Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

There is conflicting research regarding an association between fetal death and paternal exposure to Agent Orange, a phenoxy herbicide widely used in Vietnam that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Men who worked in the U.S. factories that produced Agent Orange were exposed to TCDD at levels hundreds of times higher than TCDD levels in the general population. Wives of TCDD-exposed chemical workers and wives of nonexposed neighborhood referents were interviewed to determine reproductive history. Paternal serum TCDD level at time of conception was estimated for each pregnancy using serum samples taken in 1987. Estimated TCDD levels of workers during or after exposure were high (median, 254 ppt; range, 3-16,340 ppt) compared to referent levels (median, 6 ppt; range, 2-19 ppt). No association between paternal TCDD level at the time of conception and spontaneous abortion was observed among pregnancies fathered by workers with TCDD levels of < 20 ppt [odds ratio (OR) = 0.77; 95% confidence interval (CI), 0.48-1.22], 20 to < 255 ppt (OR = 0.81; 95% CI, 0.40-1.63), 255 to < 1,120, (OR = 0.69; 95% CI, 0.30-1.58), and >or= 1,120 ppt (OR = 0.95; 95% CI, 0.42-2.17) compared to pregnancies fathered by referents. The sex ratio [males/(males + females)] of offspring also did not differ by TCDD exposure (0.53 and 0.54 among workers and referents, respectively). We did not find an association between paternal serum TCDD level and spontaneous abortion or sex ratio of offspring in this population. The estimated TCDD levels in this exposed worker population were much higher than in other studies, providing additional evidence that paternal TCDD exposure does not increase the risk of spontaneous abortion at levels above those observed in the general population. The study could not evaluate the effect of father's childhood or prenatal TCDD exposure on subsequent sex ratio.     

Obstructive Pulmonary Function Impairment among Korean Male Workers Exposed to Organic Solvents,Iron Oxide Dust,and Welding Fumes

We evaluated spirometric obstructive pulmonary function impairment among workers who were occupationally exposed to organic solvents, iron oxide dust, or welding fumes. Data were collected from records of periodic health examinations of workers. In total, 448 Korean male workers were enrolled and classified into three exposure groups: exposure to organic solvents, iron oxide dust, or welding fumes. Logistic regression analysis was performed to evaluate the association between occupational exposure and pulmonary function. Compared to exposure to organic solvents, exposure to iron oxide dust was significantly associated with obstructive pulmonary function impairment (odds ratio [OR], 9.61; 95% confidence interval [CI], 2.20–41.97). The group exposed to welding fumes did not show a significantly higher OR compare to those exposed to organic solvents (OR, 2.83; 95% CI, 0.74–10.8). These results suggest that exposure to iron oxide dust has a greater association with obstructive pulmonary function impairment than exposure to organic solvents or welding fumes.     

Exposure to organic solvents and adverse pregnancy outcome

In a large case-control study (n = 1,926) of spontaneous abortion (SAB), exposure to solvents was ascertained by a telephone interview that asked about occupational use of 18 specific solvents or products, as well as an open-ended "other" solvent category. The adjusted odds ratio for use of any solvent was 1.1 (0.8, 1.5). Solvents for which at least a doubled crude risk of SAB was found included perchlorethylene (OR = 4.7, 95% CI = 1.1, 21.1), trichloroethylene (OR = 3.1, CI = 0.9, 10.4), and paint thinners (OR = 2.3, CI = 1.0, 5.1). Comparing exposure greater than 10 hours per week versus less did not show consistent dose-response effects. By solvent class, an association was seen with aliphatic solvents (adjusted OR = 1.8, 95% CI = 1.1, 3.0), but there was no dose-response effect by hours of use. Household use of solvent-containing products was generally not strongly associated with SAB, nor did it appear to confound the association seen with occupational use. From this and other studies, occupational exposure to at least some solvents appears associated with SAB. The associations of solvent exposure and fetal growth among liveborn offspring of controls was also examined.     

