Reduced fertility among shoe manufacturing workers.

OBJECTIVES: To investigate whether fertility is reduced among female shoe manufacturing workers exposed to organic solvents. METHODS: A retrospective study was conducted on time to pregnancy (TTP) among 250 Portuguese shoe manufacturing workers exposed to solvents and 250 unexposed women working in stores of food units and storehouses. Data on TTP and related factors were collected by face-to-face interviews. The participation rate was 92%, and 81% of the workers (197 exposed women and 209 unexposed women) provided data for the analyses. Exposure assessment was based on hygienic measurements in the workplaces. TTP data were analysed with discrete proportional hazards regression. RESULTS: Female exposure to solvents was associated with reduced fertility (adjusted fecundability density ratio (FDR) 0.55, CI 0.40 to 0.74 for low exposure, and FDR 0.70, CI 0.52 to 0.94 for high exposure). The findings were robust in different sensitivity analyses. A slightly stronger association was found among women with regular menstrual cycles. Exposure for less than 6 years was more strongly associated with reduced fertility (FDR 0.50, CI 0.30 to 0.83 and FDR 0.50, CI 0.28 to 0.90 for low and high exposure, respectively) than at least 6 years of exposure (FDR 0.60, CI 0.39 to 0.92 and FDR 0.86, CI 0.57 to 1.29 for low and high exposure, respectively). There was an interaction between solvent exposure and female smoking or use of coffee, the exposed women who smoke or use coffee being highly fecund. CONCLUSIONS: The findings provide further evidence that exposure to organic solvents is hazardous for female reproduction. The observed association may be related to any of the following solvents commonly used in shoe manufacturing: n-hexane and hexane isomers, toluene, methyl ethyl ketone, acetone, ethyl acetate and dichloromethane.

Fertility and exposure to solvents among families in the Agricultural Health Study.

BACKGROUND: Several studies have reported associations between solvent exposure and reduced female fertility, but the evidence is inconclusive for male fertility. OBJECTIVES: To investigate the impact of solvent exposure on subfertility among families of male licensed pesticide applicators in the Agricultural Health Study cohort. METHODS: The couples enrolled between 1993 and 1997. Cross-sectional questionnaire information on work tasks was used to assess exposure to solvents. The data were limited to couples (wife aged less than 40 years) with an attempt at pregnancy in the last four years (n = 2112). RESULTS: Twenty eight per cent of the couples were defined as subfertile (not conceiving a pregnancy after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred). Adjusted subfertility odds ratios (OR) for exposure to solvents were calculated with logistic regression. Female (OR 1.42, 95% CI 1.15 to 1.75) and male exposure to solvents (OR 1.21 (95% CI 0.93 to 1.57) for monthly exposure and 1.40 (95% CI 0.97 to 2.03) for daily or weekly exposure) were associated with subfertility. In farming, spouses may share or exchange jobs. To account for potential dual exposure, variables for parental exposure (either parent exposed or both parents exposed) were also defined. Both were strongly associated with subfertility (OR 1.62 (95% CI 1.20 to 2.17) and OR 2.10 (95% CI 1.22 to 3.60), respectively). CONCLUSIONS: Solvents may impair fertility of either gender, though the evidence for female effects is stronger than for male effects.

Time To Pregnancy and occupational lead exposure.

BACKGROUND: Lead exposure is known to be harmful to the male reproductive system, including impairment of fertility. However, it is unclear whether currently existing low levels of exposure have this effect. AIMS: To study retrospectively current workers in lead using industries (battery manufacture, smelting, etc), and in non-lead using control industries, in four European countries, with Time To Pregnancy as the outcome variable, as part of the EU funded Asclepios Project. METHODS: Exposure assessment was mainly by blood lead values, which were available from the late 1970s, supplemented by imputed values where necessary. Three exposure models were studied: (1) short term (recent) exposure; (2) total duration of work in a lead using industry; and (3) cumulative exposure. A Cox proportional hazards model with discrete ties was used for the statistical analysis, with covariates for both partners. RESULTS: A total of 1104 subjects took part, of whom 638 were occupationally exposed to lead at the relevant time. Blood lead levels were mainly less than 50 microg/dl. No consistent association of Time To Pregnancy with lead exposure was found in any of the exposure models, although reduced fertility was observed in one category each in models (2) and (3). CONCLUSIONS: This basically negative result is unlikely to be due to the misclassification of key variables, to insufficient statistical power, or to bias, for example, response bias. If any impairment of male reproductive function exists at the levels of occupational lead exposure now current, it does not appear to reduce biological fertility.

