Food Additives Food additives Any substance the intended use of which results or may reasonably be expected to result directly or indirectly in its becoming a component or otherwise affecting the characteristics of any food including any substance intended for use in producing manufacturing packaging processing preparing treating transporting or holding food o Anything directly added to food very broad definition o Indirect additives are also important material from a microwavable pouch History o Most of the laws we follow enacted in 1958 FDA had to prove an additive was harmful before it was removed from the food in the past o 1958 law shifted the burden of proof of safety to the food industry or company now have to prove it is safe GRAS generally recognized as safe o Food additive list originally contained 675 substances and 80 were added later o If a manufacturer wants to add a substances that is not on the GRAS they are required to prove its safety to the FDA Laws for food additives vs dietary supplements o Food additives require premarket approval products with unapproved substances can be seized by the FDA o Dietary supplements do not require pre market approval harm must be demonstrated before products are seized Generally use either lab rats or dogs for testing Acute toxicity o Determine how a single dose of an additive is to rats o LD50 is median lethal dose o LD50 is measured in units of milligrams per kilogram body weight o Example LD50 median lethal does is the amount of compound that will kill half the animals within a week of being distributed o If a new compound has a low LD50 then its use will be rejected without further testing Short term toxicity o Main purpose is to find out what types of toxicity are observed at high levels of the compound of interest o Normally in two species o Duration 90 days o Measures Weight gain Food consumption Organ weights Complete blood profile Histopathological examination of organs Biochemical o Important to determine fate of compound in animals o Tests Absorption Distribution Storage Tissues accumulation Metabolism Enzyme profiles Teratogenicity o A teratogen is a compound that causes a miss read in DNA o Causes birth defects and an inheritable change o Often occurs in first few cell divisions after egg is fertilized o Studies require feeding of the compound prior to conception and then examination of the fetuses o At high enough levels vitamin a can be teratogenic but its is allowed at a higher level than it normally would because it is an essential nutrient Reproductive studies o Look for chemicals that have an effect on fertility o Three generations of animals o At least two litters per generation o Observe Fertility Live births Body weights Gross abnormalities Length of gestation Chronic feeding studies Still births Survival at least 4 days o Conducted in parallel with reproductive studies o Carried out in two species in at least two years o Control and test groups o Highest dose level would generally be the highest does that wouldn t reduce the life span of the animals o Tests are done to determine the no effect dose No effect level NOEL o Concentration that shows no harmful effects in the most sensitive o Human exposure cant exceed 1 100 the no effect dose acceptable species daily intake ADI o Doesn t apply to carcinogens their ADI is 0 Mutagenicity o Difficult to determine in intact animals o Exposure of human leukocytes in culture o Microbiological o Treated and untreated animals mated and fetuses examined Delaney Clause o Deals with carcinogens o Not permitted to add any substance to food if it induces cancer when ingested by man or animal or if it is found after test which are appropriate for the evaluation of the safety of food additives to induce cancer in man or animals Cancer testing o Usually done for a lifetime at the highest concentration that doesn t shorten the life span of the animal o Impossible to prove a negative o Mechanism must be considered Ames Test Bruce Ames o Presumptive screening test for carcinogens o All carcinogens are mutagens and some mutagens will cause cancer o Not all mutagens are carcinogens o Looks at the ability of a compound to cause mutations in bacteria made more sensitive to mutagens made sensitive by removing their DNA repair mechanism o I think that we got off on the wrong track We re concentrating almost exclusively on little bits of pollution and man made things and ignoring enormous amounts of natural mutagens and carcinogens Many vegetables including mushrooms celery and parsnips contain natural pesticides made by plants to protect against insects Those pesticides contain chemicals that are more significant carcinogens than man made chemicals Safety considerations o Issues with determining absolute safety Compounds aren t tested on human subjects Exploration of animals to humans The least toxic of compounds can have positive effects if at high enough levels Exploration of large to small doses Cost Safety of additive may be greater than the food itself o Final decision comes down to judgment Acceptable applications o Improve nutritional value o Enhance quality o Reduce waste o Improve storage quality o Enhance acceptability o Facilitate preparation o Make food more available Unacceptable applications o Disguise inferior products o Deceive consumer o Provide otherwise desirable results that lower nutritional value o Replace good manufacturing practices GMP o To use in amounts greater than are necessary Study Questions 1 How did the regulation of food additives change with the 1958 law 2 What is GRAS Why was it necessary Does it allow untested additives to enter the food supply 3 What does the Delaney clause refer to Why is the testing for cancer causing substances done at such high concentrations 4 What is the acceptable daily intake How is it determined How much of a safety factor does it contain 5 What is the difference in the regulation of foods and dietary supplements 6 What does safe mean Can absolute safety ever be proven 7 What are some acceptable uses of food additives Some unacceptable ones 8 What are the problems in determining the safety of food additives Acceptable Daily Intake ADI Antimicrobial agents Carcinogenicity Delaney Clause GRAS review Mutagen Salt Sucrose Acute Toxicity Antioxidants Chronic feeding studies Dextrose High fructose corn syrup Mutagenicity Biochemical tests Teratogenicity studies Ames Test Carcinogen Preservatives Generally Recognized As Safe