Classification of worker exposures

The classification of jobs or workers by exposure is an important undertaking in any occupational epidemiological study. Hitherto, the exposure classification designs have been strongly motivated by a desire to generate a sufficient number of exposure classes for the determination of a potential exposure-response relationship. Thus, the partitioning of exposures has been more or less arbitrary. The misclassification problems created by the selection of an arbitrary number of exposure assignment classes have not been addressed. In any quantitative exposure classification scheme, specific job titles may be indistinguishable in existing employment records; therefore, between worker variability must be addressed when characterizing worker exposures. Also, industrial hygiene exposure measurements frequently used to characterize worker exposures are often treated as valid representations of exposures; but they are neither random nor systematic evaluations of worker exposures. As a result they do not represent sampling from the proper exposure stratification of workers. These observations suggest that the selection of exposure groups should be based on a more rigorous examination of the data and its limitations. Considering the probability of any given worker being placed into the proper class as the probability of finding the mean exposure for that worker within the class boundary, the general equations to quantify the misclassification rates for any classification design as well as the exposure class limits and their width for any acceptable misclassification rate are developed. If between worker variability could not be calculated from the available exposure measurements, then it might be estimated from the proper data compiled from the literature. By considering an acceptable level of exposure misclassification, it is possible to calculate the allowable number of exposure classes and the proper partitioning ratio for these classes. Thus, the trade-off between misclassification and number of exposure classes might be a satisfactory solution to this difficulty encountered in occupational epidemiology.     

Chemical process based reconstruction of exposures for an epidemiological study. III. Analysis of industrial hygiene samples

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (beta-CD) and other substances, all available industrial hygiene exposure monitoring data were collected and summarized. From discussions with on-site industrial hygiene personnel, it was apparent that these data were not collected for epidemiological purposes and, therefore, their use in characterization of exposures was problematic as the data mostly pertained to samples collected to investigate the performance of specific tasks. These data were, however, informative for validating the exposure modeling process used to estimate historical exposures. The data summarized below clearly indicate that exposures to beta-CD were lowered across the time period of this study. Typically, the exposures recorded were less than the occupational exposure limits of the periods in which the exposures were recorded. Additionally, exposure measurements recorded in the recent past do not represent the exposure actually experienced by the worker as a strict personal protective equipment use program has been in place for the facilities studied since the mid-1980s.     

Mortality patterns among industrial workers exposed to chloroprene and other substances. II. Mortality in relation to exposure

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (CD) and other substances, including vinyl chloride monomer (VC), we analyzed mortality from all cancers combined, respiratory system (RSC) and liver cancer in relation to CD and VC exposures. Subjects were 12,430 workers ever employed at one of two U.S. sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)). Historical exposures for individual workers were estimated quantitatively for CD and VC. For sites L, M, P and G, respectively, average intensity of CD exposures (median value of exposed workers in ppm) were 5.23, 0.16, 0.028 and 0.149 and median cumulative exposures (ppm years) were 18.35, 0.084, 0.133 and 1.01. For sites L and M, respectively, average intensity of VC exposures (median value of exposed workers in ppm) was 1.54 and 0.03 and median cumulative exposures (ppm years) were 1.54 and 0.094. We performed relative risk (RR) regression modeling to investigate the dependence of the internal cohort rates for all cancers combined, RSC and liver cancer on combinations of the categorical CD or VC exposure measures with adjustment for potential confounding factors. We categorized exposure measures into approximate quartiles based on the distribution of deaths from all cancers combined. We also considered 5- and 15-year lagged exposure measures and adjusted some RR models for worker pay type (white/blue collar) as a rough surrogate for lifetime smoking history. All modeling was site-specific to account for exposure heterogeneity. We also computed exposure category-specific standardized mortality ratios (SMRs) to assess absolute mortality rates. With the exception of a one statistically significant association with duration of exposure to CD and all cancers combined in plant M, we observed no evidence of a positive association with all cancers, RSC or liver cancer and exposure to CD and/or VC using both the unlagged and lagged exposure measures: duration, average intensity or cumulative exposure to CD or VC; time since first CD or VC exposure; and duration of CD exposure or time since first CD exposure in presence or absence of VC exposure. We observed elevated and statistically significantly elevated RRs for some analysis subgroups, but these were due to inordinately low death rates in the baseline categories. With the possible exception of all cancer mortality in plant G, our additional adjustment of RRs for pay type revealed no evidence of positive confounding by smoking. We conclude that exposures to CD or VC at the levels encountered in the four study sites do not elevate mortality risks from all cancers, RSC or liver cancer. This conclusion is corroborated by our analysis of general mortality patterns among the CD cohort reported in our companion paper [G. Marsh, A. Youk, J. Buchanich, M. Cunningham, N. Esmen, T. Hall, M. Phillips, Mortality patterns among industrial workers exposed to chloroprene and other substances. I. General mortality patterns, Chem.-Biol. Interact., submitted for publication].     

