The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily.

Abstract This was an open case-control study of the possible association between parental occupational and domestic exposures to potential endocrine disrupting chemicals (EDC) assessed by questionnaire and cryptorchidism and hypospadias in their offspring in the agricultural area of Ragusa. Cases of infants born between 1998 and 2002 with either of these two malformations (n=90), and controls (n=203), were recruited through the paediatric services (for cases) and a random sample of healthy infants attending the same services born in the same period of time (for controls). Data on occupational and environmental exposures of parents prior to and during the index case (or control), were collected through interviews with both parents. Concerning occupational exposures, we did not find a statistically significant increase in risk among parents directly involved in agricultural work. We did find a non-statistically significant increase in risk for cryptorchidism in mothers employed in agriculture [adjusted odds ratios (OR) 2.97; 95% confidence interval (CI) 0.77-11.47] and with probable exposure to pesticides (adjusted OR 2.74; 95% CI 0.72-10.42). Fathers who had indirect contact with agricultural products (transport and retail) had an increased risk (not statistically significant) for cryptorchidism (adjusted OR 2.45; 95% CI 0.63-9.59) and hypospadias and cryptorchidism combined (adjusted OR 2.24; 95% CI 0.67-7.48). Increases in risk of the two malformations pooled were also observed in relation to the mother's age below 25 (adjusted OR 1.99; 95% CI 0.97-4.09), to the presence of genital disease of the father (adjusted OR 2.41; 95%C I0.94-6.17), and the mother (adjusted OR 3.47;95% CI 1.34-8.99), to low birth weight of the infant (adjusted OR 4.49; 95% CI 1.23-16.31). Increased risk was also observed for mothers consuming alcohol during pregnancy (adjusted OR 3.09; 95% CI 0.98-9.66), and for couples who conceived while using condoms (adjusted OR 2.12; 95% CI 1.02-4.41). The study therefore provides only limited support to the hypothesis of a possible association between the risk of cryptorchidism and hypospadias and the occupational exposure to EDC and agricultural work.

Cryptorchidism and hypospadias in the Sicilian district of Ragusa and the use of pesticides.

The aim of the study was to explore the role of environmental exposures to pesticides in the birth prevalence of hypospadias and cryptorchidism, in the 12 agricultural municipalities of Ragusa Sicily. Data on the birth prevalence of the two birth defects were obtained from the local pediatric services for the period 1998-2002. Municipalities were ranked according to the degree of "pesticide impact" on the basis of three quantitative criteria of intensity of agricultural activities of the population. We found a significantly higher birth prevalence of hypospadias with increasing "pesticide impact" (trend test, P=0.003). The association with cryptorchidism was not statistically significant, but when the two birth defects were pooled together, the linear trend was significant (trend test, P=0.001).

Mortality in a cohort of pesticide applicators in an urban setting: sixty years of follow-up.

The study is a further follow-up of a cohort of 168 urban pesticide applicators of the municipality of Rome who were first employed in 1946. An earlier analysis of the mortality of this group concerned the deaths observed up to 1987, and showed a significant excess in mortality from liver cancer. In this report we present an updated follow up of the mortality of the cohort, which comprises the total of 85 deaths for the entire period of observation, corresponding to 5227 person/years. The living status of each member of the cohort was ascertained through the official records up to 2005. For the 85 deceased individuals, the primary cause of death was coded according to the 9th Revision of the ICD. Standardized mortality ratios (SMR) were calculated on the basis of the age, sex, and cause specific mortality rates prevailing during the same calendar years in the province of Rome. The SMR from all causes for the whole cohort was 103.8 (90 %CI 86 124). The SMR for all cancers was 106.0 ( 90 % CI 75-146). An increased risk was observed for the exposed for cancer of the gallbladder (SMR 723.8 90% CI 129-2279), of the liver (SMR 596.3, 90 % CI 204-1365) and for cancer of the nervous system (SMR 529.2, 90 % CI 144-1368). All increases were statistically significant, but no association was found between the increased risk of these cancers and the longer duration of exposure. The increase in risk of the three cancers mentioned above (liver, nervous system and gallbladder), was further increased, when the analysis was restricted to the workers exposed prior to the 1978 ban of DDT and products containing arsenic.

[Application of epidemiology to the protection of reproductive health]. / Applicazioni dell'epidemiologia per la tutela della salute riproduttiva.

The paper discusses the use of epidemiologic research for the prevention of occupational exposures focusing the hazards to the reproductive health of workers. For reproductive risks already documented in previous studies and in the available data, what is now needed is to identify better strategies to prevention rather than undertake further studies. Research is still needed however to identify risks previously not known and to investigate their mechanisms of action. This can be achieved by undertaking studies that measure with more accuracy the exposure of workers and examine the complex interaction of these exposures on the male and female endocrine system and on the fetus. One area of particular recent interest is that of the effects of the EDCs on human reproductive health, with results that confirm the interference of these chemicals on various reproductive outcomes in experimental animals and in humans. Other uses of epidemiologic research on human reproduction are related to establishing and updating the limits of environmental and occupational exposures and in providing reliable and unbiased information to workers and the public.

