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.

Statistical issues in risk assessment of reproductive outcomes with chemical mixtures.

Establishing the relationship between a given chemical exposure and human reproductive health risk is complicated by exposures or other concomitant factors that may vary from pregnancy to pregnancy. Moreover, when exposures are to complex mixtures of chemicals, varying with time in number of components, doses of individual components, and constancy of exposure, the picture becomes even more complicated. A pilot study of risk of adverse reproductive outcomes among male wastewater treatment workers and their wives is described here. The wives of 231 workers were interviewed to evaluate retrospectively the outcomes of spontaneous early fetal loss and infertility. In addition, 87 workers participated in a cross-sectional evaluation of sperm/semen parameters. Due to the ever-changing nature of the exposure and the lack of quantification of specific exposures, six dichotomous variables were used for each specific job description to give a surrogate measure of exposure. Hence, no quantitative exposure-response relationships could be modeled. These six variables were independently assigned by two environmental hygienists, and their interrater reliability was assessed. Results are presented and further innovations in statistical methodology are proposed for further applications.

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.

Employment status as a confounder when assessing occupational exposures and spontaneous abortion.

Studies of occupational exposure and spontaneous abortion may use pregnancies during which the mother was unemployed as part or all of the unexposed comparison group. Any type of maternal employment, however, may be a risk factor for spontaneous abortion, and potential confounder in occupational reproductive studies. This study evaluates the effect of employment in a cohort of pregnancies of 1535 women. Employed pregnancies had a significantly higher rate of spontaneous abortion (14.5%) than unemployed pregnancies (11.7%) (RR = 1.23, 95% CI = 1.02, 1.49). Gravidity acted as an effect modifier, as the employment effect was seen only in multigravidous pregnancies (RR = 1.38, 95% CI = 1.11, 1.72) and not primigravidous pregnancies (RR = 0.96). The effect persisted when an independent sample of one randomly selected pregnancy per woman was used for the analysis (RR = 1.27, 95% CI = 0.90, 1.79). The data were examined for confounding by other factors which could explain the excess in spontaneous abortion among employed pregnancies. The employment effect persisted with adjustment for other risk factors including maternal age, education, income, maternal diabetes, race, alcohol usage and smoking, and prior pregnancy ending in induced abortion. Stratifying by prior pregnancy loss eliminated the employment effect among those with prior loss (RR = 1.03) but enhanced the effect among those multigravidous without the risk factor (RR = 1.50, 95% CI = 1.15, 1.97). Selection bias, also, was explored as a possible explanation of this employment effect, but could not be substantiated. Assessment of a true exposure effect requires consideration of a potential employment effect either in the design or analysis.

Fertility of workers chronically exposed to chemically contaminated sewer wastes.

Few studies have investigated the reproductive effects of exposure to chemical mixtures. The purpose of this study was to assess fertility in males exposed to mixed industrial and domestic wastes. A detailed reproductive history was obtained from the wives of 231 employees in order to evaluate fertility. Daily work records were used to define exposure status. To ascertain problems of infertility, the ratios of observed live births to expected live births (generated from U.S. birth probabilities) for exposed and nonexposed groups were calculated, and the ratios of these Standardized Fertility ratios (SRFs) were compared. Other analyses considered the couples' contraceptive history and preexposure versus postexposure experience. Though multiple statistical approaches were used to examine the data, the conclusion of this study was that exposure to chemical mixtures was not associated with a decrease in the couples' fertility.

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.

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.

Balancing cost and precision in exposure assessment studies.

Because of the cost involved both for personnel and laboratory analyses, it is incumbent that industrial hygiene (IH) sampling plans be both precise and cost effective. The purpose of this paper is to describe a method of balancing two opposing objectives, increasing precision and decreasing the cost by manipulating the number and nature of IH sample collections. Data from a pilot study were used to obtain an optimum sampling scheme for exposure assessment. The design that obtains the highest precision while controlling costs serves as the model of choice. An approach is illustrated with data from an ongoing study examining health effects of workers exposed to solvents. It is shown that there is a large variation in precision for identical IH measurements, depending on the efficiency of the sampling schedule.

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.

