IN-VITRO SCREENING FOR METABOLIC INTERACTIONS AMONG FREQUENTLY OCCURRING BINARY-MIXTURES OF VOLATILE ORGANIC-CHEMICALS IN NORWEGIAN OCCUPATIONAL ATMOSPHERE
B. Mortensen et al., IN-VITRO SCREENING FOR METABOLIC INTERACTIONS AMONG FREQUENTLY OCCURRING BINARY-MIXTURES OF VOLATILE ORGANIC-CHEMICALS IN NORWEGIAN OCCUPATIONAL ATMOSPHERE, Pharmacology & toxicology, 83(2), 1998, pp. 49-56
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.