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Peer-reviewedCC BY-NCNeurotoxicology and teratology

Neurobehavioral and Metabolic Consequences of Embryonic Triphenyl Phosphate Exposure Across the Lifespan in Zebrafish

  1. 1Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 27710, USA
  2. 2Department of Biomedical Sciences, Midwestern University, Downers Grove, IL, 60515, USA
  3. 3Nicholas School of the Environment, Duke University, Durham, NC, 27710, USA

Abstract

Triphenyl phosphate (TPP) is a second-generation flame retardant which is wide-spread in the environment and persistent in the body. Early developmental exposure to TPP has been shown to cause significant neurobehavioral alterations that persist into adulthood. Questions remain concerning the neurobehavioral effects of developmental TPP exposure across the full lifespan and relevant mechanisms of long-term dysfunction. Using a zebrafish model, the current study examined the effects of TPP exposure during the first five days after fertilization on later life sensorimotor activity, emotional function, social response and mitochondrial energetics, specifically in late adulthood. Early developmental TPP exposure was found to cause locomotor hypoactivity in larvae. In the novel tank test TPP-induced hyperactivity was seen at 2.5 months and hypoactivity at 14 months. Correspondingly, the diving response only showed a subtle effect in this test, with TPP exposed 14-month old fish showing time dependent enhancements of the diving response. In the predator avoidance test, 8-month old fish showed greater avoidance of slow predator cues after developmental TPP exposure, but these fish no longer showed this pattern when tested at 14 months old. No significant effects of developmental TPP exposure were seen with tap startle response or shoaling behavior. TPP-induced decreased mitochondrial respiration was detected in the ovaries, but none of the other organs tested. This longitudinal study shows that early developmental TPP exposure is capable to producing neurobehavioral effects, but that those effects may be differentially expressed across development. These effects were not associated with mitochondrial and bioenergetic effects in the brain in late adulthood.

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BibTeX
@article{hawkey2026neurobehavioral,
  title = {{Neurobehavioral and Metabolic Consequences of Embryonic Triphenyl Phosphate Exposure Across the Lifespan in Zebrafish}},
  author = {Andrew B. Hawkey and Perry Piatos and Zade R. Holloway and Dilanaz Unal and Jonna Boyda and Richard T. Di Giulio and Edward D. Levin},
  journal = {Neurotoxicology and teratology},
  year = {2026},
  month = aug,
  doi = {10.1016/j.ntt.2026.107711},
  url = {https://doi.org/10.1016/j.ntt.2026.107711},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Neurobehavioral and Metabolic Consequences of Embryonic Triphenyl Phosphate Exposure Across the Lifespan in Zebrafish
AU  - Andrew B. Hawkey
AU  - Perry Piatos
AU  - Zade R. Holloway
AU  - Dilanaz Unal
AU  - Jonna Boyda
AU  - Richard T. Di Giulio
AU  - Edward D. Levin
PY  - 2026
DA  - 2026/08/18
JO  - Neurotoxicology and teratology
DO  - 10.1016/j.ntt.2026.107711
UR  - https://doi.org/10.1016/j.ntt.2026.107711
AB  - Triphenyl phosphate (TPP) is a second-generation flame retardant which is wide-spread in the environment and persistent in the body. Early developmental exposure to TPP has been shown to cause significant neurobehavioral alterations that persist into adulthood. Questions remain concerning the neurobehavioral effects of developmental TPP exposure across the full lifespan and relevant mechanisms of long-term dysfunction. Using a zebrafish model, the current study examined the effects of TPP exposure during the first five days after fertilization on later life sensorimotor activity, emotional function, social response and mitochondrial energetics, specifically in late adulthood. Early developmental TPP exposure was found to cause locomotor hypoactivity in larvae. In the novel tank test TPP-induced hyperactivity was seen at 2.5 months and hypoactivity at 14 months. Correspondingly, the diving response only showed a subtle effect in this test, with TPP exposed 14-month old fish showing time dependent enhancements of the diving response. In the predator avoidance test, 8-month old fish showed greater avoidance of slow predator cues after developmental TPP exposure, but these fish no longer showed this pattern when tested at 14 months old. No significant effects of developmental TPP exposure were seen with tap startle response or shoaling behavior. TPP-induced decreased mitochondrial respiration was detected in the ovaries, but none of the other organs tested. This longitudinal study shows that early developmental TPP exposure is capable to producing neurobehavioral effects, but that those effects may be differentially expressed across development. These effects were not associated with mitochondrial and bioenergetic effects in the brain in late adulthood.
SN  - 0892-0362
SN  - 1872-9738
ER  -