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

More documents

Recommendations

Info

TABLE OF CONTENTS Page List of participants ................................................................................................................ v Abbreviations ....................................................................................................................... ix Introduction.......................................................................................................................... xi Toxicological evaluations Bifenazate* ............................................................................................................... 3 Boscalid* ................................................................................................................. 47 Cyfluthrin/beta-cyfluthrin** ................................................................................. 103 Cypermethrins (including alpha- and zetacypermethrin** ................................... 157 Cyromazine** ....................................................................................................... 227 Diazinon ................................................................................................................ 293 Haloxyfop (haloxyfop-R and haloxyfop-R methylester) ...................................... 315 Pyrimiphos-methyl ................................................................................................ 355 Quinoxyfen*...........................................................................................................367 Temephos .............................................................................................................. 403 Thiabendazole ....................................................................................................... 429 Thiacloprid* .......................................................................................................... 451 Thiophanate-methyl .............................................................................................. 557 Annex 1. Reports and other documents resulting from previous Joint Meetings of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Groups on Pesticide Residues ...................................... 575 * First full evaluation ** Evaluated within the periodic review programme of the Codex Committee on Pesticide Residues
Page 2 and 3: Pesticide residues in food — 2006
Page 6 and 7: 2006 Joint Meeting of the FAO Panel
Page 8: Dr Manfred Lützow, Feldhofweg 38,
Page 11 and 12: MRL MRT MS NOAEC NOAEL NMR OECD ppm
Page 14: TOXICOLOGICAL MONOGRAPHS AND MONOGR
Page 17 and 18: 4 All pivotal studies with bifenaza
Page 19 and 20: 6 Table 2. Mean cumulative excretio
Page 21 and 22: 8 In the bile-duct cannulation expe
Page 23 and 24: 10 D2341 glucuronide — — —
Page 25 and 26: 12 Figure 2. Chemical structures of
Page 27 and 28: 14 Figure 3. Proposed metabolic pat
Page 29 and 30: 16 Bifenazate (lot No. DS042795; pu
Page 31 and 32: 18 the study, diets were analysed f
Page 33 and 34: 20 Hepatocyte hypertrophy 0 0 5 3 4
Page 35 and 36: 22 Table 12. Haematological abnorma
Page 37 and 38: 24 and 13. The assessment used home
Page 39 and 40: 26 inspected twice daily for morbid
Page 41 and 42: 28 was increased in females at mont
Page 43 and 44: 30 behaviour were recorded daily. D
Page 45 and 46: 32 were observed in the blood smear
Page 47 and 48: 34 gestation and lactation for the
Page 49 and 50: 36 of the fetuses in each litter we
Page 51 and 52: 38 two animals with whole litter re
Page 53 and 54: 40 100 ppm (equal to 19.7 mg/kg bw
Page 55 and 56:
42 Acute toxicity Rat, LD 50 , oral
Page 57 and 58:
44 Hoffman, G. (1996b) Acute dermal
Page 60 and 61:
BOSCALID First draft prepared by D.
Page 62 and 63:
49 Within 168 h after a single oral
Page 64 and 65:
51 After a single oral dose of [ 14
Page 66 and 67:
53 Table 6. Transmembrane migration
Page 68 and 69:
55 Figure 4.Transfer of radioactivi
Page 70 and 71:
57 metabolites found in the urine a
Page 72 and 73:
59 Table 12. Summary of metabolites
Page 74 and 75:
61 Table 16. Summary of metabolites
Page 76 and 77:
63 Figure 5. Metabolic pathway of b
Page 78 and 79:
65 Metabolite Structure M510F06 O N
Page 80 and 81:
67 Metabolite Structure O OH N H M5
Page 82 and 83:
69 Metabolite Structure M510F47 O O
Page 84 and 85:
71 Table 20. Skin irritation scores
Page 86 and 87:
73 or haematology at any dose. Bloo
Page 88 and 89:
75 incidences were increased in a d
Page 90 and 91:
77 The mean liver weights were sign
Page 92 and 93:
79 (the highest score possible) wer
Page 94 and 95:
81 Diffuse hypertrophy 3 1 3 6 0 1
Page 96 and 97:
83 mode of (carcinogenic) action. N
Page 98 and 99:
85 injection with boscalid at a dos
Page 100 and 101:
87 F 0 generation parental Centrilo
Page 102 and 103:
89 on days 7 to 28 after inseminati
Page 104 and 105:
91 stability, homogeneity and corre
Page 106 and 107:
93 Total concentrations of T4 were
Page 108 and 109:
95 Overall, in short-term studies w
Page 110 and 111:
97 Rat 24-month studies of toxicity
Page 112 and 113:
