Date of Award

Summer 8-14-2015

Document Type


Degree Name

Doctor of Philosophy (PhD)


Environmental Health, Occupational Health, and Toxicology

First Advisor

Chandran Achutan


This dissertation is a compilation of studies related to the halogenated anesthetic gas isoflurane. Historically, halogenated anesthetic gases have been used in the health care industry. In 1977 the National Institute for Occupational Safety and Health (NIOSH) issued a recommended exposure limit (REL) of two parts per million (ppm) averaged over one hour of exposure for halogenated anesthetic gases (NIOSH 1977). The purpose of the standard was to protect healthcare workers from exposure to halothane, methoxyflurane, and chloroform. However, isoflurane only became available after the NIOSH REL was adopted. Therefore, the NIOSH REL is not directly applicable to isoflurane. Moreover, use of isoflurane in healthcare has diminished over the years, and it is now more widely used in medical research laboratories and veterinary clinics. The purpose of this dissertation is to demonstrate the need for an updated occupational exposure limit for isoflurane. Four studies were conducted toward the completion of this goal; a systematic review of the literature to investigate human health effects associated with occupational exposure to isoflurane, a case study of a high exposure to isoflurane and its control, an assessment of occupational exposure of isoflurane to researchers, and a comparison of the effectiveness of control methods in reducing isoflurane waste anesthetic gas (WAG).

In the first study, we searched the PubMed and Embase databases were searched for articles with data on health effects associated with occupational isoflurane exposure. Thirteen studies were found during the search that fit the review criteria. Five of the studies reported no adverse human health effects. Eight of the studies reported human health effects ranging from genetic mutations, changes in cellular function, symptoms of acute exposure, and congenital anomalies in the offspring of exposed women.

In the second study, we found that researchers working with isoflurane in a small unventilated space had exposures close to 30 ppm over a short-time period (0.48 and 1.15 hours) for the main researcher. Other members of the group had exposures above 2 parts per million (ppm). An active scavenging ventilation control which reduced isoflurane exposure by an average of 86%.

In the third study, we showed that isoflurane exposure to researchers at a medical research institution was significantly associated with scavenging technique and role of the investigator (p = 0.02 and 0.04, respectively). Researchers using passive scavenging canisters were exposed to a mean concentration of 3.18 ppm (%CV = 123) and researchers using active scavenging were exposed to a mean isoflurane concentration of 0.83 ppm (% CV = 89). Researchers who performed the greater part of the procedures were exposed to a mean of 2.71 ppm (%CV = 108) and researchers who assisted were exposed to a mean of 1.18 ppm (%CV = 97).

In the final study, we evaluated isoflurane exposures when using active scavengers, passive canister scavengers, and combinations of both scavenging techniques. We also evaluated isoflurane exposures with no scavenging control. Isoflurane concentration was significantly associated with control method (p < 0.0001). Post hoc Tukey’s comparison showed the significant difference (p = 0.05) in isoflurane concentration between no scavenging and active scavenging conditions, no scavenging and combination active and passive scavenging conditions, and passive and active scavenging conditions. There was no difference between no scavenging and passive scavenging conditions or active scavenging and combination scavenging conditions. The mean isoflurane concentration while using no scavenging controls was 10.23 ppm (%CV = 12), and was 10.35 ppm (%CV = 58) while using passive scavenging. Isoflurane concentration using active scavenging was 1.43 ppm (%CV = 15) and 0.59 ppm (%CV = 46) while using the combination scavenging method.

Researchers who use passive scavenging methods are more likely to be at risk for isoflurane exposure above 2 ppm. Researchers should use active scavenging to control isoflurane WAG.