IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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200 μg/kg, although 77% of the foods had levels below 10 μg/kg and 26% had levels below 1 μg/kg (Gilbert & Startin, 1983). Similar surveys were carried out by the Food Safety Directorate in 1992 and 1994 in the United Kingdom, with styrene concentrations similar to those found in the 1983 survey. Within each food type, higher levels of styrene were generally found for products with high fat content or packed in small containers (Ministry of Agriculture, Fisheries and Food, 1994). Between 1991 and 1999, the Food and Drug Administration’s Total Diet Study in the USA analysed 320 different foods and found styrene residues in 49 of them. In 258 samples containing styrene, the mean concentrations for individual food items varied between 10 μg/kg (eggs) and 274 μg/kg (strawberries). The median concentration for the 49 foods was 21 μg/kg (Food and Drug Administration, 2000). Several assessments have been made of estimated daily intake (EDI) of styrene in food packaged in polymers or copolymers of styrene. In 1981, the Food and Drug Administration in the USA measured the migration of styrene over a 24-h period from foam, impact and crystal polystyrene cups into 8% ethanol and water at 49 °C. The observed migration was 0.036, 0.064 and 0.210 μg/cm 2 , respectively. This corresponds to 6 μg styrene from a 2 dL (8 oz.) foam cup. Migration from foam cups into hot water, tea and coffee was one fifth of these levels: approximately 1 μg from a 2 dL (8 oz.) cup (Varner & Breder, 1981). In a 1983 study, the EDI of styrene monomer from polystyrene food packaging, including polystyrene foam cups, was in the range of 1 to 4 μg per day (Ministry of Agriculture, Fisheries and Food, 1989). More recently, Lickly et al. (1995) estimated total dietary intake of styrene monomer from polystyrene food-contact polymers to be 9 μg per day. Styrene has been detected at low levels (ppb) in several foods and beverages which had not previously been in contact with styrene-containing packaging materials (Maarse, 1992a,b; Steele, 1992, Steele et al., 1994). Much higher levels (around 40 mg/kg) have been measured in cinnamon, and enzymatic degradation of cinnamic acid derivatives was proposed as a possible source (Oliviero, 1906; Ducruet, 1984). The low-level occurrence of styrene in other foods has been suggested to result from enzymatic and/or microbial activity, but it is unclear to what extent these processes are, in fact, responsible for the levels detected (Steele et al., 1994; Tang et al., 2000). 1.5 Regulations and guidelines 1.5.1 Exposure limits and guidelines STYRENE 459 Occupational exposure limits and guidelines for styrene are presented in Table 8. A tolerable daily intake (TDI) of 7.7 μg/kg bw for styrene has been established by WHO (1993), with a guideline value of 20 μg/L in drinking-water. The Environmental Protection Agency (2001b) has set a maximum contaminant level (MCL) for styrene in public water systems in the USA at 0.1 mg/L.
460 IARC MONOGRAPHS VOLUME 82 The Food and Drug Administration (2001) has established regulations for the use of polymers and copolymers of styrene in products in contact with food in the USA. For styrene and methyl methacrylate copolymers as components of paper and paperboard in contact with fatty foods, the monomer content in the copolymer is limited to 0.5%. For styrene–acrylic copolymers, the level of residual styrene monomer in the polymer should not exceed 0.1% by weight. Table 8. Occupational exposure limits and guidelines for styrene Country or region Year Concentration (mg/m 3 ) Interpretation Australia 1993 213 TWA 426 STEL Belgium 1993 213 (sk) TWA 426 STEL Czech Republic 1993 200 TWA 1000 STEL Denmark 1993 106 TWA Finland 2002 86 TWA 430 STEL France 1993 213 TWA Germany 2001 86 (category 5) a MAK; substance with systemic effects (onset < 2 h) Hungary 1993 50 (Ca) TWA Ireland 1993 426 TWA 1065 STEL Japan 2000 85 (sk) TWA (provisional value) Mexico 1984 215 TWA 425 STEL Netherlands 1999 106 TWA Philippines 1993 426 TWA Poland 1998 50 (sk) TWA 200 STEL Sweden 1993 106 (sk) TWA 320 STEL Switzerland 1993 213 TWA 426 STEL Thailand 1993 426 TWA 852 STEL Turkey 1993 426 TWA United Kingdom 2000 430 TWA; maximum exposure limit 1065 STEL
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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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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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Page 435 and 436: 428 IARC MONOGRAPHS VOLUME 82 Lynch
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Page 439 and 440: 432 IARC MONOGRAPHS VOLUME 82 Schee
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Page 444 and 445: STYRENE This substance was consider
Page 446 and 447: EPA Method 8260B can be used to det
Page 448 and 449: Styrene is produced mainly by catal
Page 450 and 451: STYRENE 443 Table 3. Use patterns f
Page 452 and 453: STYRENE 445 most samples taken from
Page 454 and 455: STYRENE 447 successive layers of ch
Page 456 and 457: Table 4 (contd) Country and year of
Page 458 and 459: Table 5. Biological monitoring of o
Page 460 and 461: STYRENE 453 Since 1990, the long-te
Page 462 and 463: same products resulted in exposures
Page 464 and 465: STYRENE 457 Ambient air monitoring
Page 468 and 469: Table 8 (contd) Country or region Y
Page 470 and 471: 2.1 Case reports 2. Studies of Canc
Page 472 and 473: Table 10 (contd) Reference (country
Page 474 and 475: Table 10 (contd) Reference (country
Page 476 and 477: STYRENE 469 (95% CI, 1.4-5.2; 10 de
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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
Page 500 and 501: model indicated that absorbed styre
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Page 504 and 505: STYRENE 497 continuously for seven
Page 506 and 507: STYRENE 499 exposure concentrations
Page 508 and 509: STYRENE 501 The frequency of sponta
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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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