Increased lymphocyte sister chromatid exchange frequency in workers with exposure to low level of ethylene dichloride

The genotoxicity of low-level exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) in humans is not clear. We used lymphocyte sister chromatid exchange (SCE) frequency as a parameter to investigate the genotoxicity of low level EDC and VCM in VCM-manufacturing workers. The SCE frequency was determined for 51 male workers with exposure to VCM and/or EDC and for 20 male workers devoid of such exposure. Epidemiological data were obtained by questionnaire, and included history of smoking, drinking, and any medication taken, as well as a detailed occupational history. Personal- and area-sampling and analysis were conducted in order to calculate the time-weighted average (TWA) contaminant-exposure level corresponding to different job categories. Moderate EDC exposure around 1 ppm corresponded to a significantly greater SCE frequency than was the case for the low EDC exposure group (p<0.01). However, VCM exposure of similar level was not associated with increased SCE. We conclude that EDC may cause genotoxicity at a relatively low level of exposure.     

Chemical process based reconstruction of exposures for an epidemiological study. I. Theoretical and methodological issues

In the occupational hygiene component of occupational epidemiological studies the goal is to assign group average exposure levels that can be used to compute individual cumulative exposures. This task requires the availability of sufficient amounts of proper individual exposure level data. Typically, the required data are either sparse, completely lacking or happenstance data collected for purposes not suitable for the aims of the study. In the epidemiological study of mortality patterns among industrial workers exposed to chloroprene and other substances, we developed and used a process analysis and modeling based exposure reconstruction to augment, extrapolate, or interpolate the available exposure data. The models developed utilize equations based on the engineering principles and chemistry associated with the processes as determined from the process documentation and task performance habits as determined from interviews of knowledgeable personnel. The resulting equations are tractable and provide a general basis for calculating exposure levels for vapors. The validation of the results with available exposure measurements suggests that comprehensive process analysis and modeling may be used to reconstruct exposures or to evaluate exposure potential with scientifically defensible methods. Furthermore, even in the absence of validating data, the methodology developed has potentially very useful applications in predicting exposure levels to newly synthesized substances. Properly interpreted, the limitations of modeling can be minimized to obtain scientifically reasonable results.     

Vinyl chloride mutagenesis in Drosophila melanogaster.

In inhalation experiments, Drosophila males were exposed to vinyl chloride at concentrations of 200, 850, 10,000 30,000 or 50,000 ppm for 2 days, and to 30 or 850 ppm for 17 days. VCM was mutagenic in the recessive-lethal test both after short-term and long-term exposures. The lowest effective concentration (LEC) was 850 ppm after 2 day exposure, and this value could be lowered to 30 ppm by prolonging the exposure time to 17 days. With the concentration levels tested, the mutation frequency increased with concentrations and reached a plateau at 10,000 ppm. This indicates a substrate saturation effect. In contrast with the recessive lethal assay, negative results were obtained when tests on dominant lethals, translocations, entire and partial sex-chromosome loss were carried out with VCM at 30,000 ppm for 2 days. This finding of a false negative seems a logical consequence of the observed saturation effect, and strengthens the concept that there exist two effective concentrations for point mutations vs the induction of chromosome breakage events. Vinyl chloride monomer provides another example to support our view that chromosome breakage is not a reliable measure of mutagenic activity.     

Inter-rater agreement of assessed prenatal maternal occupational exposures to lead