低浓度芳香烃溶剂暴露对自然流产影响的基因多态性研究

目的 探讨女工芳香烃溶剂暴露和细胞色素P450氧化酶MSP1基因和谷胱甘肽S转移酶GSTM1基因的多态性对自然流产的影响。方法 采用回顾性流行病学调查方法。使用统一调查表，由经过培训的调查员在北京燕山地区调查了276个女工，其中有自然流产史者58人，无自然流产史者218人。结果 单因素分析发现；GSTM1缺失基因型可致女工自然流产的危险度显著增加[OR=2.07(95%CI:1.15-3.71)]，但未观察到MSP1基因及芳香烃溶剂暴露对女工自然流产的影响，采用多元Logistic回归模型。经文化程度，年龄，倒班，体重指数，被动吸烟，职业紧张混杂因素调整后，可见GSTM1缺失基因型能显著致女工自然流产危险度增加[OR=2.15(95%CI;1.17-3.98)]。以GSTM1存在基因型和MSP1野生基因型为参照组。采用多元Logistic回归模型。并将文化程度，年龄，倒班，体重指数，被动吸烟，职业紧张混杂因素放入回归模型进行调整，在调整混杂因素前后，与参照组比较，均可见MSP1杂合子/突变基因型合并GSTM1缺失基因型使女工自然流失基因型与MSP1突变纯合子/杂合子基因型之间对自然流产的影响存在相加的联合作用。     

Risk of spontaneous abortion among women exposed to polybrominated biphenyls

Accidental contamination of livestock in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. At the time of enrollment, serum was collected and analyzed for PBBs and polychlorinated biphenyls (PCBs). In 1997, women aged 18 years or older and active in the registry were invited to participate in a telephone interview about their health. Using generalized estimating equations to account for correlated outcomes within the same woman, we assessed the risk of spontaneous abortion among 529 women with 1344 potentially exposed pregnancies. PBB and PCB exposure were not associated with risk of spontaneous abortion after adjusting for maternal age at conception, age at menarche, and prior infertility. Compared to pregnancies with PBB exposure below the limit of detection, those with levels above 2.9 ppb had a non-significant reduced odds of spontaneous abortion (adjusted OR=0.73; 95% CI=0.47-1.13). Compared to pregnancies with PCB exposure below the limit of detection, those with levels above 6.5 ppb had little difference in risk (adjusted OR=0.91; 95% CI=0.59-1.41). Maternal age at conception above 34 years was significantly associated with elevated risk of spontaneous abortion (OR=2.46; 95% CI=1.10-5.49). The effect of prior infertility was of borderline significance (OR=1.52; 95% CI=0.98-2.38). Older age at menarche was associated with decreased risk of spontaneous abortion (adjusted OR=0.58; 95% CI: 0.38-0.89, comparing menarche at 12-13 with menarche <12). Our results do not support an association between exposure to PBBs or PCBs and risk of spontaneous abortion.     

Occupational paternal exposure to benzene and risk of spontaneous abortion.

OBJECTIVE--The purpose of this study was to evaluate the risk of spontaneous abortion among the wives of male workers occupationally exposed to benzene. METHODS--The wives of 823 men working in two chemical plants at the time of the study were asked to complete a questionnaire describing their pregnancies. The analysis of the 1739 pregnancies that ended in a spontaneous abortion or a birth is presented. The firms' payroll records provided all workers' employment history, including dates. Benzene exposure, graded at two levels (< 5, > or = 5 ppm), was determined for every job, so that benzene exposure for each worker's entire professional life (at these companies) could be assessed. This information was linked to the dates of the pregnancies reported in the questionnaires to enable the exposure status of each pregnancy to be defined (1270 non-exposed and 274 exposed). The frequency of spontaneous abortion, defined as the number of spontaneous abortions divided by the total of spontaneous abortions and births was evaluated. RESULTS--When adjusted for tobacco consumption, mother's age and pregnancy order, the odds ratio of the association between paternal exposure to approximately 5 ppm of benzene and the risk of spontaneous abortion was close to and statistically not different from unity (OR = 1.1; 95% CI (0.7-1.8). CONCLUSION--In this study paternal exposure to benzene did not increase the risk of spontaneous abortion.     

Evidence for adverse reproductive outcomes among women microelectronic assembly workers.

Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents.     

Evidence for adverse reproductive outcomes among women microelectronic assembly workers

Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents.     

Reduced fertility among female wood workers exposed to formaldehyde.