[Environmental/occupational exposure and testicular tumors: is there a relationship?]. / Esposizioni ambientali/occupazionali e tumore testicolare: esiste una relazione?

UNLABELLED: Although the incidence and mortality of testicular cancer are low (1), it is of interest because of its increasing incidence, its earlier onset and its geographical distribution. A part for cryptorchidism, the aetiology is unknown but previous studies have raised the hypothesis that exogenous hormones like endocrine disrupters may play a role in the development of testicular cancer. OBJECTIVE: The aim of this study is to identify possible risk factors of testicular cancer in relation to environmental and occupational exposure, of the subject himself and of his mother. In in particular the study attempts to evaluate exposure to endocrine disrupters during the critical period of the development of the testis. MATERIAL AND METHODS: This is an on going hospital case-control study conducted, at least, in six Romain hospital. Cases were recruited from hospital discharge records from 1995 to 2002. Controls were selected randomly form the orthopaedics' division. We are therefore collecting data with personal interviews from patients and their mother. Subjects are interviewed by phone (cases) or face-to-face (controls). We are interviewing also the mothers to received information on pregnancy. Estimate odds ratio (OR) and 95% confidence interval will be calculated, using a statistical software program specific for case-control studies. CONCLUSIONS: The study will contribute to clarify if the hypothesis that exposure to endocrine disrupters may be involved in the development of testicular cancer.

[Is it possible to use sex ratio at birth as indicator of the presence of endocrine disrupters in environmental pollution?]. / E possibile utilizzare il sex ratio alla nascita come indicatore di presenza di endocrine disrupters in contaminazioni ambientali?

The sex ratio at birth (male births/total births) seems to be influenced by both biological and environmental factors. Endocrine Disrupters such as dioxin, DBCP and other pesticides have been studied as possible determinants of the decline in the sex ratio observed in some western countries. High serum concentration of dioxin in about two hundred fathers exposed during the well-known Seveso accident (1976), have been found associated with a significant decline in male births. The present study examines the possible variation of the sex ratio at birth in the offspring of the entire populations residing in the municipalities around the site of the Seveso accident. We observed a reduction of male births in the eight years following the accident (1977-1984) in the two municipalities with the highest level of contamination (Meda and Seveso). This effect was no longer detectable in the subsequent decades. No reduction in the sex ratio was observed when all considered municipalities are grouped in three exposure categories, according to their distance from the centre of the contaminated area. It is concluded that variations of the sex ratio may be detected only in populations with high exposure to dioxin, but this effect is concealed when the analysis of the sex ratio is based on large populations, with lower levels of exposure.

[Study of reproductive health risks in Sicily. Congenital malformations and exposure to EDCs: a case-control study (study methodology)]. / Indagine siciliana sui rischi per la salute riproduttiva. Malformazioni congenite ed esposizione ad EDCs: uno studio caso-controllo (metodologia di studio).

INTRODUCTION: The incidence of Congenital Malformations may represent an early biological indicator for human toxicity to environmental and occupational contaminants. SCIENTIFIC OBJECTIVE: We are in the process of exploring the relation between various potential sources of parental periconceptional pregnancy exposures to Endocrine Disrupting Chemicals (EDCs) and selected Congenital Malformations in offspring. MATERIALS AND METHODS: The low incidence of Congenital Malformations leads to an epidemiological "Case-Control" study. The areas of the study are the Ragusa Municipalities and the south-east Siracusa Municipalities. We are conducting personal interviews with parents of about 100 cases with orafacial clefts or male genital malformations and 200 nonmalformed controls. The infants for the study were selected from those born during 1998-2002 in these areas. The more important variables considered are: 1--parental occupation and workplace exposures. 2--relevant confounders and recall bias. The analysis of the data will use the classical approach of case-control study (matching procedure), comparing risk factor frequency between cases and controls. CONCLUSIONS: The results of the study will allow to clarify the relationship between parental exposure to EDCs compounds and human reproduction.

Occupational exposures to metals, solvents and pesticides: recent evidence on male reproductive effects and biological markers.

This review is based primarily on the recent epidemiological studies conducted in occupational settings in order to explore the relationship between exposures to chemical agents and the possible effects on male reproductive function. The paper examines evidence of the effects of metals, solvents, pesticides and dioxin. The effects considered are primarily the possible alterations of sperm quality and reduction of fertility. Many studies have identified small groups of workers with exposures to these agents, presenting some alteration in the spermatological or fertility profile, but the results are difficult to replicate in other settings with different individuals and different levels of exposure. From examination of the concentrations of environmental and occupational pollutants in the blood and in the seminal fluid of exposed individuals, it appears that, in general, the concentrations are much lower in the seminal fluid and in sperm cells, making this a less useful marker of exposure.

