Safety evaluation of certain food additives - ipcs inchem

More documents

Recommendations

Info

PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS 125 Phytosterols isolated from soya bean (approximately 49.4% -sitosterol, 27.9% campesterol, 18.5% stigmasterol), which were esterified with fatty acids from olive oil, were administered by gavage (0, 1, 3 or 9 g/kg bw per day) to 16, 10, 10 or 16 Sprague-Dawley rats per sex, respectively, for 13 weeks. Six rats per sex from the control and highest-dose groups were kept for 4 additional weeks (recovery groups). During the study, which was carried out under GLP conditions according to OECD guidelines, clinical signs, body weights, and food and water consumption were monitored, and eyes and urine were examined. Haematology, clinical chemistry, gross necropsy and histopathology were performed at the end of the administration period, and organ weights were determined. Body weight gain was decreased in male and female rats at the highest dose. Histopathological examination showed an increased incidence of cardiomyopathy at the highest dose in males, but not in females. Slight, but statistically significant, changes in haematological parameters occurred at the two highest doses in both sexes. Values were within the normal range and were reversible during the recovery period. No other biological changes of importance were reported in this study. Based on the effects observed at the highest dose level, the lowest-observed-adverse-effect level (LOAEL) in this study was 9 g/kg bw per day, and the no-observed-adverse-effect level (NOAEL) was 3 g/kg bw per day (Kim et al., 2002). 2.2.2 Genotoxicity Phytosterols and phytosterol esters were investigated in a battery of in vitro assays (for reverse mutations in bacteria, chromosomal aberrations in human peripheral lymphocytes, gene mutations in mouse lymphoma cells). Furthermore, two in vivo assays were applied: the bone marrow micronucleus assay in rats and the rat liver assay for unscheduled deoxyribonucleic acid (DNA) synthesis. Studies were carried out according to OECD Test Guidelines 471, 473, 474, 476 and 486. Neither of the test materials showed genotoxic activity in any of the tests (Wolfreys & Hepburn, 2002) (Table 1). Lea et al. (2004) tested the phytosterol oxide concentrate described above in a series of in vitro genotoxicity tests (mutations in bacteria, chromosomal aberrations and micronucleus induction in mammalian cells). Testing was performed in compliance with United Kingdom and OECD GLP requirements. The bacterial reverse mutation assays were performed according to OECD Test Guideline 471, and the test for chromosomal aberrations was conducted according to OECD Test Guideline 473. No genotoxic activity was observed in either of the tests (Table 1). Two types of oxidation products (triols and epoxides) of a mixture of sitosterol and campesterol were synthesized, purified and administered once intraperitoneally to mice to investigate their genotoxicity in a flow cytometer–based in vivo micronucleus assay. No evidence of genotoxicity was observable up to the highest dose tested—i.e. 67 mg/kg bw for epoxides and 9.4 mg/kg bw for triols (Abramsson-Zetterberg et al., 2007) (Table 1).
