Riana Bornman

Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors

The “common sense” intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

High levels of DDT in breast milk: intake, risk, lactation duration, and involvement of gender

We investigated presence and levels of DDT in 163 breast milk samples from four South African villages where, in three of them, malaria is controlled with DDT-sprayed indoors. Mean ΣDDT levels in breast milk were 18, 11, and 9.5 mg/kg mf (milk fat) from the three DDT-sprayed villages, respectively, including the highest ΣDDT level ever reported for breast milk from South Africa (140 mg/kg mf). Understanding the causes for these differences would be informative for exposure reduction intervention. The Provisional Tolerable Daily Intake (PTDI) for DDT by infants, and the Maximum Residue Limit (MRL) were significantly exceeded. DDT had no effect on duration of lactation. There were indications (not significant) from DDT-sprayed villages that first-born female infants drink milk with more ΣDDT than first-born male infants, and vice versa for multipara male and female infants, suggesting gender involvement on levels of DDT in breast milk - requiring further investigation.

A path forward in the debate over health impacts of endocrine disrupting chemicals

Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate.

Estimation of human body concentrations of DDT from indoor residual spraying for malaria control.

Inhabitants of dwellings treated with DDT for indoor residual spraying show high DDT levels in blood and breast milk. This is of concern since mothers transfer lipid-soluble contaminants such as DDT via breastfeeding to their children. Focusing on DDT use in South Africa, we employ a pharmacokinetic model to estimate DDT levels in human lipid tissue over the lifetime of an individual to determine the amount of DDT transferred to children during breastfeeding, and to identify the dominant DDT uptake routes. In particular, the effects of breastfeeding duration, parity, and mothers age on DDT concentrations of mother and infant are investigated. Model results show that primiparous mothers have greater DDT concentrations than multiparous mothers, which causes higher DDT exposure of first-born children. DDT in the body mainly originates from diet. Generally, our modeled DDT levels reproduce levels found in South African biomonitoring data within a factor of 3.

Anti-Müllerian hormone and lifestyle, reproductive, and environmental factors among women in rural South Africa.

Background: Few data exist regarding anti-Müllerian hormone, a marker of ovarian reserve, in relation to environmental factors with potential ovarian toxicity. Methods: This analysis included 420 women from Limpopo, South Africa studied in 2010–2011. Women were administered comprehensive questionnaires, and plasma concentrations of anti-Müllerian hormone and dichlorodiphenyltrichloroethane were determined. We used separate multivariable models to examine the associations between natural log-transformed anti-Müllerian hormone concentration (ng/ml) and each of the lifestyle, reproductive, and environmental factors of interest, adjusted for age, body mass index, education, and parity. Results: The median age of women was 24 years (interquartile range [IQR] = 22 to 26); the median anti-Müllerian hormone concentration was 3.1 ng/ml (IQR = 2.0 to 6.0). Women who reported indoor residual spraying in homes with painted walls (indicative of exposure to pyrethroids) had 25% lower (95% confidence interval [CI] = -39%, -8%) anti-Müllerian hormone concentrations compared with women who reported no spraying. Little evidence of decreased anti-Müllerian hormone concentrations was observed among women with the highest dichlorodiphenyltrichloroethane levels. Compared with women who used an electric stove, no association was observed among women who cooked indoors over open wood fires. The findings also suggested lower anti-Müllerian hormone concentrations among women who drank coffee (-19% [95% CI = -31%, -5%]) or alcohol (-21% [95% CI = -36%, -3%]). Conclusions: These are among the first data regarding anti-Müllerian hormone concentrations relative to pesticides and indoor air pollution. Our results are suggestive of decreased ovarian reserve associated with exposure to pyrethroid pesticides, which is consistent with laboratory animal data.

The use of the urogenital papillae of male feral African sharptooth catfish (Clarias gariepinus) as indicator of exposure to estrogenic chemicals in two polluted dams in an urban nature reserve, Gauteng, South Africa.

