Clinical Reviews in Allergy & Immunology

, Volume 39, Issue 2, pp 95–141 | Cite as

Food Safety

  • Andrea Borchers
  • Suzanne S. Teuber
  • Carl L. Keen
  • M. Eric Gershwin


Food can never be entirely safe. Food safety is threatened by numerous pathogens that cause a variety of foodborne diseases, algal toxins that cause mostly acute disease, and fungal toxins that may be acutely toxic but may also have chronic sequelae, such as teratogenic, immunotoxic, nephrotoxic, and estrogenic effects. Perhaps more worrisome, the industrial activities of the last century and more have resulted in massive increases in our exposure to toxic metals such as lead, cadmium, mercury, and arsenic, which now are present in the entire food chain and exhibit various toxicities. Industrial processes also released chemicals that, although banned a long time ago, persist in the environment and contaminate our food. These include organochlorine compounds, such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (dichlorodiphenyl dichloroethene) (DDT), other pesticides, dioxins, and dioxin-like compounds. DDT and its breakdown product dichlorophenyl dichloroethylene affect the developing male and female reproductive organs. In addition, there is increasing evidence that they exhibit neurodevelopmental toxicities in human infants and children. They share this characteristic with the dioxins and dioxin-like compounds. Other food contaminants can arise from the treatment of animals with veterinary drugs or the spraying of food crops, which may leave residues. Among the pesticides applied to food crops, the organophosphates have been the focus of much regulatory attention because there is growing evidence that they, too, affect the developing brain. Numerous chemical contaminants are formed during the processing and cooking of foods. Many of them are known or suspected carcinogens. Other food contaminants leach from the packaging or storage containers. Examples that have garnered increasing attention in recent years are phthalates, which have been shown to induce malformations in the male reproductive system in laboratory animals, and bisphenol A, which negatively affects the development of the central nervous system and the male reproductive organs. Genetically modified foods present new challenges to regulatory agencies around the world because consumer fears that the possible health risks of these foods have not been allayed. An emerging threat to food safety possibly comes from the increasing use of nanomaterials, which are already used in packaging materials, even though their toxicity remains largely unexplored. Numerous scientific groups have underscored the importance of addressing this issue and developing the necessary tools for doing so. Governmental agencies such as the US Food and Drug Administration and other agencies in the USA and their counterparts in other nations have the increasingly difficult task of monitoring the food supply for these chemicals and determining the human health risks associated with exposure to these substances. The approach taken until recently focused on one chemical at a time and one exposure route (oral, inhalational, dermal) at a time. It is increasingly recognized, however, that many of the numerous chemicals we are exposed to everyday are ubiquitous, resulting in exposure from food, water, air, dust, and soil. In addition, many of these chemicals act on the same target tissue by similar mechanisms. “Mixture toxicology” is a rapidly growing science that addresses the complex interactions between chemicals and investigates the effects of cumulative exposure to such “common mechanism groups” of chemicals. It is to be hoped that this results in a deeper understanding of the risks we face from multiple concurrent exposures and makes our food supply safer.


Infection Food allergies Food additives Toxicology Diarrhea Food safety 



Acetyl choline


Acetyl cholinesterase


Acceptable daily intake


Anogenital distance


Androgen receptor


Agency for Toxic Substances and Disease Registry


Benzyl butyl phthalate


Bovine spongiform encephalopathy


Body weight


Centers for Disease Control and Prevention


Panel on Contaminants in the Food Chain (EU)


Dialkyl phosphate


Di(n-butyl) phthalate


1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (dichlorodiphenyl dichloroethene)


Di-(2-ethylhexyl) phthalate


Diethyl phthalate


European Food Safety Authority


European Union


Deoxynivalenol (a mycotoxin)


Fumonisin B1


Food Safety Inspection Service


Genetically modified


International Agency for Research on Cancer


Joint (WHO/FAO) Expert Committee for Food Additives and Contaminants


Maximum residue limit


National Health and Nutrition Examination Survey


No observed adverse effect level


National Research Council




Ochratoxin A




Polychlorinated biphenyl


Polychlorinated dibenzo-p-dioxin


Polychlorinated dibenzofuran


Provisional maximum tolerable daily intake


Provisional tolerable weekly intake


Reference dose (set by the USEPA)


Scientific Committee for Food




Tolerable daily intake


Tolerable weekly intake


Variant Creutzfeldt-Jakob disease


US Environmental Protection Agency


US Food and Drug Administration


US Department of Agriculture


Zearalenone (a mycotoxin)


