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

Birth Defects Res. 2023 Feb 1;115(3):357-370. doi: 10.1002/bdr2.2125. Epub 2022 Nov 11.

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.

Keywords: developmental neurotoxicity; dopamine; flame retardants; neurobehavioral dysfunction; triphenyl phosphate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine
  • Flame Retardants* / toxicity
  • Humans
  • Male
  • Organophosphates / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Zebrafish

Substances

  • triphenyl phosphate
  • Flame Retardants
  • Dopamine
  • Organophosphates