M. S. Bornman

The pine river statement: human health consequences of DDT use.

Objectives Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.

II. The effect of p‐nonylphenol on the fertility potential of male rats after gestational, lactational and direct exposure

Summary. There is growing concern that abnormalities in male reproductive health are becoming more frequent. The most fundamental change has been the striking decline in sperm counts and semen quality. The effect of maternal exposure of rats to the oestrogenic environmental substance p‐nonylphenol (p‐NP) was determined in this study. Exposure to p‐NP for the experimental period impaired general growth. The lower testicular mass indicated a direct toxic effect on the testis in animals exposed to p‐NP during foetal life, the postnatal period and after weaning until termination at 10 weeks of age. The epididymal mass was also negatively affected by p‐NP; this was supported by the decrease in the epididymal ratio. The total cauda epididymal sperm count was significantly lower in the 250 mg kg−1 p‐NP dosage group compared to the control and 100 mg kg−1 p‐NP groups. The overall lower sperm count with increased p‐NP concentrations corresponded with the decreased testicular and epididymal masses. This emphasized the toxicity of p‐NP on both testis and epididymis. Seminiferous tubule diameter, lumen diameter and seminiferous epithelium thickness were smaller in the exposed groups, even at the low dose level. These histological measurements further supported the finding of a low testicular mass. In spite of the measurements being smaller, p‐NP had no effect on the stages of spermatogenesis except for one animal with disrupted spermatogenesis in some tubules, while others were normal.

I. The effect of p-nonylphenol, an environmental toxicant with oestrogenic properties, on fertility potential in adult male rats

Summary. Infertility is a sad reality and it is now evident that several aspects of male reproductive health have changed for the worse over the past 30–50 years. para‐nonylphenol (p‐NP), an environmental toxicant with oestrogenic properties, was tested for its effect on male fertility potential. When adult male rats were exposed to 100 mg kg−1 p‐NP the histological parameters of the seminiferous tubules were adversely affected. Although spermatogenesis was already established in these males at the time exposure commenced, p‐NP still had an effect on the histology of the seminiferous tubules. Increasing the level to 250 mg kg−1 additionally resulted in a smaller weight gain and signs of epididymal toxicity, while 400 mg kg−1 also impaired testicular mass and sperm count. In the last two groups spermatogenesis was also affected in some animals. Because p‐NP had an effect on established spermatogenesis in the rat, one could speculate that the same effects might also occur in humans. It would appear that p‐NP had toxic effects on both the testis and epididymis and both structures might be important in impairing male fertility. Bio‐accumulation may enhance the negative effects at even lower p‐NP concentrations over longer exposure periods than reported here.

Histopathological alterations in the liver of the sharptooth catfish Clarias gariepinus from polluted aquatic systems in South Africa.

There is a need for sensitive bio‐monitoring tools in toxicant impact assessment to indicate the effect of toxicants on fish health in polluted aquatic ecosystems. Histopathological assessment of fish tissue allows for early warning signs of disease and detection of long‐term injury in cells, tissues, or organs. The aim of this study was to assess the degree of histopathological alterations in the liver of C. gariepinus from two dams in an urban nature reserve, (Gauteng, South Africa). Two dams (Dam 1 and Dam 2) were chosen for their suspected levels of toxicants. Water and sediments were sampled for metal and potential endocrine disrupting chemical analysis. A quantitative and qualitative histology‐based health assessment protocol was employed to determine the adverse health effects in fish. The analysis of blood constituents, fish necropsy, calculation of condition factors, and hepatosomatic indices were employed to support the findings of the qualitative and quantitative histological assessment of liver tissue. Assessment of the liver tissue revealed marked histopathological alterations including: structural alterations (hepatic cord disarray) affecting 27% of field specimens; plasma alterations (granular degeneration 98% and fatty degeneration 25%) of hepatocytes; an increase in melanomacrophage centers (32%); hepatocyte nuclear alterations (90%); and necrosis of liver tissue (14%). The quantitative histological assessment indicated that livers of fish collected from Dam 1 were more affected than the fish livers collected from Dam 2.

Multicenter study on reproducibility of sperm morphology assessments.