The African sharptooth catfish (Clarias gariepinus) is indigenous to South Africa where it is commonly found in calm waters such as lakes, streams, rivers, swamps and floodplains. The males of this gonochoristic species can be readily distinguished from females via a distinct elongated urogenital papilla with a pointed tip, located just behind the anus. This structure is an androgen controlled secondary sexual characteristic and could potentially be affected by chemicals displaying endocrine disrupting properties during development. Results of previous studies on effects on papillae of different fish species indicated that these structures could be useful as bio-indicators of exposure due to alterations in the structures. This study investigated the occurrence of abnormal morphology in urogenital papillae compared to the macroscopic and microscopic structure of the gonads of presumed male or intersex catfish sampled from the Rietvlei and Marais dams in an urban nature reserve, due to exposure to endocrine disrupting chemicals (EDCs). Macroscopic observation of the UGP, gonad examination after laparotomy and histology were done. Gonadosomatic index (GSI) and Urogenital papilla length index (UGPLI) were determined for all fish collected. Mesenteric fat analyzed for selected alkylphenols and organochlorines showed high levels of especially nonylphenol indicating long term exposure to these chemicals due to bio-accumulation. The GSI indicated that fish with intersex gonads were probably feminized males. It was concluded that use of the UGP alone, without macroscopic and microscopic analyses of the gonads, could not effectively indicate exposure to EDCs.

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.

Sustainable malaria control: transdisciplinary approaches for translational applications

With the adoption of the Global Malaria Action Plan, several countries are moving from malaria control towards elimination and eradication. However, the sustainability of some of the approaches taken may be questionable. Here, an overview of malaria control and elimination strategies is provided and the sustainability of each in context of vector- and parasite control is assessed. From this, it can be concluded that transdisciplinary approaches are essential for sustained malaria control and elimination in malaria-endemic communities.

First report of the concentrations and implications of DDT residues in chicken eggs from a malaria-controlled area

In malaria-endemic areas, where DDT is still used for vector control by indoor residual spraying (IRS), the concentrations of DDT in human blood and breast milk are high, and there are indications of human health impacts. To identify the possible avenues of exposure reduction, we created the concept of a Total Homestead Environment Approach (THEA). THEA characterizes the interactions between DDT, humans, and the biota within and around homesteads. One dietary route of human exposure and uptake of DDT, namely, chicken egg consumption, has to our knowledge never been studied. The ΣDDT in eggs from a DDT-sprayed village ranged between 5200 and 48,000 ng/g wm (wet mass), with a median of 11,000 ng/g wm. On a lipid mass-basis (lm), the mean ΣDDT for eggs from the sprayed village was 100,000 ng/g lm. The maximum egg concentration observed was three orders of magnitude higher than the median. The acceptable daily intake (ADI) was not exceeded based on the consumption of three eggs per week for a 60 kg person. This equates to an intake of 0.089 g DDT per person per year. Chicken egg consumption is therefore a possible target for exposure reduction, probably best achieved by reducing the DDT concentrations in soils.

Revised timeline and distribution of the earliest diverged human maternal lineages in southern Africa

The oldest extant human maternal lineages include mitochondrial haplogroups L0d and L0k found in the southern African click-speaking forager peoples broadly classified as Khoesan. Profiling these early mitochondrial lineages allows for better understanding of modern human evolution. In this study, we profile 77 new early-diverged complete mitochondrial genomes and sub-classify another 105 L0d/L0k individuals from southern Africa. We use this data to refine basal phylogenetic divergence, coalescence times and Khoesan prehistory. Our results confirm L0d as the earliest diverged lineage (∼172 kya, 95%CI: 149–199 kya), followed by L0k (∼159 kya, 95%CI: 136–183 kya) and a new lineage we name L0g (∼94 kya, 95%CI: 72–116 kya). We identify two new L0d1 subclades we name L0d1d and L0d1c4/L0d1e, and estimate L0d2 and L0d1 divergence at ∼93 kya (95%CI:76–112 kya). We concur the earliest emerging L0d1’2 sublineage L0d1b (∼49 kya, 95%CI:37–58 kya) is widely distributed across southern Africa. Concomitantly, we find the most recent sublineage L0d2a (∼17 kya, 95%CI:10–27 kya) to be equally common. While we agree that lineages L0d1c and L0k1a are restricted to contemporary inland Khoesan populations, our observed predominance of L0d2a and L0d1a in non-Khoesan populations suggests a once independent coastal Khoesan prehistory. The distribution of early-diverged human maternal lineages within contemporary southern Africans suggests a rich history of human existence prior to any archaeological evidence of migration into the region. For the first time, we provide a genetic-based evidence for significant modern human evolution in southern Africa at the time of the Last Glacial Maximum at between ∼21–17 kya, coinciding with the emergence of major lineages L0d1a, L0d2b, L0d2d and L0d2a.