Toxicology of Industrial Compounds

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198 EVALUATION OF TOXICITY TO THE IMMUNE SYSTEM The next problem is to find which tests can suitably be used—simply and without having to treat additional animals—for reliable identification of interactions with the immune system. Another question which has not yet been solved is relating to the dosages and the changes in immunological parameters which are still tolerable and at which times these should be determined. National and international collaborative studies Most of the guideline drafts favour a two-tiered to three-tiered approach for the screening of immunotoxic side effects, with the greatest disparities in respect of the proposals for tier I tests, ranging from just organ weights and a little more emphasis on the histology of the lymphatic organs, to a series of elaborate, supplementary function tests including, in some cases, satellite groups. Any discussion about basic tests is hampered by a lack of data from routine toxicological and/or epidemiological studies although a few years ago a number of collaborative studies were initiated, namely: ICICIS (international), US-NTP (international, USA (two)), BGA (Federal German Health Office, Germany), GEVI (France). The aim of all these studies is to check on different histological parameters and functional tests for their possibility to flag an immunotoxic potential of a compound in a routine 14 or 28 day study (rats) in an interlaboratory trial. Two immunosuppressive standards (azathioprine and/or cyclosporin A) have been used so far. Although the experimental phase is finished the evaluation of the data is still underway. Table 15.1 summarises the immunotoxicological experiments and collaborative studies currently in progress. With a few exceptions all investigations are based on a 28-day gavage study in rats. These basic tests were supplemented by extended histopathology and functional tests. ICICIS The first substance to be investigated in the international collaborative study was azathioprine. However this first attempt suffered from lack of harmonisation between the models used by the 28 participants world-wide. This made the comparability and the evaluation of the results particularly problematic. The second substance which was tested by ICICIS in a more restrictive design with slightly fewer participants was cyclosporin A. The experimental section as well as the first evaluation of the results has now been completed. As the final evaluation—including statistics—of ICICIS is likely to take some time (years?) it will not be discussed further at this point.
Table 15.1 Immunotoxicology collaborative studies Fischer 344 study (Kimber-White) H.-W.VOHR 199 An other interesting approach was done by Kimber-White and colleagues. In this study the duration of treatment was 14 days, Fischer 344 rats were used as experimental animals. Apart from the usual parameters the plaque assay (PFCA), mitogenic stimulation (ConA, LPS) and NK activity were measured.
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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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Page 162 and 163: 148 MECHANISMS OF PULMONARY SENSITI
Page 164 and 165: 150 OCCUPATIONAL ASTHMA INDUCED BY
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Page 174 and 175: 160 BIOMARKERS AND RISK ASSESSMENT
Page 182 and 183: 168 EXTRAPOLATION OF TOXICITY DATA
Page 194 and 195: 14 Molecular Approaches to Assess C
Page 196 and 197: 182 MOLECULAR APPROACHES TO ASSESS
Page 214 and 215: 200 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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248 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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