IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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Based on BUA (1989) and Agency for Toxic Substances and Disease Registry (1995a) (1) Naphthalene (2) Naphthalene 1,2-oxide (3) 1-Naphthol (α-naphthol) (4) 1-Naphthyl glucuronide or sulfate (5) trans-1,2-Dihydro-1,2-dihydroxynaphthalene (6) trans-1,2-Dihydro-2-hydroxynaphthyl-1-glucuronide (7) 1,2-Dihydroxynaphthalene (8) 1,2-Naphthoquinone (9) 2-Hydroxynaphthyl-1-sulfate or -glucuronide (10) 2-Naphthol (β-naphthol) (11) N-Acetyl-S-(1,2-dihydro-1-hydroxy-2-naphthyl)-L-cysteine (12) N-Acetyl-S-(1-naphthyl)-L-cysteine (1-naphthyl mercapturic acid) (13) 1,4-Dihydroxynaphthalene (14) 1,4-Naphthoquinone GSH = Glutathione R1 = Sulfate or glucuronate group = N-acetyl-L-cysteine residue R2 A,Q = O2- and NADPH2-dependent monooxygenase (e.g., cytochrome P450-NADP-cytochrome-c-reductase system, microsomal) B = Spontaneous isomerization C,E,J = Conjugation reaction with sulfate (sulfotransferase, cytosolic) or with glucuronic acid (UDP-glucuronyltransferase, microsomal) D = Epoxide hydrolase, synonym: epoxide hydrase (microsomal) F,N,P = Chemical dehydration G = Dihydrodiol-dehydrogenase (cystosolic); 3,5-cyclohexadiene-1,2diol-NADP-oxidoreductase H = Chemical dehydration K = Chemical hydrolysis + dehydration L = Enzymatic reaction with glutathione M = γ-Glutamyl transferase, peptidase, N-acetylase NAPHTHALENE 391
392 IARC MONOGRAPHS VOLUME 82 and three glutathione conjugates. These metabolites were also identified in animal studies, as discussed in Section 4.1.2. Urinary metabolites of naphthalene are useful biomarkers of exposure. Seventy-five workers exposed to naphthalene while distilling naphthalene oil excreted 7.48 mg/L (4.35 mg/g creatinine) 1-naphthol (geometric mean values) at the end of the workshift. For 24 non-occupationally exposed individuals, the mean urinary concentration of 1-naphthol was 0.13 mg/L (Bieniek, 1994). 1-Naphthol, 2-naphthol and 1,4-naphthoquinone (14, see Figure 1) were identified in the urine of 69 coke-plant workers exposed to a geometric mean air concentration of naphthalene of 0.77 mg/m 3 during tar distillation. The end-of-workshift urinary concentrations of 1-naphthol and 2-naphthol were 693 and 264 μmol/mol creatinine. The correlation coefficients between the urinary excretion of naphthols and exposure to naphthalene were 0.64–0.75 for 1-naphthol and 0.70–0.82 for 2-naphthol. There was a linear relationship between the overall concentration of naphthols in urine and the naphthalene concentration in air (Bieniek, 1997). In a further study of a coke plant, Bieniek (1998) measured the concentrations of 1-naphthol and 2-naphthol in urine from eight workers in coke batteries, 11 workers in the sorting department and 29 workers in the distillation department. The mean urinary concentrations of 1-naphthol and 2-naphthol were 294 and 89 μmol/mol creatinine for the coke-battery workers, 345 and 184 μmol/mol creatinine for the sorters and 1100 and 630 μmol/mol creatinine for the distillation workers, respectively. Andreoli et al. (1999) examined 15 urine samples from workers in a naphthaleneproducing plant who were exposed to 0.1–0.7 mg/m 3 naphthalene. At the end of the workshift, the median urinary concentrations of 2-naphthyl sulfate, 2-naphthyl glucuronide and 1-naphthyl glucuronide were 0.030 (range, 0.014–0.121), 0.086 (range, 0.013–0.147) and 0.084 (range, 0.021–0.448) mg/L, respectively. Since naphthalene is the most abundant component of creosote (Heikkilä et al., 1987), urinary excretion of 1-naphthol was determined in three assembly workers handling creosote-impregnated wood. The average airborne concentration of naphthalene in the breathing zone was approximately 1 mg/m 3 . The average end-of-shift concentration of 1-naphthol in urine changed from 254–722 (mean, 556) μmol/mol creatinine on Monday to 1820–2190 (mean, 2060) μmol/mol creatinine on Wednesday and 870– 2330 (mean, 1370) μmol/mol creatinine on Friday. The same metabolite was measured in the urine of six workers exposed to creosote in a plant impregnating railroad ties (Heikkilä et al., 1997). As measured by use of personal air samplers, the mean airborne concentration of naphthalene in the workers’ breathing zone was 1.5 (range, 0.37–4.2) mg/m 3 . The mean end-of-shift concentration of 1-naphthol was 20.5 (range, 3.5–62.1) μmol/L. There was a good correlation (r = 0.745) between concentrations of airborne naphthalene and urinary 1-naphthol. No 1-naphthol was detected (limit of detection < 0.07 μmol/L) in the urine of five non-exposed controls. Hill et al. (1995) measured 1-naphthol and 2-naphthol in the urine of 1000 adults without occupational exposure — a subset of the National Health and Nutrition Examination Survey III — who may have been exposed to low levels of naphthalene or pesticides that would yield
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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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20 IARC MONOGRAPHS VOLUME 82 (c) St
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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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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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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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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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