IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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(b) Experimental systems (see Table 14 for references) (i) DNA adducts A detailed description of N7, N 2 and O 6 -deoxyguanosine adducts of styrene 7,8-oxide formed in vivo and in vitro was previously presented (IARC, 1994b). Subsequent studies have reported that N7-deoxyguanosine adducts are formed in human whole blood and embryonic lung fibroblasts in vitro, as well as in salmon testis DNA, upon exposure to styrene 7,8-oxide. In addition, O 6 -deoxyguanosine adducts were induced in human lymphocytes exposed to 24 μg/mL styrene 7,8-oxide in vitro and in rat liver DNA following inhalation exposure to 1000 ppm [4.9 mg/m 3 ] styrene 7,8-oxide for 6 h per day on five days per week for 104 weeks. DNA adducts were not clearly induced in other studies in which rats were exposed to styrene 7,8-oxide by intraperitoneal injection or oral exposure. (ii) Mutation and allied effects STYRENE 511 Styrene 7,8-oxide, a monofunctional alkylating agent, has given positive results in virtually every short-term genetic assay in vitro and, to a lesser degree, in vivo. Positive results have previously been reported for gene mutations in bacteria and mammalian cells in vitro. DNA strand breaks, alkali-labile sites, and cytogenetic damage also have been reported in mammalian cells in vitro and, to some degree, in vivo. It was noted in the previous evaluation (IARC, 1994b) that the R-enantiomer of styrene 7,8-oxide may be slightly more mutagenic in S. typhimurium TA100 than the S-enantiomer (Pagano et al., 1982; Seiler, 1990; Sinsheimer et al., 1993). In contrast, Sinsheimer et al. (1993) reported that the S- but not the R-enantiomer induced chromosomal aberrations and sister chromatid exchange in mouse bone marrow. [The Working Group noted that, except when the R- or S- enantiomer of styrene 7,8-oxide was specifically tested, exposures to styrene 7,8-oxide were probably mixtures of optical isomers.] Results from studies on genetic and related effects of styrene 7,8-oxide published since the earlier evaluation are essentially all positive. In fact, only one study reported negative results, the w/w+ mosaic assay for induction of somatic mutations in insecticide-sensitive Drosophila melanogaster. However, in insecticide-resistant Drosophila strains, which have an active bioactivation system, styrene 7,8-oxide induced somatic mutations. DNA single-strand breaks and alkali-labile sites were induced in Wistar rat and human testicular and Chinese hamster V-79 cells in vitro. Four studies reported that DNA strand breaks and/or fragmentation were induced in human lymphocytes and human embryonic lung fibroblasts exposed to styrene 7,8-oxide in vitro. Similarly, positive results were reported for the induction of gene mutations at the HPRT locus in human lymphocytes and B-cell lymphoblastoid cells treated in vitro. Six studies reported that exposure to styrene 7,8-oxide in vitro induced a significant increase in sister chromatid exchange frequencies in human lymphocytes. One study also reported a significant
Table 14. Genetic and related effects of styrene 7,8-oxide Test system Result a Without exogenous metabolic system With exogenous metabolic system Dose b (LED or HID) Reference Drosophila melanogaster, somatic mutation (w/w+ mosaic assay) – 1200 μg/mL c Rodriguez-Arnaiz in feed (1998) DNA single-strand breaks and alkali-labile sites (alkaline elution), Wistar rat testicular cells in vitro + NT 12 Bjørge et al. (1996) DNA single-strand breaks and alkali-labile sites (alkaline elution), Chinese hamster V-79 cells, in vitro + NT 6 Herrero et al. (1997) DNA strand breaks, human lymphocytes in vitro + NT 6 Bastlová et al. (1995) DNA single-strand breaks and alkali-labile sites (alkaline elution), human testicular cells in vitro + NT 12 Bjørge et al. (1996) DNA single-strand breaks human embryonic lung fibroblasts in vitro + NT 1.2 Vodicka et al. (1996) DNA fragmentation, human whole blood in vitro + NT 1 Marczynski et al. (1997a) DNA damage (alkaline single-cell gel electrophoresis assay), human lymphocytes in vitro + NT 2.4 Laffon et