Toxicokinetics and distribution in female rats after chronic nonylphenol exposure

Toxicol Ind Health. 2020 Nov;36(11):925-935. doi: 10.1177/0748233720958963. Epub 2020 Oct 7.

Abstract

Our previous studies have shown that continuous exposure to nonylphenol (NP) may cause female reproductive toxicity even at low doses. To better understand this toxic effect, the aim of this study was to investigate the basic characteristics of the disposal kinetics of NP under a chronic exposure scenario to simulate human exposure. Female rats were exposed to NP at three dose levels (50-, 500-, and 10,000 µg kg-1 bw day-1, low, medium, and high dose, respectively) by gavage daily for 17 weeks. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to detect NP in rat sera and tissues. The results suggested that a two extravascular compartment model was found to better match the actual serum metabolic behavior of NP. Compared with the high-dose group, the NP absorption in the low-dose group was relatively efficient, the clearance rate was slower, and the residual amount of NP was greater. NP was found mostly in the uterus, adipose and brain tissues and to a lesser degree, in the liver, kidney, and ovary. The results indicated that the extensive organ distribution may cause corresponding toxicity even at relatively low doses.

Keywords: Nonylphenol; chronic; low-dose; oral exposure; toxicokinetics.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Metabolic Clearance Rate
  • Models, Biological
  • Phenols / pharmacokinetics*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Toxicokinetics

Substances

  • Phenols
  • nonylphenol