Pesticide residues in food â 2006: Toxicological ... - ipcs inchem

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67 Metabolite Structure O OH N H M510F23 N S H 2 N HO O Cl O N H OH M510F28 N HOOC S C H 3 NH Cl O O N H M510F29 N Cl OH H H O O H OH OH H H CO 2 H O M510F32 N Cl N H S COOH HN CH 3 O Cl O OH M510F33 N Cl N H S COOH HN CH 3 O Cl O M510F34 N Cl N H SO COOH HN CH 3 O Cl BOSCALID X-X JMPR <strong>2006</strong>
68 Metabolite Structure M510F39 N O N H SCH 3 OH H H OHO H OH OH H H CO 2 H Cl M510F40 N O Cl N H H H OHO OH OH H OH OH H H CO 2 H Cl M510F41 N O Cl N H OH H H OHO OCH 3 H OH OH H H CO 2 H Cl M510F42 N O Cl N H OH H H OHO SCH 3 H OH OH H H CO 2 H Cl O N H N M510F43 S O Cl H N N H O O OH O OH NH 2 M510F45 N O Cl N H S O H N N H O O OH NH 2 O OH Cl M510F46 or isomer N O Cl N H H H OH S O H N N H O O OH NH 2 O OH Cl BOSCALID X-X JMPR <strong>2006</strong>
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Pesticide residues in food — 2006
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TABLE OF CONTENTS Page List of part
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Dr Helen Hakansson, Institute of En
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Abbreviations used ADI ALT APDM ARf
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Introduction The toxicological mono
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BIFENAZATE First draft prepared by
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5 In a series of experiments, group
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7 In a study of the time-course of
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9 the administered dose in males an
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11 limited absorption of parent com
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13 NAME/No. STRUCTURE D1989 OCH 3 D
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15 2.1 Acute toxicity Results of st
Page 30 and 31: 17 (f) Sensitization In a study of
Page 32 and 33: 19 Table 9. Clinical chemistry effe
Page 34 and 35: 21 The degree of this finding was m
Page 36 and 37: 23 On histopathological examination
Page 38 and 39: 25 (equal to 0, 0.9, 10.4 or 25 mg/
Page 40 and 41: 27 Haemoglobin (g/dl): Before treat
Page 42 and 43: 29 weekly. Blood and urine samples
Page 44 and 45: 31 (females) (equal to 0, 1.0, 3.9,
Page 46 and 47: 33 Cytogenetic test Chinese hamster
Page 48 and 49: 35 groups of 30 males and 30 female
Page 50 and 51: 37 and placed in 10% ammonium sulfi
Page 52 and 53: 39 was > 5000 mg/kg bw. The LC 50 i
Page 54 and 55: 41 Multigeneration study of reprodu
Page 56 and 57: 43 Medical data No significant adve
Page 58: 45 Trutter, J.A. (1997a) 28-Day die
Page 61 and 62: 48 Evaluation for acceptable daily
Page 63 and 64: 50 Table 2. Radioactivity in blood
Page 65 and 66: 52 10 10 0.42 0.0462 0.63 0.0080 8.
