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

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.