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J. P. Bonde1, M. Rosenkilde1, G. Toft1, A. M. Thulstrup1, J. Olsen2. 1Department of Occupational Medicine, Aarhus University Hospital; 2University of California Los Angeles (UCLA)
ObjectivesOnly a few occupational causes of miscarriage are known in spite of a large research effort in the past 20 years. True causative agents may escape recognition because of inadequate exposure assessment, limited study size and detection bias due to the fact that only a minority of conceptions survive to clinical detection. The objective of this study was to provide guidance for future research in the field by an overall assessment of risk for late miscarriage in the entire workforce.
MethodsWe analysed prospectively the collected data of 67226 employed women who were enrolled into the Danish National Birth Cohort (DNBC) from 1997 through 2003. Information on work during pregnancy was obtained by telephone interview around the 16th week of gestation. Job titles were classified according to the International Standard Classification of Occupations (ISCO‐88). Data on miscarriage were obtained by linkage to the National Hospital Register. Hazard ratios (HRs) of late miscarriage by occupation classified at the ISCO‐88 four‐digit level with 308 occupations were computed by proportional hazard regression taking a fixed set of covariates and time at risk into account. For each occupation the reference was all other occupations.
ResultsThe proportion of pregnant women who experienced a late fetal loss from the 16th week of gestation until and including the 28th week of gestation was 0.96%. Among the 125 occupations with at least one late miscarriage, we observed 15 occupations with increased HRs and two with decreased HRs at the 5% significance level. The corresponding figures at the 1% significance level were 5 and 0. None of the 10 most frequent occupations encompassing more than 1000 women including office workers, nurses, nurses aides, day‐care workers, teachers and shop assistants had increased risk of late fetal loss.
ConclusionOur analyses of late fetal loss indicate that the search for occupational and thus preventable risk factors for spontaneous abortion should not be discontinued, although the most common female occupations are not related to increased risk of miscarriage in present‐day working conditions
Key wordsmiscarriage; occupation; impact
M. M. Brouwers1, M. van Tongeren2, A. A. Hirst3, N. Roeleveld1. 1Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre; 2Institute of Occupational Medicine, Edinburgh; 3Centre for Occupational and Environmental Health, University of Manchester
ObjectivesEndocrine disruptors include a large variety of chemicals, with occupation being one of many sources of exposure. Endocrine disruptors are thought to play a role in various reproductive disorders, such as hypospadias and cryptorchidism, two common urogenital birth defects in boys. The aim was to construct a comprehensive job exposure matrix (JEM) for estimating occupational exposure to potential endocrine disrupting chemicals, to be used in a case‐referent study on risk factors for hypospadias and cryptorchidism and in other epidemiological investigations.
MethodsA similar JEM previously reported by Van Tongeren et al in 2002 served as the basis for the development of the new JEM. Chemicals with endocrine disrupting properties were identified from the literature and information was gathered about occupational settings in which exposure can occur. Based on this information and focusing on the past 10 years, three field experts scored the probability of exposure to endocrine disruptors for 353 job titles, which had three levels: “unlikely”, “possible” and “probable”. In the case‐referent study on hypospadias and cryptorchidism, all subjects have been assigned JEM exposure scores. Currently, the individual JEM scores are combined with self‐reported occupational exposures to obtain more accurate exposure estimates.
ResultsThe JEM counts 11 chemical groups, including pesticides, polychlorinated organic compounds, phthalates, alkylphenolic compounds, organic solvents, bisphenol A, brominated flame retardants, polyaromatic hydrocarbons (PAHs), other hydrocarbons, metals and miscellaneous chemicals. Additionally, most chemical groups were subdivided in two to six subgroups. In 96 of the 353 job titles in the JEM, exposure occurred to at least one of these chemical groups. Metals, particularly copper and lead, were most often linked to job titles in the JEM. Exposure to PAHs, alkylphenolic compounds, phthalates, organic solvents, and pesticides were frequently scored as well, while exposure to the other chemical groups occurred in very few job titles. Results from the exposure assessment in the study on hypospadias and cryptorchidism will also be presented.