BACKGROUND: The aim of the study was to investigate whether exposure to formaldehyde, organic solvents or other chemicals in the wood-processing industry affects the fertility of women. METHODS: For this purpose, a retrospective study on time to pregnancy was conducted among female wood workers who had given birth during 1985-1995. Data on pregnancy history, time to pregnancy, occupational exposures, and potential confounders were collected by a questionnaire; 64% (699/1,094) participated. The exposure assessment was conducted by an occupational hygienist. The data on time to pregnancy were analyzed with the discrete proportional hazards regression. RESULTS: Exposure to formaldehyde was significantly associated with delayed conception: adjusted fecundability density ratio, FDR, was 0.64 (95% CI 0.43-0.92). At high exposure if no gloves were used, the FDR was 0.51 (% CI 0.28-0.92). Exposure to phenols, dusts, wood dusts, or organic solvents was not related to the time to pregnancy. Additionally, an association was observed between exposure to formaldehyde and an increased risk of spontaneous abortion (concerning previous spontaneous abortions, reported by the women). Associations between exposure to formaldehyde or to organic solvents and endometriosis, and between exposure to organic solvents or to dusts and salpingo-oophoritis were also suggested. CONCLUSIONS: The study suggests that a woman's occupational exposure to formaldehyde has an adverse effect on fertility.     

Spontaneous abortions and birth defects related to tap and bottled water use, San Jose, California, 1980-1985.

We recently studied pregnancies occurring during 1980-1985 in four study areas in Santa Clara County, California. Two of the areas were exposed to solvent-contaminated drinking water during 1980 and 1981, and two were unexposed. There was an overall excess of spontaneous abortions among women who reported any tapwater consumption during the first trimester of pregnancy compared with those who reported no tapwater consumption [odds ratio (OR) = 4.0; 95% confidence interval (CI) = 1.8-9.1)], regardless of exposure to the contaminated water. The odds ratio for spontaneous abortion for women reporting any vs no tapwater was 6.9 (95% CI = 2.7-17.7) after adjustment for numerous potential confounders using multiple logistic regression analyses. The elevated odds ratio of spontaneous abortion was seen among tapwater drinkers who used no filters or softener-type filters but not among women who reported use of active filters. Spontaneous abortion rates were reduced in women who reported any vs no bottled water consumption (OR = 0.26; 95% CI = 0.16-0.43). Among women who reported no tapwater consumption, no birth defects occurred among 263 live births; in comparison, among women who reported tapwater consumption, 4% of 908 live births had defects (P = 0.0001). We observed no relation between birth defects and bottled water use.     

Spontaneous abortions among women working in the pharmaceutical industry.

A register based study was conducted on the pregnancy outcome of female workers in eight Finnish pharmaceutical factories to determine whether they had a higher risk of spontaneous abortion than the general population or matched controls. Information about all female workers who had been employed in the factories during the years 1973 or 1975 (four factories) to 1980 was obtained from the employers. The workers' pregnancy data were collected from the nation wide hospital discharge register and polyclinic data of hospitals from 1973 to 1981. The total number of 1795 pregnancies included 1179 deliveries, 142 spontaneous abortions, and 474 induced abortions. The spontaneous abortion rate (the number of spontaneous abortions X 100, divided by the number of spontaneous abortions plus the number of births) during employment was 10.9% and before/after employment 10.6%. The rate for all the women in the corresponding central hospital districts was 11.3% [corrected] during the study period. A case-control study was also carried out in which the cases were 44 women who had a spontaneous abortion during employment in the pharmaceutical factory. Three age matched female pharmaceutical factory workers who had given birth to a child were chosen as controls for every case. The information about occupational exposures was collected from questionnaires completed by the occupational physician or nurse at the factory. The response rate was 93%. Exposure to chemicals was more common among the cases than among the controls. For methylene chloride, a solvent commonly used in the pharmaceutical industry, the increase in odds ratio of borderline significance (odds ratio 2.3, p = 0.06). In a logistic regression model (which included oestrogen exposure, solvent exposure frequency of the usage, and heavy lifting) the odds ratio was increased for oestrogens (odds ratio 4.2, p = 0.05) and for continuous heavy lifting (odds ratio 5.7, p = 0.02). The odds ratio for spontaneous abortions was greater among those exposed to four or more solvents (odds ratio 3.5, p=0.05) than among those exposed to one to three solvents (odds ration 0.8, p=0.74).     

