Comparative Toxicities of Halothane, Isoflurane, and Diethyl Ether at Subanesthetic Concentrations in Laboratory Animals

Stevens, Wendell C.; Eger, Edmond I.; White, Alan G.; Halsey, Michael J.; Munger, William L.; Gibbons, Robert D.; Dolan, William M.; Shargel, Richard

doi:10.1097/00000542-197504000-00008

Cited by 68 publications

(32 citation statements)

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“…Fortunately, a modified jar method was developed for easy administration of isoflurane, resulting in its inclusion in this study as an ether substitute [16]. Previous comparative toxicity studies between ether and modern clinical volatile anaesthetics, including isoflurane, in both human [25] and laboratory animals [26] have revealed that the potencies of the 2 agents are virtually analogous. Here, one of our goals was to extrapolate this consistency in precise haematological and blood chemical terms in in situ blood sampling in regular toxicology studies.…”

Section: Discussionmentioning

confidence: 99%

Diluted Isoflurane as a Suitable Alternative for Diethyl ether for Rat Anaesthesia in Regular Toxicology Studies

Nagate

Chino

Nishiyama

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Despite its explosive properties and toxicity to both animals and humans, diethyl ether is an agent long used in Japan in the anaesthesia jar method of rat anaesthetises. However, in response to a recent report from the Science Council of Japan condemning diethyl ether as acceptable practice, we searched for an alternative rat anaesthesia method that provided data continuous with pre-existing regular toxicology studies already conducted under diethyl ether anaesthesia. For this, we examined two candidates; 30% isoflurane diluted with propylene glycol and pentobarbitone. Whereas isoflurane is considered to be one of the representatives of modern volatile anaesthetics, the method of propylene glycol-diluted 30% isoflurane used in this study was our modification of a recently reported method revealed to have several advantages as an inhalation anaesthesia. Intraperitoneal pentobarbitone has long been accepted as a humane method in laboratory animal anaesthesiology. These 2 modalities were scrutinized in terms of consistency of haematology and blood chemistry with previous results using ether. We found that pentobarbitone required a much longer induction time than diethyl ether, which is suspected to be the cause of fluctuations in several haematological and blood chemical results. Conversely, only calcium ion concentration showed a slight difference from traditional results in the case of 30% isoflurane. Additionally, serum prolactin and corticosterone levels indicated that 30% isoflurane induced less stress than ether, confirming that 30% isoflurane can both provide results consistent with diethyl ether, while at the same time remove its disadvantages. As such 30% isoflurane appears to be a strong alternative anaesthetic agent for future regular toxicology studies in Japan.

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Section: Discussionmentioning

confidence: 99%

Diluted Isoflurane as a Suitable Alternative for Diethyl ether for Rat Anaesthesia in Regular Toxicology Studies

Nagate

Chino

Nishiyama

et al. 2007

The Journal of Veterinary Medical Science

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“…Moreover, prolonged elevations of sulfobromophthalein retention was found in volunteers subjected to halothane anesthesia than with isoflurane. These findings would indicate that a mild hepatic injury is not really uncommon following halothane anesthesia (46).…”

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confidence: 80%

“…Despite increasing evidence indicating that halothane is hepatotoxic, incidence of fully recognizable hepatic necrosis in human patients following halothane anesthesis is very low (47). However, Stevens et al have cautioned that perhaps the extent of hepatic injury following halothane anesthesia in man is not as rare as the incidence of massive hepatitis would suggest (46). They point out that an elevation of SGPT was frequently found in patients following halothane anesthesia.…”

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confidence: 99%

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Pathologic changes following chronic exposures to halothane: a review.

Chang¹

1977

Environ Health Perspect

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The toxic effects of halothane on the liver, kidney, and brain are reviewed. Increasing evidence has indicated that hepatic degeneration can be induced in several animal species after exposure to halothane. Recent electron microscopic investigations have also revealed cytological degeneration of the liver cells after chronic exposure to subclinical levels of halothane. Degeneration of the kidney and the nervous system after halothane exposure have also been reported. The pathological effects of halothane on the neonatal (developing) liver, kidney, and brain are also demonstrated by electron nicroscopy. Although the full significance of these observations on experimental animals in relationship to human exposure is still not known, the indication of the toxic potential of halothane on the biological system is strong and deserves further investigation.

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“…It was proven that long-term exposure of halothane, isoflurane and enflurane in anesthetic concentrations may cause liver damage in mice, rats and guinea pigs, but such harm occurs mainly under special circumstances or adverse conditions (moderate hypoxia or significant malnutrition) [10][11][12][13]. However, toxicity is attributable to indirect noxae through metabolites that were biotransformed by the cytochrome P450.…”

Section: Hepatotoxicitymentioning

confidence: 99%

Occupational Hazards of Halogenated Volatile Anesthetics and their Prevention: Review of the Literature

Molnár¹

2014

J Anesth Clin Res

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The harmful effect of inhalational anesthetics on the working environment of anesthetists is one of most controversial areas, where speculations can easily arise. In the present review the authors summarize the possible sources of environmental pollution in the operating theatre with special emphasis on the importance of air suctioning and air conditioning systems. A full-spectrum of the previously published animal and human studies is provided about the possible health hazards of inhalational agents including effects on the central nervous, reproductive and hematologic systems, on the liver functions and also on the carcinogenesis. A list of the proposed measures to decrease pollution to the minimum in the operating theatre environment is provided. It is concluded that according to the present knowledge, the use of inhalational agents may be considered safe if the prescribed limits of halogenated anesthesia gases are met.

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Comparative Toxicities of Halothane, Isoflurane, and Diethyl Ether at Subanesthetic Concentrations in Laboratory Animals

Cited by 68 publications

References 0 publications

Diluted Isoflurane as a Suitable Alternative for Diethyl ether for Rat Anaesthesia in Regular Toxicology Studies

Diluted Isoflurane as a Suitable Alternative for Diethyl ether for Rat Anaesthesia in Regular Toxicology Studies

Pathologic changes following chronic exposures to halothane: a review.

Occupational Hazards of Halogenated Volatile Anesthetics and their Prevention: Review of the Literature

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