Toxicology of Industrial Compounds

Findings of the US-NTP study (Luster)
The US-NTP study investigated 51 substances, 35 of which were declared
immunotoxic, in a comprehensive test battery in mice for changes in
functional parameters after 28-day administration of the substances. The
correlations of each of these parameters with the given classification and
with the results of host-resistance studies were calculated. The correlations
after combinations of individual tests were also calculated (Luster et al.,
1992, 1993).
The conclusion drawn from these investigations was that the
immunotoxic potential of a substance can be determined relatively reliably
by combination of 2–3 specific tests. The most powerful tests proposed by
Luster et al. for such a combination include surface markers, NK test and
PFCA. Serum titres of Ig —particularly IgA—were unfortunately not
determined.
With regard to the correlation with host resistance (HR) results it was
found that if effects were shown in the HR model there were always effects
on functional parameters, too. There were, however, also cases in which
there were effects in the functional tests although the HR studies were
negative. Although these investigations were carried out on mice and the
choice and classification of the substances are not entirely undisputed,
these findings are nevertheless confirmed by our own experience.
Discussion and prospect
H.-W.VOHR 201
It is undoubtedly too early to make any judgement. However, it appears
that apart from the histology—particularly the immuno-histology—a few
additional parameters such as analysis of surface markers of subpopulations
and serum titre assays of IgG, IgM and IgA are sufficient as screening
indicators to show the possible immunotoxic potential of a substance. One
of these is the PFCA, which presupposes, however, that satellite groups are
used or that the authorities accept injection of SRBC as GLP treatment.
Positive findings in a combination of these tests should then occasion
further elucidation of the immunotoxic potential.
In summary it can be concluded from the currently available results of the
collaborative studies that the following criteria must be fulfilled if a
substance is to be characterised as possibly immunotoxic. The substance
must:
1. Induce significant dose-related changes in one of the effective tests
listed above, or
2. induce significant changes in the highest dose group in a combination
of 2–3 of these tests.