Making Decisions about the Risks of Chemicals in Foods with Limited Scientific Information

(Page 27 of 27)

James T. Heimbach, Ph.D., F.A.C.N.
JHeimbach LLC

William Helferich, Ph.D.
Professor of Nutrition, Food Science & Human Nutrition
Univ. of Illinois

Bernadene Magnuson, Ph.D.
Senior Scientific & Regulatory Consultant
Cantox Health Sciences Intl.

Diane B. McColl, Esq.
Hyman, McNamara, and Phelps, P.C.

Robert S. McQuate, Ph.D.
CEO & Co-Founder
GRAS Associates, LLC

Ian Munro, Ph.D., F.A.T.S., FRCPath
Executive Vice President and Senior Science Consultant
Cantox Health Sciences Intl.

Barbara Petersen, Ph.D.
Practice Director and Principal Scientist
Food and Chemicals Practice
Exponent Inc.

Ashley Roberts, Ph.D.
Vice President, Food & Nutrition
Cantox Health Sciences Intl.

Joseph Scimeca, Ph.D.
Director, Global Regulatory Affairs
Corporate Food Safety & Regulatory Affairs

Martin Slayne, Ph.D.
Director, Intl. Food Safety & Nutrition
PepsiCo Intl.

Thomas Trautman, Ph.D.
Fellow, Toxicology & Regulatory Affairs
General Mills Inc.

IFT Staff

Rosetta Newsome, Ph.D.
Director, Science and Communications

Toni Tarver
Scientific and Technical Communications Manager

Additional Acknowledgments

Cory Bryant, Ph.D.
General Health Scientist, Food and Drug Administration
Office for Food Defense, Communication, and Emergency Response
Food Defense Oversight Team

Fred Shank, Ph.D.
Institute of Food Technologists


Steve Taylor, Ph.D.
Univ. of Nebraska


Adam A, Crespy V, Levrat-Verny MA, Leenhardt F, Leuillet M, Demigne C, Remesy C. 2002. The bioavailability of ferulic acid is governed primarily by the food matrix rather than its metabolism in intestine and liver in rats. J Nutr 132(7):1962–8.

Aeschbacher HU, Wolleb U, Loliger J, Spadone JC, Liardon R. 1989. Contribution of coffee aroma constituents to the mutagenicity of coffee. Food Chem Toxicol 27:227–32.

Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. 2001a. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res 61(13):5045–50.

Allred CD, Ju YH, Allred KF, Chang J, Helferich WG. 2001b. Dietary genistein stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis 22(10):1667–73.

Allred CD, Allred KF, Ju YH, Goeppinger TS, Doerge DR, Helferich WG. 2004. Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis 25(9):1649–57.

Allred CD, Twaddle NC, Allred KF, Goeppinger TS, Churchwell MI, Ju YH, Helferich WG, Doerge DR. 2005. Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized BALB/c mice. J Agric Food Chem 53(22):8542–50.

Ames BN, Gold LS. 2000. Paracelsus to parascience: the environmental cancer distraction. Mutat Res 447:3–13.

Anonymous. 1971. Wodicka rates food additive hazard as low. Food Chem News 12(49):11.

Arjmandi BH. 2001. The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency. J Am Coll Nutr 20(Suppl 5):398S–402S, 417S–20S.

Ashby J, Tennant RW. 1988. Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP. Mutat Res 204:17–115.

Ashby J, Tennant RW. 1991. Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP (National Toxicology Program). Mutat Res 257(3):229–306 [Corrigendum, 1994; 317(2):175].

Ashby J, Tennant RW, Zeiger E, Stasiewicz S. 1989. Classification according to chemical structure, mutagenicity to Salmonella and level of carcinogenicity of a further 42 chemicals tested for carcinogenicity by the U.S. National Toxicology Program. Mutat Res 223(2):73–103.

ATBC. 1994. ATBC Cancer Prevention Study Group. The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. New Engl J Med 330(15):1029–35.

ATBC. 2003. Incidence of cancer and mortality following α-tocopherol and β-carotene supplementation. A postintervention follow-up. J Am Med Assoc 290(4):476–85.

Bailey AB, Chanderbhan R, Collazo-Braier N, Cheeseman MA, Twaroski ML. 2005. The use of structure-activity relationship analysis in the food contact notification program. Regul Toxicol Pharmacol 42(2):225–35.

Bailey DG, Dresser GK. 2004. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 4(5):281–97.

Bailey DG, Dresser GK, Leake BF, Kim RB. 2007. Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 81(4):495–502.

Bandolier. 2008. Bandolier risk collection. Available from: . Accessed Apr 15, 2009.

Barlow S. 2005. ILSI Europe concise monograph series. Threshold of toxicological concern (TTC). Brussels , Belgium : Intl. Life Sciences Inst. (ILSI). Available from: . Accessed Apr 15, 2009.