al. (2001) Gene mutation, human lymphocytes, HPRT locus in vitro (+) NT 24 Bastlová et al. (1995) Gene mutation, human T-lymphocytes, HPRT locus, in vitro + NT 24 Bastlová & Podlutsky (1996) Gene mutation, human B-cell lymphoblastoid cells, HPRT locus, in vitro (+) d NT 72 Shield & Sanderson (2001) Sister chromatid exchange, human lymphocytes in vitro + NT 6 Lee & Norppa (1995) Sister chromatid exchange, human lymphocytes in vitro + NT 6 Ollikainen et al. (1998) Sister chromatid exchange, human lymphocytes in vitro + NT 6 Uusküla et al. (1995) Sister chromatid exchange, human lymphocytes in vitro + NT 6 Laffon et al. (2001) 512 IARC MONOGRAPHS VOLUME 82
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WORLD HEALTH ORGANIZATION INTERNATI
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IARC MONOGRAPHS In 1969, the Intern
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iv IARC MONOGRAPHS VOLUME 82 3.2 Th
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vi IARC MONOGRAPHS VOLUME 82 SOME M
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IARC WORKING GROUP ON THE EVALUATIO
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PARTICIPANTS 5 Observer, representi
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PREAMBLE
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10 IARC MONOGRAPHS VOLUME 82 plasms
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12 IARC MONOGRAPHS VOLUME 82 collec
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14 agents present. For processes, i
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16 IARC MONOGRAPHS VOLUME 82 Finall
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18 IARC MONOGRAPHS VOLUME 82 and mi
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20 IARC MONOGRAPHS VOLUME 82 (c) St
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22 IARC MONOGRAPHS VOLUME 82 may le
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24 IARC MONOGRAPHS VOLUME 82 It is
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26 IARC MONOGRAPHS VOLUME 82 Data r
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28 when there is strong evidence th
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30 IARC MONOGRAPHS VOLUME 82 Vol. 7
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GENERAL REMARKS ON THE SUBSTANCES C
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SOME TRADITIONAL HERBAL MEDICINES
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44 which may include, for example,
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46 2. Use of Traditional Herbal Med
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48 IARC MONOGRAPHS VOLUME 82 decade
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50 IARC MONOGRAPHS VOLUME 82 Table
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52 3.2.1 Definition of herbal medic
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54 3.2.8 Individual supply Herbal m
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58 3.3.2 Germany (see Kraft, 1999;
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60 beyond placebo, and this informa
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62 3.3.5 Canada The Canadian Food a
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64 of adverse reactions to OTC drug
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66 IARC MONOGRAPHS VOLUME 82 3.3.12
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68 IARC MONOGRAPHS VOLUME 82 Jellin
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70 IARC MONOGRAPHS VOLUME 82 Simila
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72 IARC MONOGRAPHS VOLUME 82 Figure
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74 diameter of 4-6 cm or more, lobe
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76 1.2 Use 1.2.1 Aristolochia conto
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78 1.3.3 Aristolochia fangchi Compo
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80 1.6.2 Structural and molecular f
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82 chromatographic separation with
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84 may contain aristolochic acids.
