancy loss, lactation disorders, and pregnancy complications. To test each function, a nested strategy was considered, based on progressive levels of effort available to conduct field investigations. This strategy was analogous to the three-tier classification of biomarkers used by other workshops. The lowest level of effort, corresponding to Tier 1, consists only of questionnaires, diaries, and reviews of maternal and infant medical records. The medium level of effort (Tier 2) collects data from questionnaires and diaries, and some biologic specimens. Suggested laboratory analyses included measurement of progesterone in saliva and several glycoprotein hormones in urine that evaluate menstrual dysfunction, infertility, and pregnancy loss. The highest level of effort (Tier 3) involves prospective collection of diary information and simultaneous collection of biological specimens.