Authors
Felix Salazar-Garcia, Esperanza Gallardo-Diaz, Prudencia Ceron-Mireles, Dana Loomis, Victor H. Borja-Aburto.

Title
Reproductive effects of occupational DDT exposure among male malaria control workers.

Journal
Environmental Health Perspectives: 112(5):542-547, 2004.

Summary
DDT (dichlorodiphenyltrichloroethane) was used to control vectors (mosquitoes) in malaria control programs in many developing and developed nations during later part of the last century. Many developed countries subsequently banned DDT use in the 1970's and 1980's because of demonstrated adverse effects on wild life and humans. Some countries like Mexico, continued using DDT for mosquito control up until 1999 because of its low cost, effectiveness and low toxicity to people compared to other chemicals.

Both animal experiments and human studies on females have revealed the reproductive effects (birth defects) of exposure to DDT which have been attributed to the anti-androgenic and estrogenic properties of the DDT metabolite, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), which accumulates in fat tissue. Prior studies on males have focused on sperm counts, semen analysis and reproductive hormone levels.

The present study, for the first time, focused on the reproductive effects of occupational DDT exposure in males. A historical cohort was established by the Ministry of Health in Mexico for workers who worked in the malaria control program for at least 1 year between 1956 and 1990. This study was based on cross-sectional data of 2,033 workers (who survived to the year 2000), from the sub-cohort corresponding to pacific area of Mexico. A total of 9,187 pregnancies were parented. The reproductive outcomes in this study included- congenital malformations, spontaneous abortion, and alteration of the sex ratio which were the indicators of teratogenicity, embryotoxicity, and endocrine disruption respectively.

DDT exposure was evaluated using three approaches. The first method used a dichotomous exposure variable. In the second approach, the paternal exposure for each pregnancy was classified into 4 categories - 1. Unexposed (never exposed to DDT), 2. Indirectly exposed (worked in DDT sprayed areas and DDT storage), 3. Directly exposed (applied DDT or prepared the mixture before pregnancy), and 4. Combined direct and indirect exposure (applied DDT and prepared mixtures for some years and also performed other activities where there is possibility for potential exposure before pregnancy). The third approach was based on an estimate of DDE concentration in adipose tissue which was categorized into quartiles. The estimates of concentration of DDE in adipose tissue was based on the model developed by Rivero-Rodriguez et al, and not on true laboratory measures. Other pesticides of the organochlorine group (lindane and dieldrin) and the organophosphate group (temphos, malathion, and fenthion) were also assessed apart from DDT for each pregnancy. Other factors including smoking, alcohol, exposure to other chemicals & agricultural pesticides at the time of pregnancy, maternal and paternal age and socio economic status were also assessed for the reproductive outcomes as dichotomous exposure variables.

In this study a significant association between birth defects and paternal DDT exposure was observed in all three approaches of exposure assessment. These findings were not affected by missing information on pregnancies as revealed by the sensitivity analysis and changes in the amount of DDT sprayed between years 1956 and 1999 as revealed by the addition of time variable, adding strength to the findings. Moreover the results are consistent with the prior research on DDT exposure in animals and humans. A clear dose response relationship between DDT metabolite accumulated in fat tissue and birth defects however, could not be established as a plateau was observed at higher concentrations of exposure. No clear association was observed between DDT exposure and spontaneous abortion and no change in the sex ratio was observed which was proposed as an indicator for endocrine disruption. Exposure to malathion as well as maternal age were other factors found to be associated with reproductive effects after controlling for DDT exposure. The mechanism for reproductive effects of DDT exposure in males is unclear. Sperm genetic alterations and indirect exposure to the fetus through the mother from the soiled clothing of the male partner were some hypothesized mechanisms.

One limitation of the study is the potential for bias due to the misclassification of outcomes and exposures such as the over-reporting of recent jobs and events. Another limitation is the validity of using sex ratio as an indicator for endocrine disruption.

The present study provides evidence for reproductive effects of occupational DDT exposure in males. However, there are several important limitations to this study. It is unclear who could ever have been considered as never exposed to DDT given the wide spread use and continued persistence of this pesticide even in regions of the world where it was never used. Moreover, given the persistence of organochlorines in the environment it is not reasonable to treat exposure as a dichotomous variable. Furthermore, the significance of the findings for general population remains uncertain due to lower concentration of DDT exposure in contemporary populations.