Neurobehavioral anomalies in zebrafish after sequential exposures to DDT and chlorpyrifos in adulthood: Do multiple exposures interact?

dc.contributor.author

Hawkey, Andrew B

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Holloway, Zade

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Dean, Cassandra

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Koburov, Reese

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Slotkin, Theodore A

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Seidler, Frederic J

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Levin, Edward D

dc.date.accessioned

2023-12-06T15:13:43Z

dc.date.available

2023-12-06T15:13:43Z

dc.date.issued

2021-09

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2023-12-06T15:13:42Z

dc.description.abstract

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.

dc.identifier

S0892-0362(21)00039-8

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0892-0362

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1872-9738

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https://hdl.handle.net/10161/29490

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

Neurotoxicology and teratology

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10.1016/j.ntt.2021.106985

dc.subject

Brain

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Animals

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Zebrafish

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DDT

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Chlorpyrifos

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Cholinesterase Inhibitors

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Insecticides

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Behavior, Animal

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Locomotion

dc.title

Neurobehavioral anomalies in zebrafish after sequential exposures to DDT and chlorpyrifos in adulthood: Do multiple exposures interact?

dc.type

Journal article

duke.contributor.orcid

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

pubs.begin-page

106985

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Duke

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Nicholas School of the Environment

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School of Medicine

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Trinity College of Arts & Sciences

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Neurobiology

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Pharmacology & Cancer Biology

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Psychiatry & Behavioral Sciences

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Duke Cancer Institute

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Psychology & Neuroscience

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Environmental Sciences and Policy

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Initiatives

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Duke Science & Society

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

pubs.publication-status

Published

pubs.volume

87

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