BACKGROUND: Industrial hygienists' assessments of prenatal occupational exposures based on parental job histories is a promising approach for population-based case-control studies of birth defects and other perinatal outcomes. However, evaluations of inter-rater agreement of such assessments have been limited. METHODS: We examined inter-rater agreement of occupational lead exposure assessments of maternal job reports by industrial hygienists in a population-based case-control study of parental occupational lead exposure and low birth weight. A total of 178 jobs with potential exposure to lead during the 6 months before pregnancy to the end of pregnancy were examined. Three industrial hygienists evaluated these jobs independently for exposure to lead including probability of exposure, type of exposure, route of entry, exposure frequency, duration, and intensity. Inter-rater agreement of these assessments beyond chance was evaluated using the kappa statistic (kappa). RESULTS: In general, inter-rater agreement was greater for assessment of direct exposures than assessment of indirect exposures. However, inter-rater agreement varied with the lead exposure metric under consideration, being: 1) fair to good for type of direct exposure (i.e., inorganic or organic), respiratory exposure and frequency of exposure to direct inorganic lead, hours per day of direct (i.e., inorganic or organic), and intensity of direct inorganic exposure; 2) poor for probability and type of indirect exposure (inorganic or organic); and 3) indeterminate for frequency of direct organic exposure, frequency of indirect exposures (organic or inorganic), and intensity of direct exposures (organic or inorganic). CONCLUSION: Retrospective assessment of maternal prenatal exposures to lead by industrial hygienists can provide some reliable metrics of exposure for studies of perinatal outcomes. Reliability studies of such exposure assessments may be useful for: quantifying the reliability of derived exposure metrics; identifying exposure metrics for exposure-outcome analyses; and determining the reliability of prenatal occupational exposures to other agents of interest.     

Sensitivity of Drosophila melanogaster to low concentrations of gaseous mutagens. II. Chronic exposures.

Sex-linked recessive lethal mutations were induced in Drosophila melanogaster males by gaseous 1,2-dibromoethane at concentrations ranging from 0.2 to 2 parts per million. Significant numbers of mutations could be induced at all these concentrations. Pronounced germ-cell sensitivity differences were observed. For low exposures, spermatids and spermatocytes were about 10--20 times more sensitive than spermatozoa. The dose-effect relation was linear below 60 ppm . h for the 3 cell types. At higher exposures, sterility prevented mutation detection in spermatocytes and in spermatogonia. The lowest effective exposure for spermatozoa was 18 ppm . h (0.25 ppm for 72 h). In spermatids, the lowest exposure tested, 2.3 ppm . h (0.2 ppm for 11 h) induced 4 times the spontaneous mutation rate. Therefore, using prolonged exposure periods one may be able to detect concentrations in the range of parts per billion. Thus, Drosophila appears suitable as a system for detecting very low concentrations of gaseous mutagens in industrial, agricultural and environmental atmospheres.     

Predicting the carboxyhemoglobin levels resulting from carbon monoxide exposures.

Data from a series of human exposures to carbon monoxide (CO) were analyzed to determine the fit to the theoretical Coburn-Forster-Kane (CFK) equation which describes CO absorption and excretion. The equation was found to predict carboxyhemoglobin (HbCO) saturations for both men and women at exercise rates ranging from sedentary to 300 kpm/min when they were exposed to steady CO concentrations of 50, 100, and 200 ppm for 0.33-5.25 h. Methods for determining values of each of the variables in the CFK equation were collected and a rational, efficient procedure for solving the equation by trial and error was outlined. The CFK equation was then used to prepare a graph, relating HbCO saturation to exposure duration and concentration, and also to describe the effect of several variables on the rate of CO uptake and equilibrium HbCO levels, important considerations in the determination of permissible public, occupational, and experimental exposure to CO.     

Facteurs de risques environnementaux et/ou professionnels du cancer du testicule

Despite a low overall incidence (1% of all malignant neoplasms), testicular cancer is the most common malignancy among young men. Over the last 40 years, this incidence rate has substantially risen in most industrialised countries. However, the aetiology of testicular cancer remains largely unknown. Only cryptorchidism, and to a lesser extent a family history of testicular cancer, may be considered to be well established risk factors. Numerous attempts have been made to assess the potential role of occupational exposures in adult life as a risk factor for TC, but no clear hypotheses have yet emerged from previous studies in this field. A major limitation of all occupational studies is that no single toxic substance has been clearly identified, and consequently the significant association observed between some job titles and risk of testicular cancer must be interpreted very carefully. In this respect, comparative occupational studies of exposed and non-exposed workers including rigorous and valid job-matrix exposure assessment are needed to study potential relationships between certain occupational exposures and testicular cancer.     