Beasley V. 1999. Absorption, distribution, metabolism, and elimination: differences among species. In: Veterinary toxicology. Beasley V, editor. Ithaca , NY : International Veterinary Information Service. Available from: Accessed Jan 9, 2009.

Bennetts HW, Underwood EJ, Shier FL. 1946. A specific breeding problem of sheep on subterranean clover pastures in western Australia. Aust Vet J 22:2–12.

Blackburn K, Stickeny JA, Carlson-Lynch HL, McGinnis PM, Chappel L, Felter SP. 2005. Application of the threshold of toxicological concern approach to ingredients in personal and household care products. Regul Toxicol Pharmacol 43(3):249–59.

Boon HS, Olatunde F, Zick SM. 2007. Trends in complementary/alternative medicine use by breast cancer survivors: comparing survey data from 1998 and 2005. BMC Womens Health 7:4.

Borelli RC, Visconti A, Menella C, Anese M, Fogliano V. 2002. Chemical characterization and antioxidant properties of coffee melanoidins. J Agric Food Chem 50:6527–33.

Boyer J, Brown D, Liu RH. 2004. Uptake of quercetin and quercetin 3-glucoside from whole onion and apple peel extracts by Caco-2 cell monolayers. J Agric Food Chem 52:7172–9.

BRAFO. 2008. Risk benefit analysis of foods. Benefit-risk analysis of foods of ILSI Europe. Available from: . Accessed Feb 18, 2009.

Bressler R. 2006. Grapefruit juice and drug interactions. Exploring mechanisms of this interaction and potential toxicity for certain drugs. Geriatrics 61(11):12–8.

Brewer S. 2000. Easing menopausal symptoms with dietary phytoestrogens. Community Nurse 6(6):13–5.

Bruno RS, Leonard SW, Atkinson J, Montine TJ, Ramakrishnan R, Bray TM, Trabel MG. 2006. Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic Biol Med 40(4):689–97.

[CAC] Codex Alimentarius Commission. 1997. Report of the 22nd session of the Codex Alimentarius Commission. Report nr 23-8 Jun. ALINORM 97/37.

[CAC] Codex Alimentarius Commission. 2003a. Draft working principles for risk analysis for application in the framework of the Codex Alimentarius. Appendix IV. Report nr ALINORM 03/33a.

[CAC] Codex Alimentarius Commission. 2003b. CAC Procedural manual. 13th ed. Available from: . Accessed Apr 14, 2009.

[CAC] Codex Alimentarius Commission. 2007. CAC Procedural Manual. 17th ed. Available from: . Accessed Apr 14, 2009.

[CAC] Codex Alimentarius Commission. 2009. CAC Procedural manual. 18th ed. Available from: . Accessed Apr 14, 2009.

Carter MW, Matrone G, Smart WW Jr. 1955. Effect of genistein on reproduction of the mouse. J Nutr 55(4):639–45.

Cashman K. 2003. Prebiotics and calcium bioavailability. Curr Issues Intest Microbiol 4(1):21–32.

Cassidy A, Brown JE, Hawdon A, Faughnan MS, King LJ, Millward J, Zimmer-Nechemias L, Wolfe B, Setchell KD. 2006. Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods. J Nutr 136(1):45–51.

Castenmiller JJ, West CE. 1998. Bioavailability and bioconversion of carotenoids. Ann Rev Nutr 18:19–38.

Castenmiller JJ, van de Poll CJ, West CE, Brouwer IA, Thomas CM, van Dusseldorp M. 2000. Bioavailability of folate from processed spinach in humans. Effect of food matrix and interaction with carotenoids. Ann Nutr Metab 44(4):163–9.

[CDC] Centers for Disease Control and Prevention (U.S.). 2005. Preventing chronic diseases: investing wisely in health. Available from: . Accessed Apr 14, 2009.

[CDC] Centers for Disease Control and Prevention (U.S.). 2006. Surveillance of foodborne disease outbreaks—United States, 1998–2002. MMWR surveillance summary. Available from: . Accessed Apr 14, 2009.

[CDC-NCHS] Centers for Disease Control and Prevention (U.S.) and Natl. Center for Health Statistics (U.S.). 2008. Prevalence of overweight and obesity among adults: United States, 1999–2002 [Website]. Available from: . Accessed Apr 13, 2009.

Cheeseman MA, Machuga EJ, Bailey AB. 1999. A tiered approach to threshold of regulation. Food Chem Toxicol 37:387–412.

Clary JJ. 2003. Methanol: is it a developmental risk to humans? Reg Toxicol Pharmacol 37:83–91.

Clemens R, Coughlin J. 2007. Coffee and health: surprisingly good news. Food Technol 61(1):17.