Page 67 and 68: 54 Figure 2. Transfer of radioactiv
Page 69 and 70: 56 Skin 33.07 61.59 0.5 17.94 17.29
Page 71 and 72: 58 Table 10. Summary of metabolites
Page 73 and 74: 60 Table 14. Summary of identified
Page 75 and 76: 62 Table 18. Summary of metabolites
Page 77 and 78: 64 Table 19. Structures of identifi
Page 79: 66 Metabolite Structure O M510F14 N
Page 83 and 84: 70 2. Toxicological studies 2.1 Acu
Page 85 and 86: 72 1% Tylose CB 30.000. The injecti
Page 87 and 88: 74 the end of dosing. Blood samples
Page 89 and 90: 76 examinations were carried out 8
Page 91 and 92: 78 concentrations were increased at
Page 93 and 94: 80 times were slightly, but signifi
Page 95 and 96: 82 in males and females rats at 250
Page 97 and 98: 84 End-point Test object Dose a (LE
Page 99 and 100: 86 parental rats was not markedly a
Page 101 and 102: 88 groups in conception frequencies
Page 103 and 104: 90 0.7 ± 3.5%, 1.8 ± 4.2%, 2.9 ±
Page 105 and 106: 92 In this study of developmental n
Page 107 and 108: 94 3. Observations in humans In the
Page 109 and 110: 96 was 100 ppm, equal to 10 mg/kg b
Page 111 and 112: 98 Acute toxicity Rat, LD 50 , oral
Page 113 and 114: 100 Mellert, W., Kaufmann, W. & Hil
Page 116 and 117: CYFLUTHRIN AND BETA-CYFLUTHRIN Firs
Page 118 and 119: 105 Table 1. Diastereoisomer pairs
Page 120 and 121: 107 (i) In vivo Rats Four groups of
Page 122 and 123: 109 2. Toxicological studies 2.1 Ac
Page 124 and 125: 111 Species Strain Sex Route Formul
Page 126 and 127: 113 Rat Groups of 20 male and 20 fe
Page 128 and 129: 115 group and in the groups at the
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117 cyfluthrin (purity, 95.5-95.9%)
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119 In a short-term study of exposu
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121 and dissection. At termination,
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123 2.5 Reproductive toxicity (a) M
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125 gestation. The vehicle was 1% C
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127 females was exposed during days
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129 were not seen in rats in the co
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131 men was exposed for 1 h to actu
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133 40 g/l, in a flowable concentra
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135 were removed from five males an
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137 weights and food consumption we
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139 In females at the highest dose,
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141 The dermal toxicity of cyfluthr
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143 The Meeting concluded that the
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145 Estimate of acute reference dos
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147 Cage, S. (2004) [ 14 C]-beta-cy
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149 Heimann, K.G. (1984c) FCR 4545
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151 Jones, R.D. & Hastings, T.F. (1
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153 Pauluhn, J. & Mohr, U. (1984).
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155 Von Keutz, E. (1987) FCR 4545 -
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158 Zeta-cypermethrin .............
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160 Evaluation for acceptable daily
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162 polar metabolites, which are fu
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164 for up to 70 days. Signs typica
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166 rapidly metabolized by cleavage
Page 181 and 182:
168 2. Toxicological studies 2.1 Ac
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170 Table 2. Effect of cis : trans
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172 Table 3. Significant haematolog
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174 Rabbits Occluded dermal applica
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176 1100 ppm in weeks 1-6, with inc
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178 Wistar-derived (Alderley Park)
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180 At 1500 ppm, liver APDM activit
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182 for premature deaths, 10 male a
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184 by gavage for days 7 to 19 of g
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186 observed at the intermediate an
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188 The females recovered from this
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190 tibial nerve (SPTN), trigeminal
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194 for 5 weeks. Observations inclu
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196 caused obvious irritation and r
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198 days 6-15 of gestation. After m
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200 was observed in two males at 72
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202 control and other treated group
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204 Table 14. Results of studies of
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206 (b) Developmental toxicity Rats
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208 mild and temporary paraesthesia
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210 range appeared to exist for the
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212 for which the LD 50 was > 2000
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214 substances. Since conventional
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216 Critical end-points relevant fo
Page 231 and 232:
218 Butterworth, S.T.G. & Clark, D.
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220 East Millstone, New Jersey, USA
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222 Jersey, USA. Submitted to WHO b
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224 Toxicology Laboratory (Tunstall
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226 Ullrich, B. (2003) Report on a
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228 Cyromazine was first evaluated
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230 were taken for the measurement
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232 highest dose, rather than indic
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234 Tissue residues: Tissues a < 0.