8 Hydroxydeoxyguanosine as a biomarker of workplace exposures

To date, the 8-hydroxydeoxyguanosine (8OHdG) DNA adduct has been used as a biomarker in 11 occupational health studies examining the potential for ten different workplace exposures to cause oxidative DNA damage. Exposures examined include asbestos, azo-dyes, benzene, chromium, coal dust, glassworks, rubber manufacturing, styrene, toluene and environmental tobacco smoke (ETS). Experimental designs that applied 8OHdG as biomarker varied dramatically among the studies. For example, one study detected increased urinary excretion in retired workers with a history of exposure to mining dusts, while a study of workers exposed to benzene showed that the pattern of urinary excretion of 8OHdG varied over a 24h period following exposure. All but one study reported increased 8OHdG relative to controls, but in three cases the increases were not statistically significant. Only one study demonstrated a dose-response relationship between a chemical exposure (benzene) in the workplace and elevated 8OHdG. In most cases, exposure data were lacking and the elevated 8OHdG could only be considered to be associated with a generalized job category. Numerous animal and human studies have demonstrated an effect of tobacco smoke on 8OHdG, including a study of ETS in the workplace. In the majority of occupational studies, however, smoking was found not to be a confounding variable. 8OHdG levels tended to be higher in women than men as did the response to an occupational exposure and/or smoking. Two of three studies that stratified workers by age found it to be a confounder for the 8OHdG adduct, but the relationship between age and 8OHdG was non-linear. Only one study considered the impact of dietary supplements on 8OHdG levels in workers despite the fact that diet can have a marked effect on an individual's response to oxidative stress. It is premature to consider 8OHdG as biomarker that can be used for decision making or for regulatory purposes. Nonetheless, these studies demonstrate that with additional characterization of the role 8OHdG plays in the exposure-disease continuum it may well serve as a powerful biomonitoring toolin the future.     

Future directions in butadiene risk assessment and the role of cross-species internal dosimetry

The 2005 International Symposium on the evaluation of butadiene and chloroprene health risks provided the opportunity to consider the past, present and future state of research issues for 1,3-butadiene. Considerable advancements have been made in our knowledge of exposure, metabolism, biomarkers of exposure and effect, and epidemiology. Despite this, uncertainties remain which will impact the human health risk assessment for current worker and environmental exposures. This paper reviews key aspects of recent studies and the role that biomarkers of internal dosimetry can play in addressing low to high exposure, gender, and cross-species differences in butadiene toxicity and metabolism. Considerable information is now available on the detection and quantification of protein adducts formed from the mono-, di- and dihydroxy-epoxide metabolites of butadiene. The diepoxide metabolite appears to play a key role in mutagenesis. Species differences in production of this critical metabolite are reflected by the diepoxybutane-specific hemoglobin adduct, pry-Val. To date, the pry-Val adduct has not been quantifiable in human blood samples from workers with cumulative occupational exposures up to 6.3 ppm-weeks; whereas, the pry-Val was quantifiable in the blood of mice and rats with similar cumulative exposures. Levels in mice were much higher than in rats. Further improvements in analytical sensitivity for the pyr-Val adduct are on the horizon. Epidemiology studies are also described and ongoing efforts promise to help bridge our understanding of past and future risks.     

Development and Validation of a Job Exposure Matrix for Physical Risk Factors in Low Back Pain

Objectives

The aim was to construct and validate a gender-specific job exposure matrix (JEM) for physical exposures to be used in epidemiological studies of low back pain (LBP).

Materials and Methods

We utilized two large Finnish population surveys, one to construct the JEM and another to test matrix validity. The exposure axis of the matrix included exposures relevant to LBP (heavy physical work, heavy lifting, awkward trunk posture and whole body vibration) and exposures that increase the biomechanical load on the low back (arm elevation) or those that in combination with other known risk factors could be related to LBP (kneeling or squatting). Job titles with similar work tasks and exposures were grouped. Exposure information was based on face-to-face interviews. Validity of the matrix was explored by comparing the JEM (group-based) binary measures with individual-based measures. The predictive validity of the matrix against LBP was evaluated by comparing the associations of the group-based (JEM) exposures with those of individual-based exposures.

Results

The matrix includes 348 job titles, representing 81% of all Finnish job titles in the early 2000s. The specificity of the constructed matrix was good, especially in women. The validity measured with kappa-statistic ranged from good to poor, being fair for most exposures. In men, all group-based (JEM) exposures were statistically significantly associated with one-month prevalence of LBP. In women, four out of six group-based exposures showed an association with LBP.

Conclusions

The gender-specific JEM for physical exposures showed relatively high specificity without compromising sensitivity. The matrix can therefore be considered as a valid instrument for exposure assessment in large-scale epidemiological studies, when more precise but more labour-intensive methods are not feasible. Although the matrix was based on Finnish data we foresee that it could be applicable, with some modifications, in other countries with a similar level of technology.     