ConclusionDespite its limitations, most importantly the inability to account for variability within occupations, this JEM is expected to enhance exposure assessment for occupational endocrine disruptors in studies with self‐reported data.
Key wordsjob exposure matrix; endocrine disruptors; exposure assessment
B. Mester, N. Schmeisser, W. Ahrens. Bremen Institute for Prevention Research and Social Medicine
ObjectivesWithin occupational medicine job evaluations, hazardous materials previously considered important have become less so, for example, because of changing engineering processes, while other materials, not least due to recent scientific research, have increasingly become the focus of attention. One example of substances receiving extra intention are the so‐called endocrine disruptors, chemical contaminants which interfere with human endocrine regulation. But knowledge of exposure to these substances in the occupational environment is scarce. In order to analyse the effects of endocrine disruptors in the context of epidemiological studies, suitable procedures for retrospective occupational exposure assessment and quantification are required.
MethodsWe worked out a multidimensional procedure for exposure assessment of endocrine disruptors and other workplace exposures in metalworking industries. Exposure assessment in this procedure consists of three core elements: an industry‐specific job exposure matrix (JEM), an industrial hygiene database and structured expert knowledge.
ResultsThe JEM has been developed by a newly constituted working group involving scientific, industrial and occupational association experts. The JEM contains exposure information for 20 working materials such as bisphenol A and specific phthalates in more than 200 industry‐specific working areas and job tasks. The working group also developed an industry‐specific questionnaire for taking the occupational history of employees in metalworking industries.
ConclusionWith our exposure assessment method individual exposure estimates are derived from industry‐specific and job‐specific questionnaires in a case‐control study nested in the metalworking industries using a standardised semiautomatic procedure.
Key wordsexposure assessment; industry‐specific JEM; endocrine disruptors
M. Möhner, J. Gellissen. Federal Institute for Occupational Safety and Health
ObjectivesMost occupational studies on the adverse health effects of ionising radiation are aligned with mortality, especially cancer mortality. Transgenerational effects of paternal exposure to ionising radiation have been seen in the workforce at the Sellafield nuclear reprocessing plant. The aim of the present study is to investigate if parental exposure to ionising radiation in uranium mines is associated with a higher stillbirth risk among offspring.
MethodsThe medical records of the former workforce of the closed uranium mines are stored in a health data archive operated by BAuA. This archive includes the birth registry of a hospital in the centre of the uranium mining area from 1952 onwards. Until 1958, when the exposure level was significantly reduced, a total of 4766 births were registered, including 137 stillbirths. To each stillbirth two singleton live births have been matched by date of birth and sex. For each subject, marital status, mother's age, current parental occupation (data about fathers were available only if the mother was married) and birth order were ascertained.
ResultsAbout a quarter of mothers (both in cases and in controls) had a job at the uranium mining company. Thirty‐two mothers have been classified as occupationally exposed to ionising radiation (nine in cases and 23 in controls), yielding an odds ratio of OR 0.77, 95% CI 0.36 to 1.70. Unmarried mothers had a slightly lower risk in comparison to married mothers (OR 0.66, 95% CI 0.36 to 1.18). Stillbirth risk was significantly increased with mother's age and with birth order. Taking into account only married mothers, the dataset is reduced to 113 cases and 188 controls. A paternal exposure to ionising radiation was recorded for 58.5% of cases and 57.0% of controls. The percentage of fathers classified as highly exposed was 32.7% in cases and 31.4% in controls, yielding an odds ratio of OR 1.09, 95% 0.61 to 1.96.
ConclusionThe study confirms that maternal age and birth order are important risk factors for the risk of stillbirth. Compared with this, an excess risk due to parental exposure to ionising radiation in uranium mines could not be detected.
Key wordsionising radiation; stillbirth risk; case‐control study
M. Sallmén1, J. A. Hoppin2, D. P. Sandler2, A. Blair3, D. D. Baird2. 1Finnish Institute of Occupational Health, Helsinki; 2National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC; 3National Cancer Institute, NIH, Bethesda, MD
ObjectivesPesticides are an extensively used group of potentially toxic chemicals. The effects of pesticides on female fertility are inconclusive. We investigated the impact of female pesticide exposure on infertility using data from the Agricultural Health Study (AHS), a cohort of licensed pesticide applicators and their spouses.