126 PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS Table 1. Studies of genotoxicity with phytosterols, phytosterol esters and phytosterol oxide concentrate End-point Test system Test material Concentration/ dose In vitro Reverse mutation Reverse mutation Reverse mutation Chromosomal aberration Chromosomal aberration Chromosomal aberration Salmonella typhimurium TA98, TA100, TA1535 and TA1537 S. typhimurium TA98, TA100, TA1535 and TA1537; Escherichia coli WP2 uvrA (pKM101) S. typhimurium TA98, TA100, TA102, TA1535 and TA1537 Human peripheral blood lymphocytes Human peripheral blood lymphocytes Human peripheral blood lymphocytes Gene mutation Mouse lymphoma L5178Y cells, Tk +/ locus Clastogenicity (micronucleus induction) In vivo Micronucleus induction Human peripheral blood lymphocytes Male rats, bone marrow Phytosterol mixture a Phytosterol esters a Phytosterol oxide concentrate Phytosterol mixture a Phytosterol esters a Phytosterol oxide concentrate Phytosterol esters a Phytosterol oxide concentrate Phytosterol esters c Result Reference 5–5000 μg/plate Negative b Wolfreys & Hepburn (2002) 50–5000 μg/plate Negative b Wolfreys & Hepburn (2002) 1.6–5000 μg/plate Negative b Lea et al. (2004) 40–160 μg/ml Negative b Wolfreys & Hepburn (2002) 25–200 μg/ml Negative b Wolfreys & Hepburn (2002) 131.1–500 μg/ml Negative b Lea et al. (2004) 5–80 μg/ml Negative b Wolfreys & Hepburn (2002) Up to 625 μg/ml Negative b Lea et al. (2004) 500–2000 mg/kg bw per day for 2 days Negative Wolfreys & Hepburn (2002)
Page 2 and 3:
WHO FOOD ADDITIVES SERIES: 60 Safet
Page 4 and 5:
CONTENTS Preface ..................
Page 6:
PREFACE The monographs contained in
Page 10 and 11:
ASPARAGINASE FROM ASPERGILLUS NIGER
Page 12 and 13:
Page 14 and 15:
Page 16 and 17:
Page 18 and 19:
Page 20:
Page 23 and 24:
16 CALCIUM LIGNOSULFONATE (40-65) 1
Page 25 and 26:
18 CALCIUM LIGNOSULFONATE (40-65) ~
Page 27 and 28:
20 CALCIUM LIGNOSULFONATE (40-65) A
Page 29 and 30:
22 CALCIUM LIGNOSULFONATE (40-65) c
Page 31 and 32:
24 CALCIUM LIGNOSULFONATE (40-65) T
Page 33 and 34:
Page 35 and 36:
28 CALCIUM LIGNOSULFONATE (40-65) i
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 46 and 47:
ETHYL LAUROYL ARGINATE First draft
Page 48 and 49:
ETHYL LAUROYL ARGINATE 41 and Devel
Page 50 and 51:
ETHYL LAUROYL ARGINATE 43 lauroyl a
Page 52 and 53:
ETHYL LAUROYL ARGINATE 45 arginine.
Page 54 and 55:
ETHYL LAUROYL ARGINATE 47 resulting
Page 56 and 57:
ETHYL LAUROYL ARGINATE 49 Table 4.
Page 58 and 59:
ETHYL LAUROYL ARGINATE 51 weight ch
Page 60 and 61:
ETHYL LAUROYL ARGINATE 53 stomach l
Page 62 and 63:
ETHYL LAUROYL ARGINATE 55 fibrosis
Page 64 and 65:
ETHYL LAUROYL ARGINATE 57 Table 5 (
Page 66 and 67:
ETHYL LAUROYL ARGINATE 59 first 4 d
Page 68 and 69:
ETHYL LAUROYL ARGINATE 61 The gener
Page 70 and 71:
ETHYL LAUROYL ARGINATE 63 treatment
Page 72 and 73:
ETHYL LAUROYL ARGINATE 65 gestation
Page 74 and 75:
ETHYL LAUROYL ARGINATE 67 Body weig
Page 76 and 77:
ETHYL LAUROYL ARGINATE 69 Table 6.
Page 78 and 79:
Page 80 and 81:
Page 82 and 83: ETHYL LAUROYL ARGINATE 75 Table 7 (
Page 84 and 85: ETHYL LAUROYL ARGINATE 77 About 99%
Page 86 and 87: ETHYL LAUROYL ARGINATE 79 concentra
Page 88 and 89: ETHYL LAUROYL ARGINATE 81 theoretic
Page 90 and 91: ETHYL LAUROYL ARGINATE 83 Huntingdo
Page 92 and 93: PAPRIKA EXTRACT First draft prepare
Page 94 and 95: PAPRIKA EXTRACT 87 of capsanthin ra
Page 96 and 97: PAPRIKA EXTRACT 89 biochemical para
Page 98 and 99: PAPRIKA EXTRACT 91 Table 1. Sales o
Page 100 and 101: PAPRIKA EXTRACT 93 Table 2. Estimat
Page 102 and 103: PAPRIKA EXTRACT 95 The European Sci
Page 104 and 105: PAPRIKA EXTRACT 97 The potential di
Page 106 and 107: PAPRIKA EXTRACT 99 Hornero-Mendez,
Page 108 and 109: PAPRIKA EXTRACT 101 Appendix 1. Res
Page 110 and 111: PAPRIKA EXTRACT 103 Appendix 1. (co
Page 112: PAPRIKA EXTRACT 105 Appendix 1. (co
Page 115 and 116: 108 PHOSPHOLIPASE C EXPRESSED IN PI
Page 124 and 125: PHYTOSTEROLS, PHYTOSTANOLS AND THEI
Page 170: PHYTOSTEROLS, PHYTOSTANOLS AND THEI
Page 173 and 174: 166 POLYDIMETHYLSILOXANE (addendum)
Page 183 and 184:
176 POLYDIMETHYLSILOXANE (addendum)
Page 185 and 186:
Page 187 and 188:
Page 190 and 191:
STEVIOL GLYCOSIDES (addendum) First
Page 192 and 193:
STEVIOL GLYCOSIDES (addendum) 185 r
Page 194 and 195:
STEVIOL GLYCOSIDES (addendum) 187 c
Page 196 and 197:
STEVIOL GLYCOSIDES (addendum) 189 a
Page 198 and 199:
STEVIOL GLYCOSIDES (addendum) 191 N
Page 200 and 201:
STEVIOL GLYCOSIDES (addendum) 193 2
Page 202 and 203:
STEVIOL GLYCOSIDES (addendum) 195 T
Page 204 and 205:
STEVIOL GLYCOSIDES (addendum) 197 a
Page 206 and 207:
STEVIOL GLYCOSIDES (addendum) 199 r
Page 208 and 209:
STEVIOL GLYCOSIDES (addendum) 201 l
Page 210 and 211:
STEVIOL GLYCOSIDES (addendum) 203 g
Page 212 and 213:
Page 214 and 215:
Page 216 and 217:
STEVIOL GLYCOSIDES (addendum) 209 t
Page 218 and 219:
STEVIOL GLYCOSIDES (addendum) 211 t
Page 220 and 221:
STEVIOL GLYCOSIDES (addendum) 213 s
Page 222 and 223:
STEVIOL GLYCOSIDES (addendum) 215 C
Page 224 and 225:
STEVIOL GLYCOSIDES (addendum) 217 L
Page 226:
STEVIOL GLYCOSIDES (addendum) 219 W
Page 229 and 230:
222 SULFITES: ASSESSMENT OF DIETARY
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 268:
SAFETY EVALUATIONS OF GROUPS OF REL
Page 271 and 272:
264 INTRODUCTION Figure 1. Procedur
Page 274 and 275:
DIETARY EXPOSURE ASSESSMENT OF FLAV
Page 276 and 277:
Page 278 and 279:
Page 280 and 281:
Page 282 and 283:
Page 284 and 285:
Page 286 and 287:
Page 288 and 289:
Page 290 and 291:
Page 292 and 293:
Page 294 and 295:
Page 296:
Page 299 and 300:
292 ALIPHATIC BRANCHED-CHAIN SATURA
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
332 ALIPHATIC LINEAR ,-UNSATURATED
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
Page 358 and 359:
ALKOXY-SUBSTITUTED ALLYLBENZENES PR
Page 360 and 361:
ALKOXY-SUBSTITUTED ALLYLBENZENES 35
Page 362 and 363:
Page 364 and 365:
Page 366 and 367:
Page 368 and 369:
Page 370 and 371:
Page 372 and 373:
Page 374 and 375:
Page 376 and 377:
Page 378 and 379:
Page 380 and 381:
Page 382 and 383:
Page 384 and 385:
Page 386 and 387:
Page 388 and 389:
Page 390 and 391:
Page 392 and 393:
Page 394 and 395:
Page 396 and 397:
Page 398 and 399:
Page 400 and 401:
Page 402 and 403:
Page 404 and 405:
Page 406 and 407:
Page 408 and 409:
Page 410 and 411:
Page 412 and 413:
Page 414 and 415:
Page 416 and 417:
Page 418 and 419:
Page 420 and 421:
Page 422 and 423:
Page 424 and 425:
Page 426 and 427:
Page 428 and 429:
Page 430 and 431:
Page 432 and 433:
Page 434 and 435:
Page 436 and 437:
Page 438 and 439:
Page 440 and 441:
Page 442 and 443:
Page 444 and 445:
Page 446 and 447:
Page 448 and 449:
Page 450 and 451:
Page 452 and 453:
Page 454 and 455:
Page 456 and 457:
Page 458 and 459:
Page 460 and 461:
Page 462 and 463:
Page 464 and 465:
Page 466 and 467:
Page 468 and 469:
Page 470 and 471:
Page 472 and 473:
Page 474 and 475:
Page 476 and 477:
Page 478 and 479:
Page 480 and 481:
Page 482 and 483:
Page 484 and 485:
Page 486 and 487:
Page 488 and 489:
FURAN-SUBSTITUTED ALIPHATIC HYDROCA
Page 490 and 491:
Page 492 and 493:
Page 494 and 495:
Page 496 and 497:
Page 498 and 499:
Page 500 and 501:
Page 502 and 503:
Page 504 and 505:
Page 506 and 507:
Page 508 and 509:
Page 510 and 511:
Page 512 and 513:
Page 514 and 515:
Page 516 and 517:
Page 518 and 519:
Page 520 and 521:
Page 522 and 523:
Page 524 and 525:
Page 526 and 527:
Page 528 and 529:
Page 530 and 531:
Page 532 and 533:
Page 534 and 535:
Page 536 and 537:
Page 538 and 539:
Page 540 and 541:
HYDROXY- AND ALKOXY-SUBSTITUTED BEN
Page 542 and 543:
Page 544 and 545:
Page 546 and 547:
Page 548 and 549:
Page 550 and 551:
Page 552 and 553:
Page 554 and 555:
Page 556 and 557:
MISCELLANEOUS NITROGEN-CONTAINING S
Page 558 and 559:
Page 560 and 561:
Page 562 and 563:
Page 564 and 565:
Page 566 and 567:
Page 568 and 569:
Page 570 and 571:
Page 572 and 573:
Page 574 and 575:
Page 576 and 577:
Page 578 and 579:
Page 580 and 581:
Page 582 and 583:
Page 584:
Page 587 and 588:
580 SUBSTANCES STRUCTURALLY RELATED
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 602:
ANNEXES
Page 605 and 606:
598 ANNEX 1 10. Specifications for
Page 607 and 608:
600 ANNEX 1 No. 54, 1974; WHO Techn
Page 609 and 610:
602 ANNEX 1 70. Evaluation of certa
Page 611 and 612:
604 ANNEX 1 108. Toxicological eval
Page 613 and 614:
606 ANNEX 1 148. Residues of some v
Page 615 and 616:
608 ANNEX 1 188. Safety evaluation
Page 617 and 618:
610 ANNEX 2 ECG electrocardiogram E
Page 619 and 620:
612 ANNEX 2 SI stimulation index SU
Page 621 and 622:
614 ANNEX 3 Ms J. Baines, Food Stan
Page 624 and 625:
ANNEX 4 ACCEPTABLE DAILY INTAKES, O
Page 626 and 627:
ANNEX 4 619 Food additive Specifica
Page 628 and 629:
ANNEX 4 621 3. FLAVOURING AGENTS 3.
Page 630 and 631:
ANNEX 4 623 Flavouring agent No. Sp
Page 632 and 633:
ANNEX 4 625 Flavouring agent JECFA
Page 634 and 635:
ANNEX 4 627 Actual production volum
Page 636 and 637:
ANNEX 4 629 Flavouring agent No. Sp
Page 638 and 639:
ANNEX 5 SUMMARY OF THE SAFETY EVALU
Page 640 and 641:
ANNEX 5 633 Secondary components Co
show all

Safety evaluation of certain food additives - ipcs inchem

Create successful ePaper yourself

Delete template?

Save as template?