Food Toxicology
                                                                                                                                                  Learning Objectives
                                                                                                                            • Discuss the general principles behind food processing 
                                                                                                                               and preparation.
                                         Toxicants Formed During                                                            • List the major natural processes modifying food.
                                                 Food Processing                                                            • List the major food processing approaches.
                                                                                                                            • Describe the physical chemistry background of 
                                                         Food Toxicology                                                       toxicant formation in food 
                                                                                                                               processing. 
                                               Instructor: Gregory Möller, Ph.D.                                            • Describe N-Nitrosamine 
                                                       University of Idaho                                                     formation from nitrites. 
                                                                                                                            • Explain the formation of 
                                                                                                                               polycyclic aromatic 
                                                                                                                           2 hydrocarbons in cooking.
                                                                                            Food Toxicology                                                                                  Food Toxicology
                                                Learning Objectives                                                                  Food Processing and Preparation
                          • Describe amino acid pyrolysates and their formation                                            • Conversion of raw vegetable, animal, or marine 
                             in cooking.                                                                                      products into food for consumption.
                          • Explain the formation of Maillard reaction products.                                           • Preservation of food is the most important reason.
                          • Describe Lysinoalanine cross-linkage from                                                           – Usually by reducing or eliminating microbial contamination.
                             alkali/heat treatment of proteins.                                                            • Can result in intermediate or final food products.
                          • Explore the background and                                                                     • Involves labor, energy, 
                             risk assessment of acrylamide                                                                    machinery, and knowledge.
                             formation in foods prepared at                                                                • Can be commercial or 
                             high temperatures.                                                                               consumer level. 
                          3                                                                                                4 Heldman& Hartel
                                                                                            Food Toxicology                                                                                  Food Toxicology
                              Food Processing and Preparation: Why                                                           Food Processing and Preparation: General 
                          • Preservation allows longer term availability of food.                                           •  Addition of thermal energy and elevated 
                              – Economic and food availability dimensions: shelf-life.                                         temperatures (e.g. cooking, sterilization).
                          • Major role in establishing and maintaining microbial                                            •  Removal of thermal energy and reduced 
                             food safety (e.g. pasteurization).                                                                temperatures (e.g. frozen foods).                              Encarta
                                                                                                                            •  Removal of water and reduced moisture content 
                          • Decreases toxicity of some foods (e.g. lectins beans).                                             (e.g. dried fruit).
                          • Conversion into new foods                                                                       •  Use of packaging (e.g. canning).
                             (e.g. cheese, beer).                                                                           •  Mixtures of ingredients 
                          • Supplementation, fortification                                                                     (e.g. water). 
                             of food (e.g. fortified milk).                                                                 •  Addition of modifiers and 
                                                                                                                               additives (e.g. salt, sugar, 
                          • Sensory, diversity, nutrition.                                                                     starch).  
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                                                            Food Toxicology                                                 Food Toxicology
                       Natural Processes Modifying Food                                  Food Processing Approaches
                  • Spoilage and “available”                                     • Thermal processing.
                    microorganisms (e.g. wine yeasts).                           • Blanching and pasteurization.
                  • Atmospheric O2 oxidation.                                    • Sterilization.
                  • Atmospheric CO2 pH buffering.                                • Refrigerated storage.
                  • Food enzyme release (e.g. cassava).                          • Freezing and frozen food storage.
                  • Post-harvest instability                                     • Liquid concentration.
                    (e.g. potato greening/sprouting).
                  • Environmental equilibria.                                    • Dehydration.
                    – Thermal (ambient temperature).                             • Physical processes.
                    – Moisture (ambient humidity).                                  – Mechanical separation.
                  • Contamination.                                                  –Extrusion.
                    – Water, insects, vessels, natural                           • Irradiation.
                 7    products (green potatoes, weeds).                          8
                                                            Food Toxicology                                                 Food Toxicology
                 Chemistry of Processing Toxicant Formation                       Food Processing Toxicants, Pro-Toxicants
                 • Chemical thermodynamics and kinetics apply.                   • Chemicals added or created during food processing 
                 • Non-spontaneous reactions can occur at higher                   can be anti-nutritive, toxicants, or pro-toxicants.
                   temperatures.                                                 • Anti-nutritive chemicals or processes will block, 
                 • Gibbs free energy change of a chemical reaction.                interfere, or destroy nutrient availability.
