The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome-a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men.

BACKGROUND: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) accumulates in marine mammals and fish. DDT and p,p'-DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. OBJECTIVES: The objective of this study was to assess the sperm epigenome in relation to p,p'-DDE serum levels between geographically diverse populations. METHODS: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p,p'-DDE serum levels (mean=870.734±134.030 ng/mL). We assessed the sperm epigenome in relation to serum p,p'-DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. RESULTS: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. DISCUSSION: These findings suggest that DDT and p,p'-DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.

The role of effect-based methods to address water quality monitoring in South Africa: a developing country's struggle.

Water is an important resource, and it is a worldwide struggle to provide water of good quality to the whole population. Despite good governing laws and guidelines set in place to help protect the water resources and ensure it is of good quality for various consumers, the water quality in South Africa is worsening due to lack of management. The deteriorating infrastructure is becoming progressively worse, due to corruption and insufficient funds. The ever-increasing number of toxicants, as well as the identification of emerging chemicals of concern, are also challenges South Africa is facing. Chemical analysis cannot determine the total biological effect of a mixture of chemical compounds, but this shortcoming can be addressed by adding effect-based methods (EBMs) to water quality monitoring programmes. In this paper, the current status of water quality monitoring in South Africa is discussed, as well as the capacity of the country to add EBMs to its water quality monitoring programmes to protect and improve human and animal life. Created in Biorender.com.

Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology.

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

Occurrence of legacy and replacement plasticizers, bisphenols, and flame retardants in potable water in Montreal and South Africa.

The occurrence of thirty-nine contaminants including plasticizers, bisphenols, and flame retardants in potable water from Montreal and South Africa was analyzed to determine their presence and concentrations in different water sources. In Montreal, five bottled water (BW) brands and three drinking water treatment plants (DWTP) were included. In South Africa, water was sampled from one urban DWTP located in Pretoria, Gauteng, and one rural DWTP located in Vhembe, along with water from the same rural DWTP which had been stored in small and large plastic containers. A combination of legacy compounds, typically with proven toxic effects, and replacement compounds was investigated. Bisphenols, Dechlorane-602, Dechlorane-603, and s-dechlorane plus (s-DP) were not detected in any water samples, and a-dechlorane plus (a-DP) was only detected in one sample from Pretoria at a concentration of 1.09 ng/L. Lower brominated polybrominated diphenyl ethers (PBDE)s were detected more frequently than higher brominated PBDEs, always at low concentrations of <2 ng/L, and total PBDE levels were statistically higher in South Africa than in Montreal. Replacement flame retardants, organophosphate esters (OPEs), were detected at statistically higher concentrations in Montreal's BW (68.56 ng/L), drinking water (DW) (421.45 ng/L) and Vhembe (198.33 ng/L) than legacy PBDEs. Total OPE concentrations did not demonstrate any geographical trend; however, levels were statistically higher in Montreal's DW than Montreal's BW. Plasticizers were frequently detected in all samples, with legacy compounds DEHP, DBP, and replacement DINCH being detected in 100 % of samples with average concentrations ranging from 6.89 ng/L for DEHP in Pretoria to 175.04 ng/L for DINCH in Montreal's DW. Total plasticizer concentrations were higher in Montreal than in South Africa. The replacement plasticizers (DINCH, DINP, DIDA, and DEHA) were detected at similar frequencies and concentrations as legacy plasticizers (DEHP, DEP, DBP, MEHP). For the compounds reported in earlier studies, the concentrations detected in the present study were similar to other locations. These compounds are not currently regulated in drinking water but their frequent detection, especially OPEs and plasticizers, and the presence of replacement compounds at similar or higher levels than their legacy compounds demonstrate the importance of further investigating the prevalence and the ecological or human health effects of these compounds.

Ex vivo Vitamin D supplementation improves viscoelastic profiles in prostate cancer patients.

