IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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D. SENECIO SPECIES AND RIDDELLIINE 1. Exposure Data 1.1 Origin, type and botanical data (Molyneux et al., 1991) Senecio riddellii (Asteraceae) (Riddell groundsel) is a grey-white half-shrub, 30–90 cm tall with pinnatifid and relatively hairless leaves, revealing its bright green leaf colour. It has bright yellow flowers on the stems at about the same height above the ground. This gives the plant a flat-topped appearance when in bloom. It produces flowers in late summer to early autumn and dies back to ground level after the first frost. It grows in dry, sandy soils and its roots are long and about as thick as a lead pencil. Senecio longilobus (also known as woolly groundsel and thread-leaf groundsel) is a shrubby, erect, branched, leafy plant, 30–60 cm tall. It has narrowly linear leaves which are thick, white, and occasionally pinnately lobed, up to 10 cm long. The composite yellow flower heads contain numerous clusters. In North America, this is a common plant with a range extending from Colorado to Utah, south to Texas and Mexico (Kingsbury, 1964). 1.2 Use The ‘bush tea’ used in Jamaica to treat children for a cold an a herbal tea that is popular in the south-west USA, gordolobo yerba, may contain riddelliine (Stillman et al., 1977a; Huxtable, 1980; National Toxicology Program, 2002). 1.3 Chemical constituents The plants (ragworts) from which riddelliine and other pyrrolizidine alkaloids are isolated are found in the rangelands of the western USA. Cattle, horses and, less commonly, sheep that ingest these plants can succumb to their toxic effects (called pyrrolizidine alkaloidosis). Riddelliine residues have been found in meat, milk and honey. The plants may contaminate human food sources as intact plants, and their seeds may contaminate commercial grains such as wheat (Fu et al., 2001; National Toxicology Program, 2002). The main chemical constituents of importance in S. riddellii are pyrrolizidine alkaloids. –153–
154 Four pyrrolizidine alkaloids have been identified as constituents of S. longilobus, namely riddelliine, retrorsine, senecionine and seneciphylline (Segall & Molyneux, 1978). 1.4 Sales and consumption No information was available to the Working Group. 1.5 Component with potential cancer hazard (riddelliine) Riddelliine was evaluated previously (IARC, 1976). 1.5.1 Nomenclature Chem. Abstr. Serv. Reg. No.: 23246-96-0 Chem. Abstr. Serv. Name: 13,19-Didehydro-12,18-dihydroxysenecionan-11,16-dione Synonym: Riddelline 1.5.2 Structural and molecular formulae and relative molecular mass C 18H 23NO 6 1.5.3 Chemical and physical properties of the pure substance Relative molecular mass: 349.38 (a) Description: Crystalline solid (National Toxicology Program, 2002) (b) Melting-point: 197–198 °C (decomposes) (Buckingham, 2001) (c) Solubility: Sparingly soluble in water; soluble in chloroform; slightly soluble in acetone and ethanol (National Toxicology Program, 2002) (d) Optical rotation: [α] 25 –109.5 (chloroform) (Buckingham, 2001) D 1.5.4 Analysis IARC MONOGRAPHS VOLUME 82 H C C H 3 H 2C C C C CO O H 2C H N Underivatized pyrrolizidine alkaloids, including riddelliine, from natural sources (plants and insects) have been analysed by capillary gas chromatography–mass spectro- OH CO O C H 2 CH 2OH
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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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Page 119 and 120: Table 7. Polymerase action on arist
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Page 137 and 138: 130 Figure 1. Morinda officinalis H
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Page 162 and 163: metry (Witte et al., 1992). Thin-la
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Page 168 and 169: Table 1. Genetic and related effect
Page 170 and 171: Riddelliine induced unscheduled DNA
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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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220 IARC MONOGRAPHS VOLUME 82 Figur
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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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238 IARC MONOGRAPHS VOLUME 82 aflat
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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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Table 14 (contd) Test system Result
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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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