Sperm morphology has always been considered an important tool in evaluating a mans fertilizing potential. The objective of this multicentric study was to evaluate intra- and interindividual variability and between-laboratory variation using the same or different criteria of sperm morphology assessment. Semen samples were obtained from 20 males and 32 smears were made of all samples. Eighty coded smears (4 per patient) were sent to 8 laboratories for morphology assessment. The centers applied different classification systems (strict criteria, WHO 1987, Düsseldorf criteria) and participants were asked to analyze the 80 smears twice, with an interval of 1 week between each participants two analyses. Intraclass correlations between repeats showed that sperm morphology can be assessed with acceptable within observer reproducibility. Expected increases in imprecision were observed up to coefficients of variation of >30% with decreasing morphology scores, regardless of the classification system used. Agreement in correct classification of samples as normal/abnormal was obtained in 80% of cases. Differences in reproducibility between slides may reflect an important source of heterogeneity due to smear preparation. These results emphasize the importance of external quality control systems to improve the value of sperm morphology assessments in the investigation of the male partner in a subfertile couple.

Simultaneous exposure to low concentrations of dichlorodiphenyltrichloroethane, deltamethrin, nonylphenol and phytoestrogens has negative effects on the reproductive parameters in male Spraque-Dawley rats

Many reports suggest that male reproductive health has deteriorated over the last decades, possibly due to environmental contaminants that act as endocrine disruptors. This hypothesis was tested in Sprague‐Dawley rats using a modified Organization for Economic Cooperation and Development 415 one‐generation test. Group A received cottonseed oil as control, and Groups B, C and D received deltamethrin (DM); DM and dichlorodiphenyltrichloroethane (DDT); and DM, DDT, phytoestrogens and p‐nonylphenol, respectively. Rats were exposed in utero and then received the substances for 10 weeks. The seminal vesicle mass (Group B; P = 0.046) and sperm count [Groups C (P = 0.013) and D (P = 0.003)] were lower and the anogenital distance [Group B (P = 0.047) C (P = 0.045) and D (P = 0.002)] shorter compared with the control group. The seminiferous tubule diameter [Groups B (P = <0.001), C (P = <0.001) and D (P = <0.001)] and epithelium thickness [Groups B (P = 0.030), C (P = <0.001) and D (P = <0.001)] were smaller compared with the control. The histology of the testes showed signs of apical sloughing and vacuolisation. Liver weights [Groups C (P = 0.013) and D (P = 0.005)] and liver enzymes [Group D (P = 0.013)] were also affected. These findings may indicate that simultaneous exposure to endocrine disrupting compounds contributes to the deterioration observed in male reproductive health.

Histopathological changes in the reproductive system (ovaries and testes) of Oreochromis mossambicus following exposure to DDT

This study assesses the effects of 1,1-bis (4-chlorophenyl)-2,2,2-trichloroethane (DDT) on the reproduction and gonadal histology of adult Mozambique tipalia (Oreochromis mossambicus). The fish were allowed to breed, following exposure to 2 and 5μg/l of waterborne technical-grade DDT for 40 days. Fertilized eggs were artificially incubated. In the 5μg/l exposure, posthatch survival was significantly lower, and prevalence of larval skeletal deformities significantly higher, compared to the control (p<0.05). Incomplete axial development was the common gross deformity in posthatch larvae, caused by failure to develop chondroblasts posterior to the buccopharyngeal cavity. There were no significant differences in the gonadosomatic index of exposed and non-exposed male and female adults. The exposure caused increased oocyte atresia in the ovaries and disorganization of seminiferous lobules in the testes of adults. DDT exposure reduced survival and increased deformities in larvae, at levels that did not cause severe histopathological changes to parental gonads.

Alpha-glucosidase activity and sperm motility.

Summary We correlated the activity of alpha‐glucosidase in seminal plasma with the motility and differential motility of sperm. Significant positive correlations were found between the alpha‐glucosidase activity and both motility and the percentage sperm with good forward progression. This supports the use of alpha‐glucosidase in semen as a marker of epididymal function and specifically of the development of motility.

The role of the PCA3 assay in predicting prostate biopsy outcome in a South African setting

Study Type – Diagnostic (exploratory cohort)

Prevalence of human papilloma virus in men attending the infertility clinic

Summary. Subclinical human papilloma virus is a potential carcinogen in the male and female genital tract. The sexually active male infertility population represents a high risk group for harbouring this disease. To determine the prevalence of subclinical human papillomavirus in this group, penoscopy was done on 96 male patients visiting the infertility clinic. The feasibility of routine penoscopy as part of the infertility work‐up was also investigated. Of the 96 patients 20 had acetowhite lesions on their penes with penoscopy. Thirteen patients (13.5%), 12 proven by biopsy of the aceto‐white lesions, and one proven by fluid in situ hybridization on superficial epithelial cells of the distal urethra, were positive for human papillomavirus. Two of the 12 biopsy‐positive cases were also proven positive by fluid in situ hybridization. It was concluded that human papillomavirus had a high prevalence amongst asymptomatic male patients attending the infertility clinic and that penoscopy should be included as routine investigation in the work‐up of the male infertility patient.—