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236 Because of the low total recove
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238 Name Description Compound found
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240 After each dose of [U- 14 C tri
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242 In male and female monkeys give
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244 stress and discomfort during th
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246 Table 18. Dermal absorption of
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248 rate under steady-state conditi
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252 the test substance. The method
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254 taken for haematological and bi
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256 not differ appreciably from pre
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258 Analysis of the diets showed th
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260 considered to be biologically s
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262 observed incidence probably rel
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264 c Cyromazine was assayed twice
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Page 281 and 282:
268 either sporadic or as a consequ
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270 fetuses were removed, weighed a
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272 The NOAEL for maternal toxicity
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274 In New Zealand White rabbits, c
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276 and litters with malformations.
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278 of melamine powder into the rab
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280 reduction in the survival of ma
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282 There is significantly less ris
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284 Toxicological data Cyromazine h
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286 Toxicological evaluation The Me
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288 Other toxicological studies Tox
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290 IARC (1999a) Some chemicals tha
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292 Simoneaux, B. & Marco, G. (1984
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294 Declaration of Helsinki (Cristi
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296 lowered arousal level at doses
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298 Cerebellum 3 1 51** 76** 80** 7
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300 Table 4. Maximum inhibition of
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302 auditory/physical examination w
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304 • • • • • Home-cage o
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306 Dogs Groups of four male and fo
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308 capsules. Some volunteers recei
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310 Blood was taken for measurement
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312 Human a Dietary administration
Page 327 and 328:
314 Piccirillo, V.J. (1978) Acute o
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316 Haloxyfop (racemic), its sodium
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318 Recovery of radioactivity in ur
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320 skin of nine male and nine fema
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322 1.2 Biotransformation Mice In a
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326 96%) at a concentration designe
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328 was centrilobular hepatocellula
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330 The treatment had no effect on
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332 All dogs were killed for autops
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334 with that of controls (but no s
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336 Table 4. Results of studies of
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338 doses of up to 1.0 mg/kg bw per
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340 delayed ossification in the hyo
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342 Mice In a GLP-compliant study,
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344 and in females at the highest d
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346 Between January 1999 and Januar
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348 The Meeting concluded that halo
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350 Critical end-points for setting
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352 Elcombe, B.M. (2002a) Effects o
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354 Scortichini, B.H., Bohl, R.W. &
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356 Economic Co-operation and Devel
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358 There were no treatment-related
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360 comparable to control levels. A
Page 375 and 376:
362 Groups of 17 male and 17 female
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364 No compound-related effects wer
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366 Berry, D. & Gore, C.W. (1975) P
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368 Quinoxyfen has not been evaluat
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370 In the main study, which compli
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372 Concentrations of total radioac
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374 several hydroxy-quinoxyfen meta
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376 There were no mortalities or ad
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378 at doses of ≥ 100 mg/kg bw pe
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380 In a GLP-compliant study to det
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382 control group. This was observe
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384 The homogeneity and stability o
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386 Testes weight (g) at 24 months
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388 slight (3 out of 30) hepatocell
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390 marked inanition, decreased fae
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392 Females Relative liver weightt