Clifford MN, Marks S, Knight S, Kuhnert N. 2006. Characterization by LC-MS of four new classes of p-coumaric acid-containing diacyl chlorogenic acids in green coffee beans. J Agric Food Chem 54:4095–101.

Cornwell T, Cohick W, Raskin I. 2004. Dietary phytoestrogens and health. Phytochemistry 65(8):995–1016.

Cramer H, Renaud B, Billiard M, Mouret J, Hammers R. 1979. Monoamine metabolites and cyclic nucleotides in the cerebrospinal fluid of patients with bismuth or mercury poisoning. Archiv für Psychiatrie und Nervenkrankheiten 226(3):173–81.

Daglia M, Papetti A, Aceti C, Sordelli B, Gregotti C, Gazzani G. 2008. Isolation of high molecular weight components and contribution to the protective activity of coffee against lipid peroxidation in a rat liver microsome system. J Agric Food Chem 56:11653–60.

Davies TS, Lynch BS, Monro AM, Munro IC, Nestman ER. 2000. Rodent carcinogenicity tests need be no longer than 18 months: an analysis based on 210 chemicals in the IARC monographs. Food Chem Toxicol 38(2-3):219–35.

de Kleijn MJ, Van Der Schouw YT, Wilson PW, Grobbee DE, Jacques PF. 2002. Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal U.S. women: the Framingham study. J Nutr 132(2):276–82.

Delgado-Andrade C, Morales FJ. 2005. Unraveling the contribution of melanoidins to the antioxidant activity of coffee brews. J Agric Food Chem 53:1403–7.

Delgado-Andrade C, Rufian-Henares JA, Morales FJ. 2005. Assessing the antioxidant activity of melanoidins from coffee brews by different antioxidant methods. J Agric Food Chem 53:7832–6.

de Pascual-Teresa S, Hallund J, Talbot D, Schroot J, Williams CM, Bugel S, Cassidy A. 2006. Absorption of isoflavones in humans: effects of food matrix and processing. J Nutr Biochem 17:257–64.

Demmig-Adams B, Gilmore AM, Adams WW, 3rd. 1996. Carotenoids 3: in vivo function of carotenoids in higher plants. Faseb J 10(4):403–12.

Dórea JG, da Costa THM. 2005. Review article: is coffee a functional food? Brit J Nutr 93:773–82.

Dourson ML, Felter SP, Robinson D. 1996. Evolution of science based uncertainty factors in noncancer risk assessment. Regul Toxicol Pharmacol 24:108–20.

Douglas M, Wildavsky A. 1983. Risk and Culture. Univ. Berkley , Calif. : Univ. of California Press. 221 p.

Dresser GK, Kim RB, Bailey DG. 2005. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 77(3):170–7.

Dybing E, Farmer PB, Andersen M, Fennell TR, Lalljie PD, Muller DJG, Olin S, Petersen BJ, Schlatter J, Scholz G, Scimeca JA, Slimani N, Tornqvist M, Tuijtelaars S, Verger P. 2005. Human exposure and internal dose assessments of acrylamide in food. Food Chem Toxicol 43:365–410.

[EFSA] European Food Safety Authority. 2005. Opinion of the Scientific Committee on a request from EFSA related to a harmonized approach for risk assessment of substances which are both genotoxic and carcinogenic. EFSA J 282:1–31. Available from: . Accessed Apr 15, 2009.

[EFSA] European Food Safety Authority. 2007. Report on risk-benefit analysis of foods: methods and approaches. EFSA Scientific Colloquium European Food Safety Authority 6, July 13–14, 2006, Tabiano , Italy , 157 p.

Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC. 1998. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. J Am Med Assoc 280(18):1569–75.

Ellis PR, Kendall CW, Ren Y, Parker C, Pacy JF, Waldron KW, Jenkins DJ. 2004. Role of cell walls in the bioaccessibility of lipids in almond seeds. Am J Clin Nutr 80(3):604–13.

Faist V, Erbersdobler HF. 2001. Metabolic transit and in vivo effects of melanoidins and precursor compounds deriving from the Maillard reaction. Ann Nutr Metab 45:1–12.

[FAO-WHO] Food and Agriculture Organization/World Health Organization. 2002. Joint FAO/WHO project to update principles and methods for the risk assessment of chemicals in food [Conference]; 2002 Dec 9–13; London , England .

[FAO-WHO] Food and Agriculture Organization/World Health Organization. 2006. Understanding the Codex Alimentarius. 3rd ed. Geneva , Switzerland : WHO Press. 46 p.

[FAO-WHO] Food and Agriculture Organization/World Health Organization. 2009. Project to update the principles and methods for the assessment of chemicals in food. Available from: . Accessed Apr 15, 2009.