Exposure to lead and male fertility.

Lead is a reproductive toxicant. Exposure to inorganic lead is detrimental to human semen quality. The studies of the risk of spontaneous abortion and congenital malformation have shown contradictory findings. The aim of the following review is to summarise the epidemiological evidence of the effects of inorganic lead on male fertility. The focus is on epidemiological studies of time-to-pregnancy and related fertility measures. Blood lead measurements were applied to exposure assessment in all the studies. The results of the studies on fertility rates are consistent in showing an association between lead and reduced fertility. Also, there seems to be a tendency towards stronger association at older age with increasing duration of exposure. The independent roles of exposure duration and effect modification by age may have been difficult to distinguish. There is a paucity of studies on time taken to conceive. The studies conducted only weakly suggest that male exposure to lead is associated with delayed conception. The findings of time-to-pregnancy and fertility rate studies contradict. The possible reasons for this discrepancy is discussed briefly. There are a number of mechanisms by which exposure to lead may reduce male fertility. On the basis of animal studies, alterations in sperm chromatin stabilitv or epigenetic effects may be the most probable mechanisms involved at low exposure level.

Time to pregnancy among the wives of men occupationally exposed to lead.

We conducted a retrospective study on time to pregnancy among the wives of men biologically monitored for lead to assess whether paternal occupational exposure to inorganic lead is associated with decreased fertility. After three mailings, 554 (72.2%) wives of the monitored men participated. The final study population consisted of 502 couples who did not use contraception at the beginning of the pregnancy. We assessed lead exposure from blood lead measurements and from questionnaires completed by the men. We calculated the relative fecundability density ratios with discrete proportional hazards regression. The fecundability density ratios, adjusted for potential confounders, were 0.92 [95% confidence interval (95% CI) = 0.73-1.16], 0.89 (95% CI = 0.66-1.20), 0.58 (95% CI = 0.33-0.96), and 0.83 (95% CI = 0.50-1.32) for blood lead categories 0.5-0.9, 1.0-1.4, 1.5-1.8, and > or =1.9 micromol/L, respectively, as compared with <0.5 micromol/L. The findings provide limited support for the hypothesis that paternal exposure to lead is associated with decreased fertility.

Paternal exposure to lead and infertility.

To assess whether paternal exposure to lead is associated with infertility, we performed a register-based study among married men biologically monitored for exposure to inorganic lead. We obtained information about the marriages and the wives of the men from the Finnish Central Population Register. Data on pregnancies were obtained from medical records. Paternal exposure to lead was assessed on the basis of blood lead measurements. We estimated the risk of infertility, defined as nonoccurrence of a marital pregnancy, by applying binomial regression. For the blood lead categories of 0.5-0.9, 1.0-1.4, 1.5-1.9, 2.0-2.4, and > or =2.5 micromol/L the relative risk of infertility, compared with the risk in the lowest exposure category (<0.5 micromol/L), was 1.27 (95% confidence interval 1.08-1.51), 1.35 (1.12-1.63), 1.37 (1.08-1.72), 1.50 (1.08-2.02), and 1.90 (1.30-2.59), respectively. The findings support the hypothesis that paternal exposure to lead increases the risk of infertility at low occupational exposure levels. We applied proportional hazards regression to the analysis of pregnancy delay. A delay was observed among the wives of men exposed to lead. Exposure to lead was not clearly associated with delayed pregnancy, however, when the analysis was restricted to couples with at least one pregnancy. This finding suggests that the restriction of the study on time to pregnancy to fertile couples may introduce a bias toward no association.

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.

Cancer incidence among Finnish workers exposed to aromatic hydrocarbons.

OBJECTIVES: To assess whether occupational exposure to aromatic hydrocarbons increases carcinogenic risk. METHODS: We followed cancer incidence among 3,922 male and 1,379 female workers monitored for exposure to styrene, toluene, or xylene. The follow-up after the first personal measurement comprised 66,500 person-years at risk over the period 1973-1992. We computed the indirectly standardized incidence ratios (SIR) with 95% confidence interval (CI) with regard to age-, gender-, and period-specific incidence rates of cancer in the Finnish general population. RESULTS: The overall rate of cancer incidence for the total cohort was fairly similar to that of the general population. The risk for nervous system tumors was increased at 10 years after the first personal measurement (SIR 2.80, CI 1.03-6.08). For styrene there was an excess risk for rectal cancer (SIR 3.11, CI 1.14-6.77), and risks for pancreatic and nervous system tumors were increased nonsignificantly. For toluene and xylene, no clear increase in cancer risk was found. CONCLUSIONS: The data are not supportive of an overall increase in the cancer risk for these solvents, even though we cannot rule out site-specific associations with the rectum, pancreas, and nervous system. There is supporting evidence in the epidemiology literature for pancreatic cancer risk and heavy exposure to styrene. More studies are warranted on solvents, with detailed information on lifetime exposures and habits being collected whenever possible.