  1. 1.
    Koopmans M, Duizer E (2004) Food borne viruses: an emerging problem. Int J Food Microbiol 90:23–41PubMedCrossRefGoogle Scholar
  2. 2.
    Administration USFaD (2009) While you're pregnant. Accessed 19 August 2009
  3. 3.
    Medeiros LC, Chen G, Hillers VN, Kendall PA (2008) Discovery and development of educational strategies to encourage safe food handling behaviors in cancer patients. J Food Prot 71:1666–1672PubMedGoogle Scholar
  4. 4.
    Huang DB, White AC (2006) An updated review on Cryptosporidium and Giardia. Gastroenterol Clin North Am 35:291–314 viiiPubMedCrossRefGoogle Scholar
  5. 5.
    Harman JL, Silva CL (2009) Bovine spongiform encephalopathy. J Am Vet Med Assoc 254:59–72CrossRefGoogle Scholar
  6. 6.
    Gielbert A, Davis LA, Sayers AR, Hope J, Gill AC, Sauer MJ (2008) High resolution differentiation of transmissible spongiform encephalopathy strains by quantitative N-terminal amino acid profiling (N-TAAP) of PK digested abnormal prion protein. J Mass spectrum 44:384–396CrossRefGoogle Scholar
  7. 7.
    Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925PubMedCrossRefGoogle Scholar
  8. 8.
    Sanchez-Juan P, Cousens SN, Will RG, van Duijn CM.. Source of variant Creutzfeldt-Jakob disease outside United Kingdom. Emerg Infect Dis [serial on the Internet]. 2007 Aug [accessed Sept 27, 2009]. Available from
  9. 9.
    Tyshenko MG (2007) Bovine spongiform encephalopathy and the safety of milk from Canadian dairy cattle. Vet Rec 160:215–218PubMedCrossRefGoogle Scholar
  10. 10.
    de Koeijer A, Havelaar A (2007) The future of BSE risk assessments. Introduction. Risk Anal 27:1091–1093PubMedCrossRefGoogle Scholar
  11. 11.
    Wang DZ (2008) Neurotoxins from marine dinoflagellates: a brief review. Mar Drugs 6:349–371PubMedGoogle Scholar
  12. 12.
    Hernandez-Becerril DU, Alonso-Rodriguez R et al (2007) Toxic and harmful marine phytoplankton and microalgae (HABs) in Mexican Coasts. J Environ Sci Health A Tox Hazard Subst Environ Eng 42:1349–1363PubMedGoogle Scholar
  13. 13.
    Panel on Contaminants in the Food Chain (2009) Marine biotoxins in shellfish—saxitoxin group. Scientific Opinion of the Panel on Contaminants in the Food Chain. EFSA J 1019, Accessed 30 April 2009Google Scholar
  14. 14.
    Watkins SM, Reich A et al (2008) Neurotoxic shellfish poisoning. Mar Drugs 6:431–455PubMedCrossRefGoogle Scholar
  15. 15.
    Jeffery B, Barlow T et al (2004) Amnesic shellfish poison. Food Chem Toxicol 42:545–557PubMedCrossRefGoogle Scholar
  16. 16.
    Cordier S, Monfort C et al (2000) Ecological analysis of digestive cancer mortality related to contamination by diarrhetic shellfish poisoning toxins along the coasts of France. Environ Res 84:145–150PubMedCrossRefGoogle Scholar
  17. 17.
    Panel on Contaminants in the Food Chain (2008) Marine biotoxins in shellfish – ochadaic acid and analogues. Scientific opionion of the Panel on Contaminants in the Food Chain. EFSA J 589:1–62Google Scholar
  18. 18.
    Al Bulushi I, Poole S, Deeth HC, Dykes GA (2009) Biogenic amines in fish: roles in intoxication, spoilage, and nitrosamine formation—a review. Crit Rev Food Sci Nutr 49:369–377PubMedCrossRefGoogle Scholar
  19. 19.
    Davis J et al (2006) Scombroid fish poisoning associated with tuna steaks—Louisiana and Tennessee. MMWR 56:817–819Google Scholar
  20. 20.
    Creppy EE (2002) Update of survey, regulation and toxic effects of mycotoxins in Europe. Toxicol Lett 127:19–28PubMedCrossRefGoogle Scholar
  21. 21.
    Leblanc JC, Tard A, Volatier JL, Verger P (2005) Estimated dietary exposure to principal food mycotoxins from the first French Total Diet Study. Food Addit Contam 22:652–672PubMedCrossRefGoogle Scholar
  22. 22.
    Thuvander A, Möller T, Barbieri HE, Jansson A, Salomonsson AC, Olsen M (2001) Dietary intake of some important mycotoxins by the Swedish population. Food Addit Contam 18:696–706PubMedGoogle Scholar
  23. 23.
    van Egmond HP, Schothorst RC et al (2007) Regulations relating to mycotoxins in food: perspectives in a global and European context. Anal Bioanal Chem 389:147–157PubMedCrossRefGoogle Scholar
  24. 24.
    European Commission 2002. SCOOP task 3.2.7. Assessment of dietary intake by the population in EU member states. European Commission, Jan 2002Google Scholar
  25. 25.
    Brera C, Debegnach F et al (2008) Ochratoxin a contamination in Italian wine samples and evaluation of the exposure in the Italian population. J Agric Food Chem 56:10611–10618PubMedCrossRefGoogle Scholar
  26. 26.
    Sizoo EA, van Egmond HP (2005) Analysis of duplicate 24-hour diet samples for aflatoxin B1, aflatoxin M1 and ochratoxin A. Food Addit Contam 22:163–172PubMedCrossRefGoogle Scholar
  27. 27.
    Gilbert J, Brereton P, MacDonald S (2001) Assessment of dietary exposure to ochratoxin A in the UK using a duplicate diet approach and analysis of urine and plasma samples. Food Addit Contam 18:1088–1093PubMedCrossRefGoogle Scholar
  28. 28.
    Walker R, Larsen JC (2005) Ochratoxin A: previous risk assessments and issues arising. Food Addit Contam 22(Suppl 1):6–9PubMedCrossRefGoogle Scholar
  29. 29.
    Galvano F, Pietri A et al (2008) Maternal dietary habits and mycotoxin occurrence in human mature milk. Mol Nutr Food Res 52:496–501PubMedCrossRefGoogle Scholar
  30. 30.
    Scott PM (2005) Biomarkers of human exposure to ochratoxin A. Food Addit Contam 22(Suppl 1):99–107Google Scholar
  31. 31.
    Pfohl-Leszkowicz A, Manderville RA (2007) Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans. Mol Nutr Food Res 51:61–99PubMedCrossRefGoogle Scholar
  32. 32.
    Schothorst RC, van Egmond HP (2004) Report from SCOOP task 3.2.10. Collection of occurrence data of Fusarium toxins in food and assessment of dietary intake by the population of EU member states. Subtask: trichothecenes. Toxicol Lett 153:133–143CrossRefGoogle Scholar
  33. 33.
    Rasmussen PH, Petersen A et al (2007) Annual variation of deoxynivalenol in Danish wheat flour 1998-2003 and estimated daily intake by the Danish population. Food Addit Contam 24:315–325PubMedCrossRefGoogle Scholar
  34. 34.
    Pieters MN, Bakker M et al (2004) Reduced intake of deoxynivalenol in The Netherlands: a risk assessment update. Toxicol Lett 153:145–153PubMedCrossRefGoogle Scholar
  35. 35.
    Turner PC, Rothwell JA et al (2008) Urinary deoxynivalenol is correlated with cereal intake in individuals from the United Kingdom. Environ Health Perspect 116:21–25PubMedCrossRefGoogle Scholar
  36. 36.
    Pestka JJ, Smolinski AT (2005) Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health B Crit Rev 8:39–69PubMedGoogle Scholar