Faughnan MS, Hawdon A, Ah-Singh E, Brown J, Millward DJ, Cassidy A. 2004. Urinary isoflavone kinetics: the effect of age, gender, food matrix and chemical composition. Br J Nutr 91(4):567–74.

[FDA] Food and Drug Administration (U.S.). 1958. Federal Register 23:9511; 9516.

[FDA] Food and Drug Administration (U.S.). 1959. Federal Register 24:9368.

[FDA] Food and Drug Administration (U.S.). 1985. Federal Register 50:51551.

[FDA] Food and Drug Administration (U.S.). 1988. Federal Register 53:16544–5.

[FDA] Food and Drug Administration (U.S.). 1992. Federal Register 57:22984–90.

[FDA] Food and Drug Administration (U.S.). 1993. Federal Register 58:52719.

[FDA] Food and Drug Administration (U.S.). 1994. Federal Register 59:61538.

[FDA] Food and Drug Administration (U.S.). 1995. Federal Register 60:36581–36596.

[FDA] Food and Drug Administration (U.S.). 1997. Federal Register 62:18938–42.

[FDA] Food and Drug Administration (U.S.). 2002. Federal Register 67:78172–3.

[FDA] Food and Drug Administration (U.S.). 2003. Federal Register 68:75411–2.

[FDA] Food and Drug Administration (U.S.). 2004. Federal Register 69:6788.

[FDA] Food and Drug Administration (U.S.). 2003. Federal Register 68:75411–2.

[FDA] Food and Drug Administration (U.S.). 2006. Estimating dietary intake of substances in food. Available from: . Accessed Apr 15, 2009.

[FDA] Food and Drug Administration (U.S.). 2007. Assessing the safety of food contact substances. Regulatory report. Available from: . Accessed May 13, 2009.

[FDA] Food and Drug Administration (U.S.). 2009. Regulatory meeting with manufacturers and users of bisphenol A-containing materials. Available from: . Accessed Mar 17, 2009.

[FDA-CFSAN] Food and Drug Administration (U.S.) and Center for Food Safety and Applied Nutrition (U.S.). 2000. Toxicological principles for the safety assessment of food ingredients. Redbook 2000. Available from: . Accessed Apr 15, 2009.

[FDA-USDA] Food and Drug Administration (U.S.) and Department of Agriculture (U.S.). 2000. United States food safety system. Synthesis: the United States food safety system. Available from: . Accessed Apr 15, 2009.

Felter S, Lane RW, Latulippe ME, Llewellyn GC, Olin SS, Scimeca JA, Trautman TD. 2009. Refining the threshold of toxicological concern for risk prioritization of trace chemicals in food. Food Chem Toxicol (forthcoming).

Frawley JP. 1967. Scientific evidence and common sense as a basis for food-packaging regulations. Food Cosmet Toxicol 5:293–308.

Fujioka K, Shibamoto T. 2006. Quantitation of volatiles and nonvolatile acids in an extract from coffee beverages: correlation with antioxidant activity. J Agric Food Chem 54:6054–8.

Fuster MD, Mitchell AE, Ochi H, Shibamoto T. 2000. Antioxidative activities of heterocyclic compounds formed in brewed coffee. J Agric Food Chem 48:5600–3.

Gold LS, Sawyer CB, Magaw R, Backman GM, de Veciana M, Levinson R, Hooper NK, Havender WR, Bernstein L, Peto R, Pike M, Ames BN. 1984. A carcinogenic potency database of the standardized results of animal bioassays. Environ Health Persp 58:9–319.

Gordon-Larsen P, Adair LS, Nelson MC, Popkin BM. 2004. Five-year obesity incidence in the transition period between adolescence and adulthood: the national longitudinal study of adolescent health. Am J Clin Nutr 80(3):569–75.

Gove PB, editor. 1993. Webster's third new international dictionary (unabridged). Springfield , Mass. : Merriam-Webster Inc.

Granado-Lorencio F, Olmedilla-Alonso B, Herrero-Barbudo C, Perez-Sacristan B, Blanco-Navarro I, Blazquez-Garcia S. 2007. Comparative in vitro bioaccessibility of carotenoids from relevant contributors to carotenoid intake. J Agric Food Chem 55:6387–94.

Grüner O, Bilzer N, Liebmann J. 1994. Formation of methanol in vitro and in vivo (formation of methanol after the consumption of pectin). Blutalkohol 31:228–32.

Gu L, House SE, Prior RL, Fang N, Ronis MJJ, Clarkson TB, Wilson ME, Badger TM. 2006. Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys and women. J Nutr 136:1215–21.

Hadley CW, Miller EC, Schwartz SJ, Clinton SK. 2002. Tomatoes, lycopene, and prostate cancer: progress and promise. Soc Exp Biol Med 2002:869–80.