Time to pregnancy among the wives of men exposed to organic solvents.

OBJECTIVES: To assess whether paternal exposure to organic solvents is associated with decreased fertility. METHODS: A retrospective time to pregnancy study was conducted among men biologically monitored for organic solvents. The workers were classified into exposure categories on the basis of work description and the use of solvents as reported in the questionnaires, and on biological exposure measurements. The relative fecundability density ratios (FDR--an analogue of incidence density ratio of clinically recognised pregnancies) were calculated with discrete proportional hazards regression. RESULTS: After three mailings 316 (72.1%) wives of the monitored men participated. The final study population consisted of 282 couples who did not use contraception at the beginning of pregnancy. The FDRs, adjusted for potential confounders, were 0.80 (95% confidence interval (95% CI) 0.57 to 1.11) and 0.74 (95% CI 0.51 to 1.06) for high or frequent and low or intermediate exposure, respectively. High or frequent and low or intermediate exposure were related to decreased fecundability among primigravida (FDRs 0.36; 95% CI 0.19 to 0.66 and 0.53; 95% CI 0.27 to 1.04) but not among couples with at least one previous pregnancy (FDRs 0.96; 95% CI 0.62 to 1.49 and 0.77; 95% CI 0.47 to 1.24). CONCLUSIONS: The findings of the study provide limited support for the hypothesis that paternal exposure to organic solvents might be associated with decreased fertility. Further studies with careful design are warranted.

Effects of parental occupational exposure to lead and other metals on spontaneous abortion.

The aim of this article was to summarize the epidemiologic studies on the possible impact of parental occupational exposure to lead or other metals on spontaneous abortion. For paternal exposure, the total number of abortions in the studies with adequate exposure contrast were 340 for lead, 240 for mercury, and 90 for unspecified metals and, correspondingly, for maternal exposure, about 80 for lead, 80 for mercury, 70 for nickel, and 130 for exposure to unspecified metals. Epidemiologic studies indicate that paternal exposure to lead or mercury might be associated with the risk of spontaneous abortion. For maternal exposure, no clear conclusion could be reached. In particular, paternal occupational exposure levels to metals were substantial compared with population values. Even though there are shortcomings in the present knowledge, protective goals for paternal exposure to lead and mercury are warranted. More well-designed studies on metals are needed.

Time to pregnancy among women occupationally exposed to lead.

A retrospective time-to-pregnancy study was conducted among women biologically monitored for exposure to lead. The women were participants of a previous study on spontaneous abortion. They were classified into exposure categories on the basis of questionnaire information, and individual blood lead (B-Pb) measurements. The adjusted incidence density ratios (IDR) of clinically recognized pregnancies were .93 (95% confidence interval [CI] .56 to 1.57) for very low (B-Pb < .5 mumol/L), .84 (CI .48 to 1.45) for low (B-Pb .5 to .9 mumol/L), and .80 (CI 0.42 to 1.54) for higher (B-Pb > or = 1.0 mumol/L) exposure compared with no exposure, in the discrete proportional hazards analysis. Exposure to inorganic lead was not associated with fecundability at current, low-exposure levels. The suggestive finding among the eight most heavily exposed women (B-Pb 1.4 to 2.4 mumol/L, IDR .53; CI .19 to 1.52) should be confirmed or refuted in a larger study.

Cancer incidence among Finnish workers exposed to halogenated hydrocarbons.

Epidemiologic studies and long-term carcinogenicity studies in experimental animals suggest that some halogenated hydrocarbons are carcinogenic. To investigate whether exposure to trichloroethylene, tetrachloroethylene, or 1,1,1-trichloroethane increases carcinogenic risk, a cohort of 2050 male and 1924 female workers monitored for occupational exposure to these agents was followed up for cancer incidence in 1967 to 1992. The overall cancer incidence within the cohort was similar to that of the Finnish population. There was an excess of cancers of the cervix uteri and lymphohematopoietic tissues, however. Excess of pancreatic cancer and non-Hodgkin lymphoma was seen after 10 years from the first personal measurement. Among those exposed to trichloroethylene, the overall cancer incidence was increased for a follow-up period of more than 20 years. There was an excess of cancers of the stomach, liver, prostate, and lymphohematopoietic tissues combined. Workers exposed to 1,1,1-trichloroethane had increased risk of multiple myeloma and cancer of the nervous system. The study provides support to the hypothesis that trichloroethylene and other halogenated hydrocarbons are carcinogenic for the liver and lymphohematopoietic tissues, especially for non-Hodgkin lymphoma. The study also documents excess of cancers of the stomach, pancreas, cervix uteri, prostate, and the nervous system among workers exposed to solvents.

