Toxicology of Industrial Compounds

15
Evaluation of Toxicity to the Immune System
HANS-WERNER VOHR
Bayer AG, Wuppertal
Introduction
A number of years ago the new field of immunotoxicology was established.
Very early on, calls were heard from various sides demanding that the
development of new chemicals should also take into account the influence
of these substances on the immune system (Dean, 1979; Luster et al., 1988;
Trizio, et al., 1988). These demands led on the one hand to the initiation of
a number of investigations and collaborative studies (ICICIS; BGA; US-
NTP), on the other hand to thoughts by the authorities and industry on the
introduction of guidelines (US-EPA, 1982, 1990; Sjoblad, 1988; ECETOC,
1990; UK-DOH, 1991; Hinton, 1992; OECD, 1992ab.
If we define immunotoxicology as the science of adverse effects of
substances on the immune system we can say further that these side-effects
can lead to either immunopotentiation or immunosuppression. The former
can lead to induction of autoimmune reactions and to Type I-IV
hypersensitivity reactions, the latter to reduced resistance to infection,
development of cancer and also to autoimmune phenomena.
On the basis of this definition, immunotoxicological investigations have
already been carried out for years during the development of substances;
namely with respect to DTH reactions (Type IV) in the guinea pig (Bühler,
1965; Magnusson and Kligman, 1969). As an alternative to these tests in
the guinea pig, the so-called local lymph node assay (LLNA) in the mouse
according to Kimber et al. (1989) was developed and validated and has
meanwhile been adopted as alternative test in the OECD guidelines (OECD,
1992a, b; Botham et al., 1991).
The development or selection of suitable tests for immunotoxicological
screening and thus for incorporation in guidelines presents considerable
problems. Most of the tests which have been proposed for
immunotoxicological investigations and most knowledge and experience in
immunology are based on mouse models. The standard animal in the early
phase of toxicological testing, however, is the rat. Transference of the tests
is not always easy, partly because of lack of suitable reagents.