C. Gennings, AN EFFICIENT EXPERIMENTAL-DESIGN FOR DETECTING DEPARTURE FROM ADDITIVITY IN MIXTURES OF MANY CHEMICALS, Toxicology, 105(2-3), 1995, pp. 189-197
Berenbaum (J. Theor. Biol. 114 (1985) 413-431) described a procedure f
or detecting and characterizing departure from additivity in a combina
tion of c (c greater than or equal to 2) chemicals. The attraction of
this approach is that it is based on the concentration-response relati
onship of each of the individual components and, under the assumption
of additivity, it is straight forward to predict the response of a giv
en combination. Deviations between the observed and predicted response
s for the combination are associated with departures from additivity.
Berenbaum based his conclusions regarding synergism/antagonism on nume
rical differences which do not take into account inherent biological v
ariability. We have developed a procedure which incorporates experimen
tal variation is based on each individual component's concentration-re
sponse relationship, and leads to a conclusion regarding the statistic
al significance of any departure from additivity. The procedure is ill
ustrated with an example.