Toxicology of Industrial Compounds

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248 NEUROTOXICITY TESTING OF INDUSTRIAL COMPOUNDS cortex and hippocampus, while in regions such as hypothalamus and cerebellum this process occurred entirely neonatally. It should be kept in mind that in the rat also neuronal maturation and differentiation are not completed at birth and continue to a large extent postnatally. Exposure of pregnant rats to Aroclor 1254 did lead to a number of alterations in GFAP levels in various brain regions in offspring as compared to control animals. The most striking differences were observed in brain stem. While in control animals of both sexes GFAP levels increased postnatally, the normal developmental increase in perinatally exposed animals was absent (Figure 18.3, upper panel). At 3 months the relative deficit in GFAP levels was 41 per cent for male and 30 per cent for female progeny. Already at the lowest dose of Aroclor 1254 (5 mg/kg) a maximum decrease was observed (Figure 18.3, upper panel). In addition to brain stem, a similar effect on GFAP levels was found in striatum although the relative deficit at 3 months was somewhat less. Quite an opposite pattern emerged in brain regions such as cerebellum, lateral olfactory tract and prefrontal cortex, where GFAP levels were increased relative to unexposed progeny. In hippocampus no significant changes in GFAP levels were encountered. The question arose whether the observed neurodevelopmental toxicity in rats by PCBs was specific for astroglial cells or also involved neuronal maturation, differentiation and death. For this purpose the same nervous tissues were used for quantitative assessment of a neuronal marker in the form of synaptophysin. In brains of untreated adult control rats, regionspecific differences were observed in synaptophysin concentrations, being high in the prefrontal cortex, striatum and hippocampus and relatively low in lateral olfactory tract, cerebellum and brain stem. Synaptogenesis for the brain as a whole largely takes place in the rat from birth until postnatal day 70 (Knaus et al., 1986). Regional differences in the speed of postnatal synaptogenesis from 3 weeks to 3 months were found in a number of structures being most pronounced in cerebellum (190 per cent increase) and prefrontal cortex (170 per cent increase) while in brain stem little change was observed. As a result of perinatal exposure to Aroclor 1254, altered expression of synaptophysin was observed. In most brain structures examined, including brainstem (Figure 18.3, lower panel) significant decreases in synaptophysin concentrations were found. This suggests that during development of the central nervous system, PCBs may interfere with the formation of synaptic vesicles, synaptogenesis, or formation of nerve terminals. A straightforward interpretation of the present results is not possible at this stage. However, what is clear is that perinatal exposure to PCBs may cause changes in the structural composition of the central nervous system both in the neuronal and the glial cell compartment. Apparently there are different effects on nerve cells of the CNS depending on the brain region involved. The brain stem and striatum are regions with decreased
K.J.VAN DEN BERG ET AL. 249 Figure 18.3 Developmental effects on glial fibrillary acidic protein (GFAP) and synaptophysin concentrations in brain stem after perinatal exposure to Aroclor 1254. Results are expressed as mean±SEM with the values of the control animals at day 21 set at 100 per cent. Open bars, control; shaded bars, 5 mg Aroclor 1254 per kg; closed bars, 25 mg Aroclor 1254 per kg; D 21 and D 90, postnatal days; *, p
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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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12 Biomarkers and Risk Assessment K
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160 BIOMARKERS AND RISK ASSESSMENT
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168 EXTRAPOLATION OF TOXICITY DATA
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14 Molecular Approaches to Assess C
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182 MOLECULAR APPROACHES TO ASSESS
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Page 212 and 213: 198 EVALUATION OF TOXICITY TO THE I
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Page 246 and 247: 232 PEROXISOME PROLIFERATION BENTLE
Page 248 and 249: 234 PEROXISOME PROLIFERATION KRAUPP
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Page 252 and 253: 18 Neurotoxicity Testing of Industr
Page 254 and 255: 240 NEUROTOXICITY TESTING OF INDUST
Page 270 and 271: 256 ENDOCRINE TOXICOLOGY OF THE THY
Page 294 and 295: 20 Testing and Evaluation for Repro
Page 296 and 297: 282 TESTING AND EVALUATION FOR REPR
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298 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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