Effects of mono-2-ethylhexyl phthalate on the respiratory tract in BALB/c mice

S Thor Larsen1, J Stilund Hansen, M Hammer

  • 1Department of Chemical Working Environment, National Institute of Occupational Health, Lersø Parkallé 105, DK-2100 Copenhagen O, Denmark. stl@ami.dk

Insights

Airborne mono-2-ethylhexyl phthalate (MEHP) causes shallow breathing in mice at higher concentrations. Inflammation was observed, but non-occupational exposure levels are unlikely to cause airway irritation in the general population.

Area of Science:

  • Environmental Health
  • Toxicology
  • Respiratory Medicine

Background:

  • Mono-2-ethylhexyl phthalate (MEHP) is a metabolite of di(2-ethylhexyl) phthalate (DEHP).
  • Phthalates are common environmental contaminants with potential health effects.
  • Understanding MEHP's respiratory effects is crucial for public health risk assessment.

Purpose of the Study:

  • To investigate the acute airway effects of airborne MEHP exposure in a mouse model.
  • To determine the concentration- and time-dependent respiratory responses to MEHP.
  • To assess the inflammatory potential of MEHP in the lungs.

Main Methods:

  • Bioassay using BALB/c mice exposed to varying concentrations of airborne MEHP (0.3-43.6 mg/m3) for 60 minutes.
  • Continuous monitoring of breathing patterns, including tidal volume and respiratory rate.
  • Analysis of bronchoalveolar lavage (BAL) fluid to assess inflammatory markers (macrophages, neutrophils, lymphocytes, eosinophils, epithelial cells).

Main Results:

  • MEHP induced lower airway irritation, characterized by a concentration-dependent decrease in tidal volume (shallow respiration).
  • The no-observed-effect level (NOEL) for lower airway irritation was 0.3 mg/m3.
  • A rapid shallow breathing pattern was observed around 8 mg/m3, with increased pause time at concentrations above 4.9 mg/m3.
  • Macrophage levels in BAL fluid peaked approximately 16 hours post-exposure (NOEL for inflammation: 1.7 mg/m3).
  • No significant increases in neutrophils, lymphocytes, eosinophils, or epithelial cells were found at relevant exposure levels.

Conclusions:

  • Airborne MEHP causes acute lower airway irritation and transient inflammatory responses in mice.
  • The observed effects are concentration-dependent, with established no-observed-effect levels for irritation and inflammation.
  • Non-occupational exposure levels of MEHP, derived from DEHP, are unlikely to cause significant airway irritation in the general population based on worst-case inhalation scenarios.

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