Developmental exposure to the flame retardant, triphenyl phosphate, causes long-lasting neurobehavioral and neurochemical dysfunction.

Abstract

Background

Human exposures to organophosphate flame retardants result from their use as additives in numerous consumer products. These agents are replacements for brominated flame retardants but have not yet faced similar scrutiny for developmental neurotoxicity. We examined a representative organophosphate flame retardant, triphenyl phosphate (TPP) and its potential effects on behavioral development and dopaminergic function.

Methods

Female Sprague-Dawley rats were given low doses of TPP (16 or 32 mg kg-1  day-1 ) via subcutaneous osmotic minipumps, begun preconception and continued into the early postnatal period. Offspring were administered a battery of behavioral tests from adolescence into adulthood, and littermates were used to evaluate dopaminergic synaptic function.

Results

Offspring with TPP exposures showed increased latency to begin eating in the novelty-suppressed feeding test, impaired object recognition memory, impaired choice accuracy in the visual signal detection test, and sex-selective effects on locomotor activity in adolescence (males) but not adulthood. Male, but not female, offspring showed marked increases in dopamine utilization in the striatum, evidenced by an increase in the ratio of the primary dopamine metabolite (3,4-dihydroxyphenylacetic acid) relative to dopamine levels.

Conclusions

These results indicate that TPP has adverse effects that are similar in some respects to those of organophosphate pesticides, which were restricted because of their developmental neurotoxicity.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1002/bdr2.2125

Publication Info

Hawkey, Andrew B, Janequia Evans, Zade R Holloway, Erica Pippen, Olivia Jarrett, Bruny Kenou, Theodore A Slotkin, Frederic J Seidler, et al. (2023). Developmental exposure to the flame retardant, triphenyl phosphate, causes long-lasting neurobehavioral and neurochemical dysfunction. Birth defects research, 115(3). pp. 357–370. 10.1002/bdr2.2125 Retrieved from https://hdl.handle.net/10161/29474.

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Scholars@Duke

Slotkin

Theodore Alan Slotkin

Professor of Pharmacology and Cancer Biology

We study the interaction of drugs, hormones and environmental factors with the developing organism, with particular emphasis on the fetal and neonatal nervous system. The role of biochemical factors mediating development of nerve cells and other types of tissue is a major thrust, since they influence the subsequent structural and physiological status of critical organ systems. Ongoing projects comprise five areas: (1) Mechanisms regulating development of synapses - role of endocrine and other trophic factors, intracellular messengers in developing cells, control of target organ differentiation by neural input; (2) Adverse effects of exogenous agents on development, with an emphasis on identification of mechanisms by which behavioral or physiological damage occurs - drugs of abuse (especially nicotine), hormonal imbalances, environmental contaminants (especially pesticides), food additives, intrauterine growth retardation, fetal and neonatal hypoxia; (3) Control of fetal and neonatal cardiovascular and respiratory function by the immature nervous system - normal physiological mechanisms, responses to stress, factors mediating the transition from fetal to neonatal function, reactivity during delivery, Sudden Infant Death Syndrome; (4) Breast cancer cell growth regulation - role of hormone and neurotransmitter receptors converging on common cell signaling mechanisms, and targeting of these receptors for cancer therapeutics.


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