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.     

DNA damage in lymphocytes of benzene exposed workers correlates with trans,trans-muconic acids and breath benzene levels

Benzene causes many kinds of blood disorders in workers employed in many different environments. These diseases include myelodisplastic syndrome and acute and chronic myelocytic leukemia. In the present study, five occupational work places, including six industrial process types, namely, printing, shoe-making, methylene di-aniline (MDA), nitrobenzene, carbomer, and benzene production were selected, and the levels of breath benzene, and trans,trans-muconic acids (t,t-MA) and phenol in urine were evaluated, as well as hematological changes and lymphocyte DNA damage. The concentration of benzene in breath was less than 3 ppm in the workplaces, and benzene exposure was found to be higher in work places where benzene is used, than in those where benzene is produced. At low levels of benzene exposure, urinary t,t-MA correlated strongly with benzene in air. Highest Olive tail moments were found in workers producing carbomer. Levels of breathzone benzene were found to be strongly correlated with Olive tail moment values in the lymphocytes of workers, but not with hematological data in the six workplaces types. In conclusion, the highest benzene exposures found occurred in workers at a company, which utilized benzene in the production of carbomer. In terms of low levels of exposure to benzene, urinary t,t-MA and DNA damage exhibited a strong correlation with breath benzene, but not with hematological data. We conclude that breath benzene, t,t-MA and lymphocytic DNA damage are satisfactory biomonitoring markers with respect to benzene exposure in the workplace.     

Mortality patterns among industrial workers exposed to chloroprene and other substances. I. General mortality patterns

We conducted an historical cohort study to investigate the mortality experience of industrial workers potentially exposed to chloroprene (CD) and other substances, including vinyl chloride (VC), with emphasis on cancer mortality, including respiratory system (RSC) and liver. In 1999, the International Agency for Research on Cancer (IARC) classified CD as a possible carcinogen (Group 2B); VC was classified in 1987 as a known human carcinogen (Group 1). Subjects were 12,430 workers ever employed at one of two U.S. industrial sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)), with earliest CD production dates ranging from 1942 (L) to 1969 (P). Two sites (L and M) synthesized CD with the acetylene process that produced VC exposures. We determined vital status through 2000 for 95% of subjects and cause of death for 95% of the deaths. Historical exposures for individual workers were estimated quantitatively for CD and VC. Workers ever exposed to CD ranged from 92.3% (M) to 100% (G); to VC from 5.5% (M) to 22.7% (L). We computed standardized mortality ratios (SMRs) (using national and regional standard populations) in relation to selected demographic, work history and exposure factors. We used worker pay type (white or blue collar) as a rough surrogate for lifetime smoking history. For the combined cohort, SMRs (95% CIs) for all causes combined, all cancers combined, RSC and liver cancer were, respectively, 0.72 (0.69-0.74), 0.73 (0.68-0.78), 0.75 (0.67-0.84) and 0.72 (0.43-1.13). Site-specific (L, M, P and G, respectively) SMRs were: for all cancers combined: 0.75 (0.69-0.80), 0.68 (0.56-0.80), 0.68 (0.47-0.95) and 0.59 (0.36-0.91); for RSC: 0.75 (0.66-0.85), 0.79 (0.58-1.05), 0.62 (0.32-1.09) and 0.85 (0.41-1.56); for liver cancer: 0.90 (0.53-1.44) (17 deaths), 0.24 (0.01-1.34) (1 death), 0.0 (0-2.39) (no deaths) and 0.56 (0.01-3.12) (1 death). Among all workers ever exposed to CD, SMRs were: for all cancers combined: 0.71 (0.66-0.76); for RSC: 0.75 (0.67-0.84); for liver cancer: 0.71 (0.42-1.14). We also observed no increased mortality risks among cohort subgroups defined by race, gender, worker pay type, worker service type (short/long term), time period, year of hire, age at hire, duration of employment, the time since first employment, and CD or VC exposure status (never/ever exposed). In summary, our study has many strengths and is the most definitive study of the human carcinogenic potential of exposure to CD conducted to date. We conclude that persons exposed to chloroprene or vinyl chloride at the levels encountered in the four study sites did not have elevated risks of mortality from any of the causes of death examined, including all cancers combined and lung and liver cancer, the cancer sites of a priori interest. This conclusion is corroborated by our detailed analyses of mortality in relation to qualitative and quantitative exposures to CD and VC at each of the four study sites, reported in our companion paper (Marsh et al., submitted for publication).     

