Browsing by Subject "DDT"

Now showing 1 - 5 of 5
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    A Pilot Expert Elicitation to Assess the Risks of Malaria Vector Control Strategies in East Africa
    (2007-05) Beerbohm, Elissa
    Perhaps no other issue has divided the environmental and health communities as much as DDT. The re-introduction of DDT in several East African countries, as well as the demand for evidence-based policy, has led researchers at Duke University to develop the Malaria Decision Analysis Support Tool (MDAST). One facet of the MDAST is to assess the economic, environmental, and human health risks associated with alternative strategies for managing malaria. In this pilot survey and elicitation, risks are assessed for the two most commonly used vector control strategies – indoor residual spraying and insecticide-treated bednets – in Uganda, Tanzania, and Kenya. The elicitation encompasses a broad range of hazard pathways and risks, including harm to nontarget species, agricultural trade restrictions, and vector resistance, some of which are frequently neglected in the policy debate. Preliminary results from the survey indicate that decision-makers are highly concerned with the emergence of vector resistance from ITNs, IRS with DDT, and IRS with ICON. High levels of concern were present for all additional risks associated with DDT, including human health impacts, environmental impacts, and trade restrictions. Results from the elicitation revealed that experts assessing harm to nontarget species and the potential for trade restrictions attributed the highest level of risk to mismanagement of DDT and ICON. Results from the elicitation for vector resistance were even more alarming; the expert assessed high risks of the potential for vector resistance to occur from all pathways associated with permethrin-treated bednets and IRS with DDT. Again, high risks were attributed to mismanagement of DDT and ICON, indicating that mismanagement of insecticides is the riskiest pathway of exposure.
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    Adult exposure to insecticides causes persistent behavioral and neurochemical alterations in zebrafish.
    (Neurotoxicology and teratology, 2020-03) Hawkey, Andrew B; Glazer, Lilah; Dean, Cassandra; Wells, Corinne N; Odamah, Kathryn-Ann; Slotkin, Theodore A; Seidler, Frederic J; Levin, Edward D
    Farmers are often chronically exposed to insecticides, which may present health risks including increased risk of neurobehavioral impairment during adulthood and across aging. Experimental animal studies complement epidemiological studies to help determine the cause-and-effect relationship between chronic adult insecticide exposure and behavioral dysfunction. With the zebrafish model, we examined short and long-term neurobehavioral effects of exposure to either an organochlorine insecticide, dichlorodiphenyltrichloroethane (DDT) or an organophosphate insecticide chlorpyrifos (CPF). Adult fish were exposed continuously for either two or 5 weeks (10-30 nM DDT, 0.3-3 μM CPF), with short- and long-term effects assessed at 1-week post-exposure and at 14 months of age respectively. The behavioral test battery included tests of locomotor activity, tap startle, social behavior, anxiety, predator avoidance and learning. Long-term effects on neurochemical indices of cholinergic function were also assessed. Two weeks of DDT exposure had only slight effects on locomotor activity, while a longer five-week exposure led to hypoactivity and increased anxiety-like diving responses and predator avoidance at 1-week post-exposure. When tested at 14 months of age, these fish showed hypoactivity and increased startle responses. Cholinergic function was not found to be significantly altered by DDT. The two-week CPF exposure led to reductions in anxiety-like diving and increases in shoaling responses at the 1-week time point, but these effects did not persist through 14 months of age. Nevertheless, there were persistent decrements in cholinergic presynaptic activity. A five-week CPF exposure led to long-term effects including locomotor hyperactivity and impaired predator avoidance at 14 months of age, although no effects were apparent at the 1-week time point. These studies documented neurobehavioral effects of adult exposure to chronic doses of either organochlorine or organophosphate pesticides that can be characterized in zebrafish. Zebrafish provide a low-cost model that has a variety of advantages for mechanistic studies and may be used to expand our understanding of neurobehavioral toxicity in adulthood, including the potential for such toxicity to influence behavior and development during aging.
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    A Risk‐Risk Trade‐off: Insecticide Use for Malaria Control 
    (2011-04-29) Pfau, Kristen
    Malaria is among the top causes of death in low-income countries. Because it is transmitted through a mosquito vector, programs to reduce or control these insects receive much attention. Recently, concerns have increased regarding possible chronic reproductive impairment following exposure to insecticides used in mosquito control. This project examines the human health benefits and potential human health consequences of indoor residual spraying (IRS), an increasingly popular method of insecticide use for malaria control. Meta-analysis was used to aggregate the results of published trials on efficacy of IRS in reducing malaria prevalence in a region. Statistical analysis incorporating results of all these studies led to general conclusions about the impact of any IRS program, and provided insight as to what variables resulted in greater effects in one community over another—for example, the type of insecticide used, the initial malaria prevalence in the community, and the time frame of the program. Next, the potential chronic human health consequences were assessed through a review of chemical, toxicological and epidemiological studies. Research focused on two chemicals, lambda-cyhalothrin and DDT. Screening of chemical properties and toxicological studies indicate a potential risk for negative human health outcomes from exposure to both chemicals. Identification and critique of several epidemiological studies that link exposure to IRS with negative reproductive health outcomes verify this risk for DDT. Finally, a series of interviews with malaria control experts in Tanzania provided insight on the cumulative perceptions of decision-makers regarding both the benefits and the consequences illustrated in the previous sections, as well as a variety of other facets of malaria prevention. While this project only presents a small portion of benefits and risks associated with using insecticides for malaria control, it is evident that the current risk assessment-risk management paradigm is not adequate for informing decisions on risk tradeoffs. The benefits and risks need to be considered holistically, not independently, in order to inform quality risk policies. Based on the case study of insecticide use for malaria control, a new framework is suggested in which risk tradeoffs are approached in an interdisciplinary, collaborative manner.
