Full-Life Cycle Toxicity Assessment of Sediment-Bound DDT and Its Degradation Products on Chironomus dilutus.

Because of its hydrophobicity and persistence, dichlorodiphenyltrichloroethane (DDT) is ubiquitous in sediments and poses significant risk to benthic organisms. Therefore, it is imperative to evaluate the long-term toxicity of DDT. However, limited information is available on its chronic toxicity to benthic invertebrates. Full-life cycle toxicity of sediment-bound DDT to Chironomus dilutus was assessed. Median lethal concentrations (with 95% confidence limits) of DDT and its degradation products (DDX) to C. dilutus were 334 (165-568), 21.4 (11.2-34.3), and 7.50 (4.61-10.6) nmol/g organic carbon after 10-, 20-, and 63-d exposure, respectively. In addition, median effect concentrations of DDX were 20.0 (15.0-25.3), 7.13 (4.10-10.5), and 8.92 (3.32-15.1) nmol/g organic carbon for growth, emergence, and reproduction, respectively. A toxicity spectrum was established to visually summarize chronic effects of DDX to midges. In addition, DDT degraded to dichlorodiphenyldichloroethane (DDD) and dichlorodiphenyldichloroethylene (DDE) during sediment aging, and their toxicity differed from that of the parent compound. Predicted toxic units of DDX in porewater were utilized to distinguish between toxicity from DDT and that of DDD and DDE. The results showed that DDD was the main contributor to the toxicity in C. dilutus. To improve the accuracy of sediment risk assessment of DDT, the composition of DDX should be considered. Environ Toxicol Chem 2019;38:2698-2707. © 2019 SETAC.

Cytokine expression and lymphocyte proliferative capacity in diseased harbor porpoises (Phocoena phocoena) - Biomarkers for health assessment in wildlife cetaceans.

Harbor porpoises (Phocoena phocoena) in the North and Baltic Seas are exposed to anthropogenic influences including acoustic stress and environmental contaminants. In order to evaluate immune responses in healthy and diseased harbor porpoise cells, cytokine expression analyses and lymphocyte proliferation assays, together with toxicological analyses were performed in stranded and bycaught animals as well as in animals kept in permanent human care. Severely diseased harbor porpoises showed a reduced proliferative capacity of peripheral blood lymphocytes together with diminished transcription of transforming growth factor-ß and tumor necrosis factor-α compared to healthy controls. Toxicological analyses revealed accumulation of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) in harbor porpoise blood samples. Correlation analyses between blood organochlorine levels and immune parameters revealed no direct effects of xenobiotics upon lymphocyte proliferation or cytokine transcription, respectively. Results reveal an impaired function of peripheral blood leukocytes in severely diseased harbor porpoises, indicating immune exhaustion and increased disease susceptibility.

Validation of commercial real-time PCR-arrays for environmental risk assessment: Application to the study of p,p´-DDE toxicity in Mus spretus mice liver.

Data on gene transcription profiles provide a comprehensive assessment of the toxic and defensive mechanisms that are triggered by pollutants. PCR-arrays have emerged as a reliable tool for analyzing the expression of a panel of relevant, pathway- or disease-focused genes under uniform cycling conditions. By using SYBR Green-optimized primer assays, it is possible to simultaneously amplify a sample with high specificity and amplification efficiencies. However, commercial PCR-arrays target a limited group of organisms, excluding most of those with environmental relevance, as is the case with Mus spretus mice. Our previous works with M. spretus showed a high sequence similarity between M. spretus and the model organism M. musculus allowing the use of commercial platforms with M. spretus. This work demonstrates the successful application of a commercial PCR-array designed for the model organism M. musculus to assess the biological effects caused by the organochlorine pesticide p,p´-DDE in a focused panel of stress-related genes in M. spretus mice. This cost-effective, easy-to-use platform detected quantitative gene profiling differences between M. spretus hepatic RNA samples and generated data highly concordant with those obtained by absolute qRT-PCR, the most sensitive method to quantify transcripts. This platform is also suitable for use in field studies with free-living M. spretus mice for routine environmental risk assessment. Our results provide a broad impression of the biological consequences of p,p´-DDE on the hepatic health of mice.

