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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
Abstract:
Airborne mono-2-ethylhexyl phthalate (MEHP) was studied for acute airway effects using a bioassay with BALB/c mice. Concentration- and time-dependent effects were obtained by continuous monitoring of the breathing pattern during exposure to 0.3-43.6 mg/m3 MEHP for 60 min. Additionally, inflammatory effects of MEHP were studied from bronchoalveolar lavage (BAL) fluid. MEHP showed no upper airway irritating effect. Lower airway irritation was apparent from a concentration-dependent decrease in tidal volume (shallow respiration) with a no-observed effect level (NOEL) of 0.3 mg/m3. The respiratory rate reached a maximum at about 8 mg/m3, demonstrating a rapid shallow breathing pattern. At concentrations above 4.9 mg/m3, the time of pause, another marker of lung irritation, increased concentration-dependently, resulting in a decrease in respiratory rate at high exposure levels. BAL fluid obtained from 0 to 72 hours after a 60 min exposure to 30 mg/m3 MEHP showed that the number of macrophage reached maximum about 16 hours after exposure. The NOEL was 1.7 mg/m3. BAL content of neutrophils, lymphocytes, eosinophils and epithelial cells was normal after exposure to 30 or 1.7 mg/m3 MEHP. Based on worst case inhalation scenario in the general population, no airway irritation is expected from non-occupational levels of MEHP originating from DEHP.
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.