  37. 37.
    Gelineau-van Waes J, Starr L, Maddox J, Aleman F, Voss KA, Wilberding J, Riley RT (2005) Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model. Birth Defects Res A Clin Mol Teratol 73:487–497PubMedCrossRefGoogle Scholar
  38. 38.
    Missmer SA, Suarez L, Felkner M, Wang E, Merrill AH Jr, Rothman KJ, Hendricks KA (2006) Exposure to fumonisins and the occurrence of neural tube defects along the Texas–Mexico border. Environ Health Perspect 114:237–241PubMedCrossRefGoogle Scholar
  39. 39.
    Piemontese L, Solfrizzo M et al (2005) Occurrence of patulin in conventional and organic fruit products in Italy and subsequent exposure assessment. Food Addit Contam 22:437–442PubMedCrossRefGoogle Scholar
  40. 40.
    Baert KB, De Meulenaer et al (2007) Variability and uncertainty assessment of patulin exposure for preschool children in Flanders. Food Chem Toxicol 45:1745–1751Google Scholar
  41. 41.
    Llobet JM, Falcó G, Casas C, Teixidó A, Domingo JL (2003) Concentrations of arsenic, cadmium, mercury, and lead in common foods and estimated daily intake by children, adolescents, adults, and seniors of Catalonia, Spain. J Agric Food Chem 51:838–842PubMedCrossRefGoogle Scholar
  42. 42.
    Rubio C, González-Iglesias T, Revert C, Reguera JI, Gutiérrez AJ, Hardisson A (2005) Lead dietary intake in a Spanish population (Canary Islands). J Agric Food Chem 53:6543–6549PubMedCrossRefGoogle Scholar
  43. 43.
    CDC (Centers for Disease Control and Prevention) (2003) Department of Health and Human Services. Second National Report on Human Exposure to Environmental Chemicals. Atlanta, GA, p 251Google Scholar
  44. 44.
    Agency for Toxic Substances and Disease Registry (ATSDR) (1999) Toxicological profile for mercury. Atlanta, GA, pp 1–617Google Scholar
  45. 45.
    Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, Murata K, Sørensen N, Dahl R, Jørgensen PJ (1997) Cognitive deficit in 7-year-old children with prenatal exposure to methyl mercury. Neurotoxicol Teratol 19:417–428PubMedCrossRefGoogle Scholar
  46. 46.
    Stewart PW, Reihman J, Lonky EI, Darvill TJ, Pagano J (2003) Cognitive development in preschool children prenatally exposed to PCBs and MeHg. Neurotoxicol Teratol 25:11–22PubMedCrossRefGoogle Scholar
  47. 47.
    Castoldi AF, Johansson C, Onishchenko N, Coccini T, Roda E, Vahter M, Ceccatelli S, Manzo L (2008) Human developmental neurotoxicity of methyl mercury: impact of variables and risk modifiers. Regul Toxicol Pharmacol 51:201–214PubMedCrossRefGoogle Scholar
  48. 48.
    Watanabe T, Shimbo S, Nakatsuka H, Koizumi A, Higashikawa K, Matsuda-Inoguchi N, Ikeda M (2004) Gender-related difference, geographical variation and time trend in dietary cadmium intake in Japan. Sci Total Environ 329:17–27PubMedCrossRefGoogle Scholar
  49. 49.
    Wilhelm M, Wittsiepe J, Schrey P, Budde U, Idel H (2002) Dietary intake of cadmium by children and adults from Germany using duplicate portion sampling. Sci Total Environ 285:11–19PubMedCrossRefGoogle Scholar
  50. 50.
    Anon (2009) Scientific opinion of the panel on contaminants in the food chain on a request from the European Commission on cadmium in food. EFSA J 980:1–139Google Scholar
  51. 51.
    Rogan WJ, Gladen BC, McKinney JD, Carreras N, Hardy P, Thullen J, Tinglestad J, Tully M (1986) Neonatal effects of transplacental exposure to PCBs and DDE. J Pediatr 109:335–341PubMedCrossRefGoogle Scholar
  52. 52.
    Rogan WJ, Gladen BC (1991) PCBs, DDE, and child development at 18 and 24 months. Ann Epidemiol 1:407–413PubMedCrossRefGoogle Scholar
  53. 53.
    Gladen BC, Rogan WJ (1991) Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichloroethene on later development. J Pediatr 119:58–63PubMedCrossRefGoogle Scholar
  54. 54.
    Stewart P, Reihman J, Lonky E, Darvill T, Pagano J (2000) Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance. Neurotoxicol Teratol 22:21–29PubMedCrossRefGoogle Scholar
  55. 55.
    Darvill T, Lonky E, Reihman J, Stewart P, Pagano J (2000) Prenatal exposure to PCBs and infant performance on the Fagan test of infant intelligence. Neurotoxicology 21:1029–1038PubMedGoogle Scholar
  56. 56.
    Sagiv SK, Nugent JK, Brazelton TB, Choi AL, Tolbert PE, Altshul LM, Korrick SA (2008) Prenatal organochlorine exposure and measures of behavior in infancy using the Neonatal Behavioral Assessment Scale (NBAS). Environ Health Perspect 116:666–673PubMedCrossRefGoogle Scholar
  57. 57.
    Fenster L, Eskenazi B, Anderson M, Bradman A, Hubbard A, Barr DB (2007) In utero exposure to DDT and performance on the Brazelton neonatal behavioral assessment scale. Neurotoxicology 28:471–477PubMedCrossRefGoogle Scholar
  58. 58.
    Eskenazi B, Marks AR, Bradman A, Fenster L, Johnson C, Barr DB, Jewell NP (2006) In utero exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment among young Mexican American children. Pediatrics 118:233–241PubMedCrossRefGoogle Scholar
  59. 59.
    Torres-Sánchez L, Rothenberg SJ, Schnaas L, Cebrián ME, Osorio E, Del Carmen Hernández M, García-Hernández RM, Del Rio-Garcia C, Wolff MS, López-Carrillo L (2007) In utero p,p′-DDE exposure and infant neurodevelopment: a perinatal cohort in Mexico. Environ Health Perspect 115:435–439PubMedCrossRefGoogle Scholar
  60. 60.
    Ribas-Fitó N, Torrent M, Carrizo D, Muñoz-Ortiz L, Júlvez J, Grimalt JO, Sunyer J (2006) In utero exposure to background concentrations of DDT and cognitive functioning among preschoolers. Am J Epidemiol 164:955–962PubMedCrossRefGoogle Scholar
  61. 61.
    Brouwer A, Ahlborg UG, van Leeuwen FX, van Feeley MM (1998) Report of the WHO working group on the assessment of health risks for human infants from exposure to PCDDs, PCDFs and PCBs. Chemosphere 37:1627–1643PubMedCrossRefGoogle Scholar
  62. 62.
    Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M, Fiedler H, Hakansson H, Hanberg A, Haws L, Rose M, Safe S, Schrenk D, Tohyama C, Tritscher A, Tuomisto J, Tysklind M, Walker N, Peterson RE (2006) The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci 93:223–241PubMedCrossRefGoogle Scholar
  63. 63.
    Martí-Cid R, Llobet JM, Castell V, Domingo JL (2008) Human exposure to polychlorinated naphthalenes and polychlorinated diphenyl ethers from foods in Catalonia, Spain: temporal trend. Environ Sci Technol 42:4195–4201PubMedCrossRefGoogle Scholar
  64. 64.
    Kimbrough RD, Krouskas CA (2001) Polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans and birth weight and immune and thyroid function in children. Regul Toxicol Pharmacol 34:42–52PubMedCrossRefGoogle Scholar
