This looks like a newer version of what celiac disease actually is. Just from what I've seen since 2005, they're taking into account some important new findings ... tc ... x I copied this in because trying to read the pdf was driving me nuts ... I've edited this to make it easier to read but if in doubt, go to the pdf. http://www.fda.gov/downloads/Food/S.../RiskAssessmentSafetyAssessment/UCM264152.pdf Health Hazard Assessment for Gluten Exposure in Individuals with Celiac Disease: Determination of Tolerable Daily Intake Levels and Levels of Concern for Gluten Office of Food Safety Center of Food Safety and Applied Nutrition Food and Drug Administration May 2011 The following document is a health hazard assessment for gluten exposure in a sensitive subpopulation group, specifically individuals with celiac disease (CD). It consists of several components 1. The introductory hazard identification section examines and provides an overview of the nature and characteristics of the adverse effects associated with CD found in susceptible individuals and also that of gluten proteins involved in inducing these effects. The hazard assessment section first describes the nature of the evaluation performed on the available health effects data associated with CD. This evaluation includes both a dose-response assessment and a safety assessment derived from data from individuals in this sensitive subpopulation. The former assessment describes and characterizes the dose-effect data examined for morphological and clinical adverse effects that are reflective of CD, and the latter determines the tolerable daily intake (TDI) levels of exposure for each of these types of adverse effects in sensitive individuals. The hazard assessment section also includes an exposure assessment in which a number of estimates of gluten consumption from food products are determined and presented. The final risk characterization section addresses the uncertainty issues associated with the data available and the estimates derived, and identifies the TDI of primary focus for adverse morphological and clinical effects in this assessment. In addition, these TDIs, along with the exposure estimates, were employed to derive various levels of concern (LOC) for gluten in food for individuals with CD. Hazard Identification Health Effects Celiac Disease Exposure to certain grains or certain protein components of them can result in adverse health consequences, particularly the development of celiac disease (CD), in genetically predisposed individuals (Maki and Collin, 1997; AGA, 2001; Farrell and Kelly, 2002; Green and Jabri, 2003; Dickson et al., 2006). A significant part of the genetic predisposition to CD is associated with specific human leukocyte antigen (HLA) class II genes in the major histocompatibility complex (MHC) of chromosome 6 (Godkin and Jewell, 1998; Fasano and Catassi, 2001; Green and Jabri, 2003). For the most part, individuals with CD express either the HLA-DQ2 or the HLA-DQ8 haplotypes (Green and Jabri, 2003; Konig, 2005; Kagnoff, 2005). The majority (90 95%) of those who develop CD encode the HLA-DQ2 molecules, while the rest of those who suffer from CD typically express the HLA-DQ8 molecules (Dewar et al., 2004; Konig, 2005; Kagnoff, 2005). The presence and expression of these HLA-DQ alleles are recognized as necessary for the development of CD but not alone sufficient for the disease to occur (Green and Jabri, 2003; Dewar et al., 2004; Kagnoff, 2005). The contribution of other non-HLA genes, some not yet defined, also has emerged as pivotal in the genetic susceptibility associated with the development of CD (Godkin and Jewell, 1998; Fasano and Catassi, 2001; Green and Jabri, 2003; Dewar et al., 2004; Hunt, 2008). Finally, other factors may also have a determining influence on disease susceptibility (Murray, 1999; Green and Jabri, 2003). They include environmental factors (e.g., breast-feeding, infections), abnormalities in the immune system (e.g., selective IgA deficiency), and certain geneticbased syndromes (e.g., Down syndrome, Turners syndrome) (Murray, 1999; Fasano and Catassi, 2001; Green and Jabri, 2003; AGA, 2006). CD is a permanent hypersensitivity reaction triggered by ingestion of wheat, barley, or rye2, or the plant storage proteins of these grains (Farrell and Kelly, 2002; Green and Jabri, 2003; Dickson et al., 2006) that can occur at any age (Marsh, 1992; AGA, 2001; Fasano and Catassi, 2001). It results in an immune-mediated enteropathy which is associated with damage to the lining of the small intestine (AGA, 2001; Fasano