Exposure of midwives to nitrous oxide in four hospitals.

The exposure of midwives to nitrous oxide in four hospitals was measured with personal samplers. In three of the four hospitals the average exposure was not significantly less than 100 parts per million (ppm). In one hospital the average exposure was 360 ppm; this was reduced by a factor of about 2.5 when a trial scavenging system was used. Differences in working practices and in the layout, size, and ventilation of the labour suites contributed to the observed differences in average exposure. Midwives and other staff working in the labour room are potentially at risk from excessive occupational exposure to nitrous oxide.     

Maternal occupational exposure to ionizing radiation and birth defects

So far, only a few studies investigated occupational exposure to ionizing radiation in pregnancy to cause birth defects (BDs). No association between BDs and ionizing radiation, although described for high-dose exposure, could ever be confirmed for employees, or specific job titles. Here, an explorative analysis of a prospective population-based birth cohort used to quantify the prevalence of BDs in infants between 1/2007 and 2/2008 is presented. An active examination of all livebirths by specially trained paediatricians in two defined areas was performed. Additionally, a study-specific questionnaire distributed among all becoming mothers in the surveyed regions included questions on maternal occupational exposure to ionizing radiation within the first trimester of pregnancy. In 3,816 births (including 165 infants with BDs; 4.3%), maternal answers concerning possible exposures to medical and occupational ionizing radiation were available. Relative risk (RR) estimates in mothers surveyed for occupational exposure to ionizing radiation (wearing a radiation dosimeter) and BDs in the offspring were calculated exploratively. A higher prevalence of infants with BDs (n = 4; 13.8%) was documented in newborns of the 29 surveyed mothers compared to that in 3,787 births from unexposed mothers (n = 161; 4.3%), corresponding to a RR of 3.2 (1.2–8.7). Excluding deformations, the RR increased to 4.0 (1.5–10.7). Adjustment for possible confounders did not change the results substantially.     

Biomonitoring of human genotoxicity induced by complex occupational exposures

Sensitivity, specificity and correlations among several biomarkers for monitoring occupational exposure to complex mixtures of genotoxic agents were assessed in occupational environments in Hungarian study populations. The studies have been focused on DNA adduct formation, urinary metabolites, mutations and micronuclei induced by exposures to complex organic mixtures. In two Hungarian aluminium plants, increased DNA adduct and 1-hydroxypyrene (1-OH-PY) levels were observed in workers as compared to controls. However, no association between the biomarker levels was evident on an individual basis. In Hungarian garage mechanics, DNA adduct determinations did not show increased genotoxic exposure as compared to the controls. However, ambient air measurements, significantly enhanced 1-OH-PY levels, and slightly enhanced frequency of micronuclei indicated increased polycyclic aromatic hydrocarbon (PAH) exposure in the garages, as compared to the general environment. In a Hungarian vulcanizing plant, DNA adduct determinations and 1-OH-PY did not show significantly elevated exposure levels as compared to controls. The glycophorin A (GPA) somatic mutation assay was also negative for this occupational exposure. The results support previous observations of a lack of correlation between DNA adducts detectable by 32P-postlabelling and those measured by the PAH-DNA immunoassay in the same DNA sample. These studies also demonstrate a lack of close correlation between levels of DNA adducts and urinary 1-OH-PY in the same individual.     

Case-control study of hydrocarbon exposures in patients with renal cell carcinoma.

A retrospective case-control study tested the hypothesis that exposure to hydrocarbon combustion products is associated with the development of renal cell carcinoma. One control per case, matched for sex, date of birth (within 5 years) and urologist, was chosen. Controls were patients who presented with hematuria and were shown not to have a urinary tract tumour. A total of 164 cases and 161 controls responded to mailed questionnaires and telephone interviews. Smoking more than 20 cigarettes per day was associated with the presence of metastatic renal cell carcinoma (p less than 0.001). Exposure to burning coal was associated with an increased relative risk of the disease but only when the exposure occurred between the ages of 10 and 24 years (p less than 0.05). Dose-response relations were demonstrated for intensity of exposure (p less than 0.025) and duration of occupational exposure (p less than 0.05). The distribution of latent periods from first exposure to diagnosis was bimodal, with one mode at 21 to 30 years and another at 41 to 50 years. Occupational exposure to tar or pitch or both was also associated with an increased relative risk of renal cell carcinoma (p less than 0.05).