Male fertility following occupational exposure to dichlorodiphenyltrichloroethane (DDT).

BACKGROUND: The inconsistent epidemiological results of the endocrine disrupting effects of DDT fuel a harsh debate on its global ban. OBJECTIVES: We tested the hypothesis that occupational exposure to dichloro-diphenyl-trichloroethane (DDT) causes impairment in male fertility in a cohort of DDT exposed workers, in Sardinia, Italy. METHODS: We accessed official records on date of marriage and date of birth of the first child to estimate time to pregnancy (TTP) in the spouses of 1223 workers employed in a 1946-1950 anti-malarial campaign. The TTP calculation was censored at the 13th month after date of marriage. We used a modified Cox's proportional hazard model to calculate the fecundability ratio (FR) by job, by cumulative exposure to DDT, and by time window in relation to the anti-malarial operations, adjusting by paternal age at marriage. RESULTS: Among the spouses of DDT applicators, fecundability did not vary during DDT use (FR=1.22, 95% CI 0.84-1.77) nor in the following decade (FR=1.01, 95% CI 0.67-1.50) with reference to the prior years. A significant increase occurred among the unexposed and the less exposed sub-cohorts, which generated a non-significantly reduced FR among the DDT applicator sub-cohort with reference to the unexposed following exposure. CONCLUSION: We did not find evidence of an impairment in male fertility following heavy occupational exposure to DDT. However, although fecundability was highest among the spouses of the DDT applicators in the years prior to the anti-malarial campaign, we cannot exclude that DDT exposure prevented an increase parallel to that observed among the unexposed and the less exposed sub-cohorts.

Job strain, hypoxia and risk of amyotrophic lateral sclerosis: Results from a death certificate study.

Amyotrophic lateral sclerosis (ALS) most likely results from a multifactorial gene-environment interaction. Strenuous physical activity and occupational exposures have been suggested to play a role, and an abnormal response to hypoxia has been proposed in ALS pathogenesis. To test the hypothesis of an excess risk in occupations typically leading to intermittent hypoxia at the tissue level, we accessed a large publicly available database, including death certificates from 24 U.S. states in 1984-1998. We conducted a case-control analysis of 14,628 deaths due to ALS therein reported and 58,512 controls deceased from other selected causes of death, frequency matched by age, gender and broad geographic area. ALS risk associated with physical activity, and occupations leading to intermittent hypoxia, such as fire fighters and professional athletes, were calculated with unconditional logistic regression, adjusting by age, marital status, residence, and socioeconomic status. Physical activity in general did not show an association with ALS risk. Risk associated with occupation as a professional athlete was elevated (OR = 1.81, 99% CI 0.69-4.78), but not significantly so. Fire fighters showed a significant two-fold excess ALS risk (OR = 2.0; 99% CI 1.2-3.2). Based on our findings and the current clinical, epidemiological and experimental evidence, we suggest that occupational conditions typically leading to intermittent hypoxia, such as fire fighting, might be an ALS risk factor in subjects genetically prone to an abnormal response to hypoxia.

Glucose-6-phosphate dehydrogenase polymorphism and lymphoma risk.

AIMS AND BACKGROUND: Evidence linking the glucose-6-phosphate dehydrogenase (G6PD) polymorphism and risk of non-Hodgkin's lymphoma is conflicting. Risk of non-Hodgkin's lymphoma was increased in subjects expressing the G6PD deficient phenotype, whereas subjects under medication with statins, a lipid-lowering class of drugs partially mimicking G6PD deficiency, seemed to enjoy a protective effect. METHODS: We conducted a case-control study on lymphoma risk associated with the self-reported G6PD deficient phenotype in 122 lymphoma male cases and 116 male controls in Sardinia, Italy. The association with the GdMed+ genotype, the most frequent variant expressing a deficient enzyme activity, was also tested in 49 male lymphoma cases and 31 controls. The WHO classification was used to identify lymphoma subentities. RESULTS: Neither self-reported G6PD deficient phenotype nor the GdMed+ genotype showed an association with lymphoma risk or its subentities. CONCLUSIONS: Our results do not confirm an association either positive or negative between the G6PD polymorphism and lymphoma risk.

Causes of death among lead smelters in relation to the glucose-6-phosphate dehydrogenase polymorphism.

OBJECTIVE: To assess, by updating a follow-up mortality study of a lead smelters cohort in Sardinia, Italy, the adverse health effects following occupational lead exposure in relation to the glucose-6-phosphate dehydrogenase (G6PD) polymorphism. METHOD: The 1973-2003 mortality of 1017 male lead smelters were followed-up, divided into two subcohorts according to the G6PD phenotype: whether G6PD deficient (G6PD-) or wild-type (wtG6PD). Deaths observed in the overall cohort and the two subcohorts were compared with those expected, on the basis of the age-, sex- and calendar year-specific mortality in the general male population of the island. Directly standardised mortality rates (sr) in the two subcohorts were also compared. RESULTS: Cardiovascular mortality was strongly reduced among production and maintenance workers, which is most related to the healthy worker effect. However, the sr for cardiovascular diseases was substantially lower among the G6PD- subcohort (5.0x10(-4)) than among the wtG6PD subcohort (33.6x10(-4); chi2 = 1.10; p = NS). Neoplasms of the haemopoietic system exceeded the expectation in the G6PD- subcohort (SMR = 388; 95% CI 111 to 1108). No other cancer sites showed any excess in the overall cohort or in the two subcohorts. No death from haemolytic anaemia occurred in the G6PD- subcohort. CONCLUSION: With due consideration of the limited statistical power of our study, previous results suggesting that in workplaces where exposure is under careful control, expressing the G6PD- phenotype does not convey increased susceptibility to lead toxicity are confirmed. The observed excess risk of haematopoietic malignancies seems to have most likely resulted from chance.