Hargreaves DF, Potten CS, Harding C, Shaw LE, Morton MS, Roberts SA, Howell A, Bundred NJ. 1999. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 84(11):4017–24.

Harris Interactive. 2007. Consumer concern over product recalls high [Website]. Available from: . Accessed Feb 6, 2008.

Hasnip S, Crews C, Castle L. 2006. Some factors affecting the formation of furan in heated foods. Food Addit Contam 23:219–27.

Hastwell L, Chai K, Roberts T, Webster J, Harver R, Rees R, Walmsley R. High specificity and high sensitivity genotoxicity assessment in a human cell line: validation of the GADD45α-GFP genotoxicity assay. Mutation Research 607:160–75.

HEATOX. 2007. Heat-generated food toxicants: identification, characterization and risk minimization [Website]. Available from: . Accessed Apr 13, 2009.

Helferich WG, Andrade JE, Hoagland MS. 2008. Phytoestrogens and breast cancer: a complex story. Inflammopharmacol 16(5):219–26.

Higdon JV, Frei B. 2006. Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr 46(2):101–23.

Hossain T, Rosenberg I, Selhub J, Kishore G, Beachy R, Schubert K. 2004. Enhancement of folates in plants through metabolic engineering. Proc Natl Acad Sci USA 101(14):5158–63.

Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J. 2007. Coffee and tea consumption and the risk of Parkinson's disease. Mov Disord 22:2242–8.

Huber WW, Prustomersky S, Delbanco E, Uhl M, Scharf G, Turesky RJ, Their R, Schulte-Hermann R. 2002. Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rate by the coffee components kahweol and cafestol. Arch Toxicol 76:209–17.

Huebert ND, Dasgupta M, Chen YM. 2004. Using in vitro human tissues-to predict pharmacokinetic properties. Curr Opin Drug Discov Devel 7:69–74.

[IARC] Intl. Agency for Research on Cancer. 1995. Dry cleaning, some chlorinated solvents and other industrial chemicals. Monographs on the Evaluation of Carcinogenic Risks to Humans. Nr 63. Lyon , France : Intl. Agency for Research on Cancer. p 394–407.

[IFT] Institute of Food Technologists. 1988. Assessing the optimal system for ensuring food safety: a scientific consensus. [Conference] August 29–30, 1988. Washington , DC : Institute of Food Technologists, Chicago, Ill .

[IOM] Inst. of Medicine (U.S.). 2007. Seafood choices: balancing benefits and risks. Washington , D.C. : The Natl. Academies Press. 738 p.

Jagerstad M, Skog K. 2005. Review: genotoxicity of heat-processed foods. Mutat Res 574:156–72.

[JECFA] Joint FAO/WHO Expert Committee on Food Additives. 2005. Summary and conclusions. 64th meeting of the Joint FAO/WHO Expert Committee on Food Additives. Feb. 8–17. Rome, Italy . Available from: . Accessed Mar 15, 2009.

[JECFA] Joint FAO/WHO Expert Committee on Food Additives. 2006. Evaluation of Certain Food Contaminants. WHO Technical Report Series 930. Report nr 64. Available from: . Accessed Apr 13, 2009.

Kirsch V, Hayes, RG, Mayne ST, Chatterjee N, Subar, AF, Dixon B, Alabnes D, Andriole GL, Urban DA, Peters U. 2006. Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst 98:245–54.

Kroes R., Kozianowski G. 2002. Threshold of toxicological concern (TTC) in food safety. Toxicol Lett 127:43–6.

Kroes R, Renwick AG, Cheeseman M, Kleiner J, Mengelsdorf I, Piersma A, Schilter B, Schlatter J, van Schothorst F, Vos JG, Wurtzen G. 2004. Structure-based thresholds of toxicological concern—guidance for application to substances present at low levels in the diet. Food Chem Toxicol 42:65–83.

Lamartiniere CA. 2002. Timing of exposure and mammary cancer risk. J Mammary Gland Biol Neoplasia 7:67–76.

Lamartiniere CA, Zhang JX, Cotroneo MS. 1998. Genistein studies in rats: potential for breast cancer prevention and reproductive and developmental toxicity. Am J Clin Nutr 68(Suppl 6):1400S–5S.

La Vecchia C, Tavani A. 2007. Coffee and cancer risk: an update. Eur J Cancer Prev 16:385–9.

Lee K-G, Shibamoto T. 2002. Toxicology and antioxidant activities of non-enzymatic browning reaction products: review. Food Rev Intl 18:151–75.

Lee I-M, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. 2005. Vitamin E in the primary prevention of cardiovascular disease and cancer. The women's health study: a randomized controlled trial. J Am Med Assoc 294(1):56–65.