99 Engelhardt, G. & Hoffmann, H.D.
Page 114:
101 Wiemann, C. & Hellwig, J. (1998
Page 117 and 118:
104 5. Studies on metabolites .....
Page 119 and 120:
106 After oral administration of 0.
Page 121 and 122:
108 Cattle A lactating Holstein dai
Page 123 and 124:
110 Species Strain Sex Route Formul
Page 125 and 126:
112 cyfluthrin (0.1% v/v) at a dose
Page 127 and 128:
114 glandular epithelium of the sub
Page 129 and 130:
116 In a study performed according
Page 131 and 132:
118 termination, the rats were kill
Page 133 and 134:
120 when the increase was 232%), an
Page 135 and 136:
122 Table 3. Results of studies of
Page 137 and 138:
124 weight was accompanied by a dec
Page 139 and 140:
126 highest dose. Necropsy revealed
Page 141 and 142:
128 tilted plane was assessed at se
Page 143 and 144:
130 no catalepsy. In rats, doses of
Page 145 and 146:
132 Rat Wistar Male Female Male Fem
Page 147 and 148:
134 In a study of dermal sensitizat
Page 149 and 150:
136 inhalation for 6 h per day for
Page 151 and 152:
138 Groups of 12 male and 12 female
Page 153 and 154:
140 The metabolites of cyfluthrin s
Page 155 and 156:
142 The increased incidence of malf
Page 157 and 158:
144 Offspring toxicity 50 ppm, equa
Page 159 and 160:
146 Developmental target Lowest rel
Page 161 and 162:
148 Flucke, W. (1984b) FCR 1272, Pr
Page 163 and 164:
150 Herbold, B. (1981b) Dominant le
Page 165 and 166:
152 Miksche, L. (1979) Symptoms of
Page 167 and 168:
154 Sheets, L.P., Gilmore, R.G. & H
Page 170 and 171:
CYPERMETHRIN (INCLUDING ALPHA- AND
Page 172 and 173:
159 For alpha-cypermethrin, the spe
Page 174 and 175:
161 depleted over the test interval
Page 176 and 177:
163 in the heart (67.6 and 88.7 ng
Page 178 and 179:
165 (DCVA) was rapid and confined t
Page 180 and 181:
167 Thus, the results of the studie
Page 182 and 183:
169 Rat M NS Oral Aqueous suspensio
Page 184 and 185:
171 exposure at 1600 ppm, both male
Page 186 and 187:
173 The NOAEL in rats was 1500 ppm,
Page 188 and 189:
175 No dogs died during the study.
Page 190 and 191:
177 The NOAEL was 400 ppm, equivale
Page 192 and 193:
179 Table 4. Significant findings r
Page 194 and 195:
181 Alkaline Comet assay D. melanog
Page 196 and 197:
183 To evaluate the potential (note
Page 198 and 199:
185 of cypermethrin (purity, 97%; c
Page 200 and 201:
187 hepatic APDM activity in males
Page 202 and 203:
189 of treatment. Microscopic findi
Page 204 and 205:
191 (radiochemical purity, > 99%) a
Page 206 and 207:
193 4.2 Short-term studies of toxic
Page 208 and 209:
195 increased. In both sexes at 540
Page 210 and 211:
Page 212 and 213:
199 and motor activity. In each stu
Page 214 and 215:
201 10, 17, 34 and 68 mg/kg bw per
Page 216 and 217:
203 Table 12. Statistically signifi
Page 218 and 219:
205 were reduced by 13% relative to
Page 220 and 221:
207 splayed hindlimbs, staggered ga
Page 222 and 223:
209 related directly to symptoms in
Page 224 and 225:
211 of the face which usually devel
Page 226 and 227:
213 Cypermethrin, alpha-cypermethri
Page 228 and 229:
215 (b) Alpha-Cypermethrin Species
Page 230 and 231:
217 Summary for cypermethrins, incl
Page 232 and 233:
219 Shell Toxicology Laboratory (Tu
Page 234 and 235:
221 Freeman, C. (1990a) FMC 56701 t
Page 236 and 237:
223 Hutson, D.H. (1977) Taurine con
Page 238 and 239:
225 Prinsen, G.H. & Van Sittert, W.
Page 240 and 241:
CYROMAZINE First draft prepared by
Page 242 and 243:
229 24-48 h < 0.3 0.5 48-72 h < 0.2
Page 244 and 245:
231 Seven days after an oral dose o
Page 246 and 247:
233 kinetics, the elimination half-
Page 248 and 249:
235 Cyromazine was rapidly absorbed
Page 250 and 251:
237 gastrointestinal tract (1.1-1.3
Page 252 and 253:
239 Residue concentrations of cyrom
Page 254 and 255:
241 Table 13. Quantification of fae
Page 256 and 257:
243 Hens Two hens received capsules
Page 258 and 259:
245 At the intermediate dose, the r
Page 260 and 261:
247 In order to follow the fate of
Page 262 and 263:
249 Table 21. Recovery of radioacti
Page 264 and 265:
251 Cyromazine is of low acute toxi
Page 266 and 267:
253 selected organs were weighed, a
Page 268 and 269:
255 Cyromazine lowered erythrocyte
Page 270 and 271:
257 Kidney, focal chronic epithelia
Page 272 and 273:
259 Table 25. Incidence of hepatoce
Page 274 and 275:
261 females at the intermediate dos
Page 276 and 277:
Page 278 and 279:
265 or 600 mg/kg bw did not differ
Page 280 and 281:
267 Table 29. Overall range and mea
Page 282 and 283:
269 in the number of litters and fe
Page 284 and 285:
271 30 and 60 mg/kg bw per day, res
Page 286 and 287:
273 control groups. No significant
Page 288 and 289:
275 Spina bifida 1 (1) 1 (1) 2 (2)
Page 290 and 291:
277 3. Studies on metabolites There
Page 292 and 293:
279 of most male rats in a dose-rel
Page 294 and 295:
281 receiving 3% melamine in the di
Page 296 and 297:
283 (e) Reproductive toxicity No to
Page 298 and 299:
285 Dietary administration of cyrom
Page 300 and 301:
287 Critical end-points for setting
Page 302 and 303:
289 Clayson, D.B., Fishbein L. & Co
Page 304 and 305:
291 National Toxicology Program (19
Page 306 and 307:
DIAZINON (addendum) First draft pre
Page 308 and 309:
295 appearance, behaviour, signs of
Page 310 and 311:
297 deaths occurred. Body-weight lo
Page 312 and 313:
299 cholinesterase activities were
Page 314 and 315:
301 Significant and dose-related in
Page 316 and 317:
303 p < 0.01 for both) at 2500 ppm
Page 318 and 319:
305 the brain was significantly (p
Page 320 and 321:
307 87.7%) at a concentration of 0,
Page 322 and 323:
309 No clinical signs or changes in
Page 324 and 325:
311 The lowest-observed-adverse-eff
Page 326 and 327:
313 England on behalf of Makhteshim
Page 328 and 329:
HALOXYFOP (INCLUDING HALOXYFOP-R AN
Page 330 and 331:
317 Evaluation for acceptable daily
Page 332 and 333:
319 excreted into urine with an eli
Page 334 and 335:
321 found in the faeces over the 6
Page 336 and 337:
323 (one major and two minor). The
Page 338 and 339:
325 was well tolerated for the 5 da
Page 340 and 341:
327 Rats In a 4-week probe study th
Page 342 and 343:
329 In a GLP-compliant study, group
Page 344 and 345:
331 before treatment and after 1, 2
Page 346 and 347:
333 Organs were weighed and histopa
Page 348 and 349:
335 treatment. At 6 and 12 months,
Page 350 and 351:
337 adults. Some of the livers of t
Page 352 and 353:
339 1.0, 7.5 or 20 mg/kg bw per day
Page 354 and 355:
341 increase in peroxisome prolifer
Page 356 and 357:
343 per day. The Meeting concluded
Page 358 and 359:
345 Monkeys In a GLP-compliant 4-we
Page 360 and 361:
347 seen and a NOAEL of 0.2 mg/kg b
Page 362 and 363:
349 The Meeting established a group
Page 364 and 365:
351 Summary for racemic haloxyfop,
Page 366 and 367:
353 Linscombe, V.A., Jackson, K.M.
Page 368 and 369:
PIRIMIPHOS-METHYL (ADDENDUM) First
Page 370 and 371:
357 Dogs Groups of one male beagle
Page 372 and 373:
359 In this study a NOAEL could not
Page 374 and 375:
361 resorptions. A sample of brain
Page 376 and 377:
363 Midbrain 90* 97 77* 83* 32* 41*
Page 378 and 379:
365 In one 28-day and one 56-day st
Page 380 and 381:
QUINOXYFEN First draft prepared by
Page 382 and 383:
369 Figure 1. Chemical structure of
Page 384 and 385:
371 ranged from 6 to 10 h. The tiss
Page 386 and 387:
373 peaks Q3, Q6 and Q14, while pea
Page 388 and 389:
375 2. Toxicological studies 2.1 Ac
Page 390 and 391:
377 Rats In a GLP-compliant study,
Page 392 and 393:
379 ALP (U/l) 125 128 129 112* 97 9
Page 394 and 395:
381 in the highest dose males but t
Page 396 and 397:
383 Liver, extramedullary h aematop
Page 398 and 399:
385 of the treatment period. The me
Page 400 and 401:
Page 402 and 403:
389 The NOAEL for maternal toxicity
Page 404 and 405:
391 Microsomal P450 (nmol/mg) 0.9 1
Page 406 and 407:
393 Lumbar root ganglion slight deg
Page 408 and 409:
395 being observed at 250 mg/kg bw
Page 410 and 411:
397 Levels relevant to risk assessm
Page 412 and 413:
399 References Baker, P.C. & Yano,
Page 414:
401 Szabo, J.R. & Rachunek, S.L (19
Page 417 and 418:
404 programme recommended that teme
Page 419 and 420:
406 In a study in mice, groups of f
Page 421 and 422:
408 Table 2. Oral and dermal median
Page 423 and 424:
410 2.2 Short-term studies of toxic
Page 425 and 426:
412 no-observed-effect level (NOEL)
Page 427 and 428:
414 study (31-47%) at 10 mg/kg bw p
Page 429 and 430:
416 2.3 Long-term studies of toxici
Page 431 and 432:
418 treatment-related effect. The N
Page 433 and 434:
420 The Meeting concluded temephos
Page 435 and 436:
422 bw per day in a 99-day dietary
Page 437 and 438:
424 Humans Investigation of clinica
Page 439 and 440:
426 Laws, E.R. Jr., Morales, F.R.,
Page 442 and 443:
THIABENDAZOLE (addendum) First draf
Page 444 and 445:
431 Table 1. Blood concentrations o
Page 446 and 447:
433 In a dose range-finding study,
Page 448 and 449:
435 higher for males (125% and 172%
Page 450 and 451:
437 activity was most apparent for
Page 452 and 453:
439 consumption and body-weight gai
Page 454 and 455:
441 Table 7. Incidence of external
Page 456 and 457:
443 The paper by Ogata et al. (1984
Page 458 and 459:
445 and body-weight gain (decrease
Page 460 and 461:
447 included anorexia, nausea, vomi
Page 462 and 463:
449 References Campbell, W.C. & Cuc
Page 464 and 465:
THIACLOPRID First draft prepared by
Page 466 and 467:
453 In most of the tests, the elimi
Page 468 and 469:
455 Table 3. Residual radioactivity
Page 470 and 471:
457 0.5% tragacanth orally by gavag
Page 472 and 473:
459 Thyroid 0.050 0.055 17.975 Skin
Page 474 and 475:
461 (b) 14 C-thiazolidine-labelled
Page 476 and 477:
463 2. Toxicological studies 2.1 Ac
Page 478 and 479:
465 In the main study, one test gro
Page 480 and 481:
467 The NOAEL was 200 ppm, equal to
Page 482 and 483:
469 Increased activities of asparta