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86 IARC MONOGRAPHS VOLUME 82 A bila
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88 received distilled water. The an
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90 IARC MONOGRAPHS VOLUME 82 Figure
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92 varied from undetectable (< 0.02
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94 lochic acids enhanced immune res
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96 4.4 Genetic and related effects
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Table 3 (contd) Details of study DN
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Table 4. DNA adduct formation with
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Table 4 (contd) Details of study Co
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Table 5 (contd) Species Treatment I
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Table 6. DNA adduct formation by ar
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Table 6 (contd) Test system Assay D
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Table 6 (contd) Test system Assay D
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Table 7. Polymerase action on arist
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Table 8 (contd) Test system Drosoph
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116 of the forestomach and lung of
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118 lochic acid II (three metabolit
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120 IARC MONOGRAPHS VOLUME 82 Che,
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122 IARC MONOGRAPHS VOLUME 82 Healt
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124 IARC MONOGRAPHS VOLUME 82 Nishi
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126 IARC MONOGRAPHS VOLUME 82 Schme
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128 IARC MONOGRAPHS VOLUME 82 Yang,
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130 Figure 1. Morinda officinalis H
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132 1.3.2 Morinda officinalis A num
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134 by Soxhlet extraction with ethy
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136 2.1 Case-control studies 2.1.1
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138 3. Studies of Cancer in Experim
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140 1,3-Dihydroxy-2-hydroxymethylan
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142 4.3 Reproductive and developmen
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Table 1 (contd) Test system Result
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146 5.1 Exposure data 5. Summary of
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148 IARC MONOGRAPHS VOLUME 82 Brigg
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150 IARC MONOGRAPHS VOLUME 82 Nusko
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D. SENECIO SPECIES AND RIDDELLIINE
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metry (Witte et al., 1992). Thin-la
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sex were killed after a seven-week
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4.2.2 Experimental systems SOME TRA
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Table 1. Genetic and related effect
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Riddelliine induced unscheduled DNA
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5.3 Animal carcinogenicity data In
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SOME TRADITIONAL HERBAL MEDICINES 1
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SOME MYCOTOXINS
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172 Aflatoxin G 1 IARC MONOGRAPHS V
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Table 2 (contd) Method no. Aflatoxi
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178 indicates that A. flavus and A.
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Table 4. Occurrence of aflatoxin B1
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182 IARC MONOGRAPHS VOLUME 82 aflat
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Table 6. Co-occurrence of aflatoxin
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186 IARC MONOGRAPHS VOLUME 82 Figur
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188 1.4 International exposure esti
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190 (c) Impact of establishing maxi
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192 IARC MONOGRAPHS VOLUME 82 used
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Table 10 (contd) Reference Area Uni
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198 were collapsed into a conventio
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Table 11 (contd) Reference Area Stu
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202 IARC MONOGRAPHS VOLUME 82 histo
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204 IARC MONOGRAPHS VOLUME 82 resid
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Table 12. Summary of principal case
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208 IARC MONOGRAPHS VOLUME 82 disea
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210 3. Studies of Cancer in Experim
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212 IARC MONOGRAPHS VOLUME 82 diet
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214 3.4 Administration with known c
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216 IARC MONOGRAPHS VOLUME 82 The 8
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218 observed in rat liver slices, a
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222 IARC MONOGRAPHS VOLUME 82 an α
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224 (mainly hepatocellular carcinom
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226 IARC MONOGRAPHS VOLUME 82 but i
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228 lordosis and reduction in conce
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232 IARC MONOGRAPHS VOLUME 82 sampl
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234 In eight subjects (four from Ho
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Table 16 (contd) Test system Result