Establishment of the first humpback whale fibroblast cell lines and their application in chemical risk assessment.

This paper reports the first successful derivation and characterization of humpback whale fibroblast cell lines. Primary fibroblasts were isolated from the dermal connective tissue of skin biopsies, cultured at 37 °C and 5% CO2 in the standard mammalian medium DMEM/F12 supplemented with 10% fetal bovine serum (FBS). Of nine initial biopsies, two cell lines were established from two different animals and designated HuWa1 and HuWa2. The cells have a stable karyotype with 2n=44, which has commonly been observed in other baleen whale species. Cells were verified as being fibroblasts based on their spindle-shaped morphology, adherence to plastic and positive immunoreaction to vimentin. Population doubling time was determined to be ∼41 h and cells were successfully cryopreserved and thawed. To date, HuWa1 cells have been propagated 30 times. Cells proliferate at the tested temperatures, 30, 33.5 and 37 °C, but show the highest rate of proliferation at 37 °C. Short-term exposure to para,para'-dichlorodiphenyldichloroethylene (p,p'-DDE), a priority compound accumulating in southern hemisphere humpback whales, resulted in a concentration-dependent loss of cell viability. The effective concentration which caused a 50% reduction in HuWa1 cell viability (EC50 value) was approximately six times greater than the EC50 value for the same chemical measured with human dermal fibroblasts. HuWa1 exposed to a natural, p,p'-DDE-containing, chemical mixture extracted from whale blubber showed distinctively higher sensitivity than to p,p'-DDE alone. Thus, we provide the first cytotoxicological data for humpback whales and with establishment of the HuWa cell lines, a unique in vitro model for the study of the whales' sensitivity and cellular response to chemicals and other environmental stressors.

Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

CONTEXT: Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. OBJECTIVE: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. DESIGN: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. RESULTS: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555-5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6-86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of €835 million (sensitivity analysis: €835 million-16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. CONCLUSIONS: EDC exposures in the EU contribute substantially to obesity and diabetes, with a moderate probability of >€18 billion costs per year. This is a conservative estimate; the results emphasize the need to control EDC exposures.

Organochlorine pesticides in fish from Taihu Lake, China, and associated human health risk assessment.

Because contaminants and nutrients always coexist in fish, the risk from contaminants and the benefit from nutrients, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also concomitant via fish consumption. To investigate the risk and benefit via fish consumption, concentrations of dichlorodiphenyltrichloroethane and its metabolites (DDTs), and hexachlorocyclohexanes (HCHs) in the whole- and portion-muscles of fish from Taihu Lake, China, were measured. Based on the contaminant data and nutrients from our previous study, and the associated risk and benefit via fish consumption were estimated. The concentrations of DDTs and HCHs in the whole-muscles ranged from 7.8 × 10² to 3.4×10³ pg g⁻¹ ww, and from 67.3 to 300 pg g⁻¹ ww, respectively. Of DDTs and HCHs measured, p,p'-DDE and ß-HCH were respectively the most abundant pesticides. The composition profiles of DDTs and HCHs suggested that the pesticides were mainly historical residues. The benefit-risk quotient (BRQ) of EPA+DHA vs. POPs (persistent organic pollutants including data of DDTs, HCHs, and those of polychlorinated biphenyls and polybrominated diphenyl ethers cited from our previous study) via consumption of fish from Taihu Lake was calculated. As a result, to achieve the recommended EPA+DHA intake of 250 mg d⁻¹ for a healthy adult, the consumption of most fish species from the lake can cause cancer and non-cancer risks. However, the fish consumption at the rates of 44.9 g d⁻¹ by Chinese would not lead to the risks for most of the species. The results also suggested that the risk of consuming silver carp was generally lower than other fish species, and those of dorsal muscles were lower than ventral and tail muscles.