  65. 65.
    Weisglas-Kuperus N, Vreugdenhil HJ, Mulder PG (2004) Immunological effects of environmental exposure to polychlorinated biphenyls and dioxins in Dutch school children. Toxicol Lett 149:281–285PubMedCrossRefGoogle Scholar
  66. 66.
    Heilmann C, Grandjean P, Weihe P, Nielsen F, Budtz-Jorgensen E (2006) Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls. PLoS Med 3:e311PubMedCrossRefGoogle Scholar
  67. 67.
    Longnecker MP, Wolff MS, Gladen BC, Brock JW, Grandjean P, Jacobson JL, Korrick SA, Rogan WJ, Weisglas-Kuperus N, Hertz-Picciotto I, Ayotte P, Stewart P, Winneke G, Charles MJ, Jacobson SW, Dewailly E, Boersma ER, Altshul LM, Heinzow B, Pagano JJ, Jensen AA (2003) Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. Environ Health Perspect 111:65–70PubMedCrossRefGoogle Scholar
  68. 68.
    Wilhelm M, Wittsiepe J, Lemm F, Ranft U, Krämer U, Fürst P, Röseler SC, Greshake M, Imöhl M, Eberwein G, Rauchfuss K, Kraft M, Winneke G (2008) The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24 months. Mutat Res 659:83–92PubMedCrossRefGoogle Scholar
  69. 69.
    Wilhelm M, Ranft U, Krämer U, Wittsiepe J, Lemm F, Fürst P, Eberwein G, Winneke G (2008) Lack of neurodevelopmental adversity by prenatal exposure of infants to current lowered PCB levels: comparison of two German birth cohort studies. J Toxicol Environ Health A 71:700–702PubMedCrossRefGoogle Scholar
  70. 70.
    Daxenberger A, Ibarreta D, Meyer HH (2001) Possible health impact of animal oestrogens in food. Hum Reprod Update 7:340–355PubMedCrossRefGoogle Scholar
  71. 71.
    Hageleit M, Daxenberger A, Kraetzl WD, Kettler A, Meyer HH (2000) Dose-dependent effects of melengestrol acetate (MGA) on plasma levels of estradiol, progesterone and luteinizing hormone in cycling heifers and influences on oestrogen residues in edible tissues. APMIS 108:847–854PubMedCrossRefGoogle Scholar
  72. 72.
    Lange IG, Daxenberger A, Meyer HH (2001) Hormone contents in peripheral tissues after correct and off-label use of growth promoting hormones in cattle: effect of the implant preparations Filaplix-H, Raglo, Synovex-H and Synovex Plus. APMIS 109:53–65PubMedCrossRefGoogle Scholar
  73. 73.
    Maume D, Deceuninck Y, Pouponneau K, Paris A, Le Bizec B, André F (2001) Assessment of estradiol and its metabolites in meat. APMIS 109:32–38PubMedCrossRefGoogle Scholar
  74. 74.
    Paris A, Goutal I, Richard J, Bécret A, Guéraud F (2001) Uterotrophic effect of a saturated fatty acid 17-ester of estradiol-17b administered orally to juvenile rats. APMIS 109:365–375PubMedCrossRefGoogle Scholar
  75. 75.
    van den Bogaard AE, Stobberingh EE (2000) Epidemiology of resistance to antibiotics. Links between animals and humans. Int J Antimicrob Agents 14:327–335PubMedCrossRefGoogle Scholar
  76. 76.
    Lu C, Fenske RA, Simcox NJ, Kalman D (2000) Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environ Res 84:290–302PubMedCrossRefGoogle Scholar
  77. 77.
    Boon PE, Van der Voet H, Van Raaij MT, Van Klaveren JD (2008) Cumulative risk assessment of the exposure to organophosphorus and carbamate insecticides in the Dutch diet. Food Chem Toxicol 46:3090–3098PubMedCrossRefGoogle Scholar
  78. 78.
    Young JG, Eskenazi B, Gladstone EA, Bradman A, Pedersen L, Johnson C, Barr DB, Furlong CE, Holland NT (2005) Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates. Neurotoxicology 26:199–209PubMedCrossRefGoogle Scholar
  79. 79.
    Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS (2007) Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. Am J Epidemiol 165:1397–1404PubMedCrossRefGoogle Scholar
  80. 80.
    Rauh VA, Garfinkel R, Perera FP, Andrews HF, Hoepner L, Barr DB, Whitehead R, Tang D, Whyatt RW (2006) Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics 118:e1845–e1859PubMedCrossRefGoogle Scholar
  81. 81.
    Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, Morga N, Jewell NP (2007) Organophosphate pesticide exposure and neurodevelopment in young Mexican–American children. Environ Health Perspect 115:792–798PubMedCrossRefGoogle Scholar
  82. 82.
    Perera FP, Rauh V, Tsai WY, Kinney P, Camann D, Barr D, Bernert T, Garfinkel R, Tu YH, Diaz D, Dietrich J, Whyatt RM (2003) Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population. Environ Health Perspect 111:201–205PubMedCrossRefGoogle Scholar
  83. 83.
    Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, Hoepner LA, Diaz D, Dietrich J, Reyes A, Tang D, Kinney PL, Perera FP (2004) Prenatal insecticide exposures and birth weight and length among an urban minority cohort. Environ Health Perspect 112:1125–1132PubMedCrossRefGoogle Scholar
  84. 84.
    Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, Holland NT (2004) Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environ Health Perspect 112:1116–1124PubMedCrossRefGoogle Scholar
  85. 85.
    Friedman M (2003) Chemistry, biochemistry, and safety of acrylamide. A review. J Agric Food Chem 51:4504–4526PubMedCrossRefGoogle Scholar
  86. 86.
    Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M (2002) Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 50:4998–5006PubMedCrossRefGoogle Scholar
  87. 87.
    Dybing E, Farmer PB, Andersen M, Fennell TR, Lalljie SP, Müller DJ, Olin S, Petersen BJ, Schlatter J, Scholz G, Scimeca JA, Slimani N, Törnqvist M, Tuijtelaars S, Verger P (2005) Human exposure and internal dose assessments of acrylamide in food. Food Chem Toxicol 43:365–410PubMedCrossRefGoogle Scholar
  88. 88.
    Mills C, Tlustos C, Evans R, Matthews W (2008) Dietary acrylamide exposure estimates for the United Kingdom and Ireland: comparison between semiprobabilistic and probabilistic exposure models. J Agric Food Chem 56:6039–6045PubMedCrossRefGoogle Scholar
  89. 89.
    Kopp EK, Dekant W (2009) Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses. Toxicol Appl Pharmacol 235:135–142PubMedCrossRefGoogle Scholar
  90. 90.
    Hartmann EC, Boettcher MI, Schettgen T, Fromme H, Drexler H, Angerer J (2008) Hemoglobin adducts and mercapturic acid excretion of acrylamide and glycidamide in one study population. J Agric Food Chem 56:6061–6068PubMedCrossRefGoogle Scholar
  91. 91.
    Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA (2007) A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer. Cancer Epidemiol Biomarkers Prev 16:2304–2313PubMedCrossRefGoogle Scholar
  92. 92.
    Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA (2008) Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer. Am J Clin Nutr 87:1428–1438PubMedGoogle Scholar
  93. 93.