Use of exposure data in occupational reproductive studies.

Accurately characterizing worker exposure presents some unique problems in occupational reproductive studies. The latency period between exposure and the adverse event may be relatively brief - days, weeks, or months. Inaccurately identifying the specific exposure period which initiated the adverse event may then contribute to sizeable misclassification errors. This paper discusses different types of exposure models that can be used to help reduce misclassification and delineate the exposure-effect relationships more accurately. The advantages and disadvantages of exposure data sources are also discussed.

Effects of occupational exposure to organic solvents and noise on hearing.

This study explored the effects of occupational exposure to solvents and noise on hearing. Interviews and hearing tests were conducted for printing and paint manufacturing workers. The experimental groups included unexposed (N = 50) workers and workers exposed to noise (N = 50), noise and toluene (N = 51), or an organic solvent mixture (N = 39). The risk of hearing loss was greater for the exposed groups than for the unexposed group. The adjusted relative risk estimates were four times greater [95% confidence interval (95% CI) 1.4-12.2] for the noise group, 11 times greater (95% CI 4.1-28.9) for the noise and toluene group, and five times greater (95% CI 1.4-17.5) for the solvent-mixture group. The findings suggest that exposure to the studied solvents had a toxic effect on the auditory system and that an interaction between noise and toluene took place. The audiological results of the noise and toluene group suggest a central auditory pathway involvement in the hearing losses observed.

Menstrual cycles in nurses handling antineoplastic drugs.

Given the association between high-dose antineoplastic drug therapy and effects on gonadal function, a cross-sectional study was designed to explore the relationship between low-dose occupational exposure to antineoplastic questionnaire survey of the members of two national organizations for nurses was conducted, resulting in a sample of 1,458 female subjects. Subjects obtained from the two organizations were compared on major demographic and work characteristics and were found to be similar on most factors other than occupational exposure to antineoplastic drugs. An association was found between menstrual dysfunction and current handling of cancer drugs in subjects between ages 30 and 45 years [prevalence odds ratio (OR) = 1.6, confidence interval (CI) = 1.3-1.9]. A logistic regression analysis demonstrated that subjects ages 30-45 who were currently administering antineoplastic drugs had the highest adjusted OR (3.4, CI = 1.6-7.3) when compared with subjects with no previous or current handling. Additional risk factors significantly associated with menstrual irregularity were stress level of work and the interaction of smoking and stress.

A distraction technique for control of burn pain.

Research has indicated that analgesics alone do not adequately relieve pain for 75% of patients with burns. The purpose of this study was to determine the effects of a distraction therapy, in which videos were used in combination with administration of analgesics, on intensity and quality of pain and on levels of anxiety in adults during burn dressing changes. The sample consisted of 17 patients who were randomly assigned to the treatment or the control group. The treatment group viewed video programs that were composed of scenic beauty accompanied by music. Each was asked to score his or her present pain intensity and pain rating index with the McGill questionnaire and anxiety with the Spielberger questionnaire before and after the dressing change. A nested general linear model using the "F" test in multiple regression analysis was adjusted for age, percent partial-thickness burn, and choice of topical agent demonstrated that the use of videos during the dressing changes significantly reduced pain and anxiety: present pain intensity (F = 8.69; p = 0.01), pain rating index (F = 5.57; p = 0.03), anxiety (F = 9.10; p = 0.01). It is recommended that the use of pain medication be augmented by use of videos during burn dressing changes.

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.

[Epidemiologic methods for evaluating the effects of occupational exposure on pregnancy outcome]. / Epidemiologiczne metody oceny wplywu narazenia zawodowego na wyniki ciazy.

Methodological problems of epidemiological studies of the effect of harmful factors present in the working environment on the reproduction and development of the progeny were discussed. Basic types of epidemiological studies such as retrospective and prospective cohort studies, cross-sectional and case-control studies were presented. Issues pertaining to the measurement bias and its sources in individual types of studies were raised. An appropriate selection of measures illustrating disturbances in the reproduction and development of the progeny was considered as well as adapted definitions of those measures and their correct classification. ahe methodology of an appropriate assessment of exposure to harmful factors in the working environment was also discussed.

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.