Longitudinal association between early life socio-environmental factors and attention function at the age 11 years.

Prenatal and early-life exposures can affect the course of children's neuropsychological development well into pre-adolescence, given the vulnerability of the developing brain. However, it is unknown which socio-environmental factors at early childhood can influence specific cognitive processes like attention at a later age. In this study, we aim to determine social and environmental exposures in early childhood that may be associated with attention function of 11-year-olds. We measured attention function using the continuous performance test-II (CPT-II) on 393 11-year old children from the Menorca's birth-cohort within the INMA-project (Spain), and pre-selected a list of socio-environmental observations taken when they were up to 4 years of age. We found that earlier socio-environmental characteristics, such as parental social class, educational level and maternal mental health are associated with later inattentive and impulsive symptomatology through a higher rate of omission and commission errors. In addition, omission errors were higher in children with atopy and lower in those whose mothers took dietary supplementation with folic acid and vitamins during pregnancy. Breastfeeding played a protective role against commission errors, while higher DDE and PCBs levels at age 4 were associated with slow speed response. Our findings suggest that a number of life socio-environmental factors during prenatal life and early childhood, such as socio-demographic characteristics, breastfeeding, maternal nutritional supplementation with folic acid and vitamins and exposure to some organochlorine compounds may influence inattentive and hyperactive/impulsive symptomatology during pre-adolescence.

DDTs in rice frogs (Rana limnocharis) from an agricultural site, South China: tissue distribution, biomagnification, and potential toxic effects assessment.

Contamination with agricultural pesticides such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), is among several proposed stressors contributing to the global declines in amphibian populations and species biodiversity. These chemicals were examined in insects and in the muscle, liver, and eggs of rice frogs (Rana limnocharis) from the paddy fields of an agricultural site in South China. The ΣDDT (sum of DDT, DDE, and DDD) concentrations ranged from 154 to 915, 195 to 1,400, and 165 to 1,930 ng/g lipid weight in the muscle, liver, and eggs, respectively. All the DDTs (DDT, DDE, and DDD) showed higher affinity for the liver relative to muscle tissue and can be maternally transferred to eggs in female frogs. The average biomagnification factors for DDTs ranged from 1.6 to 1.9 and 1.5 to 2.9 in female and male frogs, respectively, providing clear evidence of their biomagnification from insects to frogs. Compared with the reported DDT levels demonstrated to have toxic effects on frogs, DDTs in the present frogs are unlikely to constitute an immediate health risk. However, the adverse impacts of high DDT residues in eggs on the hatching success and their potential toxicity to the newly metamorphosed larval frogs should be assessed further.

Occurrence, source diagnosis, and biological effect assessment of DDT and its metabolites in various environmental compartments of the Pearl River Delta, South China: a review.

This review summarizes and analyzes available data in the literature (mostly after 2000) on the occurrence of dichlorodiphenyltrichloroethane (DDT) and its main metabolites, dichlorodiphenyldichloroethane (DDD) and chlorodiphenyldichloroethylene (DDE), in the environment of the Pearl River Delta (PRD), South China. Generally, the concentration levels of the sum of DDT, DDD, and DDE, designated as DDTs thereafter, have not significantly declined since 1983. However, the composition of DDTs residues has changed with time. DDTs in soil, freshwater sediment and freshwater fish species were mainly residues from chronological use. There is evidence that new point sources, such as dicofol and anti-fouling paint, may have contributed DDTs to various environmental compartments. Risk assessment against existing criteria indicated that the levels of DDTs in water and some fish species may pose adverse effects to humans or wildlife, and those in sediment/soil may also cause negative impacts to the eco-environment of the PRD.

Prenatal organochlorine exposure and measures of behavior in infancy using the Neonatal Behavioral Assessment Scale (NBAS).