                       ΔG(J/mol) = ΔH(J/mol) - T(K) • ΔS(J/molK)                 • Toxic chemicals formed from food 
                    – Importance of enzymes                                        processing will be dose dependent
                     and catalysts.                                                and subject to biotransformation, 
                 • Kinetics of quality change                                      sequestration, and elimination. 
                   are related to temperature.                                   • Pro-toxicants added or created 
                    – Arrhenius equation.                                          during food processing can 
                                                                                   undergo toxication during 
                 9                                                               10digestion or biotransformation.
                                                            Food Toxicology                                                 Food Toxicology
                 Food Processing and Preparation Toxicants                          N-Nitrosamine Formation from Nitrites
                  • N-Nitrosamine formation from nitrites.                       • Nitrite used in curing meat and fish 
                  • Polycyclic aromatic hydrocarbons.                              products. 
                  • Amino acid pyrolysates.                                      • Has antimicrobial activity, sensory 
                  • Maillard reaction products.                                    attributes, and reacts with myoglobin
                                                                                   and hemoglobin to form red nitrosyl
                  • Food irradiation - unique radiolytic products (URPs)           compounds.
                    from ionizing radiation.                                     • Nitrite reacts with 2º, 3º amines to form 
                  • Lipid oxidation products.                                      stable nitrosoamines.
                  • Lysinoalanine cross-linkage from                             • High temperature processing 
                    alkali/heat treatment of proteins.                             and protein degradation to 
                                                                                   2º, 3º amines increase rate 
                  • Acrylamide formation in foods                                  of formation.
                    prepared at high temperatures.                               • Carcinogenic, mutagenic.
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                                                                                                        Food Toxicology                                                                                                Food Toxicology
                                                 Formation of Nitrosamine                                                                       Nitrosamine: Alkylating Agent Formation
                                             +                                 +                                                                    RCH                                                                          Shibamoto
                                 NO +H                 HONO                NO +HO                                                                          2                                                                     Bjeldanes
                                     2                                                 2                                                                  N N O Dialkylnitrosamine
                                                                               R NH                                                                R'   CH2
                                                                                 2                                                                              Enzymatic -hydroxylation
                                                                                                                                                                           α
                                                                      H+ +RNNO                                                                      RCH
                                                                                2                                                                          2
                                                                                                                                                         N N O -Hydroxynitrosamine
                                                                N-Nitrosamine formation                                                                             α
                                                                                                                                                   R'   CH
                                                            NO                  NO                                                                       OH      R'  CHO Aldehyde
                                     H      O HNO           N      O
                                     N               2                          N                                                                    RCH
                                                                                     +CO                                                                    2
                                                                                           2                                                              N N O Monoalkylnitrosamine
                                            OH                     OH                                                                                   H
                                     Proline                                Nitrosopyrrolidine                                                    H
                                                                                                                                              R C      N N               R H CNN OH
                                                                                                                                              Diazoalkane                     2
                                                                                                                                                                               Diazohydroxide
                                                                                                                                                              -     +        Alkyldiazonium
                                                               O     N                                                                                    RCHN N
                                          O     N                 N
                                             N
                                                                                                                                                      N     +          +
                                                                                                                                                       2      RCHAlkylcarboniumion
                             13        Dimethylnitrosamine   Diethylnitrosamine                                                             14                       2
                                                                                                        Food Toxicology                                                                                                Food Toxicology
                                 Polycyclic Aromatic Hydrocarbons (PAH)                                                                               Polycyclic Aromatic Hydrocarbons
                             • Formed in the high temperature pyrolysis of 
                                 carbohydrates in grilling and smoking of meats.
                             • Endogenous food sources and environmental 
                                 contamination are also important.
