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

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Abbreviations used ADI ALT APDM ARfD AST AUC bw CAS CAT Cl CMC DMSO ECG F 0 F 1 F 2 FAOX FCA FOB GCMS GLP GPD GSD HPLC HPLC-UV IPCS ISO IUPAC LC 50 LC-MS LD 50 LOAEL LOQ MCH MCHC MCV MMAD MoE acceptable daily intake alanine aminotransferase aminopyrine N-demethylase acute reference dose aspartate aminotransferase area under the curve of concentration–time body weight Chemical Abstracts Service carnitine acyl transferase clearance carboxymethyl cellulose dimethylsulfoxide electrocardiogram parental generation first filial generation second filial generation fatty acid beta-oxidation Freund complete adjuvant functional observational battery gas chromatography-mass spectrometry good laboratory practice glycerophosphate dehydrogenase geometric standard deviation high-performance liquid chromatography high-performance liquid chromatography with ultraviolet light detector International Programme on Chemical Safety International Organization for Standardization International Union of Pure and Applied Chemistry median lethal concentration liquid chromatography-mass spectrometry median lethal dose lowest-observed-adverse-effect level limit of quantification mean corpuscular haemoglobin mean corpuscular haemoglobin concentration mean corpuscular volume mass median aerodynamic diameter margin of exposure ix
MRL MRT MS NOAEC NOAEL NMR OECD ppm PAM QA SER T3 T4 TLC TMDI TOCP TPO TRR TSH Vd WHO w/v w/w maximum residue level mean residence time mass spectrometry no-observed-adverse-effect concentration no-observed-adverse-effect level nuclear magnetic resonance Organisation for Economic Co-operation and Development parts per million pyridine-2-aldoxime methane sulfonate quality assurance smooth endoplasmic reticulum triiodothyronine thyroxin thin-layer chromatography theoretical maximum daily intake tri-ortho-cresyl phosphate thyroid peroxidase total radiolabelled residue thyroid-stimulating hormone volume of distribution World Health Organization weight for volume weight for weight x
Page 2 and 3: Pesticide residues in food — 2006
Page 4: TABLE OF CONTENTS Page List of part
Page 7 and 8: Dr Helen Hakansson, Institute of En
Page 12: Introduction The toxicological mono
Page 16 and 17: BIFENAZATE First draft prepared by
Page 18 and 19: 5 In a series of experiments, group
Page 20 and 21: 7 In a study of the time-course of
Page 22 and 23: 9 the administered dose in males an
Page 24 and 25: 11 limited absorption of parent com
Page 26 and 27: 13 NAME/No. STRUCTURE D1989 OCH 3 D
Page 28 and 29: 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 and 80:
66 Metabolite Structure O M510F14 N
Page 81 and 82:
68 Metabolite Structure M510F39 N O
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
Page 130 and 131:
117 cyfluthrin (purity, 95.5-95.9%)
Page 132 and 133:
119 In a short-term study of exposu
Page 134 and 135:
121 and dissection. At termination,
Page 136 and 137:
123 2.5 Reproductive toxicity (a) M
Page 138 and 139:
125 gestation. The vehicle was 1% C
Page 140 and 141:
127 females was exposed during days
Page 142 and 143:
129 were not seen in rats in the co
Page 144 and 145:
131 men was exposed for 1 h to actu
Page 146 and 147:
133 40 g/l, in a flowable concentra
Page 148 and 149:
135 were removed from five males an
Page 150 and 151:
137 weights and food consumption we
Page 152 and 153:
139 In females at the highest dose,
Page 154 and 155:
141 The dermal toxicity of cyfluthr
Page 156 and 157:
143 The Meeting concluded that the
Page 158 and 159:
145 Estimate of acute reference dos
Page 160 and 161:
147 Cage, S. (2004) [ 14 C]-beta-cy
Page 162 and 163:
149 Heimann, K.G. (1984c) FCR 4545
Page 164 and 165:
151 Jones, R.D. & Hastings, T.F. (1
Page 166 and 167:
153 Pauluhn, J. & Mohr, U. (1984).
Page 168:
155 Von Keutz, E. (1987) FCR 4545 -
Page 171 and 172:
158 Zeta-cypermethrin .............
Page 173 and 174:
160 Evaluation for acceptable daily
Page 175 and 176:
162 polar metabolites, which are fu
Page 177 and 178:
164 for up to 70 days. Signs typica
Page 179 and 180:
166 rapidly metabolized by cleavage
Page 181 and 182:
Page 183 and 184:
170 Table 2. Effect of cis : trans
Page 185 and 186:
172 Table 3. Significant haematolog
Page 187 and 188:
174 Rabbits Occluded dermal applica
Page 189 and 190:
176 1100 ppm in weeks 1-6, with inc
Page 191 and 192:
178 Wistar-derived (Alderley Park)
Page 193 and 194:
180 At 1500 ppm, liver APDM activit
Page 195 and 196:
182 for premature deaths, 10 male a
Page 197 and 198:
184 by gavage for days 7 to 19 of g
Page 199 and 200:
186 observed at the intermediate an
Page 201 and 202:
188 The females recovered from this
Page 203 and 204:
190 tibial nerve (SPTN), trigeminal
Page 205 and 206:
Page 207 and 208:
194 for 5 weeks. Observations inclu
Page 209 and 210:
196 caused obvious irritation and r
Page 211 and 212:
198 days 6-15 of gestation. After m
Page 213 and 214:
200 was observed in two males at 72
Page 215 and 216:
202 control and other treated group
Page 217 and 218:
204 Table 14. Results of studies of
Page 219 and 220:
206 (b) Developmental toxicity Rats
Page 221 and 222:
208 mild and temporary paraesthesia
Page 223 and 224:
210 range appeared to exist for the
Page 225 and 226:
212 for which the LD 50 was > 2000
Page 227 and 228:
214 substances. Since conventional
Page 229 and 230:
216 Critical end-points relevant fo
Page 231 and 232:
218 Butterworth, S.T.G. & Clark, D.
Page 233 and 234:
220 East Millstone, New Jersey, USA
Page 235 and 236:
222 Jersey, USA. Submitted to WHO b
Page 237 and 238:
224 Toxicology Laboratory (Tunstall
Page 239 and 240:
226 Ullrich, B. (2003) Report on a
Page 241 and 242:
228 Cyromazine was first evaluated
Page 243 and 244:
230 were taken for the measurement
Page 245 and 246:
232 highest dose, rather than indic
Page 247 and 248:
234 Tissue residues: Tissues a < 0.
Page 249 and 250:
236 Because of the low total recove
Page 251 and 252:
238 Name Description Compound found
Page 253 and 254:
240 After each dose of [U- 14 C tri
Page 255 and 256:
242 In male and female monkeys give
Page 257 and 258:
244 stress and discomfort during th
Page 259 and 260:
246 Table 18. Dermal absorption of
Page 261 and 262:
248 rate under steady-state conditi
Page 263 and 264:
Page 265 and 266:
252 the test substance. The method
Page 267 and 268:
254 taken for haematological and bi
Page 269 and 270:
256 not differ appreciably from pre
Page 271 and 272:
258 Analysis of the diets showed th
Page 273 and 274:
260 considered to be biologically s
Page 275 and 276:
262 observed incidence probably rel
Page 277 and 278:
264 c Cyromazine was assayed twice
Page 279 and 280:
Page 281 and 282:
268 either sporadic or as a consequ
Page 283 and 284:
270 fetuses were removed, weighed a
Page 285 and 286:
272 The NOAEL for maternal toxicity
Page 287 and 288:
274 In New Zealand White rabbits, c
Page 289 and 290:
276 and litters with malformations.
Page 291 and 292:
278 of melamine powder into the rab
Page 293 and 294:
280 reduction in the survival of ma
Page 295 and 296:
282 There is significantly less ris
Page 297 and 298:
284 Toxicological data Cyromazine h
Page 299 and 300:
286 Toxicological evaluation The Me
Page 301 and 302:
288 Other toxicological studies Tox
Page 303 and 304:
290 IARC (1999a) Some chemicals tha
Page 305 and 306:
292 Simoneaux, B. & Marco, G. (1984
Page 307 and 308:
294 Declaration of Helsinki (Cristi
Page 309 and 310:
296 lowered arousal level at doses
Page 311 and 312:
298 Cerebellum 3 1 51** 76** 80** 7
Page 313 and 314:
300 Table 4. Maximum inhibition of
Page 315 and 316:
302 auditory/physical examination w
Page 317 and 318:
304 • • • • • Home-cage o
Page 319 and 320:
306 Dogs Groups of four male and fo
Page 321 and 322:
308 capsules. Some volunteers recei
Page 323 and 324:
310 Blood was taken for measurement
Page 325 and 326:
312 Human a Dietary administration
Page 327 and 328:
314 Piccirillo, V.J. (1978) Acute o
Page 329 and 330:
316 Haloxyfop (racemic), its sodium
Page 331 and 332:
318 Recovery of radioactivity in ur
Page 333 and 334:
320 skin of nine male and nine fema
Page 335 and 336:
322 1.2 Biotransformation Mice In a
Page 337 and 338:
Page 339 and 340:
326 96%) at a concentration designe
Page 341 and 342:
328 was centrilobular hepatocellula
Page 343 and 344:
330 The treatment had no effect on
Page 345 and 346:
332 All dogs were killed for autops
Page 347 and 348:
334 with that of controls (but no s