BACKGROUND: Increased risk of thromboembolic events is associated with prostate cancer, specifically linked to activation of tissue factor. Vitamin D has potential anticoagulant effects by the downregulation of tissue factor expression. OBJECTIVES: To evaluate the effects on clot formation, the morphological and viscoelastic profiles of prostate cancer patients, before and after ex vivo supplementation of Vitamin D was studied. METHODS: Participants were recruited into a metastatic, non-metastatic and reference group. Whole blood samples were treated ex vivo with a dose of 0.5µg/kg Calcitriol. Clot kinetics were assessed using Thromboelastography®. Morphology of the blood components were studied using scanning electron microscopy (SEM). RESULTS: Results from the Thromboelastography® and SEM indicated no major differences between the non-metastatic group before and after treatment compared to the reference group. The Thromboelastography® showed that the metastatic group had an increased viscoelastic profile relating to a hypercoagulable state. Visible changes with regards to platelet activation and fibrin morphology were demonstrated with SEM analysis of the metastatic group. The viscoelastic and morphological properties for the non-metastatic group after treatment improved to be comparable to the reference group. CONCLUSION: Vitamin D supplementation may lead to a more favorable viscoelastic profile, with less dangerous clots forming.

Veterinary growth promoters in cattle feedlot runoff: estrogenic activity and potential effects on the rat male reproductive system.

The contribution of veterinary growth promoters (VGP) to the environmental burden of endocrine-disrupting chemicals (EDCs) is largely unknown. At cattle feedlots, the excrement of cattle may contain VGPs, which can contaminate aquatic systems and pose reproductive health risks. The study identifies VGPs used at cattle feedlots in South Africa and confirms associated estrogenic activity in feedlot runoff water. Using a rat model, we investigate the potential reproductive health effects and thyroid function of an environmentally relevant mixture of VGPs. Collected water samples had low levels of selected VGPs, and estrogenic activity was detected in the T47D-KBluc bioassay. Rats exposed to VGP had significant adverse effects on male reproductive health, including shortened anogenital distance, lowered sperm counts, disorganized seminiferous tubules, and thyroid parameters. In conclusion, VGP can contribute to complex environmental EDC mixtures and may adversely affect the reproductive and thyroid health of both humans and wildlife. The varied topography of individual cattle feedlots will govern the rate and extent of effluent runoff, thus continuous monitoring of VGPs in aquatic systems surrounding cattle feedlots is necessary.

Fate, occurrence and potential adverse effects of antimicrobials used for treatment of tuberculosis in the aquatic environment in South Africa.

The consumption of tonnes of anti-tubercular and other anti-microbial compounds for the control of the tuberculosis epidemic and other opportunistic diseases associated with human immunodeficiency virus presents tuberculosis-endemic countries such as South Africa, with a problem regarding the occurrence and fate of these compounds in the aquatic environment. The majority of these compounds are not readily degradable and could persist in the aquatic environment with potential detrimental effect on the aquatic microbiota ecosystem, development and dissemination of anti-microbial resistance as well as chronic toxicity in humans due to long-term exposure. This review summarises and discusses the occurrence, fate and potential adverse effects of the commonly administered anti-tubercular compounds in the aquatic environment in tuberculosis-endemic countries and South Africa in particular. It further attempts to identify information gaps in the literature regarding anti-tubercular compounds in the environment that needs further investigation so that their risk can be comprehensively assessed and impact mitigated.

Male reproductive health statement (XIIIth international symposium on Spermatology, may 9th-12th 2018, Stockholm, Sweden.

On the occasion of the XIIIth International Symposium on Spermatology held from 9 to 13 May 2018 in Stockholm (Sweden), participants (guest speakers and audience) collectively felt the need to make a public statement on the general issue of male reproductive health. Our intention is to raise awareness of what we believe is a neglected area of research despite alarming situations around the world. The disclosure strategy desired by the co-authors is to bring it to the attention of the greatest number partly by considering co-publication in the various periodicals dealing with Reproductive Biology and Andrology. BaCA's editorial office accepted this mission and found it natural that our periodical, the official journal of the French Andrology Society (SALF), should carry this message.