Lehman AJ, Fitzhugh OG. 1954. 100-fold margin of safety. Assoc Food Drug Off US Q Bull 18:33–5.

Lindenmeier M, Faist V, Hofmann T. 2002. Pronylation of proteins—a novel protein modification in bread crust showing in vitro antioxidative and phase I/II-enzyme modulating activity. J Agric Food Chem 50:6997–7006.

Lindinger W, Taucher J, Jordan A, Hansel A, Vogel . 1997. Endogenous production of methanol after the consumption of fruit. Alcohol Clin Exper Res 21(5):939–43.

Lonn E, Bosch J, Yusuf S, Sheridan P, Poque J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR. 2005. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. J Am Med Assoc 293:1338–47.

Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, Stampfer MJ, Rexrode KM, Hu FB. 2006. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 113:2045–53.

Lopez-Garcia E, van Dam RM, Li TY, Rodriquez-Artalejo F, Hu FB. 2008. The relationship of coffee consumption with mortality. Ann Intern Med 148:904–14.

Lowrance WH. 1976. Of acceptable risk: science and the determination of safety. Los Altos , Calif. : William Kaufmann Inc. 180 p.

Lu LJ, Anderson KE, Grady JJ, Nagamani M. 1996. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev 5(1):63–70.

Maga JA. 1979. Furans in foods. CRC Crit Rev Food Sci Nutr 11:355–400.

Manzocco L, Calligaris S, Mastrocola D, Nicoli MC, Lerici CR. 2001. Review of non-enzymatic browning and antioxidant capacity in processed foods. Trends Food Sci Technol 11:340–6.

Matrone G, Smart WW Jr, Carter MW, Smart VW, Garren HW. 1956. Effect of genistein on growth and development of the male mouse. J Nutr 59(2):235–41.

Mattila P, Hellstrom J, Torronen R. 2006. Phenolic acids in berries, fruits, and beverages. J Agric Food Chem 54:7193–9.

McCarron DA. 2000. The dietary guideline for sodium: should we shake it up? Yes. Am J Clin Nutr 71:1013–9.

McKinney JD, Richard A, Waller C, Newman MC, Gerberick F. 2000. The practice of structure activity relationships (SAR) in toxicology. J Toxicol Sci 56:8–17.

McMichael-Phillips DF, Harding C, Morton M, Roberts SA, Howell A, Potten CS, Bundred NJ. 1998. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 68(Suppl 6):1431S–5S.

Monteiro M, Farah A, Perrone D, Luiz C, Trugo LC, Donangelo C. 2007. Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans. J Nutr 137:2196–201.

Morehouse KM, Nyman PJ, McNeal TP, DiNovi MJ, Perfetti GA. 2008. Survey of furan in heat processed foods by headspace gas chromatography/mass spectrometry and estimated adult exposure. Food Addit Contam 25:259–64.

Mucci L, Wilson KM. 2008. Acrylamide intake through diet and human cancer risk. J Agric Food Chem 56:6013–9.

Müller L, Mauthe RJ, Riley CM, Andino CM, De Antonis D, Beels C, DeGeorge J, De Knaep AJM, Ellison D, Fagerland JA, Frank R, Fritschel B, Galloway S, Harpur E, Humfrey CDN, Jacks AS, Jagota N, Mackinnon J, Mohan G, Ness DK, et al . 2006. A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul Toxicol Pharmacol 44(3):198–211.

Munro I. 1990. Safety assessment procedures for indirect food additives: an overview. Regul Toxicol Pharmacol 12:2–12.

Munro IC. 2006. Setting tolerable upper intake levels for nutrients. J Nutr 136:490S–2S.

Munro I, Ford RA, Kennepohl E, Sprenger JG. 1996. Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food Chem Toxicol 34:829–67.

Munro IC, Kennepohl E, Kroes R. 1999. A procedure for the safety evaluation of flavouring substances. Food Chem Toxicol 37:207–32.

[NAS] Natl. Academy of Sciences (U.S.). 1989. Improving risk communication. Washington , D.C. : Natl. Academies Press. 332 p.

[NAS] Natl. Academy of Sciences (U.S.). 2000a. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington , D.C. : Natl. Academies Press. 506 p.

[NAS] Natl. Academy of Sciences. (U.S.). 2000b. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington , D.C. : Natl. Academies Press. 773 p.

[NHLBI] Natl. Heart, Lung, and Blood Inst. (U.S.). 1998. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Natl. Institutes of Health Publication nr 98-4083. Washington , D.C. : U.S. Government Printing Office.

Nkondjock A. 2009. Coffee consumption and the risk of cancer: an overview. Cancer Lett 277(2):121–5.