Page 349 and 350:
336 Table 4. Results of studies of
Page 351 and 352:
338 doses of up to 1.0 mg/kg bw per
Page 353 and 354:
340 delayed ossification in the hyo
Page 355 and 356:
342 Mice In a GLP-compliant study,
Page 357 and 358:
344 and in females at the highest d
Page 359 and 360:
346 Between January 1999 and Januar
Page 361 and 362:
348 The Meeting concluded that halo
Page 363 and 364:
350 Critical end-points for setting
Page 365 and 366:
352 Elcombe, B.M. (2002a) Effects o
Page 367 and 368:
354 Scortichini, B.H., Bohl, R.W. &
Page 369 and 370:
356 Economic Co-operation and Devel
Page 371 and 372:
358 There were no treatment-related
Page 373 and 374:
360 comparable to control levels. A
Page 375 and 376:
362 Groups of 17 male and 17 female
Page 377 and 378:
364 No compound-related effects wer
Page 379 and 380:
366 Berry, D. & Gore, C.W. (1975) P
Page 381 and 382:
368 Quinoxyfen has not been evaluat
Page 383 and 384:
370 In the main study, which compli
Page 385 and 386:
372 Concentrations of total radioac
Page 387 and 388:
374 several hydroxy-quinoxyfen meta
Page 389 and 390:
376 There were no mortalities or ad
Page 391 and 392:
378 at doses of ≥ 100 mg/kg bw pe
Page 393 and 394:
380 In a GLP-compliant study to det
Page 395 and 396:
382 control group. This was observe
Page 397 and 398:
384 The homogeneity and stability o
Page 399 and 400:
386 Testes weight (g) at 24 months
Page 401 and 402:
388 slight (3 out of 30) hepatocell
Page 403 and 404:
390 marked inanition, decreased fae
Page 405 and 406:
392 Females Relative liver weightt
Page 407 and 408:
394 were patch-tested specifically
Page 409 and 410:
396 In studies of developmental tox
Page 411 and 412:
398 Rat, LC 50 , inhalation Rabbit,
Page 413 and 414:
400 Gollapudi, B.B. & Lick, S.J. (1
Page 416 and 417:
TEMEPHOS First draft prepared by De
Page 418 and 419:
405 by thin-layer chromatography (T
Page 420 and 421:
407 In a special study to investiga
Page 422 and 423:
409 concluded that temephos was of
Page 424 and 425:
411 Table 3. Effects on mean erythr
Page 426 and 427:
413 Females 0 1.091 1.224 1.324 1.3
Page 428 and 429:
415 of up to 18 ppm. In the group a
Page 430 and 431:
417 Chromosomal aberration DNA repa
Page 432 and 433:
419 of the birds treated with temep
Page 434 and 435:
421 concentration of 1 ppm. Only on
Page 436 and 437:
423 being appreciably less than thi
Page 438 and 439:
425 Lowest relevant developmental N
Page 440:
427 WHO (1991) Safe use of pesticid
Page 443 and 444:
430 All new studies with thiabendaz
Page 445 and 446:
432 use of this dose form was consi
Page 447 and 448:
434 At 1000 mg/kg bw, qualitative e
Page 449 and 450:
436 At 100 mg/kg bw, slightly decre
Page 451 and 452:
438 There were no treatment-related
Page 453 and 454:
440 Table 6. Incidence of malformat
Page 455 and 456:
442 Dose (mg/kg bw) (grouped by exp
Page 457 and 458:
444 1157 12/21 (57.1)*** 27.2 ± 33
Page 459 and 460:
446 versus placebo): increased appe
Page 461 and 462:
448 activity, tiptoe gait, landing
Page 463 and 464:
450 Noakes, J.P. (2005a) Thianendaz
Page 465 and 466:
452 tests normally performed and th
Page 467 and 468:
454 Radiolabel was excreted primari
Page 469 and 470:
456 the excretory organs, was the r
Page 471 and 472:
458 Table 6. Excretion of radioacti
Page 473 and 474:
460 of unchanged parent compound we
Page 475 and 476:
462 M10 (KNO 1891) + M11 (KNO 1893)
Page 477 and 478:
464 on body weights. Exposure at 15
Page 479 and 480:
466 The no-observed-adverse-effect
Page 481 and 482:
468 Hepatocytes, hypertrophy 0 2 6
Page 483 and 484:
470 they may also be related to var
Page 485 and 486:
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
Page 493 and 494:
480 Prostate / uterine weight (g) 2
Page 495 and 496:
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
Page 503 and 504:
490 Sciatic nerve; No. examined 50
Page 505 and 506:
492 are caused by the higher incide
Page 507 and 508:
Page 509 and 510:
496 In a two-generation study of re
Page 511 and 512:
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
Page 533 and 534:
520 at 2500 ppm. The administration
Page 535 and 536:
522 No macroscopic changes were det
Page 537 and 538:
524 The following procedures were p
Page 539 and 540:
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
Page 545 and 546:
532 Long-term studies of toxicity a
Page 547 and 548:
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
Page 588 and 589:
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
Page 594:
581 100. Pesticide residues in food
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