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    Molecular evidence of sequential evolution of DDT- and pyrethroid-resistant sodium channel in Aedes aegypti.
    (PLoS neglected tropical diseases, 2019-06-03) Chen, Mengli; Du, Yuzhe; Wu, Shaoying; Nomura, Yoshiko; Zhu, Guonian; Zhorov, Boris S; Dong, Ke
    BACKGROUND:Multiple mutations in the voltage-gated sodium channel have been associated with knockdown resistance (kdr) to DDT and pyrethroid insecticides in a major human disease vector Aedes aegypti. One mutation, V1016G, confers sodium channel resistance to pyrethroids, but a different substitution in the same position V1016I alone had no effect. In pyrethroid-resistant Ae. aegypti populations, V1016I is often linked to another mutation, F1534C, which confers sodium channel resistance only to Type I pyrethroids including permethrin (PMT), but not to Type II pyrethroids including deltamethrin (DMT). Mosquitoes carrying both V1016G and F1534C exhibited a greater level of pyrethroid resistance than those carrying F1534C alone. More recently, a new mutation T1520I co-existing with F1534C was detected in India. However, whether V1016I or T1520I enhances pyrethroid resistance of sodium channels carrying F1534C remains unknown. METHODOLOGY/PRINCIPAL FINDINGS:V1016I, V1016G, T1520I and F1534C substitutions were introduced alone and in various combinations into AaNav1-1, a sodium channel from Aedes aegypti. The mutant channels were then expressed in Xenopus oocytes and examined for channel properties and sensitivity to pyrethroids using the two-electrode voltage clamping technique. The results showed that V1016I or T1520I alone did not alter the AaNav1-1 sensitivity to PMT or DMT. However, the double mutant T1520I+F1534C was more resistant to PMT than F1534C, but remained sensitive to DMT. In contrast, the double mutant V1016I+F1534C was resistant to DMT and more resistant to PMT than F1534C. Furthermore, V1016I/G and F1534C channels, but not T1520I, were resistant to dichlorodiphenyltrichloroethane (DDT). Cryo-EM structures of sodium channels suggest that T1520I allosterically deforms geometry of the pyrethroid receptor site PyR1 in AaNav1-1. The small deformation does not affect binding of DDT, PMT or DMT, but in combination with F1534C it increases the channel resistance to PMT and DDT. CONCLUSIONS/SIGNIFICANCE:Our data corroborated the previously proposed sequential selection of kdr mutations in Ae. aegypti. We proposed that mutation F1534C first emerged in response to DDT/pyrethroids providing a platform for subsequent selection of mutations V1016I and T1520I that confer greater and broader spectrum of pyrethroid resistance.
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    Neurobehavioral anomalies in zebrafish after sequential exposures to DDT and chlorpyrifos in adulthood: Do multiple exposures interact?
    (Neurotoxicology and teratology, 2021-09) Hawkey, Andrew B; Holloway, Zade; Dean, Cassandra; Koburov, Reese; Slotkin, Theodore A; Seidler, Frederic J; Levin, Edward D
    A sequence of different classes of synthetic insecticides have been used over the past 70 years. Over this period, the widely-used organochlorines were eventually replaced by organophosphates, with dichlorodiphenyltrichloroethane (DDT) and chlorpyrifos (CPF) as the principal prototypes. Considerable research has characterized the risks of DDT and CPF individually, but little is known about the toxicology of transitioning from one class of insecticides to another, as has been commonplace for agricultural and pest control workers. This study used adult zebrafish to investigate neurobehavioral toxicity following 5-week chronic exposure to either DDT or CPF, to or their sequential exposure (DDT for 5 weeks followed by CPF for 5 weeks). At the end of the exposure period, a subset of fish were analyzed for brain cholinesterase activity. Behavioral effects were initially assessed one week following the end of the CPF exposure and again at 14 months of age using a behavioral test battery covering sensorimotor responses, anxiety-like functions, predator avoidance and social attraction. Adult insecticide exposures, individually or sequentially, were found to modulate multiple behavioral features, including startle responsivity, social approach, predator avoidance, locomotor activity and novel location recognition and avoidance. Locomotor activity and startle responsivity were each impacted to a greater degree by the sequential exposures than by individual compounds, with the latter being pronounced at the early (1-week post exposure) time point, but not 3-4 months later in aging. Social approach responses were similarly impaired by the sequential exposure as by CPF-alone at the aging time point. Fleeing responses in the predator test showed flee-enhancing effects of both compounds individually versus controls, and no additive impact of the two following sequential exposure. Each compound was also associated with changes in recognition or avoidance patterns in a novel place recognition task in late adulthood, but sequential exposures did not enhance these phenotypes. The potential for chemical x chemical interactions did not appear related to changes in CPF metabolism to the active oxon, as prior DDT exposure did not affect the cholinesterase inhibition resulting from CPF. This study shows that the effects of chronic adult insecticide exposures may be relevant to behavioral health initially and much later in life, and that the effects of sequential exposures may be unpredictable based on their constituent exposures.