Reduction in fertility in male greenhouse workers exposed to pesticides.

The paper examines the possible interference of pesticide exposure on male fertility, by studying the time to pregnancy (TTP) in the first pregnancy of 127 greenhouse workers and 173 controls. The TTP of exposed and control population, analysed by logistic regression model, has shown an increase in the risk of conception delay among the greenhouse workers with high exposure (OR:2.4; 95% CI: 1.2-5.1).

[Occupational exposure and male fertility. Results of an Italian multicenter study in an exposed population]. / Esposizioni occupazionali e fertilità maschile. Risultati di uno studio italiano multicentrico tra popolazioni esposte.

It was believed that occupational exposure to several toxic agents could negatively affect male fertility. This paper reports the results of a study on the fertility of couples in whom the man was occupationally exposed to three different toxics: metals, solvents and pesticides, having effects on reproduction. Fertility was evaluated during the time that elapsed between attempting and achieving the first pregnancy of the couple (time to pregnancy--TTP). Exposure to occupational risks during the period preceding conception was defined on the basis of data collected from 153 workers of a mint (exposed to metal and solvents), 322 agricultural workers licensed to handle pesticides and 127 greenhouse workers. Comparing the groups exposed during the conception period with comparable non-exposed groups, we found a slight delay in conception among couples with male exposure to metals (OR = 1.3; 95% CI 0.5-3.6), to solvents (OR = 1.7; 95% CI 0.6-4.6) and to pesticides among greenhouse workers (OR = 1.6; 95% CI 0.8-3.1 for the moderately exposed and OR = 2.4; 95% CI 1.2-5.1 for the heavily exposed). No increase in the risk of conception delay was observed in agricultural workers with generic exposure to pesticides. The results of this study suggest that the workers exposed to metals and solvents and greenhouse workers exposed to pesticides experienced a delay in conception at the time of their wives' first pregnancy.

Reproductive male-mediated risk: spontaneous abortion among wives of pesticide applicators.

This study was conducted among 32 pesticide applicators occupationally exposed to pesticides to determine whether paternal exposure is associated with an increased risk of spontaneous abortion. The ratio of abortion was compared between applicators and a group of 51 food retailers (control population). The ratio of abortions/pregnancies for applicators was 0.27 and for retailers 0.07. OR for spontaneous abortion adjusted for age of wife and smoking of parents is 3.8 times greater than for the control population in the multiple logistic regression model and 7.6 times with interaction effects model.

Fertility of male workers of the italian mint.

Fertility among workers exposed to metal fumes and solvents in the Italian mint (stampers, founders, and other technical workers) was compared to the reproductive experience of the administrative staff. Data on the reproductive history and time to pregnancy were collected by interview. For workers with children, data on the time to pregnancy (TTP) for the first pregnancy was assessed in relation to occupational risk factors. The groups with the highest prevalence of pregnancy delay beyond 6 months were stampers (21%) and those exposed to solvents (21.5%). Logistic regression did not show a significant association of these job exposures with pregnancy delay, but the power of the study to show an important difference was low. The data are not inconsistent with the hypothesis that male exposure to solvents and metal fumes is associated with an increase in the TTP.

[Exposure to pesticides in greenhouses and male fertility]. / Esposizione a pesticidi in serra e fertilità maschile.

We attempt to study fertility problems among workers exposed to pesticides, comparing the reproductive experience of greenhouse workers and administrative staff working in the Health Local Units of the same geographical area (reference population). Data on reproductive history and time to pregnancy (TTP) at first pregnancy were collected by personal interview. For workers with children, we collected data on TTP in relation to the occupational risk factors. The analysis of TTP was conducted among 127 greenhouse and 173 administrative workers married and aged 20-55. The greenhouse workers reported 232 pregnancies and a mean number of 1.8 children; the controls 270 and 1.6 respectively. For greenhouse workers the mean TTP in months (5.4 with SD 5.6) resulted longer than for controls (3.9 with SD 5.6). The risk for conception delay (beyond 3 months) by exposure category of the man adjusted for age of woman, smoking of man and woman at first pregnancy resulted 2.4 higher for a subgroup of greenhouse workers with higher exposition (CI 95% 1.2-5.1).

Work stress and menstrual patterns among American and Italian nurses.