Reproductive outcomes following environmental exposure to DDT.

We used official statistics of births and stillbirths in 1945-1954 to evaluate reproductive outcomes in the general population following use of DDT during a 1946-1950 anti-malarial campaign in the Italian region of Sardinia. Due to the disruption of registration systems in the World War II years, data in the pre-DDT years were available only for 1945-1946. Such a short period of observation, and social conditions in the war and post-war years, do not allow exclusion of adverse effects of DDT on birth rate; however, we did not observe an effect. The stillbirth rate, infant mortality rate, and male/female ratio in newborns were apparently unaffected following widespread but focused use of DDT in Sardinia, Italy.

Cancer mortality among men occupationally exposed to dichlorodiphenyltrichloroethane.

Several studies have evaluated cancer risk associated with occupational and environmental exposure to dichlorodiphenyltrichloroethane (DDT). Results are mixed. To further inquire into human carcinogenicity of DDT, we conducted a mortality follow-up study of 4,552 male workers, exposed to DDT during antimalarial operations in Sardinia, Italy, conducted in 1946 to 1950. Detailed information on DDT use during the operations provided the opportunity to develop individual estimates of average and cumulative exposure. Mortality of the cohort was first compared with that of the Sardinian population. Overall mortality in the cohort was about as expected, but there was a deficit for death from cardiovascular disease and a slight excess for nonmalignant respiratory diseases and lymphatic cancer among the unexposed subcohort. For internal comparisons, we used Poisson regression analysis to calculate relative risks of selected malignant and nonmalignant diseases with the unexposed subcohort as the reference. Cancer mortality was decreased among DDT-exposed workers, mainly due to a reduction in lung cancer deaths. Birth outside from the study area was a strong predictor of mortality from leukemia. Mortality from stomach cancer increased up to 2-fold in the highest quartile of cumulative exposure (relative risk, 2.0; 95% confidence interval, 0.9-4.4), but no exposure-response trend was observed. Risks of liver cancer, pancreatic cancer, and leukemia were not elevated among DDT-exposed workers. No effect of latency on risk estimates was observed over the 45 years of follow-up and within selected time windows. Adjusting risks by possible exposure to chlordane in the second part of the antimalarial operations did not change the results. In conclusion, we found little evidence for a link between occupational exposure to DDT and mortality from any of the cancers previously suggested to be associated.

Reproductive outcomes in DDT applicators.

OBJECTIVES: To explore reproductive outcomes in relation to occupational exposure to DDT. METHODS: We inquired into the reproductive history, including total number of children, sex distribution in the offspring, time-to-pregnancy, and number of spontaneous abortions and stillbirths, of the spouses of 105 men first exposed to DDT in a 1946-1950 anti-malarial campaign in Sardinia, Italy. The time-to-pregnancy in months at the first successful conception was estimated from population Registrars. Cumulative DDT exposure during the anti-malarial campaign was retrospectively estimated. RESULTS: The stillbirth rate was elevated and the male/female ratio in the offspring was reversed among DDT-exposed workers, and particularly among DDT applicators, compared to the unexposed subjects. Among DDT applicators, the stillbirth rate increased and the male/female ratio decreased by the tertile of cumulative DDT exposure. The fecundity ratio among spouses of DDT applicators was 0.72 (95% CI, 0.41,1.21) compared to the unexposed. The average number of children and abortion rate were unaffected by DDT exposure. CONCLUSIONS: The low statistical power of our study does not allow definitive conclusions. However, the results prompt further in-depth research into adverse reproductive outcomes and reduced fertility among men heavily exposed to DDT.

Serum sex hormones in men occupationally exposed to dichloro-diphenyl-trichloro ethane (DDT) as young adults.

To explore endocrine effects in relation to para,para'-dichloro-diphenyl-dichloro ethylene (p,p'-DDE) body burden and past occupational exposure to its precursor dichloro-diphenyl-trichloro ethane (DDT), we assayed serum sex hormones, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG), and p,p'-DDE levels in 107 male participants in a 1946-1950 anti-malarial campaign in Sardinia, Italy. Cumulative DDT exposure during the anti-malarial operations was retrospectively estimated from detailed reports of the anti-malarial agency. Ortho,para-DDE, and its precursor ortho,para-DDT were always below the detection limit. p,p'-DDT was detected in 14/107 subjects, and p,p'-DDE in 106/107 subjects. The median lipid-adjusted p,p'-DDE serum concentration over the total study population was 396 parts per billion (interquartile range 157-1045), and it did not vary according to the job at the time of anti-malarial operations, nor was it affected by cumulative DDT exposure. LH, FSH, and SHBG, but not testosterone or E2, showed a significant positive correlation with age. Neither current serum p,p'-DDE nor past cumulative DDT exposure affected sex hormone concentrations. Our results suggest that (1) the low current p,p'-DDE serum concentration does not affect serum hormone levels, and (2) past cumulative DDT exposure is not correlated with the current p,p'-DDE serum level, nor does it show persistent effects on serum hormone levels.