BACKGROUND: Previous literature suggests an association between organochlorines and behavioral measures in childhood, including inattention. OBJECTIVE: This study was designed to assess whether prenatal organochlorine exposure is associated with measures of attention in early infancy. METHODS: We investigated an association between cord serum polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyl dichloroethene (DDE) levels and measures of attention from the Neonatal Behavioral Assessment Scale (NBAS) in a cohort of 788 infants born 1993-1998 to mothers residing near a PCB-contaminated harbor and Superfund site in New Bedford, Massachusetts. RESULTS: Medians (ranges) for the sum of four prevalent PCB congeners and DDE levels were 0.19 (0.01-4.41) and 0.30 (0-10.29) ng/g serum, respectively. For the 542 subjects with an NBAS exam at 2 weeks, we observed consistent inverse associations between cord serum PCB and DDE levels and NBAS measures of alertness, quality of alert responsiveness, cost of attention, and other potential attention-associated measures including self-quieting and motor maturity. For example, the decrement in quality of alert responsiveness score was -0.51 (95% confidence interval, -0.99 to -0.03) for the highest quartile of exposure to the sum of four prevalent PCB congeners compared with the lowest quartile. We found little evidence for an association with infant orientation, habituation, and regulation of state, assessed as summary cluster measures. CONCLUSIONS: Our findings provide evidence for an association between low-level prenatal PCB and DDE exposures and poor attention in early infancy. Further analyses will focus on whether organochlorine-associated decrements in attention and attention-related skills in infancy persist in later childhood.

Assessment of the genotoxic potential of benzo(a)pyrene and pp'-dichlorodiphenyldichloroethylene in Zebra mussel (Dreissena polymorpha).

The single-cell gel electrophoresis (SCGE) assay and the micronucleus (MN) test were carried out with haemocytes of Zebra mussel (Dreissena polymorpha) specimens to evaluate the potential genotoxicity of benzo(a)pyrene (BaP) and pp'-dichlorodiphenyldichloroethylene (pp'-DDE, a metabolite of pp'-DDT). Mussels were exposed to three different concentrations (0.1 microg/L, 2 microg/L, 10 microg/L) of each chemical in water during 168 h (SCGE assay) and 96 h (MN test) of exposure under laboratory conditions. These levels correspond to nominal molar concentrations of 0.4 nM, 7.9 nM and 40 nM for BaP and 0.3 nM, 6.2 nM and 31 nM for pp'-DDE, respectively. Concurrently, the levels of toxicants were measured in soft tissues of the mussels by gas-chromatographic analyses, to evaluate their temporal trends and the dose/response relationships. Significant increases of the ratio between the comet length and the diameter of the comet head (LDR) and of micronucleus frequencies in comparison with baseline levels were observed not only for all concentrations of BaP, but also for pp'-DDE (except 0.3 nM). The concentration above which DNA damage starts to be significantly increased was 0.8 nmol/g lipids for BaP and 1.6 nmol/g lipids for pp'-DDE, respectively. The results of these experiments show a clear genotoxic effect on this non-target organism not only for the well-known genotoxicant BaP, but also for the final metabolite of pp'-DDT at soft-tissue concentrations that have been found in several aquatic ecosystems worldwide.

Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort.

Prenatal exposures to organophosphate pesticides and polychlorinated biphenyls have been associated with abnormal neonatal behavior and/or primitive reflexes. In 1998-2002, the Mount Sinai Children's Environmental Health Center (New York City) investigated the effects of indoor pesticide use and exposure to polychlorinated biphenyls on pregnancy outcome and child neurodevelopment in an inner-city multiethnic cohort. The Brazelton Neonatal Behavioral Assessment Scale was administered before hospital discharge (n = 311). Maternal urine samples were analyzed for six dialkylphosphate metabolites and malathion dicarboxylic acid. A random subset of maternal peripheral blood samples from the entire cohort (n = 194) was analyzed for polychlorinated biphenyls and 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene. Malathion dicarboxylic acid levels above the limit of detection were associated with a 2.24-fold increase in the number of abnormal reflexes (95% confidence interval: 1.55, 3.24). Likewise, higher levels of total diethylphosphates and total dialkylphosphates were associated with an increase in abnormal reflexes, as was total dimethylphosphates after paraoxonase expression was considered. No adverse associations were found with polychlorinated biphenyl or 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene levels and any behavior. The authors uncovered additional evidence that prenatal levels of organophosphate pesticide metabolites are associated with anomalies in primitive reflexes, which are a critical marker of neurologic integrity.

