IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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CONTENTS v 2. Studies of cancer in humans ..................................................................135 Case−control studies ..............................................................................136 3. Studies of cancer in experimental animals ............................................138 3.1 1-Hydroxyanthraquinone ................................................................138 3.2 1,3-Dihydroxy-2-hydroxymethylanthraquinone (lucidin) ..............139 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms........................................................................................139 4.1 Absorption, distribution, metabolism and excretion ......................139 4.2 Toxic effects ....................................................................................140 4.3 Reproductive and developmental effects ........................................142 4.4 Genetic and related effects..............................................................142 4.5 Mechanistic considerations ............................................................145 5. Summary of data reported and evaluation..............................................146 5.1 Exposure data..................................................................................146 5.2 Human carcinogenicity data............................................................146 5.3 Animal carcinogenicity data ..........................................................146 5.4 Other relevant data..........................................................................147 5.5 Evaluation ......................................................................................147 6. References ..............................................................................................147 D. Senecio species and riddelliine ....................................................................153 1. Exposure data..........................................................................................153 1.1 Origin, type and botanical data ......................................................153 1.2 Use ..................................................................................................153 1.3 Chemical constituents ....................................................................153 1.4 Sales and consumption....................................................................154 1.5 Component(s) with potential cancer hazard (riddelliine) ..............154 2. Studies of cancer in humans ..................................................................155 3. Studies of cancer in experimental animals ............................................156 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms........................................................................................157 4.1 Absorption, distribution, metabolism and excretion ......................157 4.2 Toxic effects ....................................................................................158 4.3 Reproductive and developmental effects ........................................160 4.4 Genetic and related effects..............................................................160 4.5 Mechanistic considerations ............................................................163 5. Summary of data reported and evaluation..............................................163 5.1 Exposure data..................................................................................163 5.2 Human carcinogenicity data............................................................163 5.3 Animal carcinogenicity data ..........................................................165 5.4 Other relevant data..........................................................................165 5.5 Evaluation ......................................................................................165 6. References ..............................................................................................165
vi IARC MONOGRAPHS VOLUME 82 SOME MYCOTOXINS............................................................................................169 AFLATOXINS ....................................................................................................171 1. Exposure data..........................................................................................171 2. Studies of cancer in humans ..................................................................193 3. Studies of cancer in experimental animals ............................................210 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms ................................................................................215 5. Summary of data reported ......................................................................245 6. References ..............................................................................................249 Annex. Aflatoxins in foods and feeds: fungal sources, formation and strategies for reduction....................................................................275 FUMONISIN B 1 ..................................................................................................301 1. Exposure data ........................................................................................301 2. Studies of cancer in humans ..................................................................309 3. Studies of cancer in experimental animals ............................................311 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms ................................................................................316 5. Summary of data reported and evaluation..............................................343 6. References ..............................................................................................345 NAPHTHALENE ....................................................................................................367 1. Exposure data ........................................................................................367 2. Studies of cancer in humans ..................................................................385 3. Studies of cancer in experimental animals ............................................385 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms ................................................................................389 5. Summary of data reported and evaluation..............................................416 6. References ..............................................................................................418 STYRENE ................................................................................................................437 1. Exposure data ........................................................................................437 2. Studies of cancer in humans ..................................................................463 3. Studies of cancer in experimental animals ............................................475 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms ................................................................................479 5. Summary of data reported and evaluation..............................................518 6. References ..............................................................................................522 SUMMARY OF FINAL EVALUATIONS ..............................................................551 LIST OF ABBREVIATIONS USED IN THIS VOLUME ......................................553 CUMULATIVE INDEX TO THE MONOGRAPHS SERIES..................................557
Page 1 and 2: WORLD HEALTH ORGANIZATION INTERNATI
Page 3 and 4: IARC MONOGRAPHS In 1969, the Intern
Page 5: iv IARC MONOGRAPHS VOLUME 82 3.2 Th
Page 10 and 11: IARC WORKING GROUP ON THE EVALUATIO
Page 12 and 13: PARTICIPANTS 5 Observer, representi
Page 14: PREAMBLE
Page 17 and 18: 10 IARC MONOGRAPHS VOLUME 82 plasms
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Page 35 and 36: 28 when there is strong evidence th
Page 37 and 38: 30 IARC MONOGRAPHS VOLUME 82 Vol. 7
Page 40 and 41: GENERAL REMARKS ON THE SUBSTANCES C
Page 42 and 43: GENERAL REMARKS ON THE SUBSTANCES C
Page 44: GENERAL REMARKS ON THE SUBSTANCES C
Page 48: SOME TRADITIONAL HERBAL MEDICINES
Page 51 and 52: 44 which may include, for example,
Page 53 and 54: 46 2. Use of Traditional Herbal Med
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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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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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Table 8 (contd) Country or region Y
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2.1 Case reports 2. Studies of Canc
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Table 10 (contd) Reference (country
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Table 10 (contd) Reference (country
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STYRENE 469 (95% CI, 1.4-5.2; 10 de
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who had been employed in 1964-70 (t
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elationship for styrene became nega
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atio, 4.4; 95% CI, 1.1-17 in multip
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controls versus 32/32 treated). No
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3.4 Intraperitoneal administration
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Figure 1. Main metabolic pathways f
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STYRENE 483 a maximum and averaged
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(b) Distribution STYRENE 485 An ear
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STYRENE 487 rats with phenobarbital
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STYRENE 489 gavage (100-350 mg/kg b
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CYP2E1 and CYP2F2) inhibited nasal
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model indicated that absorbed styre
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female workers in the glass fibre-r
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STYRENE 497 continuously for seven
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STYRENE 499 exposure concentrations
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STYRENE 501 The frequency of sponta
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STYRENE 503 groups. Only minor gene
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concentrations of styrene in air we
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Table 12. Cytogenetic studies in ly
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Table 13. Genetic and related effec
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(b) Experimental systems (see Table
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STYRENE 515 styrene 7,8-oxide. Joha
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Styrene 7,8-oxide can bind to DNA w
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STYRENE 519 a small and non-signifi
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STYRENE 521 and immune systems, liv
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STYRENE 523 Artuso, M., Angotzi, G.
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STYRENE 525 Brugnone, F., Perbellin
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STYRENE 527 Coccini, T., Maestri, L
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STYRENE 529 Edling, C., Anundi, H.,
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STYRENE 531 Gobba, F., Galassi, C.,
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STYRENE 533 Horvath, E., Pongracz,
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STYRENE 535 logical Study and the I
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STYRENE 537 Linhart, I., Gut, I.,
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STYRENE 539 Miller, S.L., Branoff,
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STYRENE 541 Newhook, R. & Caldwell,
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STYRENE 543 Pryor, G.T., Rebert, C.
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STYRENE 545 Sielken, R.L. & Valdez-
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STYRENE 547 Tsuda, S., Matsusaka, N
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STYRENE 549 Boffetta, P. (1996b) Ex
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Agent SUMMARY OF FINAL EVALUATIONS
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554 IARC MONOGRAPHS VOLUME 82 DGAL:
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556 IARC MONOGRAPHS VOLUME 82 PMTDI
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558 IARC MONOGRAPHS VOLUME 82 Aldri
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560 IARC MONOGRAPHS VOLUME 82 Benz[
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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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