    Olesen PT, Olsen A, Frandsen H, Frederiksen K, Overvad K, Tjønneland A (2008) Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study. Int J Cancer 122:2094–2100PubMedCrossRefGoogle Scholar
  94. 94.
    Doerge DR, Young JF, Chen JJ, Dinovi MJ, Henry SH (2008) Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity. J Agric Food Chem 56:6031–6038PubMedCrossRefGoogle Scholar
  95. 95.
    Wilson NK, Chuang JC, Lyu C (2001) Levels of persistent organic pollutants in several child day care centers. J Expo Anal Environ Epidemiol 11:449–458PubMedCrossRefGoogle Scholar
  96. 96.
    Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, Jacek R, Whyatt RM (2003) Prenatal exposures to phthalates among women in New York City and Krakow, Poland. Environ Health Perspect 111:1719–1722PubMedCrossRefGoogle Scholar
  97. 97.
    Koch HM, Becker K, Wittassek M, Seiwert M, Angerer J, Kolossa-Gehring M (2007) Di-n-butyl phthalate and butyl benzyl phthalate—urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children. J Expo Sci Environ Epidemiol 17:378–387PubMedCrossRefGoogle Scholar
  98. 98.
    Duty SM, Singh NP, Silva MJ, Barr DB, Brock JW, Ryan L, Herrick RF, Christiani DC, Hauser R (2003) The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environ Health Perspect 111:1164–1169PubMedCrossRefGoogle Scholar
  99. 99.
    Duty SM, Silva MJ, Barr DB, Brock JW, Ryan L, Chen Z, Herrick RF, Christiani DC, Hauser R (2003) Phthalate exposure and human semen parameters. Epidemiology 14:269–277PubMedCrossRefGoogle Scholar
  100. 100.
    Wirth JJ, Rossano MG, Potter R, Puscheck E, Daly DC, Paneth N, Krawetz SA, Protas BM, Diamond MP (2008) A pilot study associating urinary concentrations of phthalate metabolites and semen quality. Syst Biol Reprod Med 54:143–154PubMedCrossRefGoogle Scholar
  101. 101.
    Duty SM, Calafat AM, Silva MJ, Ryan L, Hauser R (2005) Phthalate exposure and reproductive hormones in adult men. Hum Reprod 20:604–610PubMedCrossRefGoogle Scholar
  102. 102.
    Meeker JD, Calafat AM, Hauser R (2008) Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl 30:287–297PubMedCrossRefGoogle Scholar
  103. 103.
    Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL, the Study for Future Families Research Team (2005) Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 113:1056–1061PubMedCrossRefGoogle Scholar
  104. 104.
    Huang PC, Kuo PL, Chou YY, Lin SJ, CC Lee (2009) Association between prenatal exposure to phthalates and the health of newborns. Environ Int 35:14–20PubMedCrossRefGoogle Scholar
  105. 105.
    Engel SM, Zhu C, Berkowitz GS, Calafat AM, Silva MJ, Miodovnik A, Wolff MS (2009) Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort. Neurotoxicology 30:522–528PubMedCrossRefGoogle Scholar
  106. 106.
    Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, Schmidt IM, Suomi AM, Virtanen HE, Petersen DV, Andersson AM, Toppari J, Skakkebaek NE (2006) Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect 114:270–276PubMedCrossRefGoogle Scholar
  107. 107.
    Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV (2007) Human exposure to bisphenol A (BPA). Reprod Toxicol 24:139–177PubMedCrossRefGoogle Scholar
  108. 108.
    Lakind JS, Naiman DQ (2008) Bisphenol A (BPA) daily intakes in the United States: estimates from the 2003–2004 NHANES urinary BPA data. J Expo Sci Environ Epidemiol 18:608–615PubMedCrossRefGoogle Scholar
  109. 109.
    National Toxicology Program (NTP) (2008) NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A. NTP CERHR MON 22:i–iiiGoogle Scholar
  110. 110.
    Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vandenbergh JG, Walser-Kuntz DR, vom Saal FS (2007) In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 24:199–224PubMedCrossRefGoogle Scholar
  111. 111.
    Nestmann ER, Lynch BS, Musa-Veloso K, Goodfellow GH, Cheng E, Haighton LA, Lee-Brotherton VM (2005) Safety assessment and risk–benefit analysis of the use of azodicarbonamide in baby food jar closure technology: putting trace levels of semicarbazide exposure into perspective—a review. Food Addit Contam 22:875–891PubMedCrossRefGoogle Scholar
  112. 112.
    Sicherer SH, Sampson HA (2006) Food allergy. J Allergy Clin Immunol 117:S470–S475PubMedCrossRefGoogle Scholar
  113. 113.
    Etesamifar M, Wuthrich B (1998) IgE-vermittelte Nahrungsmittelallergien bei 383 Patienten unter Berucksichtigung des oralen Allergie-Syndroms. Allergologie 21:451–457Google Scholar
  114. 114.
    Dalal I, Binson I, Reifen R, Amitai Z, Shohat T, Rahmani S, Levine A, Ballin A, Somekh E (2002) Food allergy is a matter of geography after all: sesame as a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. Allergy 57:362–365PubMedCrossRefGoogle Scholar
  115. 115.
    Shek LP, Lee BW (1999) Food allergy in children—the Singapore story. Asian Pac J Allergy Immunol 17:203–206PubMedGoogle Scholar
  116. 116.
    Takahashi Y, Ichikawa S, Aihara Y, Yokota S (1998) Buckwheat allergy in 90,000 school children in Yokohama. Arerugi 47:26–33PubMedGoogle Scholar
  117. 117.
    Commission CA (1999) Report of the twenty-third session of the Codex Alimentarius Commission. Rome, 99/37Google Scholar
  118. 118.
    USPL (2004) 108-282 USPL. Food allergen labeling and consumer protection act of 2004Google Scholar
  119. 119.
    Authority ANZF (2001) Standard 1.2.3. Mandatory warning and advisory statements and declarationsGoogle Scholar
  120. 120.
    Canada H (2008) Proposed amendments to the food and drug regulations. Accessed 25 Feb
  121. 121.
    Commission E (2003) Directive 2003/89/EC of the European Parliament and of the Council amending Directive 2000/13/EC as regards indication of the ingredients present in foodstuffs. p 15Google Scholar
  122. 122.
    Ministry of Health Law (2001) Food sanitation law. The food labeling amendment. Japan,
  123. 123.
    Commission E (2005) Directive 2005/26/ECGoogle Scholar
  124. 124.
    Hansen TK, Poulsen LK, Stahl Skov P, Hefle SL, Hlywka JJ, Taylor SL, Bindslev-Jensen U, Bindslev-Jensen C (2004) A randomized, double-blinded, placebo-controlled oral challenge study to evaluate the allergenicity of commercial, food-grade fish gelatin. Food Chem Toxicol 42:2037–2044PubMedCrossRefGoogle Scholar
  125. 125.
    Rolland JM, Apostolou E, de Leon MP, Stockley CS, O'Hehir RE (2008) Specific and sensitive enzyme-linked immunosorbent assays for analysis of residual allergenic food proteins in commercial bottled wine fined with egg white, milk, and nongrape-derived tannins. J Agric Food Chem 56:349–354PubMedCrossRefGoogle Scholar
  126. 126.