Reduced fertility among women exposed to organic solvents.

A retrospective time-to-pregnancy study was performed among women biologically monitored for exposure to organic solvents. The women were participants in a previous study on spontaneous abortion. They were classified into exposure categories on the basis of work description and the use of solvents as reported in the questionnaires and on biological exposure measurements. Daily or high solvent exposure, adjusted for potential confounders, was significantly associated with reduced fecundability in the discrete proportional hazards analysis (incidence density ratio of clinical pregnancies 0.41; 95% confidence interval [CI] 0.27-0.62). The incidence density ratios were decreased also among workers who were exposed to organic solvents in shoe factories (0.28; CI 0.11-0.71), dry cleaning shops (0.44; CI 0.22-0.86), and in the metal industry (0.58; CI 0.34-0.98). The possible effects of various biases are discussed. The results of the study support the hypothesis that daily or high exposure to organic solvents is associated with reduced fertility. There is a need for safer working methods in industries where organic solvents still are used.

Carcinogenic chemicals in the occupational environment.

A survey of occupational carcinogens by the Institute of Occupational Health, Finland shows that more than 100,000 workers are exposed to carcinogenic substances. The most common exposures are silica, wood dust, tobacco smoke and lead compounds. Based on biological monitoring of workers over the years it appears that overall lead exposure has decreased but exposure to styrene, trichloroethylene and tetrachloroethylene has decreased only slightly or remained constant. The biological monitoring data are based on samples sent by the workplaces on their initiative presenting no scientifically selected sampling. Thus due caution is needed in the interpretation of the trends.

Magnetic fields of video display terminals and spontaneous abortion.

The aim of this study was to examine whether work with a video display terminal and exposure to the magnetic fields of video display terminals are related to spontaneous abortion. The study was conducted among women employed as bank clerks and clerical workers in three companies in Finland. The cases (191 spontaneous abortions) and controls (394 births) were identified from Finnish medical registers for the years 1975-1985. Use of video display terminals was defined using the workers' own reports and information provided by the companies. The assessment of exposure to the magnetic fields was based on measurements of the fields of video display terminals. The odds ratio for spontaneous abortion for working with video display terminals was not increased (odds ratio = 1.1, 95% confidence interval 0.7-1.6). However, the odds ratio for workers who had used a video display terminal with a high level of extremely low frequency magnetic fields (> 0.9 microT) was 3.4 (95% confidence interval 1.4-8.6) compared with workers using a terminal with a low level of these magnetic fields (< 0.4 microT). Adjustment for ergonomic factors and mental work load factors changed the odds ratio for magnetic field exposure only very slightly. The findings suggest the need for future studies with assessment of exposure to the magnetic fields in the actual working environment to confirm the possible risk.

Paternal occupational lead exposure and congenital malformations.

STUDY OBJECTIVE: The aim was to investigate whether occupational exposure to lead in fathers is associated with congenital malformation in their children. DESIGN: The study was a retrospective case-control study, nested within the wives of men biologically monitored for inorganic lead. Information on pregnancy outcome was obtained from medical registers. SUBJECTS: Cases were defined as wives with malformed child during 1973-82. Three age matched controls were selected for each case from the wives who had given birth during 1973-1983. The final study population was 27 cases and 57 controls. MEASUREMENTS AND MAIN RESULTS: Paternal lead exposure was assessed with blood lead measurements and data obtained from a questionnaire. The response rate was 67% among the cases and 76% among the controls. The odds ratio (OR) of congenital malformation for paternal lead exposure was increased (OR 2.4, 95% confidence interval 0.9-6.5), although not reaching statistical significance. The odds ratios varied from 1.9 to 3.2, when adjusted for one potential confounding variable at a time. CONCLUSIONS: Because of the small numbers and low participation, this study offers limited support for the hypothesis that paternal lead exposure is associated with congenital malformation. Further epidemiological studies on the reproductive hazards of paternal lead exposure are needed.