Upper airway and pulmonary effects of oxidation products of (+)-alpha-pinene, d-limonene, and isoprene in BALB/c mice

Inhal Toxicol. 2002 Jul;14(7):663-84. doi: 10.1080/08958370290084575.


The oxidation products (OPs) of ozone and the unsaturated hydrocarbons d-limonene, (+)-alpha-pinene, and isoprene have previously been shown to cause upper airway irritation in mice during 30-min acute exposures. This study evaluated the effects of OPs and the hydrocarbons themselves on the upper airways, the conducting airways, and the lungs over a longer exposure period. The time course of development of effects and the reversibility of effects were investigated; in addition, we assessed possible exacerbation of sensory responses of the airways to the unreacted hydrocarbons. Respiratory parameters in male BALB/c mice were monitored via head-out plethysmography. Exposures to OPs or hydrocarbons were for 60 min, followed by a 30-min challenge period with air or hydrocarbon, and a 15-min recovery period with air only. Experiments were also performed where limonene/ozone exposures were separated 6 h from the challenge period. Ozone concentration in the reaction mixture was 3.4 ppm, and concentrations of hydrocarbons were 47 ppm (alpha-pinene), 51 ppm (d-limonene), and 465 ppm (isoprene). Due to reaction, the ozone concentration at the point of exposure was less than 0.35 ppm; exposure to 0.30 ppm ozone for 60 min did not produce effects different from air-exposed control animals. As previously established, upper airway irritation was a prominent effect of OP exposure. In addition, over the longer exposure period we observed the development of airflow limitation that persisted for at least 45 min postexposure. All effects from limonene/ozone exposures were reversible within 6 h. Exposures to OPs did not cause enhanced upper airway irritation during challenge with the hydrocarbons, indicating that a 1-h exposure to OPs did not increase the sensitivity of the upper respiratory system. However, airflow limitation was exacerbated in animals exposed to d-limonene alone immediately following exposure to limonene OPs. These findings suggest that terpene/ozone reaction products may have moderate-lasting adverse effects on both the upper airways and pulmonary regions. This may be important in the context of the etiology or exacerbation of lower airway symptoms in office workers, or of occupational asthma in workers involved in industrial cleaning operations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Air Pollution, Indoor*
  • Animals
  • Bicyclic Monoterpenes
  • Butadienes / chemistry
  • Butadienes / toxicity*
  • Cyclohexenes
  • Hemiterpenes*
  • Irritants / chemistry
  • Irritants / toxicity*
  • Limonene
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Monoterpenes*
  • Oxidation-Reduction
  • Ozone / chemistry
  • Ozone / toxicity
  • Pentanes*
  • Respiration / drug effects*
  • Respiratory Function Tests
  • Terpenes / chemistry
  • Terpenes / toxicity*


  • Bicyclic Monoterpenes
  • Butadienes
  • Cyclohexenes
  • Hemiterpenes
  • Irritants
  • Monoterpenes
  • Pentanes
  • Terpenes
  • isoprene
  • Ozone
  • Limonene
  • alpha-pinene