Page 484 and 485:
471 Bile acid (μmol/l) 45.9 31.7 5
Page 486 and 487:
473 Week 12 40 39 42 48 37 49 45 51
Page 488 and 489:
475 At the highest dose, clotting t
Page 490 and 491:
477 reduced triglyceride concentrat
Page 492 and 493:
479 Haematological examination in s
Page 494 and 495:
481 Haematological investigations d
Page 496 and 497:
483 107 weeks. In addition, groups
Page 498 and 499:
485 Degeneration 1 0 5* 16** 0 0 0
Page 500 and 501:
487 Table 24. Relevant clinical and
Page 502 and 503:
489 The histopathological investiga
Page 504 and 505:
491 Uterus; No. examined — —
Page 506 and 507:
493 S9). Duplicate cultures were us
Page 508 and 509:
495 “Ground glass” hepatocytes
Page 510 and 511:
497 Table 30. Relevant findings in
Page 512 and 513:
499 No. of litters 25 28 26 28 No.
Page 514 and 515:
501 % Postimplantation loss per dam
Page 516 and 517:
503 Thiacloprid was not teratogenic
Page 518 and 519:
505 A slight increase in the number
Page 520 and 521:
507 Observations during handling Di
Page 522 and 523:
509 There were no deaths and no cli
Page 524 and 525:
511 day 30. Female rats were examin
Page 526 and 527:
513 Thiacloprid did not cause any s
Page 528 and 529:
515 (TA1535, TA100, TA1537, TA98 an
Page 530 and 531:
517 acid amide at 1000 ppm and thia
Page 532 and 533:
519 The NOAEL was 100 ppm, equal to
Page 534 and 535:
521 Vaginal smears were taken, exam
Page 536 and 537:
523 No. of animals delivered 27 25
Page 538 and 539:
525 (four to six rats per dose) wer
Page 540 and 541:
527 No. cannibalized 0 2 11 13 Mean
Page 542 and 543:
529 Corticosterone (ng/ml) After 9
Page 544 and 545:
531 was of low acute dermal toxicit
Page 546 and 547:
533 Mechanistic studies on uterine
Page 548 and 549:
535 The Meeting concluded that the
Page 550 and 551:
537 Reproductive toxicity Reproduct
Page 552 and 553:
539 from Bayer AG, Wuppertal, Germa
Page 554 and 555:
541 Pauluhn, J. (1998) YRC 2894 sub
Page 556 and 557:
543 1.2 Postulated mode of action (
Page 558 and 559:
545 sensitive than female rats with
Page 560 and 561:
547 Table A2. NOAELs and LOAELs for
Page 562 and 563:
549 of estrogens that catalyses the
Page 564 and 565:
551 3.8 Other modes of action Genot
Page 566 and 567:
553 Metabolite Structure / trivial
Page 568 and 569:
555 Metabolite Structure / trivial
Page 570 and 571:
THIOPHANATE-METHYL (addendum) First
Page 572 and 573:
559 Table 2. Selected findings in d
Page 574 and 575:
561 smears were obtained from five
Page 576 and 577:
563 The NOAEL for parental toxicity
Page 578 and 579:
565 Table 7. Selected maternal and
Page 580 and 581:
567 Mean litter size 8.8 8.4 9.1 7.
Page 582 and 583:
569 adverse changes in the FOB, inc
Page 584 and 585:
571 Comments Toxicological data Thi
Page 586:
573 Foss, J.A. (2005b) Oral (diet)
Page 589 and 590:
576 14. Pesticide residues in food.
Page 591 and 592:
578 49. Pesticide residues in food
Page 593 and 594:
580 83. Pesticide residues in food
show all

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?

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