[NRC] Natl. Research Council (U.S.). 1983. Risk assessment in the federal government: managing the process, national research council. Washington , D.C. : Natl. Academies Press. 192 p.

[NRC] Natl. Research Council (U.S.). 1989. Diet and health: implications for reducing chronic disease risk. Washington , D.C. : Natl. Academies Press. 749 p.

[NRC] Natl. Research Council. 1996. Carcinogens and anticarcinogens in the human diet: a comparison of naturally occurring and synthetic substances. Washington , D.C. : Natl. Academies Press. 418 p.

[NTP-CERHR] Natl. Toxicology Program (U.S.) and Center for the Evaluation of Risks to Human Reproduction. 2008. Monograph on the potential human reproductive and developmental effects of bisphenol A. NIH publication nr 08-5994. Available from: . Accessed Apr 14, 2009.

Parada J, Aguilera JM. 2007. Food microstructure affects the bioavailability of several nutrients. J Food Sci 72(2):R21–32.

Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, Brighenti F. 2003. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr 133:2812–9.

Petrakis NL, Barnes S, King EB, Lowenstein J, Wiencke J, Lee MM, Miike R, Kirk M, Coward L. 1996. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 5(10):785–94.

Power KA, Saarinen NM, Chen JM, Thompson LU. 2006. Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF-7 xenografts in ovariectomized athymic nude mice. Int J Cancer 118(5):1316–20.

Renjilian DA, Perri LG, Nezu AM, McKelveyt WF, Shermer RL, Anton SD. 2001. Individual versus group therapy for obesity: effects of matching participants to their treatment preferences. J Consult Clin Psych 69:717–21.

Renwick AG. 2006. Toxicology of micronutrients: adverse effects and uncertainty. J Nutr 136:493S–501S.

Rozman KK Klaassen CD. 2001. Absorption, distribution, and excretion of toxicants. In: Klaassen CD, editor. Casarett and Doull's toxicology. 6th ed. New York : McGraw-Hill Publishing. p 107–32.

Rulis AM. 1986. De minimis and the threshold of regulation. In: Felix CW, editor. Food protection technology. Chelsea , Mich. : Lewis Publishers Inc. p 29–37.

Sacchetti G, Di Mattia C, Pittia P, Mastrocola D. 2009. Effect of roasting degree, equivalent thermal effect and coffee type on the radical scavenging activity of coffee brews and their phenolic fraction. J Food Eng 90:74–80.

Sandman P. 1989. Social battles on environmental risks. Chem Eng News 67(Jan 30):27–8.

Sanz T, Luyten H. 2006. Release, partitioning and stability of isoflavones from enriched custards during mouth, stomach and intestine in vitro simulations. Food Hydrocolloids 20(6):892–900.

Seal CJ, de Mul A, Eisenbrand G, Haverkort AJ, Franke K, Lalljie SPD, Mykkanen H, Reimerdes E, Scholz G, Somoza V, Tuijtelaars S, van Boekel M, van Klaveren J, Wilcockson SJ, Wilms L. 2008. Risk-benefit considerations of mitigation measures on acrylamide content of foods—a case study on potatoes, cereals and coffee. Br J Nutr. 99(Suppl 2):S1–46.

Setchell KD, Brown NM, Zimmer-Nechemias L, Brashear WT, Wolfe BE, Kirschner AS, Heubi JE. 2002. Evidence for lack of absorption of soy isoflavone glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability. Am J Clin Nutr 76(2):447–53.

Simon-Hettich B, Rothfuss A, Steger-Hartmann T. 2006. Use of computer-assisted prediction of toxic effects of chemical substances. Toxicology 224(1–2):156–62.

Slayne M, Linbeback DR. 2005. Acrylamide: considerations for risk management. J AOAC Int 88(1):227–33.

Slovic P. 1987. Perception of risk. Science 236:280–5.

Snapinn SM, Jiang Q. 2007. Responder analyses and the assessment of a clinically relevant treatment effect. Trials 8:31.

Somoza V. 2005. Five years of research on health risks and benefits of Maillard reaction products: an update. Mol Nutr Food Res 2005:663–72.

Somoza V, Lindenmeier M, Wenzel E, Frank O, Erbersdobler HF, Hofmann T. 2003. Activity-guided identification of a chemopreventive compound in coffee beverage using in vitro and in vivo techniques. J Agric Food Chem 51:6861–9.

Stanger O. 2002. Physiology of folic acid in health and disease. Curr Drug Metab 3(2):211–23.

Starr C. 1969. Social benefit versus technological risk. Science 165:1232–8.

Stephens FO. 1999. The rising incidence of breast cancer in women and prostate cancer in men. Dietary influences: a possible preventive role for nature's sex hormone modifiers—the phytoestrogens (review). Oncol Rep 6(4):865–70.