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240 IARC MONOGRAPHS VOLUME 82 anima
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242 difference between the two stud
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244 IARC MONOGRAPHS VOLUME 82 HBV-t
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246 In a large cohort study in Shan
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248 experimental data in showing th
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250 IARC MONOGRAPHS VOLUME 82 Ander
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252 IARC MONOGRAPHS VOLUME 82 Buetl
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254 IARC MONOGRAPHS VOLUME 82 Denis
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256 IARC MONOGRAPHS VOLUME 82 Galla
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258 IARC MONOGRAPHS VOLUME 82 Heino
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260 IARC MONOGRAPHS VOLUME 82 Jalon
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262 IARC MONOGRAPHS VOLUME 82 Kirk,
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264 IARC MONOGRAPHS VOLUME 82 Lunn,
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266 IARC MONOGRAPHS VOLUME 82 Olubu
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268 IARC MONOGRAPHS VOLUME 82 Roll,
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270 IARC MONOGRAPHS VOLUME 82 Stett
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272 IARC MONOGRAPHS VOLUME 82 Verge
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274 IARC MONOGRAPHS VOLUME 82 Yang,
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Table 1. IARC evaluations Previous
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278 kernels and in less than 0.1% o
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280 2.5.3 Cottonseed A. flavus is a
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294 IARC MONOGRAPHS VOLUME 82 8. Re
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296 IARC MONOGRAPHS VOLUME 82 Guo,
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298 IARC MONOGRAPHS VOLUME 82 Marti
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300 IARC MONOGRAPHS VOLUME 82 Sharm
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302 (d ) Solubility: Soluble in wat
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304 1.4 Occurrence Fumonisins have
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306 Table 1 (contd) IARC MONOGRAPHS
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308 (c) Formation in commodities ot
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312 IARC MONOGRAPHS VOLUME 82 3.1 O
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314 3.2.2 Rat IARC MONOGRAPHS VOLUM
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316 with NDEA and fumonisin B 1, wh
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318 IARC MONOGRAPHS VOLUME 82 In pi
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Figure 2. Allometric relationship b
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322 IARC MONOGRAPHS VOLUME 82 obser
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324 IARC MONOGRAPHS VOLUME 82 Hepat
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326 4.2.3 Related studies IARC MONO
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328 4.3.2 Experimental systems IARC
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330 and litters on postnatal day 21
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Table 4. Genetic and related effect
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334 IARC MONOGRAPHS VOLUME 82 The f
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336 IARC MONOGRAPHS VOLUME 82 (d )
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338 IARC MONOGRAPHS VOLUME 82 treat
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340 4.5.2 Interference with fatty a
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344 5.2 Human carcinogenicity data
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346 IARC MONOGRAPHS VOLUME 82 Alber
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348 IARC MONOGRAPHS VOLUME 82 Chamb
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350 IARC MONOGRAPHS VOLUME 82 Floss
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352 IARC MONOGRAPHS VOLUME 82 Hiroo
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354 IARC MONOGRAPHS VOLUME 82 Lee,
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356 IARC MONOGRAPHS VOLUME 82 Mobio
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358 IARC MONOGRAPHS VOLUME 82 Prelu
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360 IARC MONOGRAPHS VOLUME 82 Savar
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362 IARC MONOGRAPHS VOLUME 82 Steve
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364 IARC MONOGRAPHS VOLUME 82 Flett
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366 IARC MONOGRAPHS VOLUME 82 Yu, C
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368 disulfide, carbon tetrachloride
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Table 1 (contd) Sample matrix Sampl
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Table 3. Naphthalene production (th
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374 1.4 Occurrence 1.4.1 Natural oc
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Table 5. Occupational exposure to n
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378 water assuming a water concentr
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380 (Scheepers & Bos, 1992). The av
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382 (d ) Biodegradation Studies on
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386 3.2 Inhalation exposure 3.2.1 M
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388 3.3.2 Rat Ten BD I and BD III r
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Figure 1. Main metabolic pathways o
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392 IARC MONOGRAPHS VOLUME 82 and t
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394 IARC MONOGRAPHS VOLUME 82 and 1
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396 IARC MONOGRAPHS VOLUME 82 1-240
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398 IARC MONOGRAPHS VOLUME 82 Perfu