A l'occasion du XIII eme Symposium international sur la Spermatologie qui s'est. tenu du 9 au 13 Mai 2018 à Stockholm (Suède), les participants (orateurs invités et l'auditoire) ont ressenti collectivement le besoin de faire une déclaration publique sur la question générale de la santé reproductive masculine. Notre intention est. de mieux faire connaître ce que nous pensons être un domaine de recherche négligé malgré des situations alarmantes dans le monde entier. La stratégie de divulgation souhaitée par les co-auteurs est. de le porter à l'attention du plus grand nombre en envisageant pour partie une co-publication dans les différents périodiques traitant de Reproduction et d'Andrologie. Le bureau éditorial de BaCA, a accepté cette mission et a trouvé naturel que notre périodique, journal officiel de la Société d'Andrologie en Langue Française (SALF) porte ce message.

Estrogenic activity, selected plasticizers and potential health risks associated with bottled water in South Africa.

Potential endocrine disrupting chemicals (EDCs) are present in bottled water from various countries. In South Africa (SA), increased bottled water consumption and concomitant increases in plastic packaging create important consequences for public health. This study aimed to screen SA bottled water for estrogenic activity, selected target chemicals and assessing potential health risks. Ten bottled water brands were exposed to 20 °C and 40 °C over 10 days. Estrogenic activity was assessed using the recombinant yeast estrogen screen (YES) and the T47D-KBluc reporter gene assay. Solid phase extracts of samples were analyzed for bis(2-ethylhexyl) adipate (DEHA), selected phthalates, bisphenol-A (BPA), 4-nonylphenol (4-NP), 17ß-estradiol (E2), estrone (E1), and ethynylestradiol (EE2) using gas chromatography-mass spectrophotometry. Using a scenario-based health risk assessment, human health risks associated with bottled water consumption were evaluated. Estrogenic activity was detected at 20 °C (n = 2) and at 40 °C (n = 8). Estradiol equivalent (EEq) values ranged from 0.001 to 0.003 ng/L. BPA concentrations ranged from 0.9 ng/L to 10.06 ng/L. Although EEqs and BPA concentrations were higher in bottled water stored at 40 °C compared to 20 °C, samples posed an acceptable risk for a lifetime of exposure. Irrespective of temperature, bottled water from SA contained chemicals with acceptable health risks.

Analysis of endocrine activity in drinking water, surface water and treated wastewater from six countries.

The aquatic environment can contain numerous micropollutants and there are concerns about endocrine activity in environmental waters and the potential impacts on human and ecosystem health. In this study a complementary chemical analysis and in vitro bioassay approach was applied to evaluate endocrine activity in treated wastewater, surface water and drinking water samples from six countries (Germany, Australia, France, South Africa, the Netherlands and Spain). The bioassay test battery included assays indicative of seven endocrine pathways, while 58 different chemicals, including pesticides, pharmaceuticals and industrial compounds, were analysed by targeted chemical analysis. Endocrine activity was below the limit of quantification for most water samples, with only two of six treated wastewater samples and two of six surface water samples exhibiting estrogenic, glucocorticoid, progestagenic and/or anti-mineralocorticoid activity above the limit of quantification. Based on available effect-based trigger values (EBT) for estrogenic and glucocorticoid activity, some of the wastewater and surface water samples were found to exceed the EBT, suggesting these environmental waters may pose a potential risk to ecosystem health. In contrast, the lack of bioassay activity and low detected chemical concentrations in the drinking water samples do not suggest a risk to human endocrine health, with all samples below the relevant EBTs.

Alterations in male reproductive hormones in relation to environmental DDT exposure.