Spontaneous abortions among women working in the pharmaceutical industry

A register based study was conducted on the pregnancy outcome of female workers in eight Finnish pharmaceutical factories to determine whether they had a higher risk of spontaneous abortion than the general population or matched controls. Information about all female workers who had been employed in the factories during the years 1973 or 1975 (four factories) to 1980 was obtained from the employers. The workers' pregnancy data were collected from the nation wide hospital discharge register and polyclinic data of hospitals from 1973 to 1981. The total number of 1795 pregnancies included 1179 deliveries, 142 spontaneous abortions, and 474 induced abortions. The spontaneous abortion rate (the number of spontaneous abortions X 100, divided by the number of spontaneous abortions plus the number of births) during employment was 10.9% and before/after employment 10.6%. The rate for all the women in the corresponding central hospital districts was 11.3% [corrected] during the study period. A case-control study was also carried out in which the cases were 44 women who had a spontaneous abortion during employment in the pharmaceutical factory. Three age matched female pharmaceutical factory workers who had given birth to a child were chosen as controls for every case. The information about occupational exposures was collected from questionnaires completed by the occupational physician or nurse at the factory. The response rate was 93%. Exposure to chemicals was more common among the cases than among the controls. For methylene chloride, a solvent commonly used in the pharmaceutical industry, the increase in odds ratio of borderline significance (odds ratio 2.3, p = 0.06). In a logistic regression model (which included oestrogen exposure, solvent exposure frequency of the usage, and heavy lifting) the odds ratio was increased for oestrogens (odds ratio 4.2, p = 0.05) and for continuous heavy lifting (odds ratio 5.7, p = 0.02). The odds ratio for spontaneous abortions was greater among those exposed to four or more solvents (odds ratio 3.5, p=0.05) than among those exposed to one to three solvents (odds ration 0.8, p=0.74).     

Occupational exposure to solvents and the risk of lymphomas

BACKGROUND: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy. METHODS: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. RESULTS: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1-2.8), xylene 1.7 (1.0-2.6), and benzene 1.6 (1.0-2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1-4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2-6.5) and aliphatic solvents (2.7; 1.2-5.7). CONCLUSION: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.     

Pregnancy outcome following maternal organic solvent exposure: A meta-analysis of epidemiologic studies

Background Evidence of fetal damage or demise from occupational organic solvent levels that are not toxic to the pregnant woman is inconsistent in the medical literature. The risk for major malformations and spontaneous abortion from maternal inhalation of organic solvent exposure during pregnancy was summarized using meta-analysis. Methods Medline, Toxline, and Dissertation Abstracts databases were searched to locate all research papers published in any language from 1966 to 1994. Included were studies that were case-control or cohort in design and indicated first trimester (or up to 20 weeks gestation for spontaneous abortion) maternal solvent exposure. A summary odds ratio (ORs) with 95% confidence intervals (CI) was calculated from research results combined by the Mantel-Haenszel method. Results In total, 559 studies were obtained from the literature search. Five studies for each outcome of interest qualified for inclusion in the analysis. The ORs for major malformations from five studies (n = 7,036 patients) was 1.64 (CI 1.16–2.30) and for spontaneous abortion from five studies (n = 2,899 patients) was 1.25 (CI 0.99–1.58). Conclusions Maternal occupational exposure to organic solvents is associated with a tendency toward an increased risk for spontaneous abortion and additional studies may affect the trend. There is a statistically significant association with major malformations which warrants further investigation. Am. J. Ind. Med. 34:288–292, 1998. © 1998 Wiley-Liss, Inc.     

Occupational exposures and non-Hodgkin's lymphoma in Southern Sweden

In a case-control study based on 859 consecutive non-Hodgkin's lymphoma (NHL) cases identified through a tumor registry between 1990 and 1998, the authors collected demographic, occupational, exposure, and education information. Exposures were identified through self-report, reported occupational history, and the use of a job-exposure matrix. Conditional logistic regression analyses of the 859 cases and 1,310 controls showed increased risks in workers exposed to gasoline (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.04, 2.05), aliphatic or alicyclic hydrocarbons (OR 1.75; CI 1.03, 2.99), aromatic hydrocarbons (OR 1.45; (CI 1.13, 1.86), and solvents for mole than five years (OR 1.59: CI 1.11, 2.28), as well as automobile mechanics (OR 1.82; CI 1.18, 2.81) and painters (OR 1.77; CI 1.13, 2.76). Exposures to pesticides and farming were not associated with increased risk. Prior radiotherapy was associated with increased risk (OR 2.84; (CI 1.85, 4.37). Concordance between analyses based on self-reported exposures, occupations, and the job-exposure matrix supported the links between organic solvents and prior radiotherapy and NHL but did not support associations between farming or pesticides and NHL.     