    Weber P, Steinhart H, Paschke A (2007) Investigation of the allergenic potential of wines fined with various proteinogenic fining agents by ELISA. J Agric Food Chem 55:3127–3133PubMedCrossRefGoogle Scholar
  127. 127.
    Clark S, Bock SA, Gaeta TJ, Brenner BE, Cydulka RK, Camargo CA (2004) Multicenter study of emergency department visits for food allergies. J Allergy Clin Immunol 113:347–352PubMedCrossRefGoogle Scholar
  128. 128.
    Menendez-Arias L, Moneo I, Dominguez J, Rodriguez R (1988) Primary structure of the major allergen of yellow mustard (Sinapis alba L.) seed, Sin a I. Eur J Biochem 177:159–166PubMedCrossRefGoogle Scholar
  129. 129.
    Collin P, Thorell L, Kaukinen K, Maki M (2004) The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease? Aliment Pharmacol Ther 19:1277–1283PubMedCrossRefGoogle Scholar
  130. 130.
    EUCREN (2009) Concerning the composition and labelling of foodstuffs suitable for people intolerant to gluten, January, 41/2009 EUCRENGoogle Scholar
  131. 131.
    Conner AJ, Jacobs JM (1999) Genetic engineering of crops as potential source of genetic hazard in the human diet. Mutat Res 443:223–234PubMedGoogle Scholar
  132. 132.
    Cellini F, Chesson A, Colquhoun I, Constable A, Davies HV, Engel KH, Gatehouse AM, Kärenlampi S, Kok EJ, Leguay JJ, Lehesranta S, Noteborn HP, Pedersen J, Smith M (2004) Unintended effects and their detection in genetically modified crops. Food Chem Toxicol 42:1089–1125PubMedCrossRefGoogle Scholar
  133. 133.
    EFSA GMO Panel Working Group on Animal Feeding Trials (2008) Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials. Food Chem Toxicol 46(Suppl 1):S2–S70Google Scholar
  134. 134.
    Gallo M, Sayre R (2009) Removing allergens and reducing toxins from food crops. Curr Opin Biotechnol 20:191–196PubMedCrossRefGoogle Scholar
  135. 135.
    Busse PJ, Nowak-Wegrzyn AH, Noone SA, Sampson HA, Sicherer SH (2002) Recurrent peanut allergy. N Engl J Med 347:1535–1536PubMedCrossRefGoogle Scholar
  136. 136.
    Bock SA, Munoz-Furlong A, Sampson HA (2001) Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 107:191–193PubMedCrossRefGoogle Scholar
  137. 137.
    Bock SA, Munoz-Furlong A, Sampson HA (2007) Further fatalities caused by anaphylactic reactions to food, 2001–2006. J Allergy Clin Immunol 119:1016–1018PubMedCrossRefGoogle Scholar
  138. 138.
    Radauer C, Bublin M, Wagner S, Mari A, Breiteneder H (2008) Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J Allergy Clin Immunol 121:847–852 e7PubMedCrossRefGoogle Scholar
  139. 139.
    Ivanciuc O, Garcia T, Torres M, Schein CH, Braun W (2009) Characteristic motifs for families of allergenic proteins. Mol Immunol 46:559–568PubMedCrossRefGoogle Scholar
  140. 140.
    Ivanciuc O, Midoro-Horiuti T, Schein CH, Xie L, Hillman GR, Goldblum RM, Braun W (2009) The property distance index PD predicts peptides that cross-react with IgE antibodies. Mol Immunol 46:873–883PubMedCrossRefGoogle Scholar
  141. 141.
    Selgrade MK, Bowman CC, Ladics GS, Privalle L, Laessig SA (2009) Safety assessment of biotechnology products for potential risk of food allergy: implications of new research. Toxicol Sci 110:31–39PubMedCrossRefGoogle Scholar
  142. 142.
    Ivanciuc O, Schein CH, Garcia T, Oezguen N, Negi SS, Braun W (2009) Structural analysis of linear and conformational epitopes of allergens. Regul Toxicol Pharmacol 54:S11–S19PubMedCrossRefGoogle Scholar
  143. 143.
    Strid J, Hourihane J, Kimber I, Callard R, Strobel S (2005) Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy 35:757–766PubMedCrossRefGoogle Scholar
  144. 144.
    Fox AT, Sasieni P, du Toit G, Syed H, Lack G (2009) Household peanut consumption as a risk factor for the development of peanut allergy. J Allergy Clin Immunol 123:417–423PubMedCrossRefGoogle Scholar
  145. 145.
    Batista R, Saibo N, Lourenco T, Oliveira MM (2008) Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion. Proc Natl Acad Sci U S A 105:3640–3645PubMedCrossRefGoogle Scholar
  146. 146.
    Kleter GA, Peijnenburg AA (2003) Presence of potential allergy-related linear epitopes in novel proteins from conventional crops and the implication for the safety assessment of these crops with respect to the current testing of genetically modified crops. Plant Biotechnol J 1:371–380PubMedCrossRefGoogle Scholar
  147. 147.
    Nordlee JA, Taylor SL, Townsend JA, Thomas LA, Bush RK (1996) Identification of a Brazil-nut allergen in transgenic soybeans. N Engl J Med 334:688–692PubMedCrossRefGoogle Scholar
  148. 148.
    Yum HY, Lee SY, Lee KE, Sohn MH, Kim KE (2005) Genetically modified and wild soybeans: an immunologic comparison. Allergy Asthma Proc 26:210–216PubMedGoogle Scholar
  149. 149.
    Kim SH, Kim HM, Ye YM, Kim SH, Nahm DH, Park HS, Ryu SR, Lee BO (2006) Evaluating the allergic risk of genetically modified soybean. Yonsei Med J 47:505–512PubMedCrossRefGoogle Scholar
  150. 150.
    Bucchini L, Goldman LR (2002) Starlink corn: a risk analysis. Environ Health Perpect 110:5–13CrossRefGoogle Scholar
  151. 151.
    U.S. EPA (2000) Assessment of Scientific Information Concerning StarLink Corn Cry9C Bt Corn Plant-Pesticide. Docket PF-867B. Arlington, VA: U.S. Environmental Protection Agency, 2000. Fed Reg 65:65245–65251Google Scholar
  152. 152.
    Sutton SA, Assa’ad AH, Steinmetz C, Rothenberg M (2003) A negative, double-blind, placebo-controlled challenge to genetically modified corn. J Allergy Clin Immunol 112:1011–1012PubMedCrossRefGoogle Scholar
  153. 153.
    Bernstein JA, Bernstein IL, Bucchini L, Goldman LR, Hamilton RG, Lehrer S, Rubin C, Sampson HA (2003) Clinical and laboratory investigation of allergy to genetically modified foods. Environ Health Perspect 111:1114–1121PubMedGoogle Scholar
  154. 154.
    Prescott VE, Campbell PM, Moore A, Mattes J, Rothenberg ME, Foster PS, Higgins TJ, Hogan SP (2005) Transgenic expression of bean a-amylase inhibitor in peas results in altered structure and immunogenicity. J Agric Food Chem 53:9023–9030PubMedCrossRefGoogle Scholar
  155. 155.
    Dearman RJ, Betts CJ, Caddick HT, Kimber I (2009) Cytokine profiling of chemical allergens in mice: impact of mitogen on selectivity of response. J Appl Toxicol 29:233–241PubMedCrossRefGoogle Scholar
  156. 156.
    Séralini GE, Cellier D, de Vendomois JS (2007) New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity. Arch Environ Contam Toxicol 52:596–602PubMedCrossRefGoogle Scholar
  157. 157.
    Millstone E, Brunner E, Mayer S (1999) Beyond ‘substantial equivalence’. Nature 401:525–526PubMedCrossRefGoogle Scholar
  158. 158.