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400 Siegel and Wason (1986) reviewe
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402 IARC MONOGRAPHS VOLUME 82 liver
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404 IARC MONOGRAPHS VOLUME 82 to id
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406 IARC MONOGRAPHS VOLUME 82 Alkal
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408 hyperplasia, atrophy, chronic i
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410 had deficient glucose-6-phospha
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Table 10. Genetic and related effec
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Table 10 (contd) Test system Micron
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416 assay with or without metabolic
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418 There is some evidence of devel
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420 IARC MONOGRAPHS VOLUME 82 Bjør
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422 IARC MONOGRAPHS VOLUME 82 Conkl
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424 IARC MONOGRAPHS VOLUME 82 Envir
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426 IARC MONOGRAPHS VOLUME 82 Ho, C
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428 IARC MONOGRAPHS VOLUME 82 Lynch
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430 IARC MONOGRAPHS VOLUME 82 O’B
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432 IARC MONOGRAPHS VOLUME 82 Schee
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434 IARC MONOGRAPHS VOLUME 82 Versc
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STYRENE This substance was consider
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EPA Method 8260B can be used to det
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Styrene is produced mainly by catal
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STYRENE 443 Table 3. Use patterns f
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STYRENE 445 most samples taken from
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STYRENE 447 successive layers of ch
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Table 4 (contd) Country and year of
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Table 5. Biological monitoring of o
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STYRENE 453 Since 1990, the long-te
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same products resulted in exposures
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STYRENE 457 Ambient air monitoring
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200 μg/kg, although 77% of the foo
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Page 470 and 471: 2.1 Case reports 2. Studies of Canc
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Page 480 and 481: elationship for styrene became nega
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Page 484 and 485: controls versus 32/32 treated). No
Page 486 and 487: 3.4 Intraperitoneal administration
Page 488 and 489: Figure 1. Main metabolic pathways f
Page 490 and 491: STYRENE 483 a maximum and averaged
Page 492 and 493: (b) Distribution STYRENE 485 An ear
Page 494 and 495: STYRENE 487 rats with phenobarbital
Page 496 and 497: STYRENE 489 gavage (100-350 mg/kg b
Page 498 and 499: CYP2E1 and CYP2F2) inhibited nasal
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Page 506 and 507: STYRENE 499 exposure concentrations
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Page 510 and 511: STYRENE 503 groups. Only minor gene
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Page 514 and 515: Table 12. Cytogenetic studies in ly
Page 516 and 517: Table 13. Genetic and related effec
Page 520 and 521: Table 14 (contd) Test system Result
Page 522 and 523: STYRENE 515 styrene 7,8-oxide. Joha
Page 524 and 525: Styrene 7,8-oxide can bind to DNA w
Page 526 and 527: STYRENE 519 a small and non-signifi
Page 528 and 529: STYRENE 521 and immune systems, liv
Page 530 and 531: STYRENE 523 Artuso, M., Angotzi, G.
Page 532 and 533: STYRENE 525 Brugnone, F., Perbellin
Page 534 and 535: STYRENE 527 Coccini, T., Maestri, L
Page 536 and 537: STYRENE 529 Edling, C., Anundi, H.,
Page 538 and 539: STYRENE 531 Gobba, F., Galassi, C.,
Page 540 and 541: STYRENE 533 Horvath, E., Pongracz,
Page 542 and 543: STYRENE 535 logical Study and the I
Page 544 and 545: STYRENE 537 Linhart, I., Gut, I.,
Page 546 and 547: STYRENE 539 Miller, S.L., Branoff,
Page 548 and 549: STYRENE 541 Newhook, R. & Caldwell,
Page 550 and 551: STYRENE 543 Pryor, G.T., Rebert, C.
Page 552 and 553: STYRENE 545 Sielken, R.L. & Valdez-
Page 554 and 555: STYRENE 547 Tsuda, S., Matsusaka, N
Page 556 and 557: STYRENE 549 Boffetta, P. (1996b) Ex
Page 558: Agent SUMMARY OF FINAL EVALUATIONS
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562 β-Butyrolactone 11, 225 (1976)
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564 IARC MONOGRAPHS VOLUME 82 Chlor
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566 Cyproterone acetate 72, 49 (199
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568 IARC MONOGRAPHS VOLUME 82 Diepo
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570 Ethionamide 13, 83 (1977); Supp
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572 IARC MONOGRAPHS VOLUME 82 Haema
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574 L Lasiocarpine 10, 281 (1976);
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576 IARC MONOGRAPHS VOLUME 82 Methy
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578 IARC MONOGRAPHS VOLUME 82 Nicke
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580 O Ochratoxin A 10, 191 (1976);
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582 IARC MONOGRAPHS VOLUME 82 Polyb
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584 Rhodamine 6G 16, 233 (1978); Su
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586 Sulfafurazole 24, 275 (1980); S
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588 1,1,1-Trichloroethane 20, 515 (
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590 Y Yellow AB 8, 279 (1975); Supp
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Volume 31 Some Food Additives, Feed
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