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

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13 NAME/No. STRUCTURE D1989 OCH 3 D9477 HO OCH 3 A1530 OH D9569 HO OH D9963 OCH 3 OH D9472 OH OH A1530- Sulfate OSO 3 H D9569-Monosulfate HO 3 SO OH D9569-Sulfate or Glucuronide RO OR a The name and number assigned by the Crompton Corporation are given here. BIFENAZATE X-X JMPR 2006
14 Figure 3. Proposed metabolic pathway of bifenazate in rats OCH 3 NH Bifenazate NH O O OCH 3 OCH 3 N N O D3598 O HO OCH 3 NH NH 4-Hydroxy-D2341 O O NH O NR O COOH OH R = O OH OH D2341 Glucuronide OCH 3 OCH 3 OCH 3 D1989 HO N 4-Hydroxy-D3598 N O O HO NR R = NH O O COOH OH O OH OH OH HO OCH 3 4-Hydroxy-D2341 Glucuronide A1530 D9477 OSO 3 H HO OH HO OSO 3 H A1530 Sulfate D9569 D9569 Sulfate RO OR D9569 Conjugate (Sulfate or Glucuronide) BIFENAZATE X-X JMPR 2006
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 10 and 11: Abbreviations used ADI ALT APDM ARf
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 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
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129 were not seen in rats in the co
Page 144 and 145:
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
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
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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
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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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