Phenols, quinolines, indoles, benzene, and 2-cyclopenten-1-ones are oviductal toxicants in cigarette smoke.

Previously, we showed that pyridines and pyrazines in cigarette smoke inhibit oviductal functioning in vitro in nanomolar and picomolar doses. The purpose of this study was to determine the lowest observable adverse effect levels (LOAELs) of phenols, quinolines, indoles, benzene, and 2-cyclopenten-1-ones found in mainstream smoke solutions on ciliary beat frequency, oocyte pickup rate, and infundibular smooth muscle contraction using the hamster oviduct. After solid phase extraction, mainstream smoke solution fractions were tested in the oviductal assays. The active fractions were analyzed using gas chromatography-mass spectrometry to identify individual chemicals. Using this approach, benzene, eleven phenolic, two indole, two quinoline, and two 2-cyclopenten-1-one derivatives were identified in the active fractions. Commercially available authentic standards of the identified compounds were tested in dose-response studies on hamster oviducts. The LOAELs were determined for each compound using the ciliary beat frequency, oocyte pickup rate, and infundibular smooth muscle contraction rate assays. Indole, the compound with the highest potency, showed inhibition of ciliary beat frequency (10(-13) M), oocyte pickup rate (10(-14) M), and infundibular smooth muscle contraction rate (10(-15) M) in femtomolar doses. All of the other compounds tested, except phenol, which only showed inhibition at millimolar concentrations, were inhibitory in picomolar, nanomolar, or micromolar concentrations. Derivitization of phenol increased its toxicity in the oviductal assays, especially when a methyl or ethyl group was substituted on the fourth position. The indoles, quinolines, and four phenolic compounds had both high potencies and efficacies in the oviductal assays.