IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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1.2 Sources, production and use 1.2.1 Fungi producing aflatoxins AFLATOXINS 177 Aflatoxins are produced by the common fungi Aspergillus flavus and the closely related species A. parasiticus. These are well defined species: A. flavus produces only B aflatoxins and sometimes the mycotoxin cyclopiazonic acid (CPA), while A. parasiticus produces both B and G aflatoxins, but never CPA (Schroeder & Boller, 1973; Dorner et al., 1984; Klich & Pitt, 1988; Pitt, 1993) (see Annex). This simple situation, of just two aflatoxigenic species, has been complicated by more recent taxonomic findings. Kurtzman et al. (1987) described A. nomius, a species closely related to A. flavus but which produces small bullet-shaped sclerotia, as distinct from the large spherical sclerotia produced by many A. flavus isolates. This species is also distinguished from A. flavus by the production of both B and G aflatoxins (Saito et al., 1989; Pitt, 1993). A second new species, closely related to A. nomius, was described by Peterson et al. (2001) and named A. bombycis. These two species were distinguished from each other by differences in DNA, and also by differences in growth rates at 37 °C. Like A. nomius, A. bombycis produces both B and G aflatoxins. The species A. ochraceoroseus described by Bartoli and Maggi (1978) was recently shown to be another aflatoxin producer. It also produces sterigmatocystin (Frisvad, 1997; Klich et al., 2000). Saito and Tsuruta (1993) described A. flavus var. parvisclerotigenus, which produces small spherical sclerotia, but one isolate (NRRL 3251) (Agricultural Research Service Culture Collection) reported to be representative of the new variety was considered by both Christensen (1981) and Pitt (1993) to be a typical A. flavus. This same isolate was reported by Stubblefield et al. (1970) to produce B but not G aflatoxins, in line with those assessments. Moreover, Geiser et al. (2000) showed that the production of small versus large sclerotia does not have taxonomic significance within A. flavus. Two aflatoxin-producing isolates from Japan, originally classified as aberrant A. tamarii (Goto et al., 1996), were recently described as A. pseudotamarii. Like A. flavus, this species produces B aflatoxins and CPA, but differs from A. flavus by the production of orange-brown conidia (Ito et al., 2001). In studying population genetics of A. flavus, Geiser et al. (1998) showed that A. flavus from an Australian peanut field comprised two distinct subgroups, which they termed Group I and Group II, and suggested that Group II differed from Group I (A. flavus sensu stricto) sufficiently to be raised to species level. Further studies by Geiser et al. (2000) and independent observations have confirmed that A. flavus Group II comprises a distinct species, which will be described as ‘Aspergillus australis’. Unlike any other known species, A. australis produces both B and G aflatoxins and also CPA. It appears to occur almost exclusively in the southern hemisphere, where it has been found in Argentina, Australia, Indonesia and South Africa. The current status of taxonomic information and mycotoxin production by species that produce aflatoxins is summarized in Table 3. This information, complex though it is, should not be allowed to obscure the importance of the older species. The evidence
178 indicates that A. flavus and A. parasiticus are responsible for the overwhelming proportion of aflatoxins found in foodstuffs throughout the world. Of the other species, only A. australis, which appears to be widespread in the southern hemisphere and is common in Australian peanut soils, may also be an important source of aflatoxins in a few countries. 1.2.2 Production and reduction Apart from natural formation, aflatoxins are produced only in small quantities for research purposes, by A. flavus or A. parasiticus fermentations on solid substrates or media in the laboratory. Aflatoxins are extracted by solvents and purified by chromatography. Total annual production is less than 100 g (IARC, 1993). Aflatoxins occurring naturally in foods and feeds may be reduced by a variety of procedures. Improved farm management practices, more rapid drying and controlled storage are now defined within GAP (Good Agricultural Practice) or HACCP (Hazard Analysis: Critical Control Point) (FAO, 1995). By segregation of contaminated lots after aflatoxin analyses and by sorting out contaminated nuts or grains by electronic sorters, contaminated lots of peanuts or maize can be cleaned up to produce food-grade products. Decontamination by ammoniation or other chemical procedures can be used for rendering highly contaminated commodities suitable as animal feeds. More detailed information on these topics is given in the Annex to this Monograph. 1.2.3 Uses IARC MONOGRAPHS VOLUME 82 Table 3. Aspergillus species capable of producing aflatoxins Species Mycotoxins produced AFB AFG CPA Aflatoxins are not used commercially, only for research. Major sources Geographical distribution A. flavus + – – All kinds of foods Ubiquitous in warmer latitudes A. parasiticus + + – Peanuts Specific areas A. nomius + + – Bees USA, Thailand A. pseudotamarii + – + Soil Japan A. bombycis + + – Silkworm frass Japan, Indonesia A. ochraceoroseus + – – Soil Africa A. australis + + + Soil, peanuts Southern hemisphere AFB, B aflatoxins; AFG, G aflatoxins; CPA, cyclopiazonic acid
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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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Page 137 and 138: 130 Figure 1. Morinda officinalis H
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Page 160 and 161: D. SENECIO SPECIES AND RIDDELLIINE
Page 162 and 163: metry (Witte et al., 1992). Thin-la
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Page 221 and 222: 214 3.4 Administration with known c
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Page 225 and 226: 218 observed in rat liver slices, a
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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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288 IARC MONOGRAPHS VOLUME 82 Figur
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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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342 IARC MONOGRAPHS VOLUME 82 Figur
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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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