IN-VITRO SCREENING FOR METABOLIC INTERACTIONS AMONG FREQUENTLY OCCURRING BINARY-MIXTURES OF VOLATILE ORGANIC-CHEMICALS IN NORWEGIAN OCCUPATIONAL ATMOSPHERE

Surveys of Norwegian industrial occupational atmosphere between 1983 t o 1996, have identified the 12 most frequent occurring binary combinat ions of volatile organic chemicals. These combinations were tested in vitro for mutual inhibition or enhancement of metabolism by the head s pace vial equilibration technique with liver S9 obtained from in vivo untreated or pretreated (with the binary mixture) rats. The in vitro s ystem responded to in vivo pretreatment by increasing the metabolic ra te of several potentially toxic organic chemicals such as toluene, xyl ene, styrene, and dichloromethane. In untreated liver S9, the metaboli sm of several of the tested binary pairs was inhibited when coexposed in vitro to their most prevalent follower as shown for instance for et hanol (with ethyl acetate), dichloromethane (with styrene) and mutuall y between toluene and xylene. This inhibitory effect disappeared, howe ver, for several of the solvents when combined with the in vivo induce d liver S9, a situation which may be the most relevant for occupationa l exposure. It is concluded that several metabolic interactions occur between low-molecular weight volatile chemicals found in occupational air. These are both inductive and inhibitory in nature and a further m echanistic evaluation including a higher number of differentiated dosa ge levels, must be performed before a possible health hazard can be co nfirmed or rejected for the investigated combinations.