Svilaas A, Sakhi AK, Andersen LF, Svilaas T, Strom EC, Jacobs DR, Ose L, Blomhoff R. 2004. Intakes of antioxidants in coffee, wine, and vegetables are correlated with plasma carotenoids in humans. J Nutr 134:562–67.

Tang AL, Shah NP, Wilcox G, Walker KZ, Stojanovska L. 2007. Fermentation of calcium-fortified soymilk with lactobacillus: effects on calcium solubility, isoflavone conversion, and production of organic acids. J Food Sci 72(9):M431–6.

Taylor C, Yetley EA. 2008. Nutrient risk assessment as a tool for providing scientific assessments to regulators. J Nutr 138(10):1987S–91S.

Taylor SL, Crevel RW, Sheffield D, Kabourek JL, Baumert JL. 2009. Threshold dose for peanut: a risk characterization based upon published results from challenges of peanut-allergic individuals. J Allergy Clin Immunol 123(2):S173.

This P, De La Rochefordiere A, Clough K, Fourquet A, Magdelenat H. 2001. Phytoestrogens after breast cancer. Endocr Relat Cancer 8(2):129–34.

Truhaut R. 1991. The concept of the acceptable daily intake: a historical review. Food Addit Contam 8:151–62.

Unlu NZ, Bohn T, Francis DM, Nagaraja HN, Clinton SK, Schwartz SJ. 2007. Lycopene from heat-induced cis-isomer-rich tomato sauce is more bioavailable than from all-trans-rich tomato sauce in human subjects. Br J Nutr 98(1):140–6.

[USDA-ARS] Department of Agriculture (U.S) and Agricultural Research Service (U.S.). 1997. What we eat in America 1994-96, 1998, table set 10. Available from: . Accessed Apr 14, 2009.

Valerio LG, Arvidson KB, Chanderbhan RF, Contrera JF. 2007. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling. Toxicol Appl Pharmacol 222(1):1–16.

van Dam RM. 2006. Coffee and type 2 diabetes: from beans to beta-cells. Nutr Metab Cardiovasc Dis 16:69–77.

van Dam RM. 2008. Coffee consumption and risk of type 2 diabetes, cardiovascular diseases, and cancer. Appl Physiol Nutr Metab 33:1269–83.

VandeCreek L, Rogers E, Lester J. 1999. Use of alternative therapies among breast cancer outpatients compared with the general population. Altern Ther Health Med 5(1):71–6.

Van het Hof KH, Tijburg LB, Pietrzik K, Westrate JA. 1999. Influence of feeding different vegetables on plasma levels of carotenoids, folate, and vitamin C: effect of disruption of the vegetable matrix. Br J Nutr 82(3):203–12.

Wang TT, Sathyamoorthy N, Phang JM. 1996. Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis 17(2):271–5.

[WHO] World Health Organization. 1994. International programme on chemical safety. Assessing human health risks of chemicals: derivation of guidance values for health-based exposure limits. Environmental health criteria 170. Geneva , Switzerland : WHO Press. 73 p.

[WHO] World Health Organization. 1999. International programme on chemical safety. Assessing human health risks of chemicals. Principles for the assessment of risk to human health from exposure to chemicals. Environmental health criteria 210. Geneva , Switzerland : WHO Press. Available from: . Accessed Apr 15, 2009.

[WHO] World Health Organization. 2001. International programme on chemical safety. Guidance document for the use of chemical specific adjustment factors (CSAFs) for interspecies differences and human variability in dose concentration response assessment. Geneva , Switzerland : WHO Press. 76 p.

Wilkes JG, Hass BS, Buzatu DA, Pence LM, Archer JC, Beger RD, Schnackenberg LK, Halbert MK, Jennings L, Kodell RL. 2008. Modeling and assaying dioxin-like biological effects for both dioxin-like and certain non-dioxin-like compounds. Toxicol Sci 102(1): 187–95.

Yanagimoto K, Lee KG, Ochi H, Shibamoto T. 2002. Antioxidative activity of heterocyclic compounds found in coffee volatiles produced by Maillard reaction. J Agric Food Chem 50(19):5480–4.

Yanagimoto K, Ochi H, Lee KG, Shibamoto T. 2004. Antioxidative activities of fractions obtained from brewed coffee. J Agric Food Chem 52:592–6.

Yoon M, Barton HA. 2008. Predicting maternal rat and pup exposures: how different are they? Toxicol Sci 102(1):15–32.

Zaripheh S, Erdman JW. 2002. Factors that influence the bioavailability of xanthophylls. J Nutr 132(3):531S–4S.

Zhi J, Rakhit A, Patel IH. 1995. Effects of dietary fat on drug absorption. Clin Pharmacol Ther 58(5):487–91.

Story Tools