In utero exposure to DDT and performance on the Brazelton neonatal behavioral assessment scale.

We investigated whether decrements in neonatal neurodevelopment, as determined by the Brazelton neonatal behavioral assessment scale (BNBAS), were associated with in utero exposure to dichlorodiphenyltrichloroethane (DDT): p,p'-dichlorodiphenyl trichloroethane (p,p'-DDT), o,p'-dichlorodiphenyl trichloroethane (o,p'-DDT) and p,p'-DDT's primary breakdown product p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) (heretofore collectively referred to as DDT/DDE). Our subjects were a birth cohort of 303 infants whose mothers were low-income Latinas living in the Salinas Valley, an agricultural community in California. We assessed neonates < or =2 months old using the seven BNBAS clusters (habituation, orientation, motor performance, range of state, regulation of state, autonomic stability, and reflex) and examined performance in relationship to DDT/DDE measures in maternal serum samples collected during pregnancy. We did not find any detrimental associations between in utero DDT/DDE levels and neonatal performance on the BNBAS. In this same cohort, we previously demonstrated that exposures to DDT/DDE were related to decrements in neurodevelopment at 6-24 months of age. The failure to observe effects on the BNBAS in these same children may be due to limited sensitivity of a single BNBAS assessment or a delay in the manifestations of neurodevelopmental effects of DDT/DDE until after the neonatal period.

Bayesian isotonic regression and trend analysis.

In many applications, the mean of a response variable can be assumed to be a nondecreasing function of a continuous predictor, controlling for covariates. In such cases, interest often focuses on estimating the regression function, while also assessing evidence of an association. This article proposes a new framework for Bayesian isotonic regression and order-restricted inference. Approximating the regression function with a high-dimensional piecewise linear model, the nondecreasing constraint is incorporated through a prior distribution for the slopes consisting of a product mixture of point masses (accounting for flat regions) and truncated normal densities. To borrow information across the intervals and smooth the curve, the prior is formulated as a latent autoregressive normal process. This structure facilitates efficient posterior computation, since the full conditional distributions of the parameters have simple conjugate forms. Point and interval estimates of the regression function and posterior probabilities of an association for different regions of the predictor can be estimated from a single MCMC run. Generalizations to categorical outcomes and multiple predictors are described, and the approach is applied to an epidemiology application.

The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p'-DDE.

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p -DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p -DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners.

Membrane lipid composition of Bacillus stearothermophilus as affected by lipophilic environmental pollutants: an approach to membrane toxicity assessment.

The thermophilic eubacterium Bacillus stearothermophilus is used as a model to identify membrane perturbing effects of lipophilic compounds. A parallelism has been established between the toxicity of the organochlorine insecticide DDT and its metabolite, DDE, in bacterial growth and the effects on cell functions and physical perturbations induced at the membrane (Donato et al. 1997a, Arch Environ Contam Toxicol 33:109-116; Donato et al. 1997b, Appl Environ Microbiol 63:4948-495). In the present work, the use of B. stearothermophilus as a model of screening for chemical toxicity has been implemented. Because the regulation of the lipid composition of the membrane is a common strategy in response to adverse growth conditions, we studied the effects of DDE on the lipid composition and the consequent alterations of membrane physical properties in comparison to the parental compound DDT. As expected, different adaptation responses were induced by the compounds, being DDT more effective as compared with DDE. Collected data are consistent with the stronger perturbations induced by DDT on growth and membrane functions. It is concluded that the membrane lipid composition of the bacterium is a very sensitive criterium to detect membrane-mediated toxic effects at low concentrations of lipophilic xenobiotics.