Other limitation of the use of the PEF methodology to assess
carcinogenic potential is that PEFs have been proposed on the basis of
studies performed with individual PAHs. However, inhalation exposure
to PAHs is always to a mixture of PAHs. Larsen and Larsen (1998)
called for caution in using PEFs, as studies on mixtures of individual
PAHs have shown that they may interact metabolically in a number of
different ways, resulting in synergistic, additive or antagonistic effects
and nothing definitive can be concluded on the resulting tumorigenic
actions of individual PAHs in complex mixtures (Larsen and Larsen,
1998). Culp et al. (1998) found that the carcinogenicity of oral coal tar
mixture was greater than that of pure BaP, suggesting a synergistic or
additive effect of the PAH compounds contained within the coal tar
mixture. On the other hand, the use of benzo(a)pyrene as a marker of
the mixture, does not imply that the total carcinogenic effect of the
PAH mixture is a consequence of benzo(a)pyrene, but that this
individual compound (i.e. benzo(a)pyrene) represent a constant
proportion of the total carcinogenicity.