Toxicology of Industrial Compounds

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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
Table 15.2 Summary of immunotoxicity testing recommendations for direct food additives H.-W.VOHR 203 Abbreviations: CBC=complete blood cell count; WBC=white blood cell count; Ig=Immunoglobin; NK=natural killer; IL-2=interleukin 2; SRBC=sheep red blood cells; TNP-LPS=trinitrophenol lipopolysaccharide. * Recommended for inclusion in basic testing. potential of a compound on the basis of the routine 28 day treatment of rats (Basketter et al., 1994; ECETOC, 1994). A central point in these
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Toxicology of Industrial Compounds
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This edition published in the Taylo
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8. Pulmonary Toxicity Studies with
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Preface A large number of chemical
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Contributors May Akrawi Department
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Beverly M.Kulig TNO Toxicology, Dep
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Richard A.Versen Schuller MTC, Heal
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1 Biomonitoring and Absorption of I
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4 BIOMONITORING AND ABSORPTION OF I
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10 BIOMONITORING AND ABSORPTION OF
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2 Toxicokinetics and Biodisposition
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14 TOXICOKINETICS AND BIODISPOSITIO
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3 Metabolic Activation of Industria
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38 METABOLIC ACTIVATION OF INDUSTRI
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4 Sizing up the Problem of Exposure
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46 SIZING UP THE PROBLEM OF EXPOSUR
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5 Metabolism of Reactive Chemicals
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62 METABOLISM OF REACTIVE CHEMICALS
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6 Methods for the Determination of
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74 METHODS FOR THE DETERMINATION OF
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PART THREE Pulmonary toxicology of
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92 CARCINOGENIC POTENTIAL OF MAN-MA
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100 CARCINOGENIC POTENTIAL OF MAN-M
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118 PULMONARY TOXICITY STUDIES WITH
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130 PULMONARY HYPERREACTIVITY TO IN
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10 Mechanisms of Pulmonary Sensitiz
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140 MECHANISMS OF PULMONARY SENSITI
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150 OCCUPATIONAL ASTHMA INDUCED BY
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Page 182 and 183: 168 EXTRAPOLATION OF TOXICITY DATA
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Page 196 and 197: 182 MOLECULAR APPROACHES TO ASSESS
Page 212 and 213: 198 EVALUATION OF TOXICITY TO THE I
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Page 252 and 253: 18 Neurotoxicity Testing of Industr
Page 254 and 255: 240 NEUROTOXICITY TESTING OF INDUST
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252 NEUROTOXICITY TESTING OF INDUST
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254 NEUROTOXICITY TESTING OF INDUST
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256 ENDOCRINE TOXICOLOGY OF THE THY
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20 Testing and Evaluation for Repro
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282 TESTING AND EVALUATION FOR REPR
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PART SIX Toxicity of selected class
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302 SPECIAL POINTS IN THE TOXICITY
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310 TOXICOLOGY OF TEXTILE CHEMICALS
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318 ANTIOXIDANTS AND LIGHT STABILIS
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340 TOXICOLOGY OF SURFACTANTS Inter
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342 TOXICOLOGY OF SURFACTANTS Figur
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344 TOXICOLOGY OF SURFACTANTS probl
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346 TOXICOLOGY OF SURFACTANTS nonio
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348 TOXICOLOGY OF SURFACTANTS and t
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350 TOXICOLOGY OF SURFACTANTS long-
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352 TOXICOLOGY OF SURFACTANTS COULS
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354
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25 Low Dose of a Genotoxic Carcinog
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358 CARCINOGENESIS AT LOW DOSE Tabl
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360 CARCINOGENESIS AT LOW DOSE year
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26 Controversial Mechanistic and Re
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364 CONTROVERSIAL ISSUES IN SAFETY
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374 INDEX 2-bromo-glutathionyl 64 B
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376 INDEX Gas chromatography/mass s
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378 INDEX mRNA analysis 211 Mutagen
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380 INDEX Surfactants 338-55 acute
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