DDT [1, 1, 1-trichloro-2,2-bis (p-chlorophenyl)-ethane] compounds are used for indoor residual spraying (IRS) to control malaria mosquitoes. DDT is an endocrine disruptor chemical in experimental conditions, but little is known of adverse effects related to living conditions with continual uptake across a time span by all possible means of exposure. Based on estrogenic and/or anti-androgenic effects found in animal studies, we hypothesized that chronic DDT/DDE exposures in men may be associated with changes in male reproductive hormones. We tested this hypothesis by compared the magnitude and direction of associations between DDT and DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene) concentrations and male reproductive hormones in samples collected from IRS and non-IRS areas. We sampled a cross-section of 535 men (aged 18-40 years). Men living in IRS villages had significantly higher DDT and DDE concentrations compared with men from non-IRS villages. Men with DDT or DDE uptake (as reflected in detectable plasma concentrations) had significantly higher total-, free and bio-available testosterone (T), and lower follicle stimulating hormone (FSH) concentrations; lower luteinizing hormone (LH) concentrations were only evident with DDT uptake. To establish a dose-dependent effect, four sub-categories were defined. Men with the highest DDT (74-519 µg/g) and DDE (173-997 µg/g) concentrations had significantly higher total-, free and bio-available T, and lower FSH concentrations compared with subjects with non-detectable isomer concentrations. Estradiol concentrations were significantly higher in men with DDT and DDE concentrations in both the third (DDE: 27-172 µg/g; DDT: 5-73 µg/g) and fourth (DDE: 173-997 µg/g; DDT: 74-519 µg/g) categories. Men from IRS villages were significantly more likely to have higher total and bioavailable T as well as higher estradiol concentrations OR = 2.5 (95% CI 1.2, 3.2); OR 2.5 (95% CI 1.6, 4.0) and OR = 2.3 (95% CI 1.3, 4.1) compared to men from non-IRS villages, after controlling for age, BMI, personal use of pesticides, and smoking. Men living in IRS villages with life-long exposure (17.6 (±6) years) at the current residence with multiple exposure modalities incurred the highest degree of physiological imbalance over and above circulating isomer concentrations. Further studies are needed to elucidate the health implications of these findings.

Comparison of in vitro and in vivo bioassays to measure thyroid hormone disrupting activity in water extracts.

Environmental chemicals can induce thyroid disruption through a number of mechanisms including altered thyroid hormone biosynthesis and transport, as well as activation and inhibition of the thyroid receptor. In the current study six in vitro bioassays indicative of different mechanisms of thyroid disruption and one whole animal in vivo assay were applied to 9 model compounds and 4 different water samples (treated wastewater, surface water, drinking water and ultra-pure lab water; both unspiked and spiked with model compounds) to determine their ability to detect thyroid active compounds. Most assays correctly identified and quantified the model compounds as agonists or antagonists, with the reporter gene assays being the most sensitive. However, the reporter gene assays did not detect significant thyroid activity in any of the water samples, suggesting that activation or inhibition of the thyroid hormone receptor is not a relevant mode of action for thyroid endocrine disruptors in water. The thyroperoxidase (TPO) inhibition assay and transthyretin (TTR) displacement assay (FITC) detected activity in the surface water and treated wastewater samples, but more work is required to assess if this activity is a true measure of thyroid activity or matrix interference. The whole animal Xenopus Embryonic Thyroid Assay (XETA) detected some activity in the unspiked surface water and treated wastewater extracts, but not in unspiked drinking water, and appears to be a suitable assay to detect thyroid activity in environmental waters.

Endocrine Disruptors and Health Effects in Africa: A Call for Action.

BACKGROUND: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made. OBJECTIVES: This commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa. DISCUSSION: We identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa. CONCLUSION: To address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.

Estrogenic activity, chemical levels and health risk assessment of municipal distribution point water from Pretoria and Cape Town, South Africa.