                                  – Products of combustion.                                                                                            Benzo[a]pyrene
                             • Carcinogenic, mutagenic.                                                                                                                              Benzo[b]fluoranthrene
                                                                                                                                                          Chrysene
                             15                                                                                                             16 Benzo[a]anthracene
                                                                                                        Food Toxicology                                                                                                Food Toxicology
                                             PAH Carcinogenic Activation                                                                      Protein Reaction: Processing and Storage
                                Bayregion 11                                                                       Marquardt                                                                                                        Hurrell
                                     10                                                                                                           Oxidizing Lipids          Reducing Sugars
                                9
                                 8                                                                                                                Treatments                      Polyphenols
                                     7                                  O
                                                                          7,8-Epoxide                                                                              Protein
                                     O
                                                                                                                                                  Organoleptic Nutritional             Possible
                                HO                      HO                                                                                        Changes         Changes               Toxicity
                                         OH                     OH
                                  7,8-Diol-epoxide             7,8-Diol
                                     (reactive)                                                                                                                                    Tryptophan
                                                                                                                                                  Lysine Methionine Cystine
                             17       DNA                                                                                                   18
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                                                                                                              Food Toxicology                                                                                                      Food Toxicology
                               Simplified Scheme of the Maillard Reactions                                                                          Maillard Reaction: Non-Enzymatic Browning
                                                                           Reducing Sugar + Amino Compound                                           Coffee
                                             CH      DEOXYKETOSYLCOMPOUND
                                                3                                                       STRECKER                                     Bread                        Desirable color, 
                                             CO                      HC                               DEGRADATION                                    Cocoa                       flavor and aroma 
                                                          methyl           O                               aminoacid+                                Cooked meats (pyrazines, aldehydes)
                                             COdicarbonyl             C O                                  dicarbonyl
                                                      intermediates          3-Deoxyhexosone                                                         Beer
                                             CHOH                     CH2       intermediates
                                                                      CHOH                              Strecker                                     Milk                          Nutritional losses
                                             Fission                                                    aldehyde +                                   Infant food              Undesirable color, flavor
                                                                 DEHYDRATION                            aminocompound+
                                                                                                        CO
                                      yields short chain                                                   2
                                    carbonyls, dicarbonyls
                                                                  yields 5-hydroxy
                                                               methyl-2-furaldehyde
                                                             MELANOIDINFORMATION
                                                        bythe polymerization of intermediate
                               19 Hurrell            compounds, production of N-heterocyclics                                                       20 Hurrell
                                                                                                              Food Toxicology                                                                                                      Food Toxicology
                                                      Amino Acid Pyrolysates                                                                                            Formation of β-Carbolines
                                • Heterocyclic aromatic amines (HCAs) formed during                                                                        Free                                                                                 Friedman 
                                                                                                                                                       Tryptophan                                                                  HO
                                    broiling of meat, fish, or other high protein-rich foods.                                                                            O                Carbonylamine                                 C O
                                • High temperature thermal degradation products of                                                                                            OH
                                    tryptophan (β-carbolines) and other amino acids                                                                                     NH       HEAT               H NH                               N
                                                                                                                                                                           2                   N       C                    N
                                    (imidazo-quinoline or imidazo-quinoxalin-2-amine                                                                          N                                H R                          H         C
                                                                                                                                                              H              H                          OH                        H    R
                                    derivatives - IQ compounds).                                                                                                       R C
                                • Also formed from the reaction                                                                                                            O                               HO
                                    of Maillard products (pyridines                                                                                                                                           C O
                                    or pyrazines, and aldehydes)                                                                                                                 -CO2
                                    with creatinine.                                                                                                                       N                                NH
                                                                                                                                                                N       C                        N       C
                                • Mutagenic (form DNA adducts).                                                                                                 H                                H          R
                                                                                                                                                                         R                             H
                                                                                                                                                             Β - Carboline                      Schiff-base
                               21 Erbersdobler                                                                                                      22
                                                                                                              Food Toxicology                                                                                                      Food Toxicology
                               Imidazo-Quinolines & Imidazo-Quinaxolines                                                                            Imidazo-Quinolines & Imidazo-Quinaxolines
                                   Hexose        Amino acid              Creatine                                          Friedman                                             NH
                                                                     NH                                             N                                                               2
                                                    NH3+                                                                                                                  N
                                   C H O    +                                     OH                         N
                                     6 12 6         CH    O-    H N     N                                                                                                       N
                                                R                2                         Y       Z               N                                                                            IQ
                                   Strecker            O                       O
                                 Degradation
                                                                                           X       N                                                             N
                                                                                                                  R                                       2-amino-3-methylimidazo
                                     Y       Z        O               N                                                                                        (4,5-f)quinoline
                                                        CR                     O
                                                    ++
                                                      H          HN      N
                                     X       N                           H                                                                                                        NH
                                                                                                                                                                                      2
                                     Z=CHPyridine Aldehyde              Creatinine                                                                                         N
                                     Z=NPyrazine                                                                                                                                             MeIQx
                                                        X      Y      Z     R                                                                                      N             N
                                     IQ                 H      H     CH     H
                                     MeIQ               H      H     CH Me                                                                                         N
                                     MeIQx              H     Me      N     H                                                                            2-amino-3,8-dimethylimidazo
                               23 7, 8 diMeIQx          Me    Me      N     H                                                                       24         (4,5-f)quinoxaline
                                     4, 8 diMeIQx       H     Me      N    Me
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