MethodsEnrolment in the AHS occurred between 1993 and 1997, and 75% of eligible couples participated. Questionnaire information on pesticide use history was used to assess female and male exposure to pesticides. We limited the analysis to couples (wife less than 40 years of age) with an attempt at pregnancy in the last 4 years (n=2111). Infertility was defined as failure to conceive after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred. Infertility odds ratios (OR) for female exposure to pesticides were calculated with logistic regression, with adjustment for male pesticide exposure and other potential confounders.
ResultsMore than 60% of the wives were exposed to pesticides, and 30 specific pesticides were used by at least five infertile subjects. Fertility was not associated with use of home or lawn pesticides, or with use of only the five most commonly used and widely available pesticides (glyphosate, carbaryl, malathion, 2,4‐D and diazinon). However, exposure to one or two (n=206; OR 1.5; 95% CI 1.1 to 2.2) or three or more other agricultural pesticides (n=118; OR 1.9; 95% CI 1.2 to 3.0) was associated with infertility. Further analyses among the 324 women who mixed or applied less common agricultural pesticides demonstrated significantly elevated risks for use of permethrin (OR 2.6; 95% CI 1.4 to 4.8), lindane (OR 4.4; 95% CI 1.2 to 16) and trichlorfon (OR 7.7; 95% CI 1.0 to 58). Odds ratios were greater than 2.0 but not statistically significant for chlordane and EPTC.
ConclusionMixing or applying agricultural pesticides may impair female fertility. The findings for many individual pesticides were based on small numbers of exposed women and it was not possible to ascertain timing of exposure relative to pregnancy attempt times. Nonetheless, these suggestive results are consistent with prior studies suggesting a role for organochlorine and pyrethroid pesticides in infertility.
Key wordsfemale exposure; infertility; pesticides
G. Toft1, L. Rylander2, A. Giwercman2, M. Spanó3, G. C. Manicardi4, D. Bizzaro5, J. K. Ludwicki6, V. Zvyezday7, E. C. Bonefeld‐Jorgensen8, H. S. Pedersen9, J. P. Bonde10. 1Department of Occupational Medicine, Aarhus University Hospital; 2Lund University; 3ENEA, Rome; 4University of Modena; 5Univerity of Ancona; 6National Institute of Hygiene; 7Kharkiv State Medical University; 8Aarhus University; 9The Primary Health Care Clinic, Nuuk; 10Aarhus University Hospital
ObjectivesTo study fertility within and between populations with large contrasts in blood concentrations of endocrine disrupting environmental pollutants.
MethodsCouple fertility and biomarkers of male reproductive function were investigated in Greenland, Sweden, Poland and Ukraine. Time‐to‐pregnancy interviews were obtained in 2269 women and blood samples in 1992 women and 1172 men, and a subset of 798 men provided a semen sample. Serum concentrations of 2,2′,4,4′,5,5′‐hexachlorobiphenyl (CB‐153) and 1,1‐dichloro‐2,2‐bis (p‐chlorophenyl)‐ethylene (DDE) were measured in both genders. Xenobiotic activation of the estrogen (ER), androgen (AR) and aryl hydrocarbon (AhR) receptors was measured by CALUX assays in a subset of 362 men.
ResultsThe median serum concentrations of CB‐153 and DDE in the four regions spanned more than one order of magnitude while regional differences in xenobiotic CALUX activities were less. Male and female serum concentrations of POPs were related to reduced fertility among Inuit couples, while DDE and CALUX activities were not related to fertility in any region. Effects on sperm count, morphology and seminal markers of apoptosis were not observed, but progressive sperm motility decreased with increasing CB‐153 serum concentrations in all regions and rather strong PCB related effects on sperm chromatin integrity were seen among Caucasian but not Inuit men. Several associations between POP blood levels and male reproductive hormones, Y/X sperm chromosome ratio and biochemical markers of accessory gland function were seen but findings were not consistent across regions.
ConclusionPOPs may interfere with male reproductive function without major impact on fertility or sperm counts in European populations. PCBs seem more to blame than DDT.
Key wordsendocrine disrupter; fertility; organochlorine