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been detected in drinking water from various countries. Although various water treatment processes can remove EDCs, chemicals can also migrate from pipes that transport water and contaminate drinking water. This study investigated the estrogenic activity in drinking water from various distribution points in Pretoria (City of Tshwane) (n = 40) and Cape Town (n = 40), South Africa, using the recombinant yeast estrogen screen (YES) and the T47D-KBluc reporter gene assay. The samples were collected seasonally over four sampling periods. The samples were also analysed for bisphenol A (BPA), nonylphenol (NP), di(2-ethylhexyl) adipate (DEHA), dibutyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), diisononylphthalate (DINP), 17ß-estradiol (E2), estrone (E1) and ethynylestradiol (EE2) using ultra-performance liquid chromatography-tandem mass spectrophotometry (UPLC-MS/MS). This was followed by a scenario based health risk assessment to assess the carcinogenic and toxic human health risks associated with the consumption of distribution point water. None of the water extracts from the distribution points were above the detection limit in the YES bioassay, but the EEq values ranged from 0.002 to 0.114 ng/L using the T47D-KBluc bioassay. BPA, DEHA, DBP, DEHP, DINP E1, E2, and EE2 were detected in distribution point water samples. NP was below the detection limit for all the samples. The estrogenic activity and levels of target chemicals were comparable to the levels found in other countries. Overall the health risk assessment revealed acceptable health and carcinogenic risks associated with the consumption of distribution point water.

Pesticide residues and estrogenic activity in fruit and vegetables sampled from major fresh produce markets in South Africa.

Food is likely to be one of the major pathways through which people are exposed to endocrine-disrupting chemicals. With the exception of residual effects, there are concerns that a number of naturally occurring and synthetic chemicals exert adverse effects upon endocrine systems in wildlife and humans. The current study reports selected pesticide concentrations and the total estrogenic activity of fruit and vegetables using the recombinant yeast oestrogen screen (YES) and T47D-KBluc reporter gene assays. A total of 53 food samples (27 fruit and 26 vegetables) from Johannesburg and Tshwane fresh produce markets (in South Africa) were analysed. Of these, 17 contained one to three different pesticide residues with concentrations ranging between 0.01 and 0.68 mg kg(-1), whereas in the rest of the samples no residues were detected. All pesticides detected except in one sample were below the maximum residue level (MRL), but others were unauthorised for use in specified fruit and vegetables. Estrogenic activity was detected in 26.4% (14 samples) of the samples tested, and the estradiol equivalents ranged from 0.007 to 2 pg g(-1). Although the estrogenic activity was low, it may contribute to adverse health effects. Continuous monitoring for pesticides in fruit and vegetables is important in view of the unauthorised pesticides detected in produce from South Africa and the endocrine-disrupting chemical activity found.

Changes in retinol-binding protein concentrations and thyroid homeostasis with nonoccupational exposure to DDT.

BACKGROUND: The insecticide dichlorodiphenyltrichloroethane (DDT) has been used for malaria vector control in the northern and eastern parts of the Vhembe District of Limpopo Province, South Africa, since 1945. Bioaccumulation of DDT raises concern because it reportedly affects thyroid function. OBJECTIVE: Our objective was to investigate the association between DDT uptake (as reflected in plasma concentrations) and thyroid homeostasis while considering related factors. METHODS: We compared dietary intake, serum retinol-binding protein (RBP), transthyretin (TTR) and albumin concentrations, and liver and thyroid function between cases with evidence of a body burden of DDT in the circulation (concentration of any DDT isomer ≥ 0.02 µg/g lipid; n = 278) and controls (concentration of all DDT isomers < 0.02 µg/g lipid; n = 40) in a cross-sectional study. Further analyses were performed to assess the relevance of changes in RBP status associated with DDT uptake. RESULTS: RBP concentrations below the reference range were more prevalent in cases (54% vs. 10% in controls; χ² = 27.4; p < 0.001), which could not be explained by nutrient intake. We observed significantly lower thyroid hormone concentrations among cases (p ≤ 0.01). We also observed a significant linear trend for serum concentrations of free thyroxine and free triiodothyronine (p < 0.001) and a significant quadratic trend for serum thyroid-stimulating hormone (p = 0.025) and TTR (p < 0.001) across the control group and case groups with normal and relatively low RBP concentrations. Relatively low RBP concentrations were associated with significantly higher DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) isomer concentrations and with a higher DDE/DDT ratio (p ≤ 0.01), which signifies long-term exposure. Inadequate intake of vitamin A and zinc were observed in 84% and 58%, respectively, of the total study population. CONCLUSION: RBP concentrations appear to decrease in the presence of long-term DDT uptake, which may have deleterious effects on thyroid function and vitamin A nutritional status. This is of major concern in a population with poor vitamin A and zinc intake.