    Shaw J, Roberts G, Grimshaw K, White S, Hourihane J (2008) Lupin allergy in peanut-allergic children and teenagers. Allergy 63:370–373PubMedCrossRefGoogle Scholar
  159. 159.
    Nel A, Xia T, Mädler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627PubMedCrossRefGoogle Scholar
  160. 160.
    Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, Choi BS, Lim R, Chang HK, Chung YH, Kwon IH, Jeong J, Han BS, Yu IJ (2008) Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol 20:575–583PubMedCrossRefGoogle Scholar
  161. 161.
    Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H, ILSI Research Foundation/Risk Science Institute Nanomaterial Toxicity Screening Working Group (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8. doi: 10.1186/743-8977-2-8 PubMedCrossRefGoogle Scholar
  162. 162.
    Oberdörster G, Oberdörster E, Oberdörster J (2007) Concepts of nanoparticle dose metric and response metric. Environ Health Perspect 115:A290PubMedCrossRefGoogle Scholar
  163. 163.
    Yoshida S, Gershwin ME (1993) Autoimmunity and selected environmental factors of disease induction. Semin Arthritis Rheum 22:399–419PubMedCrossRefGoogle Scholar
  164. 164.
    Neuhausen SL, Steele L, Ryan S, Mousavi M, Pinto M, Osann KE, Flodman P, Zone JJ (2008) Co-occurrence of celiac disease and other autoimmune diseases in celiacs and their first-degree relatives. J Autoimmun 31:160–165PubMedCrossRefGoogle Scholar
  165. 165.
    Shimada A, Kanazawa Y, Motohashi Y, Yamada S, Maruyama T, Ikegami H, Awata T, Kawasaki E, Kobayashi T, Nakanishi K, Kawabata Y, Kurihara S, Uga M, Tanaka S (2008) Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese. J Autoimmun 30:207–211PubMedCrossRefGoogle Scholar
  166. 166.
    Braun N, Wade NS, Wakeland EK, Major AS (2008) Accelerated atherosclerosis is independent of feeding high fat diet in systemic lupus erythematosus-susceptible LDLr(−/−) mice. Lupus 17:1070–1078PubMedCrossRefGoogle Scholar
  167. 167.
    Ezendam J, de Klerk A, Gremmer ER, van Loveren H (2008) Effects of Bifidobacterium animalis administered during lactation on allergic and autoimmune responses in rodents. Clin Exp Immunol 154:424–431PubMedCrossRefGoogle Scholar
  168. 168.
    Meresse B, Ripoche J, Heyman M, Cerf-Bensussan N (2009) Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis. Mucosal Immunol 2:8–23PubMedCrossRefGoogle Scholar
  169. 169.
    Anderson RP (2008) Coeliac disease: current approach and future prospects. Intern Med J 38:790–799PubMedCrossRefGoogle Scholar
  170. 170.
    Moro JR, Iwata M, von Andriano UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8:685–698PubMedCrossRefGoogle Scholar
  171. 171.
    Toth B, Garabuczi E, Sarang Z, Vereb G, Vamosi G, Aeschlimann D, Blasko B, Becsi B, Erdodi F, Lacy-Hulbert A, Zhang A, Falasca L, Birge RB, Balajthy Z, Melino G, Fesus L, Szondy Z (2009) Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells. J Immunol 182:2084–2092PubMedCrossRefGoogle Scholar
  172. 172.
    Van Limbergen J, Stevens C, Nimmo ER, Wilson DC, Satsangi J (2009) Autophagy: from basic science to clinical application. Mucosal Immunol 2:315–330PubMedCrossRefGoogle Scholar
  173. 173.
    Vojdani A (2009) Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Nutr Metab (Lond) 6:22CrossRefGoogle Scholar
  174. 174.
    Christen U, Hintermann E, Holdener M, von Herrath MG (2009) Viral triggers for autoimmunity: Is the 'glass of molecular mimicry' half full or half empty? J Autoimmun (in press)Google Scholar
  175. 175.
    Elagin RB, Balijepalli S, Diacovo MJ, Baekkeskov S, Jaume JC (2009) Homing of GAD65 specific autoimmunity and development of insulitis requires expression of both DQ8 and human GAD65 in transgenic mice. J Autoimmun 33:50–57PubMedCrossRefGoogle Scholar
  176. 176.
    Hsing LC, Kirk EA, McMillen TS, Hsiao SH, Caldwell M, Houston B, Rudensky AY, Leboeuf RC (2009) Roles for cathepsins S, L, and B in insulitis and diabetes in the NOD mouse. J Autoimmun (in press)Google Scholar
  177. 177.
    Kanazawa Y, Shimada A, Oikawa Y, Okubo Y, Tada A, Imai T, Miyazaki J, Itoh H (2009) Induction of anti-whole GAD65 reactivity in vivo results in disease suppression in type 1 diabetes. J Autoimmun 32:104–109PubMedCrossRefGoogle Scholar
  178. 178.
    Lempainen J, Vaarala O, Makela M, Veijola R, Simell O, Knip M, Hermann R, Ilonen J (2009) Interplay between PTPN22 C1858T polymorphism and cow's milk formula exposure in type 1 diabetes. J Autoimmun 33:155–164PubMedCrossRefGoogle Scholar
  179. 179.
    Marino E, Grey ST (2008) A new role for an old player: do B cells unleash the self-reactive CD8+ T cell storm necessary for the development of type 1 diabetes? J Autoimmun 31:301–305PubMedCrossRefGoogle Scholar
  180. 180.
    Marttila J, Huttunen S, Vaarala O, Suzuki K, Elliott JF, Narvanen A, Knip M, Simell O, Ilonen J (2008) T-cell reactivity to insulin peptide A1–12 in children with recently diagnosed type 1 diabetes or multiple beta-cell autoantibodies. J Autoimmun 31:142–148PubMedCrossRefGoogle Scholar
  181. 181.
    Subleski JJ, Wiltrout RH, Weiss JM (2009) Application of tissue-specific NK and NKT cell activity for tumor immunotherapy. J Autoimmun 33:275–281PubMedCrossRefGoogle Scholar
  182. 182.
    Xiao X, Ma B, Dong B, Zhao P, Tai N, Chen L, Wong FS, Wen L (2009) Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. J Autoimmun 32:85–93PubMedCrossRefGoogle Scholar
  183. 183.
    Yang J, Danke N, Roti M, Huston L, Greenbaum C, Pihoker C, James E, Kwok WW (2008) CD4+ T cells from type 1 diabetic and healthy subjects exhibit different thresholds of activation to a naturally processed proinsulin epitope. J Autoimmun 31:30–41PubMedCrossRefGoogle Scholar
  184. 184.
    Curotto de Lafaille MA, Lafaille JJ (2009) Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30:626–635PubMedCrossRefGoogle Scholar
  185. 185.
    Silano M, Vincentini O, De Vincenzi M (2009) Toxic, immunostimulatory and antagonist gluten peptides in celiac disease. Curr Med Chem 16:1489–1498PubMedCrossRefGoogle Scholar
  186. 186.
    Song F, Wardrop RM, Gienapp IE, Stuckman SS, Meyer AL, Shawler T, Whitacre CC (2008) The Peyer's patch is a critical immunoregulatory site for mucosal tolerance in experimental autoimmune encephalomyelitis (EAE). J Autoimmun 30:230–237PubMedCrossRefGoogle Scholar
  187. 187.
    Nakanishi Y, Tsuneyama K, Fujimoto M, Salunga TL, Nomoto K, An JL, Takano Y, Iizuka S, Nagata M, Suzuki W, Shimada T, Aburada M, Nakano M, Selmi C, Gershwin ME (2008) Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J Autoimmun 30:42–50PubMedCrossRefGoogle Scholar
  188. 188.
