Toxicology of Industrial Compounds

202 EVALUATION OF TOXICITY TO THE IMMUNE SYSTEM
But also findings in lymphoid organs which are remarkable with respect to
quality, severity or quantity of changes should be of sufficient relevance to
warrant further assessment.
Finally I would like to point out the problems involved in the evaluation
of immunological changes.
• In contrast to other data obtained in routine toxicology, historical data
and routine experience with respect to the functional tests are so far
almost entirely lacking. On account of this paucity of data a decision as
to the right effect level for the functional tests can only be made on the
basis of subjective judgement at present. The discussion of uniform
criteria is only just beginning.
• If effects only occur secondarily, e.g. on account of inflammatory
processes, they are not specifically immunotoxic. It must be discussed
whether such effects on the immune system, which is only doing its
normal job in these cases, can be classed as immunotoxic at all.
• The immune system can show an ‘oscillating’ response to a substance. A
substance may have a stimulating effect in a low dose range and an
inhibitory effect in a high range or vice versa. Such reactions are also
dose-related effects.
• Most immunotoxic investigations have so far used known
immunosuppressive drugs. There are, however, little data—particularly
from rat studies— on immunostimulant substances. Since the other
unwanted side-effect apart from immunosuppression is immune
potentiation, future collaborative investigations must urgently
concentrate on such substances. Before this, no final evaluation and thus
no recommendations on relevant tests can be made.
For pharmaceuticals (Hinton, 1992), pesticides (US-EPA, 1990, 1993) and
veterinary medicinal chemicals (EEC, 1991) final drafts or notes for
guidance for the screening of the immunotoxic potential of a compound
already exist. These draft proposals for immunotoxicity parameters for
incorporation into new guidelines are shown in Tables 15.2 (FDA) and
15.3 (US-EPA).
For industrial chemicals advanced screening of lymphoid organs also
with respect to functional parameters had been expected to be incorporated
into the adopted OECD guideline No. 407 (1992). But recommendations
made by van Loveren and Vos (1992) have not yet been taken into
consideration for this update of OECD guideline 407. The proposal of
these authors recommended more histopathology (gut associated lymphoid
tissue), measurement of serum immunoglobulins, bone marrow cellularity,
cytofluorimetry of spleen cells and measurement of NK cell activity.
A task force ‘Immunotoxicology’ initiated by ECETOC has put forward
proposals on hazard identification and risk assessment of immunotoxic