Gender differences in risk of renal cell carcinoma and occupational exposures to chlorinated aliphatic hydrocarbons.

BACKGROUND: Organic solvents have been associated with renal cell cancer; however, the risk by gender and type of solvents is nuclear. METHODS: We evaluated the risk of renal cell carcinoma among men and women exposed to all organic solvents-combined, all chlorinated aliphatic hydrocarbons (CAHC)-combined, and nine individual CAHC using a priori job exposure matrices developed by NCI in a population-based case-control study in Minnesota, U.S. We interviewed 438 renal cell cancer cases (273 men and 165 women) and 687 controls (462 men and 225 women). RESULTS: Overall, 34% of male cases and 21% of female cases were exposed to organic solvents in general. The risk of renal cell carcinoma was significantly elevated among women exposed to all organic solvents combined (OR = 2.3; 95% CI = 1.3-4.2), to CAHC combined (OR = 2.1; 95% CI = 1.1-3.9), and to trichloroethylene (TCE) (OR = 2.0; 95% CI = 1.0-4.0). Among men, no significant excess risk was observed among men exposed to any of these nine individual CAHCs, all CAHCs-combined, or all organic solvents-combined. DISCUSSION: These observed gender differences in risk of renal cell carcinoma in relation to exposure to organic solvents may be explained by chance based on small numbers, or by the differences in body fat content, metabolic activity, the rate of elimination of xenobiotics from the body, or by differences in the level of exposure between men and women, even though they have the same job title.     

The use of electric bed heaters and the risk of clinically recognized spontaneous abortion

We conducted a prospective cohort study to evaluate the relation of spontaneous abortion and electric bed heater use during the first trimester of pregnancy. Compared with non-users, rates of spontaneous abortion were lower for women who used electric bed heaters. The adjusted odds ratio and 95% confidence interval (CI) for the two major devices used, electric blankets (N = 524) and waterbeds (N = 796), were, respectively, 0.8 (95% CI = 0.5-1.1) and 0.9 (95% CI = 0.7-1.2). An increase of risk with increasing intensity (setting-duration combination) of use was not observed. Users of electric blankets at low settings for most of the night (N = 171) had lower risks of spontaneous abortion than non-users (adjusted odds ratio = 0.5; 95% CI = 0.3-1.0). Twenty women who used electric blankets at a high setting for 1 hour or less had an adjusted odds ratio of 3.0 (95% CI = 1.1-8.3), but we found no spontaneous abortions among the few women (N = 13) who used a high setting for 2 or more hours. We found that exposure rankings of the magnetic field time-weighted average and a rate of change metric did not correspond monotonically to the pattern of spontaneous abortion risks and that electric blankets contribute less to overnight time-weighted average magnetic fields than has been thought.     

Risk of non-Hodgkin's lymphoma among men occupationally exposed to organic solvents

An occupational history of exposure to organic solvents, defined as daily occupational exposure for at least one year, was more common among 167 men with newly diagnosed non-Hodgkin's lymphoma than among 130 healthy referents from the general population (38 versus 14%). Categorization in five-year age groups gave 3.3 as a Mantel-Haenszel estimate of the odds ratio (95% CI 1.9-5.8). The odds ratio was 6.5 (95% CI 3.2-13.3) for localized supradiaphragmatic tumors and 2.3 (95% CI 1.3-4.3) for other lymphoma presentations. In a logistic model including age and organic solvent, phenoxy acid, and chlorophenol exposure, it could be shown that solvent exposure was an independent risk factor and that no important interaction occurred between the risk factors. With increasing duration of exposure there was a significantly increased risk of lymphoma, a finding implying a dose-response relationship. There was no significant difference in tumor histology between the exposed and unexposed patients. These findings support the concept that occupational exposure to organic solvents is a risk factor for non-Hodgkin's lymphoma. The results also confirm a strong association between such exposure and an initial supradiaphragmatic location of the lymphomas.