    D'Aldebert E, Biyeyeme Bi Mve MJ, Mergey M, Wendum D, Firrincieli D, Coilly A, Fouassier L, Corpechot C, Poupon R, Housset C, Chignard N (2009) Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology 136:1435–1443PubMedCrossRefGoogle Scholar
  189. 189.
    Mackay IR, Leskovsek NV, Rose NR (2008) Cell damage and autoimmunity: a critical appraisal. J Autoimmun 30:5–11PubMedCrossRefGoogle Scholar
  190. 190.
    Meroni PL (2008) Pathogenesis of the antiphospholipid syndrome: an additional example of the mosaic of autoimmunity. J Autoimmun 30:99–103PubMedCrossRefGoogle Scholar
  191. 191.
    Pai S, Thomas R (2008) Immune deficiency or hyperactivity-Nf-kappa b illuminates autoimmunity. J Autoimmun 31:245–251PubMedCrossRefGoogle Scholar
  192. 192.
    Pauley KM, Cha S, Chan EK (2009) MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 32:189–194PubMedCrossRefGoogle Scholar
  193. 193.
    Podolsky DK, Gerken G, Eyking A, Cario E (2009) Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency. Gastroenterology 137:209–220PubMedCrossRefGoogle Scholar
  194. 194.
    Poletaev AB, Stepanyuk VL, Gershwin ME (2008) Integrating immunity: the immunculus and self-reactivity. J Autoimmun 30:68–73PubMedCrossRefGoogle Scholar
  195. 195.
    Vijay-Kumar M, Gewirtz AT (2008) Guardians of the gut: newly appreciated role of epithelial toll-like receptors in protecting the intestine. Gastroenterology 135:351–354PubMedCrossRefGoogle Scholar
  196. 196.
    Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, Sampson EJ, Lucier GW, Jackson RJ, Brock JW (2000) Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect 108:979–982PubMedCrossRefGoogle Scholar
  197. 197.
    Wilkinson CF, Christoph GR, Julien E, Kelley JM, Kronenberg J, McCarthy J, Reiss R (2000) Assessing the risks of exposures to multiple chemicals with a common mechanism of toxicity: how to cumulate? Regul Toxicol Pharmacol 31:30–43PubMedCrossRefGoogle Scholar
  198. 198.
    Boon PE, van Klaveren JD (2003) Cumulative exposure to acetylcholinesterase inhibiting compounds in the Dutch population and young children. Toxic equivalency approach with acephate and phosmet as index compounds. Wageningen, The Netherlands, pp 1–31, Accessed 24 April 2009
  199. 199.
    Jensen AF, Petersen A, Granby K (2003) Cumulative risk assessment of the intake of organophosphorus and carbamate pesticides in the Danish diet. Food Addit Contam 20:776–785PubMedCrossRefGoogle Scholar
  200. 200.
    Moser VC, Simmons JE, Gennings C (2006) Neurotoxicological interactions of a five-pesticide mixture in preweanling rats. Toxicol Sci 92:235–245PubMedCrossRefGoogle Scholar
  201. 201.
    Moser VC, Casey M, Hamm A, Carter WH Jr, Simmons JE, Gennings C (2005) Neurotoxicological and statistical analyses of a mixture of five organophosphorus pesticides using a ray design. Toxicol Sci 86:101–115PubMedCrossRefGoogle Scholar
  202. 202.
    Laetz CA, Baldwin DH, Collier TK, Hebert V, Stark JD, Scholz NL (2009) The synergistic toxicity of pesticide mixtures: implications for risk assessment and the conservation of endangered Pacific salmon. Environ Health Perspect 117:348–353PubMedGoogle Scholar
  203. 203.
    Nellemann C, Dalgaard M, Lam HR, Vinggaard AM (2003) The combined effects of vinclozolin and procymidone do not deviate from expected additivity in vitro and in vivo. Toxicol Sci 71:251–262PubMedCrossRefGoogle Scholar
  204. 204.
    Christiansen S, Scholze M, Axelstad M, Boberg J, Kortenkamp A, Hass U (2008) Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat. Int J Androl 31:241–248PubMedCrossRefGoogle Scholar
  205. 205.
    Hass U, Scholze M, Christiansen S, Dalgaard M, Vinggaard AM, Axelstad M, Metzdorff SB, Kortenkamp A (2007) Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. Environ Health Perspect 115(Suppl 1):122–128PubMedCrossRefGoogle Scholar
  206. 206.
    Metzdorff SB, Dalgaard M, Christiansen S, Axelstad M, Hass U, Kiersgaard MK, Scholze M, Kortenkamp A, Vinggaard AM (2007) Dysgenesis and histological changes of genitals and perturbations of gene expression in male rats after in utero exposure to antiandrogen mixtures. Toxicol Sci 98:87–98PubMedCrossRefGoogle Scholar
  207. 207.
    Howdeshell KL, Furr J, Lambright CR, Rider CV, Gray WVS, LE J (2007) Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: altered fetal steroid hormones and genes. Toxicol Sci 99:190–202PubMedCrossRefGoogle Scholar
  208. 208.
    Howdeshell KL, Wilson VS, Furr J, Lambright CR, Rider CV, Blystone CR, Hotchkiss AK, Gray LE Jr (2008) A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague-Dawley rat in a cumulative, dose-additive manner. Toxicol Sci 105:153–165PubMedCrossRefGoogle Scholar
  209. 209.
    Hotchkiss AK, Parks-Saldutti LG, Ostby JS, Lambright C, Furr J, Gray VJG, LE J (2004) A mixture of the “antiandrogens” linuron and butyl benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biol Reprod 71:1852–1861PubMedCrossRefGoogle Scholar
  210. 210.
    Rider CV, Wilson VS, Howdeshell KL, Hotchkiss AK, Furr JR, Lambright CR, Gray LE Jr (2009) Cumulative effects of in utero administration of mixtures of “antiandrogens” on male rat reproductive development. Toxicol Pathol 37:100–113PubMedCrossRefGoogle Scholar
  211. 211.
    Crofton KM (2008) Thyroid disrupting chemicals: mechanisms and mixtures. Int J Androl 31:209–223PubMedCrossRefGoogle Scholar
  212. 212.
    David RM (2000) Exposure to phthalate esters. Environ Health Perspect 108:A440PubMedCrossRefGoogle Scholar
  213. 213.
    Koch HM, Drexler H, Angerer J (2003) An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population. Int J Hyg Environ Health 206:77–83PubMedCrossRefGoogle Scholar
  214. 214.
    Wittassek M, Wiesmüller GA, Koch HM, Eckard R, Dobler L, Müºller J, Angerer J, Schlüter C (2007) Internal phthalate exposure over the last two decades—a retrospective human biomonitoring study. Int J Hyg Environ Health 210:319–333PubMedCrossRefGoogle Scholar
  215. 215.
    Fromme H, Gruber L, Schlummer M, Wolz G, Böhmer S, Angerer J, Mayer R, Liebl B, Bolte G (2007) Intake of phthalates and di(2-ethylhexyl)adipate: results of the Integrated Exposure Assessment Survey based on duplicate diet samples and biomonitoring data. Environ Int 33:1012–1020PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Andrea Borchers
    • 1
  • Suzanne S. Teuber
    • 1
  • Carl L. Keen
    • 2
  • M. Eric Gershwin
    • 1
  1. 1.Division of Rheumatology, Allergy, and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisUSA
  2. 2.Department of NutritionUniversity of California at DavisDavisUSA

Personalised recommendations