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394 were patch-tested specifically
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396 In studies of developmental tox
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398 Rat, LC 50 , inhalation Rabbit,
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400 Gollapudi, B.B. & Lick, S.J. (1
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TEMEPHOS First draft prepared by De
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405 by thin-layer chromatography (T
Page 420 and 421:
407 In a special study to investiga
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409 concluded that temephos was of
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411 Table 3. Effects on mean erythr
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413 Females 0 1.091 1.224 1.324 1.3
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415 of up to 18 ppm. In the group a
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417 Chromosomal aberration DNA repa
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419 of the birds treated with temep
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421 concentration of 1 ppm. Only on
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423 being appreciably less than thi
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425 Lowest relevant developmental N
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427 WHO (1991) Safe use of pesticid
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430 All new studies with thiabendaz
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432 use of this dose form was consi
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434 At 1000 mg/kg bw, qualitative e
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436 At 100 mg/kg bw, slightly decre
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438 There were no treatment-related
Page 453 and 454:
440 Table 6. Incidence of malformat
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442 Dose (mg/kg bw) (grouped by exp
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444 1157 12/21 (57.1)*** 27.2 ± 33
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446 versus placebo): increased appe
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448 activity, tiptoe gait, landing
Page 463 and 464:
450 Noakes, J.P. (2005a) Thianendaz
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452 tests normally performed and th
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454 Radiolabel was excreted primari
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456 the excretory organs, was the r
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458 Table 6. Excretion of radioacti
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460 of unchanged parent compound we
Page 475 and 476:
462 M10 (KNO 1891) + M11 (KNO 1893)
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464 on body weights. Exposure at 15
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466 The no-observed-adverse-effect
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468 Hepatocytes, hypertrophy 0 2 6
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470 they may also be related to var
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472 weights of males were approxima
Page 487 and 488:
474 Thyroid weight (mg): Week 12 6
Page 489 and 490:
476 Table 17. Relevant findings in
Page 491 and 492:
478 Dogs In a dose range-finding st
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480 Prostate / uterine weight (g) 2
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482 the treatment groups receiving
Page 497 and 498:
484 No gross findings were observed
Page 499 and 500:
486 received a macroscopic examinat
Page 501 and 502:
488 Although decreased concentratio
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490 Sciatic nerve; No. examined 50
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492 are caused by the higher incide
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496 In a two-generation study of re
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498 In dams that died or were sacri
Page 513 and 514:
500 No clinical signs or increased
Page 515 and 516:
502 Table 33. Selected variations a
Page 517 and 518:
504 Days 16-21 73.3 78.7 62.5 44.3*
Page 519 and 520:
506 Thiacloprid was not teratogenic
Page 521 and 522:
508 Table 37. Motor and locomotor a
Page 523 and 524:
510 Day 91 19.78 20.00 19.58 18.22*
Page 525 and 526:
512 Table 40. Selected findings in
Page 527 and 528:
514 plate incorporation procedure,
Page 529 and 530:
516 (iv) Comparative study on liver
Page 531 and 532:
518 and relative liver weight in an
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520 at 2500 ppm. The administration
Page 535 and 536:
522 No macroscopic changes were det
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524 The following procedures were p
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526 litter for the group at 1000 pp
Page 541 and 542:
528 Hepatic enzyme activities in th
Page 543 and 544:
530 subtypes 1A1, 2B1, 2D1 and othe
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532 Long-term studies of toxicity a
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534 The Meeting concluded that ther
Page 549 and 550:
536 Estimate of acceptable daily in
Page 551 and 552:
538 dated 27 July, from Bayer AG, W
Page 553 and 554:
540 Kroetlinger, F. (1995a) YRC 289
Page 555 and 556:
542 Wetzig, H. & Geiss, V. (1998b)
Page 557 and 558:
544 Table A1. NOAELs and LOAELs for
Page 559 and 560:
546 2.2 Postulated mode of action (
Page 561 and 562:
548 • • • Chromosomal aberrat
Page 563 and 564:
550 Table A3. NOAELs and LOAELs for
Page 565 and 566:
552 Appendix 2 Table B1. List of an
Page 567 and 568:
554 Metabolite Structure / trivial
Page 569 and 570:
556 Metabolite Structure / trivial
Page 571 and 572:
558 Evaluation for acute reference
Page 573 and 574:
560 increased thyroid weights in th
Page 575 and 576:
562 Table 4. Results of bone-marrow
Page 577 and 578:
564 malformations between the contr
Page 579 and 580:
566 In a study of prenatal developm
Page 581 and 582:
568 combination of heparin and an a
Page 583 and 584:
570 Table 10. Selected findings fro
Page 585 and 586:
572 In a short-term study of neurot
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ANNEX 1 Reports and other documents
Page 590 and 591:
577 31. Pesticide residues in food:
Page 592 and 593:
579 66. Pesticide residues in food
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581 100. Pesticide residues in food
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