Semenology training programs: 8 years' experience.

OBJECTIVE: To evaluate the immediate effect of hands-on training on the quality of technical skills of laboratory technicians. DESIGN: Retrospective analytical study. SETTING: Academic institutions and private infertility clinics. PARTICIPANTS: One hundred and ten laboratory technicians. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): First, 110 participants from 16 African countries attended 5-day semenology workshops at Tygerberg Hospital. During these workshops the methodology as described by the World Health Organization manual for the analysis of human semen, namely, sperm concentration, motility, vitality, and morphology, formed part of the curriculum. Second, two experienced morphology readers from the Tygerberg group presented 23 1-day sperm morphology workshops in nine other countries. RESULT(S): The semenology workshops indicated a significant improvement in the evaluation of sperm concentration only, whereas pretraining and posttraining results for motility did not differ. Vitality reports did not differ from those of the experienced worker in the first place. Calculation by means of a linear regression model showed a significant decrease in the mean posttraining scores from the pretraining scores for the sperm morphology courses. CONCLUSION(S): Training improved technical skills for the evaluation of morphology and sperm concentration. The evaluation of graded sperm motility seems to be more difficult to teach over a short period.

Impaired semen quality associated with environmental DDT exposure in young men living in a malaria area in the Limpopo Province, South Africa.

The pesticide DDT [1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane] is 1 of the 12 persistent organic pollutants (POPs) under negotiation at the Stockholm Convention to restrict or ban their production and use because of their toxicity, resistance to breakdown, bioaccumulation, and potential for being transported over long distances. DDT has estrogenic potential, and the main metabolite, p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), is a potent antiandrogen. In response to mounting evidence on the endocrine-disrupting influence of environmental chemicals on human health, this epidemiological study was initiated to test the hypothesis that nonoccupational exposure to DDT affects male reproductive parameters. In a cross-sectional study, healthy male subjects (n=311) between 18 and 40 years (23+/-5) of age were recruited from 3 communities in an endemic malaria area in which DDT is sprayed annually. A semen analysis according to World Health Organization (WHO) standards was performed. The Hamilton Thorne Computer Assisted Sperm Analysis (CASA) system was simultaneously used to determine additional sperm motility parameters. Blood plasma samples were assayed for p,p'-DDT and metabolites as a measure of exposure. The exposure levels were expressed as lipid-adjusted p,p'-DDT and p,p'-DDE values. The mean p,p'-DDT and p,p'-DDE concentrations were 90.23 microg/g(+/-102.4) and 215.47 microg/g(+/-210.6), respectively. The multivariate linear regression analyses indicated that mean CASA motility was lower with a higher p,p'-DDE concentration (beta=-0.02, P=.001) and the CASA parameter beat cross-frequency (BCF) was higher with a higher p,p'-DDT concentration (beta=0.01, P=.000). There was also a statistically significant positive association between percent sperm with cytoplasmic droplets and p,p'-DDT concentration (beta=0.0014, P=.014). The ejaculate volume (mean 1.9+/-1.33 mL) was lower than the normal range (>or=2.0 mL) according to WHO, and a significant decrease with increasing p,p'-DDE values was seen for both square root-transformed volume (beta=-0.0003; P=.024) and count (beta=-0.003; P=.04). Although there were no associations between either p,p'-DDT or p,p'-DDE concentrations and the rest of the seminal parameters, the incidence of teratozoospermia (99%; normal sperm<15%) was high. Twenty-eight percent of the study group presented with oligozoospermia (<20x10(6) sperm/mL), which had a significant positive association with p,p'-DDE (odds ratio [OR]=1.001, P=.03). There was a significant positive association between participants with asthenozoospermia (32%) and p,p'-DDT (OR 1.003, P=.006) and p,p'-DDE (OR 1.001, P=.02). The results imply that nonoccupational exposure to DDT is associated with impaired seminal parameters in men. The high exposure levels of p,p'-DDT and p,p'-DDE are of concern because these levels could have far-reaching implications for reproductive and general health.