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© 1988 Oxford University Press

research-article

Experimental Evaluation of Haloalkanes and Liver Injury1

GABRIEL L. PLAA

Département de pharmacology, Faculté de médecine, Université de Montréal Montreéal Queébec. Canada H3c 3J7

Received November 6, 1987; accepted November 18, 1987

Experimental Evaluation of Haloalkanes and Liver Injury. PLAA, G. L. (1988). Fundam. Appl. Toxicol 10, 563–570. Potentiation of haloalkane-induced hepatotoxicity by ketones and keto-genic substances is used to illustrate questions that are raised when considering biological interactions involving toxicants. The following characteristics are considered: The effect of the poten-tiator (ketone or ketogenic agent) on the dose-response characteristics of the haloalkane toxicant; the recovery process of the potentiated tissue injury; dose-response characteristics of the potentiators (minimally effective dosages); correlation of the potentiation with blood levels of the potentiator (threshold concentrations). The relative specificity of the haloalkanes for interaction are discussed, as well as the potentiation of various forms of hepatic injury (acute, chronic, necrogenic. and cholestatic). Enhanced bioactivation of the haloalkane toxicant is a major mechanism of action for the potentiator; other possible contributing mechanisms, however, require consideration. Mixtures of haloalkanes, leading to enhanced liver injury, can also be potentiated by ketones.


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