and Catassi, 2001; Dickson et al., 2006). The mucosal lesion in the small intestine that is characteristic of CD typically involves abnormal morphology such as inflammatory cell infiltrate in the lamina propria, influx of lymphocytes in the epithelium, flattened or irregular epithelial cells, hyperplasia of crypts, stunted and disorganized microvilli and ultimately, a significant degree of villous atrophy (Marsh, 1992; AGA, 2001; Fasano and Catassi, 2001; Farrell and Kelly, 2002; Green and Jabri, 2003; Dickson et al., 2006). The most significant histological abnormalities are usually found in the proximal small intestine (e.g., duodenum) with the abnormalities less severe distally along the small intestine, but the disorder can progress distally (e.g., jejunum), and even involve the entire small intestine in some individuals (MacDonald et al., 1964; Dickson et al., 2006; Murray et al., 2008). A diverse array of clinical signs and symptoms are often associated with untreated CD (Fasano and Catassi, 2001). Many are tied, at least in part, to the enteropathy associated with CD. However, the manifestation of the clinical responses in CD, along with their severity, are not associated with the extent of this enteropathy in the small intestine or the degree of mucosal damage seen (Rostom et al., 2006; Brar et al., 2007; Murray et al., 2008; Murray and Rubio-Tapia, 2008). The extent and emergence of clinical responses seen is thought to be related to the length of the small intestine affected by enteropathic changes with more symptomatology present as mucosal histopathology progresses distally starting from the duodenum (Fasano and Catassi, 2001; Farrell and Kelly, 2002; Green and Jabri, 2003; Dickson et al., 2006). The so-called classic signs and symptoms of CD include chronic diarrhea or constipation, steatorrhea, recurrent abdominal distension or abdominal pain, nausea and/or vomiting (Maki and Collin, 1997; AGA, 2001; Fasano and Catassi, 2001; Green et al., 2001; Farrell and Kelly, 2002; Green and Jabri, 2003; Dickson et al., 2006). Often seen with the enteropathy of CD are aspects of malabsorption and related sequelae associated with substantial morbidity such as anemia, nutritional deficiencies, growth disturbances, weight loss and osteopenia or osteoporosis (Maki and Collin, 1997; AGA, 2001; Fasano and Catassi, 2001; Green et al., 2001; Meyer et al., 2001; Farrell and Kelly, 2002; Green and Jabri, 2003; Dickson et al., 2006). Other signs and symptoms that have been reported in those afflicted by CD are, among many others, fatigue, irritability, malaise, anorexia, mouth ulcers, headaches, mood changes, depression, pain and various neurological responses (Maki and Collin, 1997; AGA, 2001; Fasano and Catassi, 2001; Green et al., 2001; Farrell and Kelly, 2002; Green and Jabri, 2003). However, these clinical reactions are not always exhibited in CD. Many individuals can have underlying histological abnormalities in the small intestine mucosa that characterizes them as having CD but they remain asymptomatic or subclinical (Maki and Collin, 1997; AGA, 2001; Fasano and Catassi, 2001; Green and Jabri, 2003; Dickson et al., 2006). This disease status is sometimes referred to as silent CD (Maki and Collin, 1997; Green and Jabri, 2003). Further, in some cases of CD, individuals appear to be asymptomatic or they do not report the classic CD-related gastrointestinal symptoms (Fasano and Catassi, 2001), but closer evaluation of their clinical state reveals they often experience some degree of atypical CD-related condition(s) (e.g., anemia, fatigue, neurological problems, short stature) not always readily recognized, at least initially, by the patients or their physicians as CD (Ventura et al., 1999; Fasano and Catassi, 2001; Green and Jabri, 2003). This often leads to a delayed diagnosis of many years (often >10 years) for CD sufferers with contributing factors to this delay being adherence first to one or more alternate diagnoses and/or consultation with more than one physician prior to receiving a correct diagnoses of their illness (Green and Jabri, 2003; Green et al., 2001) . Finally, some investigators (Maki and Collin, 1997; Fasano and Catassi, 2001; Murray et al., 2003) have noted a change in the nature and/or pattern of the presentation of the signs and symptoms in those afflicted with CD in recent decades. A greater proportion of newly diagnosed cases exhibit atypical clinical features of the disease than seen in the past where the typical, classic CD-associated gastrointestinal symptoms were more likely identified.