OBJECTIVES: This study assessed whether job stress alters menstrual patterns among nurses working in 2 different settings: a tertiary care hospital in New York (99 nurses) and a university hospital in Rome (25 nurses). METHODS: Data on menstrual patterns were collected by a daily diary in which the nurses recorded their basal body temperature (BBT) and their menstrual bleeding status for a 3-month period. The BBT curves were used to classify cycles as biphasic or monophasic, and as adequate or inadequate with respect to the luteal phase. Job stress was evaluated by both objective (environmental and work characteristics) and subjective (perceived stress) criteria. RESULTS: The American nurses, especially those assigned to high stress units, had an increased risk for long and monophasic cycles [relative risk (RR) 4.3, 95% confidence interval (95% CI) 1.1-16.2 and RR 5.5, 95% CI 1.2-25.5, respectively]. Among those who perceived their stress at work to be high or reported strenuous work activity, the risk for longer cycles was also raised (RR 2.3, 95% CI 0.6-8.0 and RR 1.6, 95% CI 0.7-4.2, respectively). Luteal phase inadequacy followed the same pattern. Similar trends were observed in the Italian data. In addition, the rotating shiftwork pattern prevalent in the Italian group was possibly associated with higher rates of short cycles and inadequate luteal phases when compared with those of nurses working fixed shifts either day or night. CONCLUSIONS: Menstrual function may be affected by stressful work conditions.

[Limits of exposure in the prevention of damage of reproduction: an operational proposal]. / Limiti di esposizione per la prevenzione di danni alla riproduzione: una proposta operativa.

Recent studies have shown that the reproductive system may be particularly vulnerable to some environmental agents. This requires the definition of specific exposure limits to safeguard the reproductive health of both males and females and, not only of pregnant women. The paper presents such limits of exposure for a number of reproductive toxicants. These were defined on the basis of experimental and epidemiological evidence, taking into consideration the precautionary principle.

Time to pregnancy and occupation in a group of Italian women.

BACKGROUND: It is estimated that 10-15% of all couples have experienced an infertility problem. The objective of this study was to evaluate the effect of occupation on the time interval between when a couple starts unprotected intercourse and a clinically recognizable pregnancy time to pregnancy (TTP). METHODS: Data from 622 women who successfully delivered in the week preceding the interview were analysed using the Cox proportional hazards regression. Thirty independent variables were included in the full model. RESULTS: Eleven per cent of women had to wait more than one year before conceiving (mean TTP = 6.7 months). The regression analysis showed that the most important determinants of TTP are the age of the woman (rate ratio = 0.44 for age 35+) and her parity (rate ratio = 1.39). TTP also increased significantly with maternal smoking (rate ratio = 0.77), and decreased with coital frequency (rate ratio = 1.24 for > or = 6 per month) and consumption of coffee (rate ratio = 1.29). None of the female occupational exposures has been found to have an independent statistically significant effect, while male occupation in industry and exposure to welding fumes were associated with an increase of TTP (rate ratio = 0.73 and 0.78, respectively). CONCLUSIONS: Female occupational exposures seem to have only a small effect on TTP compared with biological and lifestyle factors. The present data also suggest that work-related factors may have a bigger influence on male fecundity.

Effects of prolonged autovehicle driving on male reproduction function: a study among taxi drivers.

This study had the purpose of exploring the possible association between the work exposures of professional drivers and their reproductive health, by studying a group of 201 taxi drivers in the city of Rome. Data on work and reproductive history were collected by interviews. Biological markers examined in 72 subjects included salivary testosterone levels, sperm quality (i.e., sperm concentration, sperm morphology, and motility), and fertility experience, including time to pregnancy. Their spermatologic profile was compared with that of a control group of 50 healthy subjects of similar age and smoking habits. The results showed that taxi drivers, compared to the controls, had a significantly lower prevalence of normal sperm forms (45.8% vs. 64.0%); this was particularly true for those with a longer time on this job. This result was confirmed by a multivariate analysis in which confounders such as age, smoking, and alcohol consumption were controlled. The other sperm parameters did not differ in the study and the control groups. Among the life-style factors, we found smoking to be associated with poorer sperm morphology. Moderate alcohol consumption was associated with a better seminologic profile, while the pattern in respect to coffee intake was inconclusive. Subjects with poor semen quality also more frequently exhibited longer time to pregnancy of their partner. The results suggest that prolonged urban automobile driving might be a risk factors for sperm quality, and particularly for sperm morphology, but the finding needs further confirmation.

Maternal mortality and the problem of accessibility to obstetric care; the strategy of maternity waiting homes.

One of the major causes of maternal mortality is the distance and consequent delay in treatment of childbirth complications. Some developing countries are attempting to reduce delays in treatment by moving women at risk into maternity waiting homes (MWHs), located near a hospital, a few days prior to the date of confinement. This paper illustrates some typical examples of MWHs in different countries. The approach of MWHs is appropriate in some settings but it requires a high degree of coordination between peripheral prenatal care services and second and third level health care facilities. This study discusses some of the issues related to the successful functioning of MWHs, and provides an analytical framework for the planning, management and evaluation of these facilities.